Showing papers in "Obstetrical & Gynecological Survey in 2006"

Effect of Screening and Adjuvant Therapy on Mortality From Breast Cancer

Abstract: In several countries, a drop in mortality from breast cancer has been documented starting in 1975. Both early detection by mammographic screening and advances in management are plausible explanations. The National Institutes of Health have used a competitive peer review process to develop 7 independent statistical models of breast cancer incidence and mortality. A consortium of investigators used the same sources to obtain data on screening mammography, adjuvant treatment, and health benefits relating to the rate of death from breast cancer in the years 1975-2000. The use of mammographic screening in women age 40 and over increased markedly over the period 1985 to 2000. The use of adjuvant treatment depended on numerous factors beside the calendar year, including age, tumor stage, and estrogen-receptor status. The proportion of women given adjuvant treatment increased from virtually none in 1975 to approximately 80% in 2000. By 2000, half of all women were using tamoxifen. All 7 models predicted similar proportional reductions in mortality from a combination of screening and adjuvant therapy. The proportion of overall reduction in breast cancer deaths ascribed to screening ranged from 28% to 65% (median, 46%). The remaining decrease in mortality was associated with adjuvant treatment. Variation between models in the absolute contribution of screening was greater than for treatment. Combined screening and adjuvant therapy reduced breast cancer mortality by 25 to 38% (median, 30%). The proportion of decreased mortality ascribed to adjuvant treatment was 12 to 21% (median, 19%). For each of the 7 models, the combination of screening and adjuvant treatment lowered mortality slightly less than the sum of contributions from screening and adjuvant therapy alone. The investigators conclude from these findings that both mammographic screening and adjuvant treatment have helped to lower deaths from breast cancer in the United States.

Diagnostic Performance of Digital versus Film Mammography for Breast-Cancer Screening

Abstract: Previous trials, limited in many respects, have not found digital mammography to be significantly more accurate than the standard film method. A total of 42,760 asymptomatic women seen at 33 sites in the United States and Canada requested screening mammography and underwent both film and digital examinations. Two radiologists independently interpreted the film and digital mammograms. All participants either had breast biopsy within 15 months after evaluation or had a follow-up mammogram 10 months or longer after entry to the study. The results were assessed by receiver operating characteristic analysis. Both digital and film mammograms were positive in 0.5% of women. Another 2.2% had only a positive digital study, whereas 1.9% had only a positive film study. In the remaining women, approximately 95% of the total, both imaging studies were negative. Of 335 breast cancers diagnosed within 455 days after entry to the study, approximately three fourths were found within a year after evaluation. There were no substantial differences between the digital and film findings with respect to histology or stage of disease. The area under the curve was similar for the 2 studies and was not influenced by race or the risk of breast cancer. Digital mammography did, however, perform significantly better than the film method in women less than 50 years of age, in those having heterogeneously dense or very dense breasts, and premenopausal or perimenopausal women. The digital and film methods performed equally well in women age 50 years and older, those with fatty breasts or scattered fibroglandular densities, and those who were postmenopausal.

Whole-Body Hypothermia for Neonates With Hypoxic???Ischemic Encephalopathy

Abstract: This randomized, controlled trial had as its goal to determine whether whole-body cooling, begun within 6 hours of birth and continuing for 72 hours, reduces disability and mortality in term infants with moderate or severe encephalopathy. Infants entered into the study had a gestational age of 36 weeks or longer, were admitted with either severe acidosis or perinatal complications, and required resuscitation at birth. They were randomized to usual care or whole-body cooling and were reassessed neurodevelopmentally at age 18 to 22 months. The 102 infants assigned to hypothermia were placed on a blanket precooled to 5°C and the esophageal temperature, measured with a probe, was reduced to 33.5°C. A second blanket then was attached to the cooling system decrease variability in esophageal temperature. A skin probe monitored the temperature of the abdominal-wall skin. At both sites, temperature was monitored continuously and recorded every 15 minutes for 4 hours and then hourly for 8 hours. After 72 hours, the set point of the automatic control on the cooling system was increased by 0.5°C per hour. After 6 hours, the esophageal probe was removed and warming continued until the set point of the warmer reached 36.5°C. The 106 control infants were exposed to an overhead radiant warmer to maintain an abdominal-wall skin temperature of 36.5°C to 37.0°C. The incidence of death or moderate/severe disability was 44% in treated infants and 62% of control infants (risk ratio [RR], 0.72; 95% confidence interval [CI], 0.54-0.95). Approximately one fourth of actively treated infants (24%) and 37% of control infants died (RR, 0.68; 95% CI, 0.44-1.05). No increase in major disability was observed in surviving infants. Cerebral palsy occurred in 19% of the hypothermia group and 30% of control infants (RR, 0.68; 95% CI, 0.38-1.22). These results suggest that whole-body cooling, or hypothermia, is a safe and effective means of limiting mortality and reducing disability in newborn infants with moderate or severe encephalopathy.

First-Trimester or Second-Trimester Screening, or Both, for Down???s Syndrome

Abstract: Debate continues over whether to screen pregnant women for fetal Down syndrome in the first or the second trimester of pregnancy or in both trimesters. The First- and Second-Trimester Evaluation of Risk Factors (FASTER) Trial obtained direct comparative data on current screening methods from 38,167 women with singleton pregnancies who were cared for at 15 U.S. centers over approximately 3 years in 1999-2002. Down syndrome was found in 117 instances. Inclusion criteria included a maternal age of 16 or older and a fetal crown-rump length of 36 to 79 mm-consistent with a gestational age of 10 weeks 3 days through 13 weeks 6 days. First-trimester screening combined measurement of the nuchal translucency with maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) levels. Quadruple screening in the second trimester, from 15 to 18 weeks gestation, included alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin. Stepwise sequential screening, in which the Down syndrome risk estimate was provided after each test, was compared with "fully integrated" screening, which yielded only a single risk result after both the first- and second-trimester screening tests had been done. Although first-trimester serum screening and measurement of nuchal translucency gave similar results, the combination proved to be superior for detecting Down syndrome at 11 to 13 weeks gestation. When the false-positive rate was 5%, first-trimester combined screening at 11,12, and 13 weeks identified 87%, 85%, and 82% of Down syndrome cases, respectively. The detection rate for second-trimester quadruple screening was 81%. Quadruple screening outperformed triple screening, resulting in a higher detection rate at a lower false-positive rate. With fully integrated screening, in which the first-trimester studies were performed at 11 weeks gestation, 96% of cases were detected. For women younger than 35 years of age, first-trimester combined screening detected 75% of cases at a 5% false-positive rate, compared with 77% and 2.3%, respectively, for second-trimester quadruple screening and 77% and 0.4% for fully integrated screening. In women aged 35 and older, first-trimester combined screening detected 95% of cases with a false-positive rate of 22%. The respective figures for second-trimester quadruple screening were 92% and 13%, and for integrated screening with first-trimester markers measured at 11 weeks, 91% and 2%. In stepwise sequential screening, women have combined screening in the first trimester and results are provided immediately. Women with positive results are offered chorionic villus sampling. Women with negative results return at 15 weeks for quadruple testing, and a combined risk estimate is provided at that time. Using this approach and setting the false-positive rate for each component at 2.5%, 95% of cases were detected with a false-positive rate of 4.9%. For fully integrated screening, in which both first- and second-trimester tests are done but the woman gets only one risk estimate after the second-trimester tests are completed, setting the Down syndrome detection rate at 95% resulted in a false-positive rate of 4%. First-trimester combined screening is an effective means of detecting Down syndrome, assuming that there is adequate quality control for measuring nuchal translucency. Both stepwise sequential screening and fully integrated screening have high detection rates at acceptably low false-positive results. The lower false-positive rate must be weighed against the advantages of earlier diagnosis using sequential screening.

Combined oral contraceptives in women with systemic lupus erythematosus

Abstract: The Oral Contraceptives part of the Safety of Estrogens in Lupus Erythematosus National Assessment (OC-SELENA) study was a prospective, randomized, double-blind trial carried out at 15 U.S. centers that examined the effects of oral contraceptives on disease activity in 183 premenopausal women with systemic lupus erythematosus. Initially, disease was inactive in 76% of participants and active but stable in the remaining 24%. Participants were assigned to receive 35 μg triphasic ethinyl estradiol plus 0.5, 0.75, or 1 mg norethindrone, or placebo, for 12 28-day cycles. None of the subjects had moderate to high titers of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. Just over one third of patients in each group failed to comply throughout the 12-month study. Only seven of 91 women given oral contraceptives and seven of 92 placebo recipients had a severe flare of disease during the study. Two flares in the active treatment group occurred when the study drug was omitted. On Cox proportional-hazards analysis, the relative risk (RR) of a severe flare occurring during OC treatment, compared with placebo, was 0.93 (95% confidence interval [CI], 0.33-2.65). The estimated difference was less than the maximum clinically acceptable difference. Participants in both groups who had active disease at the outset were likelier than those whose disease was inactive to have a severe flare. The estimated RR, adjusted for treatment, was 3.5 (95% CI, 1.23-9.99). Rates of moderate or mild flares were similar in the treatment and placebo groups. The likelihood of having at least one flare of any degree during 12 months of follow up was 76% for actively treated patients and 69% for those in the placebo group (RR, 1.09; 95% CI, 0.76-1.55). One OC-treated patient had deep venous thrombosis (DVT) and one had a clotted graft. In the placebo group, there was one case each of DVT, ocular thrombosis, and superficial thrombophlebitis, and one woman died after the trial ended. These findings endorse the use of oral contraceptives, including estrogen, as a birth control measure by women having inactive or active but stable systemic lupus erythematosus. These patients are at relatively low risk of developing thrombosis.

Adult weight change and risk of postmenopausal breast cancer

Abstract: Several prospective studies have found that weight gain starting in the early adult years is associated with an increased risk of postmenopausal breast cancer. Endogenous hormones are a primary factor in breast cancer, and adiposity can alter circulating hormone levels, especially in postmenopausal women. This prospective cohort study, based on data from the Nurses' Health Study, followed 87,143 postmenopausal women 30 to 55 years of age for up to 26 years (from 1976-2002) to discern the influence, if any, of weight change since age 18. Weight change since menopause was estimated in 49,514 women who were followed for as long as 24 years. A total of 4393 cases of invasive breast cancer were documented in postmenopausal women in this study. The participants had gained an average of 12 kg since age 18 and 3 kg since menopause during an average postmenopausal interval of 11 years. Compared with women who maintained their body weight or gained less than 2 kg since age 18, those who gained weight had a higher body mass index throughout follow up and drank less alcohol. In addition, they were less likely to exercise and to have used postmenopausal hormones (PMH) for longer than 5 years. Women who had gained 25 kg or more since age 18 had a multivariate-adjusted relative risk (RR) of developing invasive breast cancer of 1.45 (95% confidence interval [CI], 1.27-1.66). Weight gainers who had used PMH at any time were at increased risk compared with those never using hormones. For all postmenopausal women and for those who had used PMH at any time, weight loss correlated with a lower risk of breast cancer. Compared with women who maintained their body weight, those who had gained 10 kg or more since menopause were more likely to have breast cancer (RR, 1.18; 95% CI, 1.03-1.35). Women who had never used PMH, who had lost 10 kg or more of body weight since menopause, or who had maintained their weight loss all were at lower risk than those who maintained their weight. For the total study population, 15% of cases of breast cancer could be attributed to weight gain of 2 kg or more since age 18 and 4.4% to a gain of 2 kg or more since menopause. Population-attributable risks incurred by women not using PMH were 24.2% for weight gain since age 18 and 7.6% for weight gain since menopause. These findings suggest that weight loss-even if deferred until after menopause-may lower the risk of invasive breast cancer. It is never too late to lose weight.

Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer

Abstract: Estrogen receptor (ER) status is, in itself, a weak prognostic factor in women with breast cancer, but it does strongly predict outcomes in patients who may respond to endocrine treatment. Women who have ER-positive tumors do substantially better as a group than do those with ER-negative disease. There is mounting evidence that improved chemotherapy confers more benefit on patients with ER-negative tumors. The authors retrospectively analyzed the results of adjuvant chemotherapy in relation to ER status in a total of 6644 women with lymph node-positive breast cancer. Participants were enrolled in one of 3 consecutive randomized chemotherapy trials carried out by the Cancer and Leukemia Group B and the US Breast Cancer Intergroup. Drugs offered in the three trials included cyclophosphamide, doxorubicin, fluorouracil, and paclitaxel. A clear majority of women, approximately 60%, had ER-positive tumors. In all 3 studies, differences in outcome relating to treatment group were significant for ER-negative but not for ER-positive patients who received tamoxifen. Nevertheless, women with ER-positive tumors had a numerically lower risk of both recurrent disease and death with more intensive treatment. The pattern of risk over time was similar for ER-negative patients across the 3 studies; the risk was comparatively high in the first 2 to 3 years after treatment. Risks for ER-positive patients also were similar across studies, but-in contrast to ER-negative patients-the risk of an event in the first few years was very low. This, however, appeared to reflect tamoxifen therapy rather than ER status. The risk for ER-positive patients who did not receive tamoxifen was similar to that for ER-negative patients. Absolute improvement in disease-free and overall survival rates was substantially greater in ER-negative women. For instance, 23% more ER-negative patients lived 5 years without disease if given chemotherapy compared with 7% of ER-positive patients. The respective figures for overall survival were 17% versus 4%. The investigators believe that women with ER-positive breast cancer may reasonably decide to receive chemotherapy, but they should recognize that the expected benefit is less than for their peers with ER-negative tumors. At present, the outlook for women with ER-negative tumors is approaching that for optimally treated women with ER-positive disease. Modern intensive (and extensive) chemotherapy offers substantial benefit to ER-negative women in terms of overall survival and disease-free survival.

Low-Fat dietary pattern and risk of invasive breast cancer: The women's health initiative randomized controlled dietary modification trial

Abstract: Despite a longstanding belief that a low-fat diet can reduce the risk of breast cancer, no controlled intervention trials have been reported. This randomized, controlled, primary prevention trial, based on the Women's Health Initiative cohort, enrolled 48,835 postmenopausal women 50 to 79 years of age at 40 U.S. clinical centers in the years 1993-2005. Forty percent of participants received a diet designed to lower the intake of total fat to 20% of energy, provide at least 5 servings daily of fruit and vegetables, and include at least 6 daily servings of grains. There was no explicit weight loss goal. The remaining 60% of women continued on their usual diets. The intervention group took part in an intensive behavioral modification program administered by a specially trained nutritionist. Participants received an individualized goal of total fat grams based on height and were trained to monitor their dietary intake. The comparison women were given informational materials, including dietary guidelines. At baseline, dietary and other variables, including body weight, were nearly identical in the intervention and control groups. Women in the diet group had a small decrease in energy consumption. The difference between groups in change from baseline in the percentage of energy from fat ranged from 10.7% after 12 months to 8.1% at year 6. The intervention group ate more fruits and vegetables, but there was less difference in grain consumption. The annualized incidence rate of invasive breast cancer during an average follow up of 8.1 years was 0.42% in the intervention group and 0.45% in the comparison group. The hazard ratio was 0.91% with a 95% confidence interval of 0.83 to 1.01. Rates of total cancer (excluding non-melanoma skin cancer), breast cancer mortality, and total mortality all were slightly lower for the intervention group, but the differences were not significant at the 0.05 level. Women who actively participated in the dietary intervention program and those consuming a high-fat diet at baseline had lower hazard ratios. The breast cancer risk also was lower in women with a relatively high baseline percentage of energy from fat. Tumor grade and size, lymph node status, and stage of breast cancers all were similar in the intervention and comparison groups. A lower hazard ratio was noted for progesterone receptor-negative tumors, but there was no apparent association with estrogen receptor status. A low-fat diet failed to lessen the risk of invasive breast cancer in this large trial of postmenopausal women during a follow up averaging approximately 8 years. Nevertheless, the trends observed, although not statistically significant, warrant longer-term studies. Any beneficial effects of reduced fat intake might take years to fully emerge.

Denosumab in postmenopausal women with low bone mineral density

Abstract: Despite the availability of drugs that lower the risk of bone fracture in osteoporotic patients, few patients comply fully with current treatments. The investigators evaluated denosumab-previously known as AMG 162-a fully human monoclonal antibody (immunoglobulin G 2 ) that binds strongly and specifically to RANKL or receptor activator of nuclear factor-KB ligand. RANKL is a protein expressed by osteoblastic stromal cells and is the major mediator of osteoclast differentiation, activation, and survival. RANKL underlies osteoclast-mediated bone resorption. Denosumab acts by blocking the interaction of RANKL with RANK and mimics the effects of osteoprotegerin. This randomized, placebo-controlled study examined the effects of subcutaneously administered denosumab over 12 months in 412 postmenopausal women aged up to 80 years with low bone mineral density (BMD) defined as a T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur. Participants were assigned to receive denosumab either every 3 months in a dose of 6, 14, or 30 mg or every 6 months in a dose of 14, 60, 100, or 120 mg; alendronate orally in a dose of 70 mg once a week (on an open-label basis); or placebo. The primary end point was the percentage change in BMD at the lumbar spine after 12 months. A total of 369 women, 90% of the original sample, completed 12 months of treatment. BMD at the lumbar spine increased from 3.0% to 6.7% at 12 months in women given denosumab compared with a decrease of 0.8% in placebo recipients (P <.001). Total hip BMD increased by a mean of 1.9% to 3.6% with denosumab treatment and fell 0.6% in placebo patients (P <.001). BMD also increased in the distal radius in women given denosumab. Alendronate increased BMD compared with placebo at 12 months. Serum levels of C-telopeptide, a marker of bone turnover, decreased in women given denosumab compared with placebo patients. Alendronate also lowered markers of bone turnover. A small reduction in the albumin-adjusted serum calcium level was noted in the denosumab group, and concentrations of intact parathyroid hormone increased. Side effects were similar in all groups except for dyspepsia, which was significantly more frequent in women given alendronate. Denosumab deserves further study as a possible treatment for osteoporosis in postmenopausal women.

Squamous vulvar intraepithelial neoplasia : 2004 modified terminology, ISSVD vulvar oncology subcommittee

Abstract: The terminology for squamous vulvar intraepithelial neoplasia (VIN) was established in 1986 by the International Society for the Study of Vulvar Disease (ISSVD). In this classification, abnormal changes in vulvar tissue seen on cytology are categorized as VIN 1, VIN 2, or VIN 3. Although the grading is similar to that used for cervical intraepithelial lesions (CIN), there is no evidence that VIN and CIN have a similar natural history or that the grading of VIN represents a biologic continuum. It is now accepted that VIN 1 has a low malignant potential and is not a precursor to VIN 2 or 3. As originally described, VIN 1 denotes basally cellular changes in the basal epithelial that are relatively uncommon and are an effect of exposure to human papillomavirus (HPV). Its diagnosis varies from pathologist to pathologist and is not reproducible. The categories of VIN 2 and VIN 3 have been useful in describing high-grade disease, but they do not differentiate between lesions usually associated with high-risk HPV types (VIN, usual type) and other lesions not resulting from exposure to HPV (VIN, differentiated). The ISSVD proposal for vulvar intraepithelial neoplasia uses the term VIN for all high-grade squamous lesions. Two different categories of VIN are to be used VIN, usual type, is related to HPV. It is further subdivided into 3 histologic subtypes: warty, basaloid, and mixed. These lesions are unifocal or multifocal and may present clinically as patches, erosion, plaques, papules, and nodules with hyperkeratotic, verrucous, pigmented red or white changes. The progression of VIN, usual type, to invasive cancer in untreated patients has been unequivocally demonstrated, especially in women over 30 years of age or immunocompromised women. A variant of VIN, usual type, associated with genital warts or pregnancy is seen in some younger women and can regress spontaneously. VIN, differentiated type, is not associated with HPV and is related to lichen sclerosa and/or squamous cell hyperplasia. It is a less common diagnosis usually seen in older women. It usually presents as a warty papule or hyperkeratotic plaque. It is commonly seen during follow up of women who have been treated for lichen sclerosus or invasive vulvar cancer. Rarely, a pagetoid type of VIN is seen that cannot be classified as either VIN, usual type, or VIN, differentiated type. This type of VIN can be termed VIN, unclassified.

Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women

Abstract: Raloxifene is a nonsteroidal selective estrogen receptor modulator that has favorable effects on markers of cardiovascular risk and has been associated with a reduced risk of coronary heart disease (CHD) in postmenopausal women. Raloxifene also has antiestrogenic effects on the breast and in animals has suppressed the growth of estrogen-stimulated mammary cancers. The Raloxifene Use for The Heart (RUTH) trial was a randomized, double-blind, placebo-controlled study carried out at 177 sites in 26 countries. The 10,101 participants were women aged 55 and older who were at least 12 months postmenopausal and who either had established CHD or were at increased risk. They were assigned to receive either 60 mg raloxifene orally each day or a placebo. The 2 groups were similar in baseline characteristics except for slightly higher cardiovascular risk scores for women assigned to raloxifene. During a median follow up of 5.6 years, no significant differences were found with respect to deaths from coronary causes, nonfatal myocardial infarction, or hospital admission because of an acute coronary syndrome. Women with established CHD and those at increased risk for CHD had similar outcomes. For the primary coronary outcome, the results of as-treated analyses were comparable to those of intention-to-treat analyses. Raloxifene was associated with a decreased incidence of invasive breast cancer; the hazard ratio was 0.56 with a 95% confidence interval of 0.38 to 0.83. The absolute risk reduction for every 1000 women given raloxifene for 1 year was 1.2 cases for both invasive breast cancer and estrogen receptor-positive invasive breast cancer. Among secondary outcomes, the incidence of stroke did not differ significantly between the raloxifene and placebo groups, but fatal strokes were 49% more frequent in raloxifene-treated women. Venous thromboembolic events were 44% more frequent in the raloxifene group. Incidence rates of all breast cancers and of clinical vertebral fractures were lower in the raloxifene group. More than 90% of women in both groups reported adverse events. Rates of discontinuance because of side effects were 22% in the raloxifene group and 20% in the placebo group. Serum levels of low-density lipoprotein cholesterol declined in women given raloxifene but increased in placebo recipients. Levels of high-density lipoprotein cholesterol increased in both groups but more so in women treated with raloxifene. Raloxifene treatment, given for a median of over 5 years to postmenopausal women at increased risk of CHD, did not significantly alter CHD risk in the RUTH study. Its beneficial effects in lowering the risk of invasive breast cancer and vertebral fracture must be weighed against increased risks of fatal stroke and venous thromboembolism.

Passive Immunization During Pregnancy for Congenital Cytomegalovirus Infection

Abstract: Approximately 1 % of all newborn infants reportedly have congenital cytomegalovirus (CMV) infection. The disorder is symptomatic in approximately one in 10 infants, and clinically significant neurologic sequelae develop in nearly half of them. Neurologic defects eventually develop in as many as 13% of newborn infants who lack symptoms. This prospective study evaluated hyperimmune globulin for treating or preventing fetal CMV infection. Participants were pregnant women with primary CMV infection. Women with primary infection for longer than 6 weeks were offered amniocentesis and treatment with 200 U/kg of intravenous hyperimmune globulin if CMV DNA was identified in amniotic fluid. If necessary, subsequent doses of 400 U/kg were given intravenously or into the umbilical cord or amniotic fluid. Women who declined amniocentesis were offered preventive treatment (100 U/kg of hyperimmune globulin per month). Untreated women served as control subjects. Of women with documented fetal infection, only one of 31 given hyperimmune globulin delivered an infant with CMV disease compared with 7 of 14 untreated women. On logistic regression analysis, treatment significantly lowered the risk of congenital disease. For prevention of fetal infection, 37 women received monthly infusions of hyperimmune globulin 2 to 11 weeks after presumed maternal seroconversion. Of these, 6 (16%) delivered an infected infant compared with 19 of 47 (40%) of untreated women. Treatment was the only factor that predicted a significant reduction in the risk of congenital infection. Treatment, whether therapeutic or preventive, correlated significantly with increased titers of CMV-specific immunoglobulin G. The percentage of total natural killer cells was significantly less in women receiving hyperimmune globulin. No adverse events were observed. Intravenous treatment with CMV-specific hyperimmune globulin is safe and may be effective both in preventing congenital infection and treating established infection.

Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes. The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial

Abstract: The selective estrogen receptor modulator (SERM) tamoxifen has long been used to treat both early and advanced breast cancer. Raloxifene is a second-generation SERM that, in addition to combatting osteoporosis, may also lessen the risk of invasive breast cancer in postmenopausal women; The National Surgical Adjuvant Breast and Bowel Project (NSABP) Study of Tamoxifen and Raloxifene (STAR) is a prospective, randomized, double-blind trial conducted at nearly 200 clinical centers throughout North America. Participating were 19,747 postmenopausal women whose mean age was 58.5 years and whose 5-year breast cancer risk was increased at 4.03%. The minimal 5-year risk for entering the trial was 1.66%. The women received either 20 mg tamoxifen or 60 mg raloxifene daily for 5 years. During a mean follow up of 3.9 years, there were 163 cases of invasive breast cancer in women assigned to receive tamoxifen and 268 in those assigned to raloxifene, for respective incidence rates of 4.3 and 4.4 per 1000 and a risk ratio (RR) of 1.02 (95% confidence interval [CI], 0.82-1.28). Noninvasive breast cancers were less numerous in the tamoxifen group (RR, 1.40; 95% CI, 0.98-2.00), but uterine cancers were more frequent in this group (RR, 0.62; 95% CI, 0.35-1.08). No group differences were documented for invasive cancer at other sites, ischemic heart disease events, or strokes. Thromboembolic events were less frequent in raloxifene-treated women. Women in the 2 treatment groups had similar numbers of osteoporotic fractures. Those taking raloxifene had fewer cataracts and underwent fewer cataract surgeries. There was no difference in total deaths, and causes of death were similarly distributed in the 2 groups.

Duration of lactation and incidence of type 2 diabetes

Abstract: Lactation places a considerable metabolic burden on mothers through increasing energy requirements, but there are reports that lactation may lower the risk that type 2 diabetes will develop in the future. The authors report a prospective observational cohort study examining the association between type 2 diabetes and the history of lactation in 83,585 parous women enrolled in the Nurses' Health Study (NHS). In addition, a retrospective observational cohort study was undertaken in 73,418 parous women taking part in the Nurses' Health Study II (NHS II). A history of breast feeding was obtained from 64% of women in the NHS cohort and 85% of those in the NHS II cohort. In both groups, the lifetime duration of breast feeding increased with parity. Women who breastfed for longer times were relatively less likely to have a family history of diabetes. In the NHS cohort, there were 5145 cases of type 2 diabetes during 1,239,709 person-years of follow up in the years 1986-2002. The NHS II cohort included 1132 women diagnosed as having type 2 diabetes during 778,876 person-years of follow up in 1989-2001. An increased duration of lactation was associated with a lower risk of type 2 diabetes. Women in the NHS group who gave birth in the past 15 years had a 15% reduction in the risk of diabetes for each additional year of lactation. The corresponding risk reduction in the NHS II cohort was 14%. These estimates were made while controlling for current body mass index and other risk factors relevant to type 2 diabetes. Women in the NHS II cohort who had a history of gestational diabetes were at markedly increased risk of developing type 2 diabetes, but lactation had no influence on the risk of diabetes in these women. In these large cohorts of parous women, those reporting an increased duration of breast feeding were at reduced risk of developing type 2 diabetes. Along with clinical reports of improved glucose metabolism in lactating women, these findings suggest that lactation may lower the risk of type 2 diabetes in young and middle-aged women. The physiological factors underlying this association require further study.

Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment: Commentary

Abstract: Nongravid individuals are known to be at high risk of having a relapse of depression if antidepressant therapy is discontinued. Pregnant women presumably are also at risk, despite the long held view of pregnancy as somehow protecting against psychiatric illness. This prospective study compared the risk of relapse in pregnant women who maintained or discontinued antidepressive drug treatment. The participants were 201 pregnant women cared for at centers expert in managing psychiatric disorders during pregnancy. All of them had a history of major depression before pregnancy, were at less than 16 weeks gestation, and had been euthymic for at least 3 months before the last menses. The women were currently receiving antidepressant therapy or had received it within 12 weeks before the last menstrual period. Participants were assessed using the Hamilton Rating Scale for Depression (HAM-D), the Structured Clinical Interview mood module for depression, and the Clinical Global Impressions Scale. The mean age at the first episode of depression was 19 years and the mean duration of depression exceeded 15 years. Just over half the participants had a current or past history of comorbid psychiatric illness—most often anxiety and eating disorders—and 44% reported 5 or more prior recurrent depressive episodes. More than 90% of women were receiving antidepressant therapy at baseline, most often with a selective serotonin reuptake inhibitor or a dual-action antidepressant. Relapse occurred in 68% of women who discontinued their antidepressant medication and in 26% who remained on treatment. Half of all relapses occurred in the first trimester and 90% by the end of the second trimester. The risk of relapse was 45% for women who increased their medication (most likely in response to increasing symptoms indicating impending relapse) and 35% for those who decreased it. Mean HAM-D scores were 23.7 and 20.8, respectively, for those who discontinued or maintained their medication. There were no suicide attempts during the study. The time to relapse was shorter in women who increased or stopped medication than in those who maintained or decreased treatment; 60% of women who discontinued their medication at the beginning of pregnancy restarted it. After adjusting for several possibly confounding factors, women who stopped treatment had a 5-fold increase in the risk of relapsing during pregnancy compared with those who maintained their medication. Women who reintroduced their medication after stopping it had a lesser risk of relapse, although they remained more vulnerable than those who did not alter their medication. The risk of relapse during pregnancy was increased in women who had been ill for longer than 5 years and in those having more than 4 episodes of recurrent depression. These findings suggest that pregnancy does not protect against a relapse of major depression. Affected women should be made aware of the risk of discontinuing their antidepressant medication during pregnancy.

Condom use and the risk of genital human papillomavirus infection in young women

Abstract: The use of condoms substantially reduces the risk of transmitting HIV, but whether it has a similar effect on other sexually transmitted infections remains uncertain. Several studies have, in fact, found that condom use does not lower the risk of infection by human papillomavirus (HPV) in women. The present longitudinal study was an attempt to clarify the temporal relationship between condom use and HPV infection in 82 female university students 18 to 22 years of age who either had never had vaginal intercourse or had their first intercourse with one man in the past 3 months. The participants monitored their sexual behavior, and cervical and vulvovaginal samples were taken every 4 months to test for HPV DNA and for Papanicolaou testing. Follow up averaged 34 months. The cumulative 12-month incidence of a first HPV infection after first intercourse was 37%, and the 24-month cumulative incidence of cervical squamous intraepithelial lesions was 15%. Reports of having new partners in the past 8 months correlated with an increased risk of HPV infection. More frequent condom use by partners was associated with a decreased risk as was a report of partners having no previous partners. Neither the number of episodes of vaginal intercourse nor having a circumcised partner significantly influenced the risk of infection. Women whose partners had always used condoms in the past 8 months were significantly less likely to acquire HPV infection than those whose partners used condoms less than 5% of the time. Similar trends were evident for high- and low-risk types of HPV; for HPV types 6, 11, 16, and 18; and for incident cervical and vulvovaginal HPV infection. No incident cervical squamous intraepithelial lesions were found during 32 subject-years at risk in women whose partners always used condoms. In contrast, less consistent or no use of condoms was associated with 14 lesions occurring during 97 subject-years at risk. This study reveals a strong inverse temporal relationship between the use of condoms by male sex partners and the risk of HPV infection in women. Consistent condom use by male partners may protect women against infection by high-risk types of HPV that could lead to cervical cancer.

Polycystic ovary syndrome and mental health: A review.

Abstract: UNLABELLED Although physical symptoms of polycystic ovary syndrome (PCOS) are increasingly recognized by practicing clinicians, little attention has focused on psychological correlates of this frequent endocrine disorder. This review of medical and psychological literature indicates that PCOS is associated with several mental health problems, including depression and anxiety, body dissatisfaction and eating disorders, diminished sexual satisfaction, and lowered health-related quality of life. Although the causal direction of these relationships has not been established, it is clear that effective and comprehensive treatment of women with PCOS must encompass careful attention to psychological symptomatology. Recommendations for the assessment of specific mental health problems, management of related physical concerns, and treatment of obesity among women with PCOS are presented. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES After completion of this article, the reader should be able to explain that, in addition to physiologic changes, women with polycystic ovary syndrome (PCOS) have various mental health problems and lowered health-related quality of life issues and state that treatment must address these concerns.

Risk of pelvic fractures in older women following pelvic irradiation

Abstract: Pelvic fractures, especially hip fractures, are a major cause of illness and death in older women. Radiation therapy is known to cause bone damage and may increase the risk of fracture, but the risk associated with standard-course fractionation is insufficiently understood. This retrospective cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry, linked to Medicare claims data, to learn whether women having pelvic radiotherapy for anal, cervical, and rectal cancers are at increased risk of pelvic fracture. The 6428 participants were women aged 65 and older whose pelvic malignancy was diagnosed in 1986–1999. The study population included 2855 women who received radiotherapy and 3573 who did not. The study women had an average age of 74.5 years and were followed up for 4.3 years on average. A total of 2449 women were followed for 5 years or longer after receiving a diagnosis of cancer. Pelvic fractures developed in 8.6% of women during follow up. Nine of 10 injuries were hip fractures. In addition, 5.4% of women had an arm or spinal fracture. For all 3 tumor types, the cumulative incidence of pelvic fractures was greater in women receiving radiotherapy. Using a proportional hazards model to control for other factors, radiotherapy remained a significant risk factor for pelvic fracture. Hazard ratios associated with radiotherapy were 3.16, 1.66, and 1.65, respectively, for women having anal, cervical, and rectal cancers. Blacks were at lower risk of fracture, but there was no statistically significant relationship between race and radiation therapy. Older women receiving radiotherapy for pelvic cancer should be aware of the risk of fracture and considered for preventive measures such as monitoring of bone mineral density, treatment to prevent osteoporosis, and strategies for preventing falls. In addition, it may be possible to alter methods of radiotherapy so as to minimize the dose to bone.

Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section : Pragmatic randomized trial

Abstract: Corticosteroids given antenatally have reduced the incidence of respiratory distress in preterm infants. The randomized ASTECS trial was done to learn whether steroids have this effect when given to term infants delivered electively by cesarean section. A total of 998 women at 10 maternity units were randomized to receive either 2 intramuscular 12-mg doses of betamethasone within 48 hours before delivery or no steroid treatment. The treatment and control groups were similar in maternal age, asthma, and smoking history, as well as infant gender and birth weight. Of 35 newborn infants admitted to special units because of respiratory distress, 24 had not received steroid (P = 0.02). The relative risk of an infant in the treatment group being admitted to a special unit with respiratory distress was 0.46 (95% confidence interval [CI], 0.23-0.93). The risk ratio for transient tachypnea of the newborn was 0.54 (95% CI, 0.26-1.12). The risk ratio for respiratory distress syndrome in treatment cases was 0.21 (95% CI, 0.03-1.32). Respiratory distress was equally severe for treatment and control infants admitted to special care units. Logistic regression analysis showed that the predicted likelihood of admission to special care with respiratory distress at 37 weeks gestation was 5.2% in the treatment group and 11.4% in the control group. The respective figures at 38 weeks were 2.8% and 6.2%, and at 39 weeks, 0.6% and 1.5%. Adverse effects, most often generalized flushing, were noted in 7 mothers given steroid treatment. Antenatal treatment with betamethasone reduces the need for admitting newborn infants to special care units with respiratory distress after term cesarean delivery. Delaying delivery to 39 weeks gestation also is helpful.

Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature.

Abstract: Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (+/-standard deviation) patients' age was 26.7 +/- 4.9 years, the mean gestational age when WE manifested was 14.3 +/- 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 +/- 2.8 weeks. Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum.

Low-fat dietary pattern and risk of colorectal cancer: The women's health initiative randomized controlled dietary modification trial

Abstract: Previous studies have failed to document positive effects of a low-fat diet on the risk of colorectal cancer. The risk was examined in relation to the dietary pattern in the Women's Health Initiative Dietary Modification Trial. This randomized, controlled trial enrolled 48,835 postmenopausal women 50 to 79 years of age seen at 40 clinical centers throughout the United States in the years 1993-1998. The interventional diet called for at least 5 daily servings of vegetables and fruits and at least 6 servings of grains with the goal of lowering total fat to 20% of energy intake. An intensive behavioral intervention entailed 18 group sessions in the first year and, subsequently, quarterly sessions led by specially trained and certified nutritionists. Dietary goals were individualized on the basis of height. Motivational interviewing was part of the program. Forty percent of participants were assigned to the intervention and 60% to a comparison group of women who were given dietary guidelines but were not asked to change their diets. The 2 groups had similar risk profiles for colorectal cancer. During a mean follow-up interval of 8.1 years, the reduction in percentage of energy from fat was approximately 70% of that planned. Fewer than one third of women met the goal after 12 months and only 14%' at year 6. Consumption of saturated fat did decline, and women in the intervention group did eat more fruits, vegetables, and grains. Dietary intake of folate and plasma carotenoid levels increased significantly, whereas serum cholesterol levels declined. Rates of invasive colorectal cancer were 0.13% per year in the intervention group and 0.12% in the comparison group. The hazard ratio (HR) was 1.08, with a 95% confidence interval (CI) of 0.90-1.29. The cumulative hazard of colorectal cancer was very similar in the 2 management groups, and no time trend for invasive colorectal cancer was evident. Outcomes were similar in the 2 groups, and there were no significant differences in total cancer incidence, total cancer mortality, or total mortality. Tumor characteristics were similar in the 2 groups. Annualized incidence rates of self-reported colonic polyps or adenomas were lower in the intervention group (HR, 0.91; 95% CI, 0.87-0.95). The risk of colon cancer increased with advancing age, but intervention did not interact with age at baseline. This large trial gave no evidence that, when taken by midlife to late-life postmenopausal women, a low-fat diet decreases the risk of colorectal cancer over 8 years of observation.

The effect of timing of cord clamping on neonatal venous hematocrit values and clinical outcome at term : A randomized, controlled trial

Abstract: In present-day Western practice, the umbilical cord is clamped within 10 to 15 seconds after birth, but this has not proved to be better than waiting 1 to 3 minutes. Some studies show that delayed cord clamping prevents iron deficiency anemia in the first year of life, presumably because approximately 80 mL of blood is "transfused" within a minute after birth and 100 mL after 3 minutes. Other studies, however, suggest that delay in clamping the cord may increase the risk of polycythemia, respiratory symptoms, and hyperbilirubinemia. The present randomized, controlled study examined the effects of clamping the umbilical cord at different intervals after uneventful birth (15 seconds and 1 and 3 minutes) on the venous hematocrit of term newborn infants after 6 hours of life. Hematocrit was estimated in blood taken from the antecubital vein. A total of 291 women were randomized to one of 3 groups with respective average actual clamp times of 13, 60, and 169.5 seconds. Clamp times complied with the randomized goal in at least 90% of all groups. Infant hematocrit values at age 6 hours were 53.5% with early clamping, 57% in the 1-minute group, and 59% in the 3-minute group. Significantly more early-clamp infants had a hematocrit of less than 45% at 6 hours, and significantly more infants in the 3-minute group had a value exceeding 65%, denoting polycythemia. At 24 to 48 hours, a hematocrit of less than 45% was significantly more frequent in the early-clamp group, but rates of high hematocrit did not differ significantly with clamp time. The 3 groups of infants had comparable plasma bilirubin levels 24 to 48 hours after birth. There were no significant group differences in adverse neonatal events, and infants in all groups followed a similar course through the first month of life. There were no substantial differences between mothers in the 3 groups in either the volume of postpartum blood loss or the hematocrit 24 hours after giving birth. Delaying clamping of the umbilical cord for 1 to 3 minutes after birth appears to increase the infant's hematocrit within a physiological range without harmful effects. The investigators recommend this practice to increase the amount of iron stored by the newborn infant.

Conjugated equine estrogens and coronary heart disease : The women's health initiative

Abstract: In the Women's Health Initiative study, 10,739 postmenopausal women 50 to 79 years of age who had undergone hysterectomy were randomized to receive 0.625 mg daily of conjugated equine estrogens (CEE; Premarin) or placebo. The participants were seen at 40 clinical centers in the United States starting in 1993 and continuing until the trial was ended after 6.8 years rather than after 8.5 years as planned. Follow up averaged 7.1 years. At the end of the study, 54% of women assigned to receive CEE and 53.5% of those assigned to placebo had stopped using their study medication. The hazard ratio (HR) for coronary heart disease (CHD) events (coronary death and nonfatal myocardial infarction) was 0.95 (nominal 95% confidence interval [CI], 0.79-1.16). The HR for women who took at least 80% of assigned medication was 0.91 (nominal 95% CI, 0.69-1.20). The HR for the primary outcome at year 6 or later was 0.81 (95% CI, 0.60-1.10). Hazard ratios increased progressively with advancing age. The HR for women 50 to 54 years of age at baseline was 0.60 (95% CI, 0.25-1.44). Younger women had coronary revascularization less frequently when given CEE rather than placebo. For women aged 50 to 59 years at baseline, the HR of a composite outcome (myocardial infarction, coronary death, coronary revascularization, and confirmed angina) was 0.66 (95% CI, 0.45-0.96). In women aged 60 or over, secondary coronary outcomes did not differ between the CEE and placebo groups. CEE provided no overall protection against coronary death or nonfatal myocardial infarction in these posthysterectomy women, although a somewhat lower risk of CHD events was a possibility in women 50 to 59 years of age at baseline who received CEE.

Recurrence of Pre-eclampsia Across Generations: Exploring Fetal and Maternal Genetic Components in a Population Based Cohort

Abstract: Previous studies indicate that women born after a pregnancy complicated by preeclampsia are at increased risk in their own pregnancies. This increase in risk could reflect the inheritance of genes that enhance maternal susceptibility to preeclampsia or transmission to the fetus of fetal genes that can trigger preeclampsia. If fetal genes do play a role, it is logical that an increased risk of preeclampsia could also be transmitted through the father. These possibilities were examined in a population-based cohort study based on data in a medical birth registry in Norway from 1967 to 2003. Linked generational data were available on 438,597 mother-offspring units and 286,945 father-offspring units. Compared with women born after nonpreeclamptic pregnancies, women born after a preeclamptic pregnancy had an increased risk of having the disorder in both their first pregnancy (odds ratio [OR], 2.2; 95% confidence interval [CI], 2.0-2.4) and their second (relative risk [RR], 1.5; 95% CI, 1.1-2.1). For men born after a preeclamptic pregnancy, the risk of preeclampsia in their partner's first pregnancy was also increased (RR, 1.5; 95% CI, 1.3-1.7). Sisters of affected women, whose own births were not complicated by preeclampsia, were nevertheless at increased risk compared with women with no family history of the disorder (RR, 2.0; 95% CI, 1.7-2.3). No increased risk was found for brothers of affected women whose own births were not complicated by preeclampsia. Data on the clinical severity of the preeclampsia were available from 1999 on. Women having a child between 1999 and 2003 who had early-onset or clinically severe preeclampsia were much more likely to have been born after a preeclamptic pregnancy (RR, 3.0; 95% CI, 2.4-3.7). A similar but more modest effect was noted in men who fathered a pregnancy complicated by severe or early preeclampsia (RR, 1.9; 95% CI, 1.4-2.5). These findings support the view that both maternal genes and fetal genes from either parent may contribute to preeclampsia. The maternal association is stronger than the fetal (or paternal) association.

Managing ovarian masses during pregnancy.

Abstract: The management of adnexal masses during pregnancy can be challenging for the patient and the clinician The specter of a possible malignancy can sway the decision for intervention versus expectant management The etiologies of ovarian masses are reflective of the patient's age; and, therefore, benign entities such as functional ovarian cysts, benign cystic teratomas, and serous cystadenomas predominate In the unusual cases when cancer is present, they are typically germ cell and borderline ovarian tumors, and are commonly low stage and low grade Ultrasound is the primary modality used to detect ovarian masses and to assess the risk of malignancy Morphologic criteria more accurately identify benign cysts compared with malignant tumors Tumor markers are used primarily to monitor disease status after treatment rather than establish the ovarian tumor diagnosis as a result of lack of specificity, because several markers can be elevated inherent to the pregnancy itself (eg, CA-125, beta-hCG) Expectant management is recommended for most pregnant patients with asymptomatic, nonsuspicious cystic ovarian masses Surgical intervention during pregnancy is indicated for large and/or symptomatic tumors and those that appear highly suspicious for malignancy on imaging tests The extent of surgery depends on the intraoperative diagnosis of a benign versus a malignant tumor Conservative surgery is appropriate for benign masses and borderline ovarian tumors More aggressive surgery is indicated for ovarian malignancies, including surgical staging Although rarely necessary, chemotherapy has been used during pregnancy with minimal fetal toxicity in patients with advanced-stage ovarian cancer in which the risk of maternal mortality outweighs the fetal consequences

Combined Lifestyle Modification and Metformin in Obese Patients with Polycystic Ovary Syndrome: A Randomized, Placebo-controlled, Double-blind Multicentre Study

Abstract: Metformin therapy reportedly benefits women with polycystic ovary syndrome (PCOS). Its effect is presumably based on lowering serum insulin levels. Metformin inhibits glucose production in the liver and also enhances insulin sensitivity at the cellular level. This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of lifestyle change and metformin therapy in 143 women with PCOS who were oligomenorrheic or amenorrheic and had a body mass index (BMI) greater than 30 kg/m2. All patients received standard dietary advice and were placed on an individualized high-carbohydrate, low-fat diet. Metformin, given in a dose of 850 mg twice daily, was compared with placebo over 6 months. The 69 patients placed on metformin and the 74 given placebo had similar characteristics at baseline and had been infertile for similar periods. Menstrual cycles became significantly more frequent in both metformin-treated and placebo patients. The median improvement was one cycle per 6 months. Reductions in body weight and BMI were documented in both groups. None of these parameters differed significantly between the actively treated and placebo patients. In neither group did insulin sensitivity or lipid profiles change significantly. Patients given metformin had significant reductions in waist circumference and the free androgen index. On logistic regression analysis, considering metformin therapy, percentage of weight loss, initial BMI, and age, only the percentage weight loss correlated with improved menstrual function. There were 2 pregnancies in each group. In this trial, metformin did not enhance weight loss or menstrual frequency in obese patients with PCOS compared with placebo patients. Only weight loss during dietary management made menstruation more frequent.

Periodontal disease and adverse pregnancy outcomes : A systematic review

Abstract: Increasing evidence implicates periodontal disease as a factor associated with such systemic disorders as myocardial infarction, stroke, and diabetes. Adverse pregnancy outcomes also have been associated with periodontal disease. They include preterm birth, low birth weight, miscarriage, and preeclampsia. The authors undertook a comprehensive database review to identify existing evidence that supports a relationship between persistent subclinical infection of periodontal origin and adverse pregnancy outcomes. The 25 studies accepted for review included 13 case-control (including cross-sectional) studies, 9 cohort studies, and 3 controlled trials, 2 of which were randomized. The studies were carried out in 14 countries. In all, 8 of the 25 studies suggested an association between periodontal disease and an increased risk of adverse pregnancy outcomes. Odds ratios ranged from 1.10 to 20.0. Seven other studies yielded no evidence of such an association. Two case-control studies suggested that periodontal disease is a risk factor for preterm low birth weight. Two clinical trials, one of them randomized, indicated that the risk may be reversed by oral prophylaxis and treatment. A study that failed to support an association between periodontal disease and either preterm birth or low birth weight did suggest a connection with pregnancy loss at 12 to 24 weeks gestation. A correlation analysis pointed to a relationship between decreased birth weight or gestational age and more severe periodontal disease. Although the observational studies analyzed do not consistently implicate periodontal disease in adverse pregnancy outcomes, several studies do suggest the possibility of such an association. Randomized, controlled trials are in progress to determine whether periodontal treatment will lower rates of some adverse pregnancy outcomes. In addition, studies are needed to detect any association between periodontal disease and an increased risk of preeclampsia, gestational diabetes, early pregnancy loss, or restricted intrauterine growth.

Human Papillomavirus Infections With Multiple Types and Risk of Cervical Neoplasia

Abstract: Although particular human papillomavirus (HPV) genotypes have been implicated in the origin of cervical cancer, little is known about whether multiple-type HPV infections influence the risk of cervical lesions. Coinfection with multiple HPV types reportedly is more frequent in younger women and those with cytologic abnormalities or impaired immune responses. The planned use of HPV testing in programs screening for cervical cancer makes this issue especially important. The investigators sought an association between multiple HPV types and cervical lesions in 2113 Brazilian women taking part in a study of the natural history of HPVs and cervical neoplasms. Cervical specimens were typed by the polymerase chain reaction technique. Use of a repeated measurement design allowed assessment of the relationship between concurrent and cumulative numbers of HPV types and both any-grade squamous intraepithelial lesions (SILs) and high-grade SIL (HSIL). The mean follow up was 40 months and the mean number of visits was 7.4. Between 1.9% and 3.2% of women at any given visit were infected by multiple HPVs. The cumulative rate of infection by multiple types of HPV in the first year and the first 4 years of follow up, respectively, were 12.3% and 22.3%. The risk of HSIL increased markedly with the number of HPV types. Odds ratios were 41.5 (95% confidence interval [CI], 5.3-323.2) for single-type infections; 91.7 (95% CI, 11.6-728.1) for infection by 2 or 3 HPV types; and 424.0 (95% CI, 31.8-5651.8) for infection by 4 to 6 types, all compared with women who remained HPV-negative during the first year of follow up. Excess risk levels persisted after excluding women infected by HPV-16, those with high-risk types of HPV, and those with persistent infections. The risk level was especially high for coinfections by HPV-16 and HPV-58. The risk of HSIL appeared to be substantially greater for women infected by 4 to 6 HPV types compared with those having 2 to 3 types or single-type infection. These findings suggest a synergistic effect of infection by multiple HPV types on cervical carcinogenesis. It seems likely that HPV typing will increasingly become a part of clinical practice. Also, with the advent of HPV vaccination, HPV testing may prove useful in following immunized persons.

Vitamins C and E and the risks of preeclampsia and perinatal complications

Abstract: Women diagnosed with preeclampsia may be in a state of oxidative stress, but trials designed to show whether antioxidants such as vitamins C and E lessen the risk of preeclampsia have given mixed results. The Australian Collaborative Trial of Supplements is a randomized multicenter study of supplemental antioxidants in nulliparous women at 14 to 22 weeks gestation who had singleton pregnancies and were normotensive at the outset. Participants received either 4 daily tablets combining 250 mg of vitamin C as ascorbic acid and 100 IU of vitamin E as d-alpha-tocopherol succinate (total daily doses of 1000 mg and 400 IU, respectively) or placebo tablets containing microcrystalline cellulose. A total of 1877 women were entered into the trial. The supplemented and control groups were similar at baseline. Preeclampsia developed in 6.0% of patients given vitamin supplements and 5.0% of the placebo group for a relative risk of 1.20 (95% confidence interval [CI], 0.82-1.75). There also were no significant group differences in the risk of death, serious infant outcomes, or having a small-for-gestational age infant. Rates of preterm birth were comparable in the 2 groups. Significantly fewer infants whose mothers received supplemental vitamins had respiratory distress syndrome (relative risk, 0.17; 95% CI, 0.04-0.75), and fewer required surfactant. There were no differences in the need for mechanical ventilation or in measures of growth. Vitamin-supplemented women were likelier than those in the placebo group to be admitted antenatally for hypertension and also likelier to receive antihypertensive drug treatment. Preeclampsia was similarly severe in the 2 groups, and comparable numbers of women took magnesium sulfate or had labor induced because of hypertension. These findings indicate that daily supplements of vitamins C and E do not lessen the risk of preeclampsia or other abnormal perinatal outcomes in nulliparous pregnant women. Routine supplementation therefore cannot be recommended.

Intraperitoneal cisplatin and paclitaxel in ovarian cancer

Abstract: This randomized, phase III trial by the Gynecologic Oncology Group (GOG) was designed to compare treatment with intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer. study. End points were the progression-free and overall survival. Eligibility criteria included a primary diagnosis of stage III ovarian cancer with no residual mass greater than 1.0 cm after surgical treatment, at least a moderate activity level, normal blood counts, and adequate renal and hepatic function. Patients randomized to the intravenous therapy group received 135 mg intravenous paclitaxel per square meter of body surface area over a 24-hour period on day 1 and 75 mg intravenous cisplatin per square meter on day 2. Patients in the intraperitoneal therapy group were given 135 mg intravenous paclitaxel per square meter of body surface for 24 hours followed by 100 mg intraperitoneal cisplatin per square meter on day 2 and 60 mg intraperitoneal paclitaxel per square meter on day 8. New cycles were not started until neutrophil counts were greater than 1500 cells/mm 3 , platelet counts were ≥1,000,000 cells/mm 3 , and creatinine levels were ≤2.0 mg/dL. Participants were removed from the study when new cycles were delayed for more than 3 weeks. In the intraperitoneal group, patients who experienced grade 2 abdominal pain were given lower doses of the intraperitoneal drug. Persistent grade 2 abdominal pain, or grade 3 abdominal pain, or complications involving the intraperitoneal catheter resulted in a conversion to intravenous therapy for the remaining cycles. Carboplatin replaced cisplatin if severe toxicity resulting from cisplatin developed. Of the 415 women who met all eligibility criteria, 210 were randomized to the intravenous group, and 205 were assigned to the intraperitoneal group. Ninety percent of patients in the intravenous group completed six cycles of chemotherapy, and 83% received six cycles of the assigned intravenous therapy. In comparison, 83% of women in the intraperitoneal group completed six cycles of chemotherapy, but only 42% received all six cycles of the assigned intraperitoneal therapy. Compared with the intravenous group, the intraperitoneal therapy group had significantly more grade 3 or 4 adverse events, the most severe of which were fatigue, pain, or hematologic, gastrointestinal, metabolic, or neurologic toxic effects (P ≤.001 for all). After a median follow up of 48.2 months for the intravenous group and 52.6 months for the intraperitoneal therapy group, the median progression-free survivals were 18.3 months and 23.8 months, respectively (Fig. 1). The median overall survival was 49.7 months in the intravenous group compared with 65.6 months for the intraperitoneal group (Fig. 2). Quality-of-life assessments were made at baseline, before the fourth cycle, 3 to 6 weeks after the sixth cycle, and 12 months after the sixth cycle. After adjustments for confounding factors, the patients receiving intraperitoneal therapy reported lower quality-of-life scores at the prefourth cycle assessment (P <.001) and 3 to 6 weeks after completion of therapy (P =.009) compared with the patients in the intravenous group. However, 12 months after treatment, there were no differences in quality of life between the two groups.