Protease inhibitor therapy and fetal growth potential in HIV-positive women

Our objective was to test if protease inhibitors (PIs) increase the incidence of fetal growth restriction (FGR). Human immunodeficiency (HIV)-seropositive women were studied. At birth the neonatal weight percentile was assigned by predicted growth potential (GP), accounting for race, parity, weight, height, gestational age, birthweight, and gender (Gardosi, 1992). FGR was defined as GP < 10% percentile. Maternal age, CD4 count, viral load, weight gain, prenatal care, tobacco, alcohol, substance abuse, and PI use were related to FGR using chi-square and multiple regression analysis. Ninety-three of 191 women received PI. In these, FGR occurred in 27 (29%) compared with 15 (15.3%) in the non-PI group ( P = 0.02). Maternal CD4 count ( P < 0.0001) was the primary determinant, and smoking ( P = 0.037) was an independent cofactor for FGR (Nagelkerke r2 = 0.24). Twenty-six of 82 (31.7%) smokers had FGR, versus 16 of 109 (14.7%) of nonsmokers (odds ratio, 2.69; 95% confidence interval, 1.33 to 5.46; P = 0.005). After exclusion of the CD4 count, PI became a cofactor for FGR ( P = 0.021 and Nagelkerke r2 = 0.104). We concluded that maternal HIV status and smoking determine the risk for FGR. Although PIs increase the risk for FGR, this effect appears to depend on maternal disease severity.     

A longitudinal study of arrested batterers, 1995-2005: career criminals

An examination of the abuse and criminal careers of 342 men arraigned in the Quincy, Massachusetts, District Court for a crime of domestic violence between 1995 and 1996 through 2004 reveals decade-long criminal and abuse careers largely undeterred by arrest, prosecution, probation supervision, incarceration, and batterer treatment. Although only a minority reabused (32%) or were arrested for any crime (43%) within a year of the study court arraignment, over the next decade, the majority (60%) reabused, and almost three fourths were rearrested for a domestic abuse or non-domestic abuse crime. The research suggests that short-term cessation of domestic violence achieved after a variety of interventions may not indicate longer-term behavior change.     

Accuracy of fetal fibronectin to predict preterm birth in twin gestations with symptoms of labor

OBJECTIVE: To investigate accuracy of fetal fibronectin testing to predict preterm birth in twin gestations with symptoms of preterm labor. METHODS: We reviewed charts of all patients with twin gestations who underwent fetal fibronectin testing and presented with complaints of preterm labor between January 1, 2000, and June 30, 2004. We also reviewed the charts of all singleton gestations with similar complaints that had fetal fibronectin testing between January 1, 2000, and December 31, 2001. All samples were processed using a rapid fetal fibronectin detection system. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of fetal fibronectin testing in singleton and twin gestations in predicting delivery within 14 days of testing. RESULTS: Four hundred twenty-nine singletons and 87 twins met the inclusion criteria. The birth rate before 34 weeks of gestation for singletons was 3.5% compared with the rate of twin pregnancies of 28.7%. Fetal fibronectin predicted delivery within 14 days of testing with a sensitivity, specificity, and positive and negative predictive values in singleton gestations of 82%, 90%, 17%, and 99%, respectively. In twin gestations, fetal fibronectin predicted delivery within 14 days of testing with a sensitivity, specificity, and positive and negative predictive values of 71%, 74%, 19%, and 97%, respectively. CONCLUSION: As noted in singleton pregnancies, fetal fibronectin testing in twins has a high negative predictive value. Fetal fibronectin evaluation may be a useful tool in screening twins with symptoms of preterm labor, because a negative result places these women at a low risk for delivering within 2 weeks of testing.     

Management of cervical weakness based on the measurement of cervical resistance index

OBJECTIVE: To assess the value of measuring cervical resistance index (CRI) as an aid to selecting patients with a history of spontaneous mid-trimester miscarriage for cervical cerclage in subsequent pregnancies. STUDY DESIGN: An observational study of 175 patients with a history of one or more spontaneous mid-trimester losses and 123 non-pregnant women who had CRI measurements performed while undergoing routine gynaecological surgery. Those women whose CRI indicated an incompetent cervix were recommended for cervical cerclage in future pregnancies while women with a normal CRI were recommended for conservative management without cerclage. RESULTS: The median CRI in the 123 control women was 38.26 N while the median CRI in the study group was 17.00 N. In 62 of the 175 study women (35%) the CRI findings were at variance with the history of previous mid-trimester loss; 30 (16.6%) were deemed competent on CRI whereas the history suggested incompetence and 32 (18.4%) were incompetent on CRI while the history suggested that the cervix should be competent. The 175 study women had had 486 previous pregnancies with a successful outcome in 27.4% of the pregnancies. Ninety-four patients have now had 148 pregnancies with a successful outcome in 75.8% of the pregnancies. CONCLUSIONS: Non-pregnant women with a history of spontaneous mid-trimester miscarriage have a significantly lower cervical resistance index than parous women who have not suffered mid-trimester loss. In 35% of patients the CRI was at variance with the history of the previous loss. CRI may be a useful technique to aid the diagnosis of cervical weakness allowing a rational selection for treatment with prophylactic cervical cerclage.     

Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions

Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast/Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk ovarian cancer. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2 or MSH6, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancer as well as a 9-12% lifetime risk of ovarian cancer. Genetic risk assessment enables physicians to provide individualized evaluation of the likelihood of having one of these gynecologic cancer predisposition syndromes, as well the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Hereditary cancer risk assessment is a process that includes assessment of risk, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from hereditary cancer risk assessment for Hereditary Breast/Ovarian Cancer and the Lynch/Hereditary Non-Polyposis Colorectal Cancer syndrome.     

Prophylactic antibiotics for the prevention of preterm birth in women at risk: a meta-analysis

BACKGROUND: Preterm birth (PTB) is the major determinant of perinatal morbidity and mortality. Infection is implicated in a large proportion of preterm deliveries, but there is no consensus regarding the efficacy of antibiotic prophylaxis for women at risk. AIM: To determine whether antibiotic treatment reduces the risk of preterm delivery in asymptomatic pregnant women at risk of PTB. METHOD: Relevant publications were identified via electronic searches of MEDLINE (1966 to August 2005), The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Central Register of Controlled Trials (the Cochrane Library, Issue 3, 2005) and PubMed using multiple search terms related to PTB and antibiotics. Publications were limited to randomised controlled trials comparing antibiotics with placebo given to asymptomatic non-labouring women. A random effect model was used, and combined risk ratios calculated for the various risk groups. Associations between treatment effect and the rate of PTB were analysed by meta-regression. RESULTS: Seventeen trials were included, 12 identifying women at risk by abnormal vaginal flora, three on women at high risk from a previous PTB and two recruiting women based on positive fetal fibronectin status. There was no significant association between antibiotic treatment and reduction in PTB irrespective of criteria used to assess risk, the antimicrobial agent administered, or gestational age at time of treatment (overall combined random effect for delivery at less than 37 weeks RR 1.03 (95% CI 0.86-1.24)). CONCLUSIONS: Treating women at risk of PTB with antibiotics does not reduce the risk of subsequent PTB.     

Tertiary cytoreductive surgery in recurrent ovarian cancer: selection criteria and survival outcome

OBJECTIVES: Studies of tertiary cytoreductive surgery (TCS) in recurrent epithelial ovarian cancer are limited, and appropriate patient selection remains a clinical challenge. We sought to evaluate the impact of TCS on survival and to determine predictors of optimal tertiary resection. METHODS: Between January 1997 and July 2004, 47 women with recurrent epithelial ovarian cancer underwent TCS at two institutions. All patients received initial platinum and taxane-based chemotherapy following primary cytoreductive surgery. Clinico-pathologic factors and survival were retrospectively abstracted from medical records. Optimal TCS was defined as microscopic residual disease. RESULTS: Thirty of 47 (64%) patients underwent optimal TCS. Size of tumor implants<5 cm on preoperative imaging was the only significant predictor of achieving optimal TCS. Overall survival after TCS was statistically longer in patients with microscopic versus macroscopic residual disease (24 versus 16 months, p=0.03). After controlling for age, time to progression and optimal TCS, only the presence of diffuse disease at tertiary exploration remained a significant poor predictor of survival. However, in a cohort of patients with limited disease implants, multivariate analysis indicated that optimal TCS retained prognostic significance as a positive predictor of survival. Twelve patients (26%) experienced severe postoperative complications, including six with pulmonary embolism, four with fistulae and two with postoperative myocardial infarctions. CONCLUSIONS: Size of disease implants on preoperative imaging may guide the selection of candidates for TCS. In those patients with limited disease implants at laparotomy, optimal TCS is associated with improved survival.     

The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer

OBJECTIVE: The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment. METHODS: Retrospective single institution analysis of patients surgically staged for IIIA endometrial cancer at Duke University Medical Center from 1973 to 2002. Stage IIIA patients were stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae or uterine serosa (group IIIA2, n=20). Comparison was made with previously reported group of 467 patients with surgical stage I/II disease. Recurrence and survival were analyzed using Kaplan-Meier estimations and Cox proportional hazards model. RESULTS: Mean age of 57 patients with stage IIIA endometrial cancer was 63. Adjuvant therapies were administered to 89% patients (74% radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively. Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32 84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included extrapelvic component. In multivariable analysis of stage I-IIIA patients (n=517), positive cytology but not adnexal/serosal metastasis was predictive of death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07-2.71). CONCLUSION: Among patients with stage IIIA endometrial cancer, metastasis to adnexae or serosa does not appear to confer worse prognosis than positive cytology alone. Positive cytology is an independent predictor of prognosis among patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for these groups remains unclear, recurrence patterns suggest that systemic therapies are appropriate.