Mary D. Sammel

The medical management of ectopic pregnancy: a meta-analysis comparing 'single dose' and 'multidose' regimens

OBJECTIVE Medical management of an unruptured ectopic pregnancy with intramuscular methotrexate is common and cost-effective. Two treatment protocols, the “single dose” and the “multidose,” have been advocated and independently reported in the medical literature. This analysis systematically compares the success and prevalence of side effects of these two regimens. DATA SOURCES Published data on women with an ectopic pregnancy medically managed were identified using a MEDLINE search from 1966 to 2001 using key words and review of the references of each manuscript. METHODS OF STUDY SELECTION Studies were selected based on dosing regimen, number of subjects, and study quality. Data regarding outcome, number of doses administered, side effects, and baseline characteristics were extracted. Data were summarized, and the associations of failed management and the presence of side effects with treatment protocol were calculated. Baseline serum chorionic gonadotropin values and the presence of embryonic fetal actively were controlled for with multivariable logistic regression. TABULATION, INTEGRATION, AND RESULTS The overall success rate for women treated with methotrexate for an ectopic pregnancy was 89% (1181 of 1327). The single dose was much more commonly used. The use of single dose was associated with a significantly greater chance of failed medical management than the use of the multidose in both crude (odds ratio [OR] 1.71; 1.04, 2.82) and adjusted analyses (OR 4.74; 1.77, 12.62). The single-dose regimen was associated with fewer side effects (OR 0.44; 0.31, 0.63). Women who experienced side effects were more likely to have successful treatment regardless of regimen. CONCLUSION The multidose regimen is more effective than the single-dose regimen.

Symptoms associated with menopausal transition and reproductive hormones in midlife women.

OBJECTIVE: To test the hypothesis that prevalence of women with menopausal symptoms of hot flushes; aches, joint pain, and stiffness; depressed mood; poor sleep; decreased libido; or vaginal dryness increases with progression through the menopausal transition. METHODS: Women in the Penn Ovarian Aging Study were assessed longitudinally for 9 years. Data were obtained from structured interviews, a validated symptom questionnaire, menstrual bleeding dates and early follicular hormone measures (estradiol [E2], follicle-stimulating hormone [FSH], and inhibin b). Menopausal stages were based on menstrual bleeding patterns. Other risk factors included age, race, history of depression, current smoking, body mass index, and perceived stress. Generalized linear regression models for repeated measures were used to estimate associations among the variables with each symptom. RESULTS: The prevalence of hot flushes; aches, joint pain, and stiffness; and depressed mood increased in the menopausal transition. Menopausal stage was associated with hot flushes (P<.001); aches joint pain, and stiffness (P<.001); and depressed mood (P=.002). Within-woman fluctuations of E2 were associated with hot flushes and aches. Poor sleep, decreased libido, and vaginal dryness were not associated with menopausal stages. There was 80% power to detect an absolute difference of 11% for libido and vaginal dryness and 17% for poor sleep in the prevalence of these symptoms in the late menopausal transition compared with premenopausal status. CONCLUSION: The study highlights the role of menopausal stages for some symptoms of midlife women and indicates that stages in the transition to menopause are associated with hot flushes; aches, joint pain, and stiffness; and depressed mood. Fluctuations of E2, decreased levels of inhibin b, and increased FSH levels were associated with these symptoms. LEVEL OF EVIDENCE: II

Violent injuries among women in an urban area

BACKGROUND Although the rate of death from injuries due to violent acts is much higher among black women than among white women in the United States, little is known about the nature and correlates of violent injuries among black women living in urban areas. METHODS In this case-control study conducted at three emergency departments in one inner-city community (in west Philadelphia), we studied 405 adolescent girls and women who had been intentionally injured and 520 adolescent girls and women (control subjects) who had health problems not related to violent injury. Data were collected by conducting standardized interviews with use of questionnaires and by screening urine for illicit drugs. Individual logistic-regression models were constructed to identify factors associated with violent injuries inflicted by partners and those inflicted by persons other than the partners of the victims. RESULTS The male partners of the injured women were much more likely than the male partners of control subjects to use cocaine (odds ratio, 4.4; 95 percent confidence interval, 2.3 to 8.4) and to have been arrested in the past (odds ratio, 3.1; 95 percent confidence interval, 1.8 to 5.2). Fifty-three percent of violent injuries to the women had been perpetrated by persons other than their partners. Womens use of illicit drugs and alcohol abuse were factors associated with both violence on the part of partners and violence on the part of other persons. Neighborhood characteristics, including low median income, a high rate of change of residence, and poor education, were independently associated with the risk of violent injuries among women. CONCLUSIONS Women in this urban, low-income community face violence from both partners and other persons. Substance abuse, particularly cocaine use, is a significant correlate of violent injuries. Standard Census data may help identify neighborhoods where women are at high risk for such violence and that would benefit from community-level interventions.

DEFINING MENOPAUSE STATUS: CREATION OF A NEW DEFINITION TO IDENTIFY THE EARLY CHANGES OF THE MENOPAUSAL TRANSITION

Objective: Several menopausal staging definitions are currently being used in ongoing studies designed to identify changes occurring during menopause. The objective of this study was to determine which definition captures the earliest hormonal changes in the menopausal transition. Design: In this prospective cohort study, women aged 35 to 47 years were followed for 5 years. Women were classified as premenopausal, early transition, late transition, and postmenopausal by 2 different menopausal staging systems defined by bleeding patterns. Definitions from the Study of Women Health Across the Nation (SWAN) and Stages of Reproductive Aging Workshop (STRAW) were compared. A new menopausal staging system (PENN-5) was also developed with five groups rather than four to distinguish among women with more subtle changes in cycle length. For each staging system, a linear regression model was created comparing mean hormone values (inhibin B, FSH, LH, E2) and menopausal stages at each assessment. Race, body mass index, cycle day, smoking, and follow-up time were included in the model. Results: Statistically significant differences in mean inhibin B and FSH levels, but not estradiol levels, were detected between the earliest menopausal stages of each definition. Significant differences in LH values were detected among the earliest stages of the SWAN and STRAW definitions, but not the PENN-5 definition. Conclusions: Subtle changes in menstrual cycle length reflect significant changes in inhibin B and FSH levels during the menopausal transition. Therefore, it appears that subtle changes in bleeding pattern may be helpful in identifying the earliest hormonal changes during menopausal transition.

Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined.

OBJECTIVE: To analyze the change in serial human chorionic gonadotropin (hCG) levels in women symptomatic with pain or bleeding who presented with nondiagnostic ultrasonography but were ultimately confirmed to have a viable intrauterine pregnancy. METHODS: The rise in serial hCG measures were modeled over time, with the start point defined in 2 ways: by last menstrual period and by date of presentation for care. Both semiparametric (spline) curves and linear random-effects models were explored. The slope and projected increase of hCG were calculated to define 99% of viable intrauterine pregnancies. RESULTS: A total of 287 subjects met inclusion criteria and contributed 861 measurements of hCG. On average, these subjects contributed 3.00 observations and were followed up for 5.25 days. A linear increase in log hCG best described the pattern of rise. Curves derived from last menstrual period and day of presentation do not differ substantially. The median slope for a rise of hCG after 1 day was 1.50, (or a 50% increase); 2.24 after 2 days (or a 124% rise), and 5.00 after 4 days. The fastest rise was 1.81 at 1 day, 3.28 at 2 days, and 10.76 at 4 days. The slowest or minimal rise for a normal viable intrauterine pregnancy was 24% at 1 day and 53% at 2 days. CONCLUSION: These data define the slowest rise in serial hCG values for a potentially viable gestation and will aid in distinguishing a viable early pregnancy from a miscarriage or ectopic pregnancy. The minimal rise in serial hCG values for women with a viable intrauterine pregnancy is “slower” than previously reported, suggesting that intervention to diagnosis and treat an abnormal gestation should be more conservative. LEVEL OF EVIDENCE: II-2

Anti-Mullerian Hormone as a Predictor of Time to Menopause in Late Reproductive Age Women

CONTEXT Anti-mullerian hormone (AMH) has emerged as a marker of ovarian reserve and a possible surrogate measure of reproductive aging. OBJECTIVE The aim of the study was to evaluate the predictive value of AMH levels in determining the median time to menopause for late reproductive age women and the predictive ability of AMH compared to FSH and inhibin b. DESIGN AND SETTING A 14-yr follow-up in the Penn Ovarian Aging Study, 1996-2010, was conducted for a randomly identified population-based cohort. SUBJECTS A total of 401 late reproductive age women participated in the study. MAIN OUTCOME MEASURE Observed time to menopause was measured. RESULTS All participants were premenopausal, with a mean (SD) age of 41.47 (3.52) yr and a median AMH level of 0.68 ng/ml at baseline. AMH strongly predicted time to menopause; age further improved predictions. Among women with a baseline AMH level below 0.20 ng/ml, the median time to menopause was 5.99 yr [95% confidence interval (CI), 4.20-6.33] in the 45- to 48-yr age group and 9.94 yr (95% CI, 3.31-12.73) in the 35- to 39-yr age group. With higher baseline AMH levels above 1.50 ng/ml, the median time to menopause was 6.23 yr in the oldest age group and more than 13.01 yr in the youngest age group. Smoking significantly reduced the time to menopause (hazard ratio, 1.61; 95% CI, 1.19-2.19; P = 0.002). AMH was a stronger predictor of time to menopause than FSH or inhibin b. CONCLUSIONS AMH is a strong predictor of median time to menopause in late reproductive age women. Age and smoking are significant and independent contributors to the predictions of AMH.

Efficacy of Escitalopram for Hot Flashes in Healthy Menopausal Women: A Randomized Controlled Trial

CONTEXT Concerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have resulted in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes. OBJECTIVE To determine the efficacy and tolerability of 10 to 20 mg/d escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity, and bother of menopausal hot flashes. DESIGN, SETTING, AND PATIENTS A multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 205 women (95 African American; 102 white; 8 other) between July 2009 and June 2010. INTERVENTION Women received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks. MAIN OUTCOME MEASURES Primary outcomes were the frequency and severity of hot flashes assessed by prospective daily diaries at weeks 4 and 8. Secondary outcomes were hot flash bother, recorded on daily diaries, and clinical improvement (defined as hot flash frequency ≥50% decrease from baseline). RESULTS Mean (SD) daily hot flash frequency was 9.78 (5.60) at baseline. In a modified intent-to-treat analysis that included all randomized participants who provided hot flash diary data, the mean difference in hot flash frequency reduction was 1.41 (95% CI, 0.13-2.69) fewer hot flashes per day at week 8 among women taking escitalopram (P < .001), with mean reductions of 4.60 (95% CI, 3.74-5.47) and 3.20 (95% CI, 2.24-4.15) hot flashes per day in the escitalopram and placebo groups, respectively. Fifty-five percent of women in the escitalopram group vs 36% in the placebo group reported a decrease of at least 50% in hot flash frequency (P = .009) at the 8-week follow-up. Reductions in hot flash severity scores were significantly greater in the escitalopram group (-0.52; 95% CI, -0.64 to -0.40 vs -0.30; 95% CI, -0.42 to -0.17 for placebo; P < .001). Race did not significantly modify the treatment effect (P = .62). Overall discontinuation due to adverse events was 4% (7 in the active group, 2 in the placebo group). Three weeks after treatment ended, women in the escitalopram group reported a mean 1.59 (95% CI, 0.55-2.63; P = .02) more hot flashes per day than women in the placebo group. CONCLUSION Among healthy women, the use of escitalopram (10-20 mg/d) compared with placebo resulted in fewer and less severe menopausal hot flashes at 8 weeks of follow-up. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00894543.

Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome

OBJECTIVE To improve the interpretation of future studies in women who are initially diagnosed with a pregnancy of unknown location (PUL), we propose a consensus statement with definitions of population, target disease, and final outcome. DESIGN A review of literature and a series of collaborative international meetings were used to develop a consensus for definitions and final outcomes of women initially diagnosed with a PUL. RESULT(S) Global differences were noted in populations studied and in the definitions of outcomes. We propose to define initial ultrasound classification of findings into five categories: definite ectopic pregnancy (EP), probable EP, PUL, probable intrauterine pregnancy (IUP), and definite IUP. Patients with a PUL should be followed and final outcomes should be categorized as visualized EP, visualized IUP, spontaneously resolved PUL, and persisting PUL. Those with the transient condition of a persisting PUL should ultimately be classified as nonvisualized EP, treated persistent PUL, resolved persistent PUL, or histologic IUP. These specific categories can be used to characterize the natural history or location (intrauterine vs. extrauterine) of any early gestation where the initial location is unknown. CONCLUSION(S) Careful definition of populations and classification of outcomes should optimize objective interpretation of research, allow objective assessment of future reproductive prognosis, and hopefully lead to improved clinical care of women initially identified to have a PUL.

Response to first drug trial predicts outcome in childhood temporal lobe epilepsy

Objective: To construct a clinical prediction model for the early identification of children destined to develop refractory temporal lobe epilepsy (TLE) 2 years after epilepsy onset. Methods: Patients with TLE between 1 and 18 years old seen in the Division of Neurology at Children’s Hospital of Philadelphia during 1999 were identified through billing records and chart review. Data were abstracted independently on 5 candidate predictor variables for refractory TLE and on seizure frequency outcome at 2 years after epilepsy onset. Results: One hundred twenty patients met inclusion criteria and had at least 2 years of follow-up. Forty-five of 120 patients (37.5%) had refractory TLE at 2 years after onset, and 75 of 120 (62.5%) were seizure free. Three significant predictors of refractory TLE were found on bivariate analysis: an early risk factor for epilepsy (risk ratio = 3.5 [95% CI 2.2, 5.6]), temporal lobe abnormality on MRI scan (2.9 [95% CI 1.9, 4.6]), and failure of the first antiepileptic drug (AED) trial (16.5 [95% CI 6.3, 43.9]). Logistic regression indicated that the best model to predict refractory TLE contained only the variable “failure of first AED trial,” with a positive predictive value of 0.89 (95% CI 0.76, 0.96) and negative predictive value of 0.95 (95% CI 0.87, 0.99) to predict “refractory TLE” at 2 years. Conclusions: Failure of first AED trial accurately predicts refractory TLE at 2 years after onset, based on retrospective cohort data in children. If verified prospectively and with longer follow-up, this finding should support earlier consideration of surgical options.

Treatment of localized periodontal disease in pregnancy does not reduce the occurrence of preterm birth: results from the Periodontal Infections and Prematurity Study (PIPS)

OBJECTIVE The purpose of this study was to test whether treating periodontal disease (PD) in pregnancy will reduce the incidence of spontaneous preterm delivery (SPTD) at < or = 35 weeks of gestation. STUDY DESIGN A multicenter, randomized clinical trial was performed. Subjects with PD were randomized to scaling and root planing (active) or tooth polishing (control). The primary outcome was the occurrence of SPTD at <35 weeks of gestation. RESULTS We screened 3563 subjects for PD; the prevalence of PD was 50%. Seven hundred fifty-seven subjects were assigned randomly; 378 subjects were assigned to the active group, and 379 subjects were assigned to the placebo group. Active treatment did not reduce the risk of SPTD at <35 weeks of gestation (relative risk, 1.19; 95% confidence interval [CI], 0.62-2.28) or composite neonatal morbidity (relative risk, 1.30; 95% CI, 0.83-2.04). There was a suggestion of an increase in the risk of indicated SPTD at <35 weeks of gestation in those subjects who received active treatment (relative risk, 3.01; 95% CI, 0.95-4.24). CONCLUSION Treating periodontal disease does not reduce the incidence of SPTD.