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Objective: To evaluate the safety and acceptability of a novel dosing regimen of methotrexate to treat ectopic pregnancy. Design: Prospective study. Setting: Three academic medical centers. Patient(s): One hundred one patients with ectopic pregnancy who elected to have medical therapy. Intervention(s): Intramuscular methotrexate 50 mg/m2 was administered on days 0 and 4; additional doses of methotrexate were given on day 7 and/or day 11 if hCG levels did not decrease by 15% during the follow-up period. Main Outcome Measure(s): Adverse events, acceptability, and resolution of pregnancy without surgical treatment. Result(s): With this protocol, 87% of patients were treated successfully. Of those protocols that were considered failures, only 3% of patients experienced rupture of ectopic pregnancy. Treatment was well-tolerated; most side effects were reported as mild and transient. Ninety-one percent of the 61.5% of patients who responded to the satisfaction questionnaire reported satisfaction with this regimen. Conclusion(s): This “2-dose” protocol minimizes the number of injections and surveillance visits, compared with the “multiple dose” regimen, and methotrexate is administered more frequently than with the “single dose” regimen. The protocol may optimize the balance between convenience and efficacy. In a limited number of women, no safety concerns were noted with up to 4 doses of methotrexate in a 2-week period without leucovorin rescue. [Copyright &y& Elsevier]

Regulation of the intestinal mucus layer by goblet cells is important for preventing inflammation and controlling infection. IL-33, a cytokine upregulated in inflammatory bowel disease and helminth infection, induces intestinal goblet cells, but the mechanism remains unclear. Enteroids are three-dimensional structures of primary small intestinal epithelial cells that contain all differentiated intestinal epithelial cell types. We developed an enteroid-immune cell coculture model to determine the mechanism through which IL-33 affects intestinal goblet cell differentiation. We report that IL-33 does not directly induce goblet cell differentiation in murine enteroids; however, IL-13, a cytokine induced by IL-33, markedly induces goblet cells and gene expression consistent with goblet cell differentiation. When enteroids are cocultured with CD90+ mesenteric lymph node cells from IL-33-treated mice, IL-33 then induces IL-13 secretion by group 2 innate lymphoid cells and enteroid gene expression consistent with goblet cell differentiation. In cocultures, IL-33-induced Muc2 expression is dependent on enteroid Il4ra expression, demonstrating a requirement for IL-13 signaling in epithelial cells. In vivo, IL-33-induced intestinal goblet cell hyperplasia is dependent on IL-13. These studies demonstrate that IL-33 induces intestinal goblet cell differentiation not through direct action on epithelial cells but indirectly through IL-13 production by goup 2 innate lymphoid cells. [ABSTRACT FROM AUTHOR]

: ObjectiveTo compare signs and symptoms between patients with recurrent and single ectopic pregnancies.: DesignCase-control study.: SettingUniversity medical center.: Patient(s)Three hundred six women with single ectopic pregnancies and 61 women with recurrent ectopic pregnancies.: Intervention(s)None.: Main outcome measure(s)Risk factors, historical factors, and findings at presentation that may predispose to recurrent ectopic pregnancy.: Result(s)The risk of recurrent ectopic pregnancy was increased with a history of surgery, history of live birth, and history of spontaneous miscarriage and not with a history of gonorrhea, chlamydia, pelvic inflammatory disease, Caesarean section, or pregnancy termination. Patients with a recurrent ectopic pregnancy had a nonsignificant trend toward higher initial hCG values. The majority of ultrasounds in both groups were nondiagnostic on presentation. The patients with recurrent ectopic pregnancy were less likely to have bleeding on initial presentation, though both groups had similar complaints of pain.: Conclusion(s)Secondary prevention of ectopic pregnancy is problematic because of the paucity of risk factors that can be modified to diminish the odds of recurrence. Clinicians'' ability to both diagnose and counsel patients at risk for recurrent ectopic pregnancy can be optimized by awareness of the clinical features of this condition. [Copyright &y& Elsevier]

: ObjectiveThe diagnosis of ectopic pregnancy (EP) is often confirmed at presentation (acute), but often requires serial β-hCG levels to confirm the diagnosis (chronic). The purpose of this study is to analyze whether these clinical presentations represent a spectrum of disease.: DesignThe retrospective cohort study of 452 patients diagnosed with EP at the University of Pennsylvania in the years 1990–1999.: SettingUniversity of Pennsylvania, Philadelphia, Pennsylvania.: Patient(s)Four hundred fifty-two patients diagnosed with EP. Patients diagnosed with EP were divided into two groups according to the time of diagnosis.: Main outcome measure(s)A total of 37 parameters were examined including historic and demographic factors, findings at presentation, and treatment and outcome variables.: Result(s)The two groups were similar in terms of historic EP risk factors. Multivariable analysis demonstrates that women with a chronic presentation were less likely to have received fertility medications (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.06–0.84), less likely to present with pain (OR 0.29; 95% CI 0.12–0.71), have a lower β-hCG level at presentation (9,849 mIU/mL ± 16,726 vs. 1,787 mIU/mL ± 4,717), lower chance of rupture (OR 0.19; 95% CI 0.05–0.73), and less frequently have blood type 0.: Conclusion(s)Women diagnosed with ectopic pregnancy can be categorized into two groups, those with an acute presentation and those with a chronic presentation. Differences in risk factors, presentation, and outcome may reflect differences in trophoblast viability or invasive potential. [Copyright &y& Elsevier]

OBJECTIVE:To evaluate the accuracy of the diagnosis of presumed ectopic pregnancy.METHODS:This was a retrospective cohort analysis at a tertiary care medical center. The patient population was composed of 1) clinically stable pregnant women with human chorionic gonadotropin (hCG) above 2000 mIU/mL and no evidence of an intrauterine pregnancy by ultrasound, or 2) women with an abnormal rise or fall of serial hCG below 2000 mIU/mL. Outcome was determined by pathologic evidence of chorionic villi in the endometrial curettings (or fallopian tube), or complete resolution of hCG.RESULTS:Overall, 38.4% (43/112) of the women were diagnosed with a miscarriage and 61.6% (69/112) were found to have an ectopic pregnancy. No significant difference was found in race, age, gravity, parity, hCG trends, or time to diagnosis between women with ectopic pregnancies and those with miscarriages. Patients were more likely to be diagnosed with an ectopic pregnancy if the initial hCG value was below the discriminatory zone (relative risk 2.44; 95% confidence interval 1.07, 5.52). Ultrasound correlated well with the final diagnosis (P = .001) but was not definitive.CONCLUSION:In an effort to save time, avoid dilation and curettage (D&C), and treat with methotrexate, the presence of an ectopic pregnancy is often presumed. The presumed diagnosis of ectopic pregnancy is inaccurate in almost 40% of cases. A D&C is necessary to differentiate an ectopic pregnancy from a miscarriage before a woman is presumptively treated with methotrexate. [Copyright &y& Elsevier]

Supplemental Digital Content is available in the text. OBJECTIVES: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children. DESIGN: Post hoc analysis of a Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with newly inserted central venous catheter. INTERVENTIONS: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2–0.5 international units/mL versus usual care. MEASUREMENTS AND MAIN RESULTS: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37–2.44) in infants and 0.24 (95% credible interval, 0.04–0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78–437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7–74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17–61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count. CONCLUSIONS: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin. [ABSTRACT FROM AUTHOR]

The article discusses a research study on using a single-tablet such as levonorgestrel 1.5 milligrams (mg) as emergency contraceptive for young females and assess pregnancy, repeat use and adverse events. Study participants include females from 11-17 years of age who request for emergency contraception from teen productive health clinics then assessed for pregnancy after 8 weeks. Conclusions indicated the need to restrict young females from using single-tablet emergency contraception.

Objective: To evaluate the effect activity has on the vaginal distribution of a 1200 mg miconazole nitrate gelatin encapsulated insert, an antifungal agent commonly used to treat vaginal vulvocandidiasis. Method: Nine subjects underwent two sessions of serial magnetic resonance imaging after insertion of the insert. One session required that the subjects ambulate between images; the other session required the subjects remain supine between images. Vaginal distribution of the insert was quantified by calculating surface contact and linear distance in every image. Comparison of spread was then done between images taken in active subjects and images taken in resting subjects. Time until capsule dissolution was also compared between the two groups. Results: No statistically significant difference was seen in spread of insert between the active and resting group. Activity also had no significant effect on capsule dissolution. Conclusion: Activity does not appear to hinder the spread of the insert, suggesting that this medication can be used daytime or nighttime. [ABSTRACT FROM AUTHOR]

Objective: To validate recently characterized curves of hCG rise and fall that are seen in viable and nonviable pregnancies in a population of women who have pregnancies of unknown location. Design: Historical cohort study. Setting: University hospital. Patient(s): One thousand two hundred forty-nine women with symptomatic early pregnancies. Intervention(s): None. Main Outcome Measure(s): Comparison of observed hCG values to predicted hCG values; time to diagnosis of ectopic pregnancy; accuracy of diagnosis. Result(s): Of the 1,249 patients included in this study, 196 had ectopic pregnancy (EP); 261, intrauterine pregnancy (IUP); and 792, spontaneous abortion (SAB). By determining the rate of change in hCG values from two consecutive visits and comparing them with a minimal rise of 35% in 2 days (the bound that is defined by the 99.9% confidence interval [CI] for the rise of hCG in an IUP) or a minimal fall of 21%–35% (the bound that is defined by the 90% CI for the fall of hCG in an SAB), we were able to make the diagnosis of EP an average of 2.5 days sooner than by standard clinical practice. Only 12% of patients had an EP go undiagnosed by using these rules, because the curve of rise or fall of their hCG mimicked that of a non-EP gestation. Conclusion(s): Recently redefined curves of rise and fall in hCG for IUP and SAB are valid for clinical use on the basis of our application to this large cohort of patients. Using them can shorten the time needed to make the diagnosis of EP. Use of a more conservative cutoff for minimal rise in hCG, one as slow as 35% over 2 days, to characterize a potentially viable gestation would minimize potential interruption of a desired pregnancy. [Copyright &y& Elsevier]

Objective: To evaluate the association between ectopic pregnancy (EP) and clinical and historical factors among women presenting with pain and/or bleeding in early pregnancy. Design: Nested case–control study. Setting: University medical center. Patient(s): Women with symptomatic early pregnancies of unknown location presenting for care between January 1, 1990 and July 31, 1999. Intervention(s): None. Main Outcome Measure(s): Clinical and historical risk factors were compared between women with EP and women with ongoing intrauterine pregnancies or spontaneous abortions. Result(s): The following factors were associated with increased risk of EP: prior EP (odds ratio, 2.98 [95% confidence interval, 1.88–4.73] for one prior EP and 16.04 [5.39–47.72] for 2 or more), pelvic inflammatory disease history (1.5 [1.11–2.05]), pain at presentation (1.42 [1.06–1.92]), vaginal bleeding at presentation (1.42 [1.04–1.93]), and hCG of 501–2,000 mIU/mL (1.73 [1.24–2.42]). Age younger than 25 years (0.59 [0.41–0.85]) and a history of abortion were protective from EP (0.58 [0.38–0.90]). Prior nontubal pelvic surgery, past intrauterine device use, prior cesarean section, and current cervical infection demonstrated no association with EP. Conclusion(s): Evaluation of women with a symptomatic early pregnancy confirms and refutes some of the classical risk factors for EP. Prior EP is a strong risk factor, whereas pelvic inflammatory disease has an unexpected weak association. Previous abortion was found to have a negative association, whereas nontubal surgery, cesarean section, and a history of or concomitant cervical infection have no association. Knowledge of historical and clinical factors associated with EP may aid in early diagnosis. [Copyright &y& Elsevier]

The study analyzes serial human chorionic gonadotrophin (hCG) levels in women with symptomatic early pregnancies that ultimately received diagnosis of ectopic pregnancy. The number of women with ectopic pregnancy who experience an increase in hCG is the same as those who experience a decrease in hCG. Thus, the hCG profile of women with ectopic pregnancies is similar to that of an intrauterine pregnancy or a completed spontaneous abortion.

OBJECTIVE: To evaluate the association of an ultimate diagnosis of miscarriage with various clinical symptoms and historical factors in a cohort of women presenting with pain, bleeding, or both in the first trimester of pregnancy. METHODS: This was a case-control study from a population of women presenting for care with pelvic pain or vaginal bleeding in the first trimester of pregnancy whose diagnoses were not definite upon initial evaluation. Analyses were performed in 2 ways. In one instance cases were defined as women ultimately definitively diagnosed with a miscarriage and controls were defined as women with a pregnancy that did not result in miscarriage (ectopic pregnancy or ongoing intrauterine pregnancy). The second analysis compared women with a miscarriage only to women who had an ongoing intrauterine pregnancy. RESULTS: A total of 2,026 women were evaluated, with 1,192 ultimately diagnosed with a spontaneous abortion, 367 with ectopic pregnancy, and 467 with a viable intrauterine pregnancy. Although many risk factors were individually associated with miscarriage in preliminary analysis, in the final analysis only extremes in age (« 25 and » 35) and the complaint of bleeding (odds ratio [OR] 7.35, 95% confidence interval[CI] 5.74–9.41) were associated with miscarriage. The complaint of pain (OR 0.72, 95% CI 0.57–0.92), human chorionic gonadotropin (hCG) value greater than 500 (hCG ≤ 500 IU/mL compared with hCG 501–2000: OR 0.52, 95% CI 0.39–0.69) and concurrent cervical infection (OR 0.69, 95% CI 0.55–0.88) were negatively associated with miscarriage. CONCLUSION: Few factors predict miscarriage in women who present with a symptomatic first trimester pregnancy of unknown location. Heavy bleeding was most strongly associated with miscarriage. Concurrent cervical infections should not be overlooked as a cause of bleeding in early pregnancy and were not associated with miscarriage. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of combination estrogen/androgen therapy on muscle mass, strength and endurance, serum hormone and lipid profiles, and quality of life measures in postmenopausal women. Methods: Prospective, randomized, placebo-controlled pilot study at a tertiary care medical center. Fifty postmenopausal women were randomized to a 12-week course of (1) dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen (CEE) 0.625 mg daily, (3) DHEA 50 mg + CEE 0.625 mg daily, or (4) placebo. Main outcome measures of lower extremity muscle (calf) mass, functional muscle parameters, serum hormone and lipid levels, and quality of life (QOL) were obtained at baseline and after treatment. Statistical analysis compared percent change from baseline values and treatment differences among outcomes. Results: Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo. Compared with no hormone therapy, none of the supplemental hormone groups caused significant changes in muscle mass, muscle strength, muscle endurance, feelings of well-being, sleep, or sexual function. Conclusions: Androgen replacement therapy, with DHEA, to menopausal women increases serum androgen levels without any appreciable effect on muscle cross-sectional area, muscle strength, muscle function, or improvement in health-related QOL. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to estimate a standard curve of serum human chorionic gonadotropin (hCG) decline that characterizes spontaneous abortion. METHODS: Data were extracted from a clinical database of women with symptomatic early pregnancies and nondiagnostic ultrasonography who required follow-up with serial hCG levels. The evaluation was restricted to women who had a pregnancy of unknown location, a decrease in serum levels, and who were ultimately diagnosed with miscarriage (a decrease in serum hCG to < 5 mIU/mL in the absence of surgical intervention or confirmation of products of conception after dilation and curettage). The starting point of the curve was the hCG concentration at presentation, with serial levels plotted until the time of definitive diagnosis. Semiparametric statistical techniques were used to characterize the shape of the curve. We present slopes for the decrease in log hCG levels and the projected rate of fall. RESULTS: Of the 1,543 patients, 710 were diagnosed with miscarriage. A quadratic curve for log hCG with a steeper rate of decline for large initial hCG values best described the pattern of change. One curve could not fully estimate the decline because the rate was dependent on the initial hCG level. In other words, more rapid decline was associated with a higher starting concentration. The rate of decline ranged from 21% to 35% at 2 days and 60% to 84% at 7 days, depending on initial hCG value. CONCLUSION: The rate of hCG decrease in spontaneous abortions is described by a quadratic profile, with a faster decline in hCG value with higher presentation levels. A rate of decline less than 21% at 2 days or 60% at 7 days suggests retained trophoblasts or an ectopic pregnancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Because lower initial hCG concentrations are associated with slower rates of decline in spontaneous abortions, the aim of this study was to provide a detailed description of the expected rates of hCG decline in patients presenting with very low initial hCG levels and who ultimately were confirmed to have spontaneous abortions. When initial levels lie between 50 and 500 mIU/mL, the slowest expected percentage decline ranges from 12% to 24% in 2 days and from 34% to 68% in 7 days. [Copyright &y& Elsevier]