Medicolegal Review: Essure Lawsuits and Legal Strategies Adverse to Gynecologists.

The minimally invasive Essure procedure for hysteroscopic sterilization is an ongoing target for litigation. Although efficacious, this device has been scrutinized by the US Food and Drug Administration (FDA) owing to alleged complications. Patients affected by these potential complications are filing lawsuits against Bayer, the manufacturer of Essure. Many of these lawsuits have been barred by preemption, a legal doctrine that limits what can be required of a product by state lawsuits once the FDA approves it; however, in the lawsuits that have been allowed to proceed, the manufacturer has used a legal strategy termed the "learned intermediary doctrine" in an effort to shift blame to the gynecologist to absolve itself of liability. The learned intermediary only requires that a manufacturer inform the gynecologist of the risks associated with the device, and the gynecologist, in turn, must notify the patients through adequate informed consent. To incorporate the necessary components of informed consent, a gynecologist should include what a reasonable practitioner would consider pertinent to the discussion, as well as what a prudent patient would want to know to make a treatment decision. This disclosure entails explaining the risks, benefits, and alternatives, which should be clearly documented in the medical records. Understanding the importance of proper documentation and the legal strategies used in suits will help gynecologists lessen liability exposure when using a medical device, such as Essure, that is being targeted for litigation.

Medicolegal Review of Methotrexate Administration to Viable Intrauterine Pregnancies.

Objective: To examine 3 legal cases in which physicians prescribed methotrexate to women with a viable intrauterine pregnancy, presumed to be ectopic, resulting in adverse fetal outcomes. Study Design: We conducted an electronic literature search for legal cases using the keywords "methotrexate" and "pregnancy" in the LexisNexis legal research engine as well as an Internet-wide search using the additional keyword "verdict." We manually searched the resultant list of identified cases and categorized the studies identified in the search by verdict, award amount, and outcome of the embryo exposed to methotrexate. Results: The monetary awards are typically greater when the embryo exposed to methotrexate lives and requires continuous medical and custodial care as compared to when the fetus dies in utero or shortly after birth. Conclusion: Physicians who, with all good intentions, prescribe methotrexate to women with a viable pregnancy, presumed to be ectopic, could find them-selves liable for an adverse fetal outcome. For the benefit of patients, their unborn offspring, and the liability exposure of the physician, it is important to be very cautious when prescribing methotrexate.

The BRCA1 tumor suppressor binds to inositol 1,4,5-trisphosphate receptors to stimulate apoptotic calcium release.

The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein.

Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells.

Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.

Dystroglycan in human fetal membranes decreases in later gestation and with spontaneous membrane rupture.

BACKGROUND/AIMS: The transmembrane protein dystroglycan (DG) is known to anchor the cell membrane to the extracellular matrix, and is susceptible to cleavage by matrix metalloproteinases. This study tested the hypothesis that changes in DG abundance in fetal membranes (FM) occur late in gestation, with spontaneous rupture of membranes (SROM), and during labor. METHODS: FM were collected from a prospective cohort consisting of four groups of patients (term labor, term unlabored, preterm labor, and preterm unlabored). FM were subjected to immunohistochemical staining using antibodies specific for α- and ß-DG subunits, and staining intensity was graded by a blinded pathologist. RESULTS: α- and ß-DG staining was significantly decreased at term and after SROM (p < 0.05), but not in the presence of labor. CONCLUSIONS: Decreased DG intensity was seen in FM of patients at term and with SROM, but no change was observed with labor.

Disparities in use of laparoscopic hysterectomies: a nationwide analysis.

STUDY OBJECTIVE: To determine patient and hospital characteristics that were associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy. DESIGN: Canadian Task Force Classification II-3. METHODS: In this retrospective cohort study, we analyzed the 2010 Healthcare Cost and Utilization Project Nationwide Inpatient Sample database. All women who underwent laparoscopic or abdominal hysterectomy for either menorrhagia or leiomyoma were included based on International Classification of Diseases, Ninth Revision coding. A linear model with binomial distribution and logit link function was used to determine patient and hospital characteristics associated with hysterectomy approach. MAIN RESULTS: A total of 32 436 patients were included in this study. Of these, 32% patients underwent laparoscopic hysterectomies, and 67% underwent abdominal hysterectomies. With regard to patient characteristics, women younger than 35 years old were more likely to undergo laparoscopic hysterectomy when compared with each of the other age categories (p < .001). White women were more likely to undergo laparoscopic hysterectomy than black women, Hispanic women, or women classified as "other" races (p < .001 for all comparisons). With regard to median income, patients from the lowest national quartile were less likely to undergo laparoscopic hysterectomy when compared with each of the other 3 national quartiles for income (p = .01, p < .001, p = .001, respectively). Payment by private insurance was associated with laparoscopic hysterectomy when compared with payment by Medicare or payment by insurance category "other" (p < .001 for both). With regard to hospital characteristics, hospitals in the Northeast were more likely to have laparoscopic hysterectomies than hospitals in the Midwest or South (p < .001 for both comparisons); urban hospitals were more likely than rural hospitals (p < .001); teaching hospitals were more likely than nonteaching hospitals (p < .001); and government-owned hospitals were less likely than private, nonprofit or private, investor owned (p < .001 for both comparisons). CONCLUSIONS: Despite the increased popularity of and training in laparoscopic hysterectomies, there remains an obvious disparity in its delivery with regard to patient and hospital characteristics. Further investigation is needed on the etiology of this disparity and interventions that may alleviate it.

Trends in the national distribution of laparoscopic hysterectomies from 2003 to 2010.

STUDY OBJECTIVE: The purpose of this analysis was to compare the trends in undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy) based on patient age, race, median income and insurance type, from 2003 to 2010. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: National sample of hospital admissions after hysterectomy. PATIENTS: Health Cost and Utilization Project-Nationwide Inpatient Sample database was used to review records of women who underwent hysterectomy for either menorrhagia or leiomyoma from 2003-2010. INTERVENTION: The predicted probability of undergoing laparoscopic hysterectomy was determined for each year according to patient age, race, median income, and insurance type. The slopes of these values (i.e. the trend) was compared for each subgroup (i.e. black, white, Asian, etc.) in these categories. MAIN RESULTS: A total of 530, 154 cases were included in this study. Total number of hysterectomies decreased by 39% from 60,364 to 36,835 from 2003 to 2010. The percent of hysterectomies that were laparoscopic increased from 11% in 2003 to 29% in 2010. All groups analyzed experienced an increase in predicted probability of undergoing a laparoscopic hysterectomy. Of all women undergoing hysterectomy, the probability of undergoing a laparoscopic hysterectomy remained highest for women who were less than 35 years old, white, with the highest median income, and with private insurance from 2003-2010. The slope was significantly greater for (1) white females versus all other races analyzed (p<0.01), (2) females in the highest income quartile versus females in the lowest income quartile (p<0.01) and (3) females with private insurance versus females with Medicaid (p<0.01) or Medicare (p<0.01). CONCLUSIONS: There remains a gap in distribution of laparoscopic hysterectomies with regards to age, race, median income and insurance type that does not seem to be closing, despite the increased availability of laparoscopic hysterectomies.

Analysis of tubal patency after essure placement.

STUDY OBJECTIVE: To evaluate tubal patency after hysteroscopic sterilization using the Essure microinsert (Conceptus Inc, San Carlos, CA). DESIGN: A retrospective longitudinal cohort study. DESIGN CLASSIFICATION: II-3. SETTING: Patients undergoing hysteroscopic sterilization in the outpatient clinic of a university-based hospital in Southeast Texas from July 2009 to November 2011. PATIENTS: Two hundred twenty-nine women (ages 21-44 yrs, 71% Hispanic) desiring sterilization with a history of regular menses, demonstrated prior fertility (≥1 live birth), and the ability to use an alternative contraceptive method for at least 90 days after coil placement were included. Twenty six patients in this cohort were excluded because of failure to perform a hysterosalpingogram (HSG), tubal perforation, severe dyspareunia, a history of ectopic pregnancy, tubal surgery, or cervical intraepithelial neoplasia. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: HSGs were assessed for microinsert location and tubal occlusion. Two hundred three patients were included for analysis. After the successful bilateral hysteroscopic placement of Essure microinserts in fallopian tubes, all patients returned for the first follow-up HSG a mean of 103 ± 38 days after the procedure. Patients with fallopian tube patency at the initial HSG returned for second and/or third HSGs as needed at 192 ± 45 and 291 ± 97 days, respectively. Correct device placement was confirmed in 100% of cases at the first HSG. The tubal patency rates at the 90-day and 180-day HSGs were 16.1% (95% confidence interval, 7.4%-31.7%) and 5.8% (95% CI, 1.2%-24.4%), respectively. These rates were estimated by the accelerated failure time model with log normal distribution and interval censored time to event. The 16.1% 90-day tubal patency rate is significantly different from the 8% rate reported by Cooper et al in the 2003 multicenter phase III pivotal trial (p <.001). CONCLUSION: Our data indicate that hysteroscopic sterilization with Essure results in a higher initial tubal patency rate than previously reported. Multivariate analyses are needed to identify factors associated with an increased risk of postprocedure tubal patency.

Implementation of health information technology to maximize efficiency of resource utilization in a geographically dispersed prenatal care delivery system.

This study investigated the utilization of health information technology (HIT) to enhance resource utilization in a geographically dispersed tertiary care system with extensive outpatient and delivery services. It was initiated as a result of a systems change implemented after Hurricane Ike devastated southeast Texas. A retrospective database and electronic medical record review was performed, which included data collection from all patients evaluated 18 months prior (epoch I) and 18 months following (epoch II) the landfall of Hurricane Ike. The months immediately following the storm were omitted from the analysis, allowing time to establish a new baseline. We analyzed a total of 21,201 patients evaluated in triage at the University of Texas Medical Branch. Epoch I consisted of 11,280 patients and epoch II consisted of 9922 patients. Using HIT, we were able to decrease the number of visits to triage while simultaneously managing more complex patients in the outpatient setting with no clinically significant change in maternal or fetal outcome. This study developed an innovated model of care using constrained resources while providing quality and safety to our patients without additional cost to the health care delivery system.

Postpartum Teenagers' Views on Providing Contraception in School-Based Health Clinics.

BACKGROUND: To determine characteristics of teen pregnancies in southeast Texas and the opinions of postpartum teenagers with regard to having contraceptive services available in high school clinics. METHODS: A cross-sectional study of postpartum teenagers interviewed during their hospital stay. RESULTS: Of 404 postpartum teenagers interviewed, 86% had unplanned pregnancies. Approximately 53% of respondents first had intercourse at less than 16 years of age. Of the 130 teenagers who had used contraception prior to pregnancy, 85% became pregnant because they were unable to visit the clinic to obtain a contraceptive refill or replacement. In multivariate modeling, factors associated with using contraceptives prior to pregnancy included black race (p < .001) and more than 1 previous pregnancy (p < .001). Variables associated with having an unplanned pregnancy included having discussed contraceptives at home or school (p = 0.049). Of the 404 postpartum teenagers surveyed, 223 (82%) were in favor of having contraceptive services offered in high school clinics. CONCLUSIONS: Contraceptive education is not sufficient to prevent teenage pregnancy. Increase in access is critical as teenagers with previous pregnancies were more likely to use contraception, likely due to their interaction with the medical community during the antecedent pregnancy. One possible solution is to bring contraceptive services to the teenagers, by offering them at school based health systems. A majority of teenagers surveyed in this study supported this proposal.

Enmeshed in Controversy: Use of Vaginal Mesh in the Current Medicolegal Environment.

UNLABELLED: Vaginal mesh has been a valuable tool in the treatment of stress urinary incontinence and pelvic organ prolapse. As our knowledge of the long-term outcomes and complications of this product has evolved, however, vaginal mesh has become the subject of legal scrutiny. Therefore, it is imperative that physicians understand pertinent litigation techniques to optimize their informed consent and documentation processes and protect themselves. OBJECTIVES: Our objective is to familiarize physicians who use vaginal mesh with how law suits involving transvaginal mesh are construed. We also describe the current medicolegal environment surrounding the use of these products. METHODS: The food and drug administration public safety communications, food and drug administration Manufacturer and User Facility Device Experience database, and LexisNexis legal search engine were used to review data relevant to current vaginal mesh litigation. This information was used to create a medicolegal review. RESULTS: Litigation involving transvaginal mesh follows 3 paths. The first consists of claims against the manufacture of transvaginal mesh with allegations, such as design defects, failure to warn, and misrepresentation. The second is a defensive legal strategy called the learned intermediary doctrine, used by manufacturers to shift liability from themselves to surgeons. The manufacturers claim that the duty to inform patients of potential complications lies with the surgeon. The third involves claims by patients against surgeons for lack of informed consent, alleging that they were not sufficiently informed of potential complications associated with transvaginal mesh before insertion. CONCLUSIONS: To lessen the liability, a surgeon using transvaginal mesh should inform patients of potential complications associated with the products and document informed consent in their medical records.

Detection of benign endometrial masses by endometrial stripe measurement in premenopausal women.

OBJECTIVE: Our objective was to estimate whether a transvaginal endometrial stripe of less than 5 mm in premenopausal women would exclude endometrial polyps and intracavitary leiomyomata, thereby eliminating the need for sonohysterography. METHODS: Data from 206 consecutive sonohysterograms performed in premenopausal women with abnormal uterine bleeding between August 1998 and October 2001 were collected retrospectively. Endometrial stripe measurements were obtained in the sagittal plane before sonohysterography. Baseline endometrial stripe images were reviewed by one of the authors, who was blinded to sonohysterography and pathology results, to evaluate for gross endometrial abnormalities on transvaginal ultrasonography. RESULTS: Endometrial stripe measurements were obtained before sonohysterography in 200 of the 206 consecutive exams in premenopausal subjects. Of the 80 subjects with an endometrial stripe measurement less than 5 mm, 11 had endometrial polyps and 5 had submucosal fibroids on sonohysterography. With an endometrial stripe thickness of less than 5 mm, the sensitivity was 74% (95% confidence interval 62-84), the specificity was 46% (95% confidence interval 38-54), the positive predictive value was 37%, and the negative predictive value was 80%. The detection of pathology was not improved by excluding cases with an abnormal-appearing endometrial stripe on the baseline transvaginal images. The use of other endometrial stripe cutoff values did not improve the diagnostic accuracy. CONCLUSION: Using an endometrial stripe cutoff of 5 mm in premenopausal women would miss significant intracavitary pathology. The sonographic evaluation of abnormal uterine bleeding in premenopausal women should include sonohysterography or equivalently accurate testing regardless of endometrial stripe thickness.

Intervention to improve follow-up for abnormal Papanicolaou tests: a randomized clinical trial.

OBJECTIVE: To evaluate the effect of a theory-based, culturally targeted intervention on adherence to follow-up among low-income and minority women who experience an abnormal Pap test. METHOD: 5,049 women were enrolled and underwent Pap testing. Of these, 378 had an abnormal result and 341 (90%) were randomized to one of three groups to receive their results: Intervention (I): culturally targeted behavioral and normative beliefs + knowledge/skills + salience + environmental constraints/barriers counseling; Active Control (AC): nontargeted behavioral and normative beliefs + knowledge/skills + salience + environmental constraints/barriers counseling; or Standard Care Only (SCO). The primary outcome was attendance at the initial follow-up appointment. Secondary outcomes included delay in care, completion of care at 18 months, state anxiety (STAI Y-6), depressive symptoms (CES-D), and distress (CDDQ). Anxiety was assessed at enrollment, notification of results, and 7-14 days later with the CDDQ and CES-D. RESULTS: 299 women were included in intent-to-treat analyses. Adherence rates were 60% (I), 54% (AC), and 58% (SCO), p = .73. Completion rates were 39% (I) and 35% in the AC and SCO groups, p = .77. Delay in care (in days) was (M ± SD): 58 ± 75 (I), 69 ± 72 (AC), and 54 ± 75 (SCO), p = .75. Adherence was associated with higher anxiety at notification, p < .01 and delay < 90 days (vs. 90+) was associated with greater perceived personal responsibility, p < .05. Women not completing their care (vs. those who did) had higher CES-D scores at enrollment, p < .05. CONCLUSIONS: A theory-based, culturally targeted message was not more effective than a nontargeted message or standard care in improving behavior.

Dystroglycan expression in human placenta: basement membrane localization and subunit distribution change between the first and third trimester.

OBJECTIVES: This study describes the distribution of dystroglycan (DG) in human placenta, membranes, and uterine decidua. STUDY DESIGN: Dystroglycan expression was characterized by Western blotting, immunohistochemistry, and immunofluorescence microscopy using human tissues and cultured cells. RESULTS: Both α-DG and ß-DG are expressed in the term syncytiotrophoblast, and α-DG is localized to the basement membrane. In first-trimester chorionic villi, α-DG and ß-DG are localized to the periphery of the cytotrophoblast. Expression varies in term fetal membranes. α-Dystroglycan is not detectable in choriocarcinoma cells or HTR cells, but ß-DG is present in both normal and cleaved forms. CONCLUSION: Dystroglycan is expressed at high levels in human trophoblasts, and localization of the α- and ß-subunits varies with gestational age and trophoblast differentiation. Because DG expression inversely correlates with invasiveness in many cancers, its pattern of expression in trophoblasts suggests a possible function in inhibition of placental invasion.

Structure-Function Of The Tumor Suppressor BRCA1.

BRCA1, a multi-domain protein, is mutated in a large percentage of hereditary breast and ovarian cancers. BRCA1 is most often mutated in three domains or regions: the N-terminal RING domain, exons 11-13, and the BRCT domain. The BRCA1 RING domain is responsible for the E3 ubiquitin ligase activity of BRCA1 and mediates interactions between BRCA1 and other proteins. BRCA1 ubiquitinates several proteins with various functions. The BRCA1 BRCT domain binds to phosphoproteins with specific sequences recognized by both BRCA1 and ATM/ATR kinases. Structural studies of the RING and BRCT domains have revealed the molecular basis by which cancer causing mutations impact the functions of BRCA1. While no structural data is available for the amino acids encoded by exons 11-13, multiple binding sites and functional domains exist in this region. Many mutations in exons 11-13 have deleterious effects on the function of these domains. In this mini-review, we examine the structure-function relationships of the BRCA1 protein and the relevance to cancer progression.