Debra Brandt

Pelvic organ prolapse in older women: prevalence and risk factors.

OBJECTIVE: We sought to estimate the prevalence of pelvic organ prolapse in older women using the Pelvic Organ Prolapse Quantification examination and to identify factors associated with prolapse. METHODS: Women with a uterus enrolled at one site of the Womens Health Initiative Hormone Replacement Therapy randomized clinical trial were eligible for this ancillary cross-sectional study. Subjects underwent a Pelvic Organ Prolapse Quantification examination during a maximal Valsalva maneuver and in addition completed a questionnaire. Logistic regression was used to identify independent risk factors for each of 2 definitions of prolapse: 1) Pelvic Organ Prolapse Quantification stage II or greater and 2) the leading edge of prolapse measured at the hymen or below. RESULTS: In 270 participants, age (mean ± SD) was 68.3 ± 5.6 years, body mass index was 30.4 ± 6.2 kg/m2, and vaginal parity (median [range]) was 3 (0–12). The proportions of Pelvic Organ Prolapse Quantification stages (95% confidence intervals [CIs]) were stage 0, 2.3% (95% CI 0.8–4.8%); stage I, 33.0% (95% CI 27.4–39.0%); stage II, 62.9% (95% CI 56.8–68.7%); and stage III, 1.9% (95% CI 0.6–4.3%). In 25.2% (95% CI 20.1–30.8%), the leading edge of prolapse was at the hymen or below. Hormone therapy was not associated with prolapse (P = .9). On multivariable analysis, less education (odds ratio [OR] 2.16, 95% CI 1.10–4.24) and higher vaginal parity (OR 1.61, 95% CI 1.03–2.50) were associated with prolapse when defined as stage II or greater. For prolapse defined by the leading edge at or below the hymen, older age had a decreased risk (OR 0.50, 95% CI 0.27–0.92) and less education, and larger babies had an increased risk (OR 2.38, 95% CI 1.31–4.32 and OR 1.97, 95% CI 1.07–3.64, respectively). CONCLUSION: Some degree of prolapse is nearly ubiquitous in older women, which should be considered in the development of clinically relevant definitions of prolapse. Risk factors for prolapse differed depending on the definition of prolapse used. LEVEL OF EVIDENCE: II-2

Postoperative activity restrictions: any evidence?

OBJECTIVE: Because of a widespread but untested belief that increased intra-abdominal pressure contributes to pelvic floor disorders, physicians commonly restrict various activities postoperatively. Our aim was to describe intra-abdominal pressures during common physical activities. METHODS: Thirty women of wide age and weight ranges who were not undergoing treatment for pelvic floor disorders performed 3 repetitions of various activities while intra-abdominal pressures (baseline and maximal) were approximated via microtip rectal catheters. We calculated median peak and net pressures (centimeters of H2O). We assessed correlations between abdominal pressures and body mass index, abdominal circumference, and grip strength (a proxy for overall strength). P < .025 was considered significant. RESULTS: Median peak abdominal pressures ranged from 48 (lifting 8 lb from a counter) to 150 (lifting 35 lb from the floor), with much variation. Many activities did not raise the intra-abdominal pressure more than simply getting out of a chair, including lifting 8, 13, and 20 lb from a counter, lifting 8 or 13 lb from the floor, climbing stairs, walking briskly, or doing abdominal crunches. Body mass index and abdominal circumference each correlated positively with peak, but not net, pressures. Age and grip strength were not associated with abdominal pressure. CONCLUSION: Some activities commonly restricted postoperatively have no greater effect on intra-abdominal pressures than unavoidable activities like rising from a chair. How lifting is done impacts intra-abdominal pressure. Many current postoperative guidelines are needlessly restrictive. Further research is needed to determine whether increased intra-abdominal pressure truly promotes pelvic floor disorders. LEVEL OF EVIDENCE: III

Doppler velocimetry determined redistribution of fetal blood flow: Correlation with growth restriction in diamniotic monochorionic and dizygotic twins☆☆☆★

OBJECTIVE Our purpose was to study fetal growth and blood flow distribution in diamniotic monochorionic compared with dizygotic (diamniotic dichorionic) twins by use of Doppler velocimetry of the umbilical artery and middle cerebral artery. STUDY DESIGN Study candidates were divided into group A, consisting of 33 pairs (66 fetuses) of diamniotic monochorionic twins, and group B, 50 pairs (100 fetuses) of diamniotic dichorionic twins. Diamniotic monochorionic placentation was confirmed by microscopic placental examination for group A. Diamniotic dichorionic placentation was ensured for group B by selecting only twins with different-sex pairs (dizygotic twins). Targeted ultrasonography with biometry was performed in each twin, and Doppler recordings of the umbilical artery and middle cerebral artery were obtained. Waveforms were analyzed and the systolic/diastolic ratio, the resistance index, and a measure of blood flow redistribution (brain-sparing effect), the cerebral/placental ratio, was calculated for each fetus. Growth status at birth was assessed by the number of small-for-gestational-age infants (< or = 10th percentile), low-birth-weight infants (< or = 25th percentile), and percent of growth discordance between twins. Intertwin differences were assessed by delta values (value of larger twin minus value of smaller twin). RESULTS Diamniotic monochorionic compared with dizygotic twins demonstrated a significantly greater probability of blood flow redistribution. For the study population as a whole, the brain-sparing effect was noted in 67% of small-for-gestational-age babies and only 7% of non-small-for-gestational-age infants (p < or = 0.001). For the diamniotic monochorionic pregnancies blood flow redistribution occurred in 6 of 10 small-for-gestational-age infants (60%) and 6 of 46 non-small-for-gestational-age infants (13%). In the diamniotic monochorionic group small-for-gestational-age compared with non-small-for-gestational-age infants were more likely to show blood flow redistribution, which was the result of significantly decreased resistance in the middle cerebral artery and significantly increased resistance in the umbilical artery. Small-for-gestational-age infants (< or = 10th percentile) occurred much less frequently in the dizygotic group. Two of two small-for-gestational-age infants in the dizygotic group showed blood flow redistribution. Although the extremes of birth weight were more common in the diamniotic monochorionic group, both groups had relatively large numbers of small babies with birth weights in the lower 25th percentile (50.0% for diamniotic monochorionic and 44.0% for dizygotic twins, not significant). However, 42.3% (11/26) of diamniotic monochorionic twins who were in the low-birth-weight group showed blood flow redistribution compared with only 3.3% (1/30) whose birth weights were > or = 25th percentile (p < or = 0.001). In the dizygotic twins 10% of lower-birth-weight infants redistributed blood flow compared with 1% in the higher-birth-weight group, a nonsignificant difference. Diamniotic monochorionic compared with dizygotic twins were delivered earlier (32.9 weeks vs 34.8 weeks, p < or = 0.001), were smaller (1832 gm vs 2304 gm, p < or = 0.001), showed higher birth weight discordance (29.8% vs 14%, p < or = 0.05), and had greater numbers (19.7% vs 2.3%, p < or = 0.01) of infants at < or = 10th percentile birth weight. CONCLUSIONS Diamniotic monochorionic twins from the lower-birth-weight groups more often show blood flow redistribution compared with dizygotic twins of similar low birth weights. Placental vascular connections and the attendant hemodynamic changes in the fetuses of diamniotic monochorionic twins probably account for this difference. Brain-sparing events occur commonly without clinical twin transfusion syndrome in this group. These findings have implications for management.

Informed consent and genomic incidental findings: IRB chair perspectives

It is unclear how genomic incidental finding (GIF) prospects should be addressed in informed consent processes. An exploratory study on this topic was conducted with 34 purposively sampled Chairs of institutional review boards (IRBs) at centers conducting genome-wide association studies. Most Chairs (96%) reported no knowledge of local IRB requirements regarding GIFs and informed consent. Chairs suggested consent processes should address the prospect of, and study disclosure policy on, GIFs; GIF management and follow-up; potential clinical significance of GIFs; potential risks of GIF disclosure; an opportunity for participants to opt out of GIF disclosure; and duration of the researchers duty to disclose GIFs. Chairs were concerned about participant disclosure preferences changing over time; inherent limitations in determining the scope and accuracy of claims about GIFs; and making consent processes longer and more complex. IRB Chair and other stakeholder perspectives can help advance informed consent efforts to accommodate GIF prospects.

A Closer Look at the Recommended Criteria for Disclosing Genetic Results: Perspectives of Medical Genetic Specialists, Genomic Researchers, and Institutional Review Board Chairs

Next generation sequencing offers benefit of improved health through knowledge, but comes with challenges, such as inevitable incidental findings (IFs). The applicability of recommended criteria for disclosure of individual results when applied to disclosure of IFs is not well known. The purpose of this study was to examine how medical genetic specialists, genomic researchers, and Institutional Review Board (IRB) chairs perceive the importance of recommended criteria when applied to genetic/genomic IFs. We conducted telephone interviews with medical genetic specialists (genetic counselors, genetic nurses, medical geneticists, laboratory professionals), genomic researchers, and IRB chairs (N = 103). Respondents rated and discussed the importance of nine recommended criteria regarding disclosure of genetic/genomic IFs. Stakeholders agreed the most important criteria for disclosure were: (1) the IF points to a life-threatening condition; (2) there is a treatment; (3) individuals indicate in writing they wanted to be informed of IFs. Criteria rated less important were: analytic validity, high penetrance, association with a young age of onset and relative risk more than 2.0. Respondents indicated that some technical criteria were confusing, and in need of context. Our findings suggest that development of guidelines regarding management of IF include multiple stakeholders’ perspectives and be based on a common language.

Non-surgical management of stress urinary incontinence: ambulatory treatments for leakage associated with stress (ATLAS) trial.

Background Non-surgical treatment for stress urinary incontinence (SUI) is recommended as first-line therapy, yet few prospective studies and no randomized trials compare the most common non-surgical treatments for SUI. Purpose To present the design and methodology of the ambulatory treatments for leakage associated with stress (ATLAS) trial, a randomized clinical trial comparing three interventions for predominant SUI in women: intravaginal continence pessary; behavioral therapy (including pelvic floor muscle training and exercise and bladder control strategies); and a combination of the two treatments. Methods Treatment outcome measures, collected at 12 weeks and six and 12 months post randomization, include the Patient Global Impression of Improvement (PGI-I), the Stress Incontinence Scale of the Pelvic Floor Distress Inventory (PFDI), seven-day bladder diaries, Pelvic Floor Impact Questionnaire (PFIQ), Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ-12), Patient Satisfaction Questionnaire (PSQ) and the Medical Outcomes Study Short Form Health Survey (SF-36). Limitations The study design reduces most common biases, but some degree of selection bias may remain. Conclusion This trial will provide useful information to help counsel women with stress and mixed incontinence about the relative efficacy and satisfaction with pessary, behavioral therapy and both treatments combined.

Researcher and Institutional Review Board Chair Perspectives on Incidental Findings in Genomic Research

AIMS Genomic research can produce findings unrelated to a studys aims. The purpose of this study was to examine researcher and Institutional Review Board (IRB) chair perspectives on genomic incidental findings (GIFs). METHODS Nineteen genomic researchers and 34 IRB chairs from 42 institutions participated in semi-structured telephone interviews. Researchers and chairs described GIFs within their respective roles. Few had direct experience with disclosure of GIFs. Researchers favored policies where a case by case determination regarding whether GIF disclosure would be offered after discovery, whereas IRB chairs preferred policies where procedures for disclosure would be determined prior to approval of the research. CONCLUSIONS Researcher and IRB chair perspectives on management of GIFs overlap, but each group provides a unique perspective on decisions regarding disclosure of GIFs in research. Engagement of both groups is essential in efforts to provide guidance for researchers and IRBs regarding disclosure of GIFs in research.

Individual genetic and genomic research results and the tradition of informed consent: exploring US review board guidance

Background Genomic research is challenging the tradition of informed consent. Genomic researchers in the USA, Canada and parts of Europe are encouraged to use informed consent to address the prospect of disclosing individual research results (IRRs) to study participants. In the USA, no national policy exists to direct this use of informed consent, and it is unclear how local institutional review boards (IRBs) may want researchers to respond. Objective and methods To explore publicly accessible IRB websites for guidance in this area, using summative content analysis. Findings Three types of research results were addressed in 45 informed consent templates and instructions from 20 IRBs based at centres conducting genomic research: (1) IRRs in general, (2) incidental findings (IFs) and (3) a broad and unspecified category of ‘significant new findings’ (SNFs). IRRs were more frequently referenced than IFs or SNFs. Most documents stated that access to IRRs would not be an option for research participants. These non-disclosure statements were found to coexist in some documents with statements that SNFs would be disclosed to participants if related to their willingness to participate in research. The median readability of template language on IRRs, IFs and SNFs exceeded a ninth-grade level. Conclusion IRB guidance may downplay the possibility of IFs and contain conflicting messages on IRR non-disclosure and SNF disclosure. IRBs may need to clarify why separate IRR and SNF language should appear in the same consent document. The extent of these issues, nationally and internationally, needs to be determined.

Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen).

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n=299) and from non-pregnant controls (n=134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p=0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function.

Understanding Goals of Care Statements and Preferences among Patients and Their Surrogates in the Medical ICU.

Treatment decisions should be based on patients’ goals of care to provide an ethical, patient-centered framework for decision making. The purpose of this study is to improve our understanding about how patients’ and surrogates’ goals of care are communicated and interpreted in an medical intensive care unit (MICU). One hundred patients admitted to an MICU, or their surrogates, responded to an open-ended question about goals of care for their hospitalization followed by a closed-ended question regarding their most important goal of care. Investigators interpreted participants’ open-ended responses and compared these interpretations with participants’ closed-ended, most important goal selections. Investigators’ interpretations of participants’ open-ended goals of care responses matched participants’ closed-ended most important goal of care in only 28 of 100 cases. However, there was good interrater reliability between investigators in their interpretation of participants’ open-ended responses, with agreement in 78 of 100 cases. Clinicians should be cautious in interpreting patients’ or surrogates’ responses to open-ended questions about goals of care. A shared understanding of goals of care may be facilitated by alternating open-ended and closed-ended questions to clarify patients’ or surrogates’ responses.