Symptomatic improvement after mesh removal: a prospective longitudinal study of women with urogynaecological mesh complications.

OBJECTIVE: To compare clinical characteristics and outcomes in patients undergoing excision of polypropylene urogynaecological mesh for pain, mesh exposure or both. DESIGN: Prospective, longitudinal cohort. SETTING: Academic tertiary referral centre. POPULATION: Women undergoing complete vaginal mesh excision for mesh exposure and/or pain. METHODS: Clinical and patient-reported outcomes assessing pain (visual analog scale, VAS), bother (Pelvic Floor Distress Inventory, PFDI) and functional impact (Pelvic Functional Impact Questionnaire, PFIQ) were collected at baseline, 6, 12 and 24 months after complete mesh excision. Outcomes were compared by mesh type (sling, prolapse [transvaginal or sacrocolpopexy mesh], both) and complication (pain, exposure, both). MAIN OUTCOME MEASURES: 'Much better' or 'Very much better' on Patient Global Impression of Improvement (PGI-I) up to 2 years after removal. RESULTS: Of 173 women, 48 underwent removal for pain, 27 for exposure and 98 for exposure plus pain. 'Moderate to severe' baseline symptoms were reported by 75%; the most prevalent and severe symptom was dyspareunia. Patients with pain alone were most bothered (PFDI median 234.2, interquartile range 83, P = 0.02) and had the highest functional impact (PFIQ median 181, interquartile range 138, P < 0.001). After excision, only 33.3% of women with pain alone reported 'improved' symptoms (PGI-I), versus 73.9% with exposure, 58.3% with exposure plus pain (P = 0.03) with no differences in PGI-I by mesh type. VAS scores decreased in all groups, but PFDI and PFIQ did not improve in pain patients. CONCLUSIONS: In women experiencing a pain complication after urogynaecological mesh insertion, mesh removal often does not improve symptoms. TWEETABLE ABSTRACT: Only 33% of women with pain complications have improved symptoms after urogynaecological mesh removal.

Palliative care education in gynecologic oncology: a survey of the fellows.

INTRODUCTION: Gynecologic oncologists regularly care for patients at the end of life, yet little is known about their training or preparedness to deal with issues of palliative care. We sought to examine the training provided to gynecologic oncology fellows as well as their perceived preparedness to provide palliative care. METHODS: A self-administered survey was distributed to all fellows enrolled in all gynecologic oncology fellowships during the 2009 academic year. The instrument assessed attitudes, training, experience, and preparedness regarding caring for patients at the end of life. Descriptive, bivariate and multivariable analyses were performed. RESULTS: Sixty-one percent (103/168) of fellows completed the survey. Most (89%) feel that palliative care is integral to their training, but few (11%) have had any palliative care training, including either a rotation or fellowship. Using a scale of 1-10, fellows rated teaching quality on two common training opportunities, specifically managing postoperative complications (7.8) and endometrial cancer patients (8.7), as significantly higher than teaching on managing patients at the end of life (5.5; p<0.001). Fellows rated the quality of end of life teaching as significantly lower than overall teaching (55% vs. 92%; p=0.001). Their self-assessment regarding overall preparedness to deal with end of life issues was associated with higher end of life teaching quality and experience caring for more than 10 dying patients. CONCLUSIONS: The quantity and quality of training in palliative care are lower compared to other common procedural and oncological issues. Gynecologic oncology fellowship programs need to incorporate a palliative care training curriculum.

Universal prenatal HIV screening: are we there yet?

The objectives of this study were to determine the prevalence of and factors associated with prenatal HIV screening and the availability of HIV test results in medical records in Pittsburgh, PA, USA. Three hundred postpartum women were surveyed about demographics and prenatal care provider(s) and practice setting and were asked to recall prenatal HIV screening and reasons for accepting or declining a HIV test. Medical records were reviewed for documentation of HIV results. Overall, 65% of women reported screening. White race, higher annual household income and fewer lifetime sexual partners were independently associated with decreased likelihood of prenatal HIV screening. Provider presentation of screening as standard practice and provider encouragement were associated with prenatal HIV screening. Only 38% of medical records contained HIV results at the time of labour. Universal and routine offering of prenatal HIV screening as standard practice, in conjunction with encouragement from health-care providers, may increase patient acceptability and the uptake of prenatal HIV screening.

Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis.

OBJECTIVES: To compare cervical concentrations of numerous cytokines/chemokines in women with bacterial vaginosis (BV) compared with the levels detected after BV resolution and determine if hormonal contraceptive use modulates the local inflammatory response to BV. METHODS: Cervical secretions from 81 women with BV at enrollment and normal flora at one-month follow-up were analysed for 10 different cytokines/chemokines using multiplexed fluorescent bead-based immunoassays. RESULTS: BV was associated with significantly higher concentrations of IL-1 beta, tumour necrosis factor (TNF), interferon-gamma, IL-2, IL-4, and IL-10 compared with the levels detected in the presence of normal vaginal flora. Analysis of results stratified by contraceptive practice demonstrated significantly lower levels of numerous cytokines among women with BV using hormonal contraceptives compared with those women with BV not using hormonal contraceptives. Hormonal contraceptive use was also associated with a statistically significant lesser change in TNF levels between the two study visits compared with the amount of change detected between visits among women who denied their use. CONCLUSIONS: Despite increases in the levels of both pro and anti-inflammatory cytokines in the lower genital tract of women with BV, the overall balance of these two types of molecules was maintained. The character of this local inflammatory response may help explain the typical absence of overt signs of inflammation among women with BV. In addition, hormonal contraceptive use was associated with significantly lower levels of the pro-inflammatory molecules TNF, interferon-gamma, and granulocyte macrophage colony-stimulating factor in women with BV, but did not significantly reduce the levels of IL-10, a key anti-inflammatory cytokine. These results suggest the possibility of an association between hormonal contraceptive use and altered genital tract immunity.

Safety and efficacy evaluations for vaginal and rectal use of BufferGel in the macaque model.

BACKGROUND: The nonhuman primate model allows for safety and efficacy testing of topical microbicide products. GOAL: The goal of this study was to evaluate the safety and efficacy of vaginal and rectal applications of BufferGel (ReProtect, Inc.). STUDY DESIGN: The safety of repeated product applications was evaluated by microflora, pH, vaginal colposcopy, and rectal lavage. To test efficacy in preventing chlamydia, infection was documented by culture and nucleic acid amplification tests. RESULTS: Repeated vaginal or rectal applications of BufferGel were not associated with significant changes in microflora. BufferGel use had a transient acidifying effect on vaginal and rectal pH. Colposcopic observations remained relatively normal in all test animals. A slightly increased incidence of epithelial desquamation was noted after rectal product use compared with the control group. BufferGel did not prevent cervical or rectal chlamydial infection. CONCLUSION: BufferGel has an acceptable safety profile after repeated vaginal and rectal use, but does not prevent chlamydial infection in the macaque models.

Impact of menopause on collagen subtypes in the arcus tendineous fasciae pelvis.

OBJECTIVE: The arcus tendineous fasciae pelvis (ATFP) provides support to the anterior vagina. The objective of this study was to determine the impact of menopause on the structural components of the ATFP. STUDY DESIGN: Biopsy specimens of the ATFP were obtained from 10 premenopausal, 5 postmenopausal, and 12 postmenopausal women on hormone therapy. Scanning confocal microscopy of fluorescent micrographs was used to define the amount of collagen subtypes, smooth muscle, and elastin. Collagen fiber orientation was determined by scanning electron microscopy. RESULTS: The ATFP is comprised primarily of parallel bundles of type III collagen fibers (84%), an intermediate amount of elastin (13%), and very little smooth muscle. The ratio of collagen I/(III+V) was decreased in postmenopausal not on hormones relative to premenopausal women (P=.04) due to a 75% decrease in collagen I (P=.046). The decrease in collagen I and change in collagen ratios was not present in women on hormone therapy. Comparison of the amounts of elastin and smooth muscle showed no difference in the ATFP of premenopausal and postmenopausal women. CONCLUSION: Menopause in the absence of hormone therapy is associated with a decrease in quantity of collagen I in the ATFP resulting in a decrease in the ratio of collagen I/(III+V). This may compromise the tensile strength and an increase susceptibility to anterior vaginal wall prolapse.

Accuracy of serum beta-human chorionic gonadotropin cutoff values at 42 and 49 days' gestation.

OBJECTIVE: The accuracy of serum beta-human chorionic gonadotropin levels as cutoff values for estimating gestational age was studied. MATERIAL AND METHODS: A database was created using information from previously performed research studies, which allowed entry of women both less than and greater than 49 days' gestation, involving medical abortion. Serum beta-human chorionic gonadotropin determinations and vaginal ultrasonography were performed in all studies before treatment. A total of 574 women had data available for analysis. A receiver operating characteristic curve was created to evaluate the predictive value of potential beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation. RESULTS: Appropriate serum beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation were 23,745 mIU/mL (sensitivity, 96%; specificity, 91%; positive predictive value, 68%; negative predictive value, 99%) and 71,160 mIU/mL (sensitivity, 95%; specificity, 62%; positive predictive value, 76%; negative predictive value, 91%), respectively. Under 42 days' gestation, the serum beta-human chorionic gonadotropin-time relationship appears to be linear, with a greater diversity of individual values after 42 days. CONCLUSION: Serum beta-human chorionic gonadotropin values can be used with reasonable accuracy to screen for a gestational age up to 49 days' gestation.

Vasopressin during abdominal hysterectomy: a randomized controlled trial.

OBJECTIVE: To investigate if the use of vasopressin during abdominal hysterectomy would decrease blood loss. METHODS: Fifty-one patients undergoing abdominal hysterectomy with the diagnosis of leiomyomatous uterus were randomized and received either vasopressin 10 units/10 mL of normal saline or 10 mL of normal saline, injected 5 mL bilaterally, 1 cm medial to the uterine vessels into the lower uterine segment. The sample size was determined assuming a one-third reduction in total blood loss would be clinically relevant. A power analysis determined that 25 patients would be required in each group to assure a power of 0.80, at the.05 significance level. RESULTS: Overall, the two groups were very similar with regard to their demographics, preoperative diagnosis, and relevant findings at the time of surgery. The mean total blood loss in the vasopressin and placebo groups was 445.41 mL and 748.42 mL, respectively. Total blood loss was significantly decreased by 40% in the vasopressin group compared with the placebo group (P <.001). There was no statistically significant difference between the two groups with respect to possible confounding variables or surgical complications. CONCLUSION: Injection of vasopressin into the uterus at the time of abdominal hysterectomy significantly reduces blood loss without increasing morbidity. We have shown that it is a useful adjunct during abdominal hysterectomy.

Neuron-specific expression of therapeutic proteins: evaluation of different cellular promoters in recombinant adenoviral vectors.

In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in the context of adenoviral vectors. Both the synapsin 1 gene and the tubulin alpha1 gene promoters were strictly neuron specific in cocultures of primary neurons with their essential feeder cells. The neuron-specific enolase gene promoter exhibited only weak activity in cultured hippocampal neurons and was not neuron specific in preparations of cerebellar granule cells. By attaining virtually 100% transduction efficiency we were able to generate "quasi-transgenic" primary neuron cultures using both differentiated and completely undifferentiated hippocampal neurons. In a functional assay, we used the synapsin promoter to evaluate the effect of Bcl-X(L) overexpression on potassium-withdrawal-induced apoptosis of cerebellar granule neurons. We found nearly complete inhibition of caspase-9 and -3 activation and apoptosis, indicating a major role for mitochondrial pathways in this paradigm of neuronal cell death. The excellent suitability of the synapsin promoter as a strong panneuronal promoter was further demonstrated by its restricted neuronal activity in various brain regions of adult rats in vivo.