Knowledge of the risk factors and symptons associated with endometrial cancer in British South Asian and British white women

ABSTRACT Objective: To explore differences in the background knowledge of Endometrial Cancer (EC), its risk factors, symptoms and prognosis of Endometrial Cancer (EC) between British White (BW) and British South Asian (BSA) women who had undergone treatment for stage I endometrial cancer within the past 3-years. Study design: Face-to-face, semi-structured interviews exploring knowledge; diagnosis; treatment; follow-up; and survivorship were undertaken and analysed using Thematic Analysis. Results: Twenty-one women were interviewed (13 BW and 8 BSA). BW and BSA women reported similar views, experiences and concerns with regards to EC. Knowledge appeared to differ amongst the two groups with BSA women reporting being more aware that unscheduled vaginal bleeding could be associated with a malignancy but having lower levels of knowledge of the risk factors that can lead to EC, compared to BW women. There was a lack of understanding of the difference between cervical cancer and EC and as a result, many women reported taking reassurance from negative cervical cytology as excluding EC and there was also the misconception amongst some of the women that there was a link between sexual behaviour and EC. Women from both groups used the lay healthcare system to discuss their situation/symptoms, however BSA women reported to have specifically sought out women within their social network who had previously undergone treatment for EC. Conclusions: Greater effort is needed to raise awareness in both the BW/BSA communities of the symptoms associated with EC that should prompt medical review. Educational efforts are required to overcome the reported perception that EC is synonymous with cervical cancer and cannot be detected by cervical screening

Management of refractory overactive bladder

Key content Overactive bladder does not respond to first-line treatment in over 50% of cases. There is no agreed definition of what constitutes refractory overactive bladder. Botulinum toxin injection is effective, with a long duration of action but appreciable rates of urinary retention and infection (around 10% and 20%, respectively). There remain some questions about the preferred dose and the schedule of repeat dosing. There are few data on cost-effectiveness of botulinum toxin. Sacral nerve stimulation is an invasive, complex and expensive procedure. Sacral nerve stimulation is effective, but reoperation rates and complications are common. Percutaneous tibial nerve stimulation is a less invasive, cheaper alternative to sacral nerve stimulation but long-term efficacy is yet to be confirmed. Learning objectives To understand the available data on the efficacy and safety of botulinum toxin use. To be aware of the need for thorough assessment of patients, and the importance of multidisciplinary team review and appropriate detailed counselling. To understand the available data on the efficacy and safety of the alternative methods of neuromodulation. Ethical issues The long-term benefits and risks of these treatments are not fully defined. Is it ethical to commence potentially lifelong treatment without robust, high-quality data confirming safety

Emerging treatments for overactive bladder: clinical potential of botulinum toxins

Overactive bladder (OAB) is a symptom syndrome including urgency, frequency, and nocturia - with or without incontinence. It is a common manifestation of detrusor overactivity (DO). DO is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. OAB is, therefore, both a motor and sensory disorder. Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum and has been used in medicine for many years. Over the last 10 years, it has been used for the treatment of DO and OAB when standard treatments, such as bladder training and oral anticholinergic medication, have failed to provide symptom relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release from the neurons in the motor end plate and also at sensory synapses, although the clinical effect is not permanent due to the growth of new connections within treated tissues. It is known that botulinum toxin modulates vanillioid, purinergic, capsaicin, and muscarinic receptor expression within the lamina propria, returning them to levels seen in normal bladders. Clinically, the effect of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon the symptom of urgency, and also large effects on frequency, nocturia, leakage episodes, and continence rates. These effects have been seen consistently within eight randomized trials and numerous case series. Botulinum toxin appears safe, with the only common side effect being that of voiding difficulty, occurring in up to 10% of treated patients. Dosing regimens are variable, depending on which preparation is used, but it is clear that dose recommendations have fallen over the last 5 years. There is limited evidence about the efficacy of repeat treatments. Botulinum toxin is an effective and safe second-line treatment for patients with OAB and DO

Risk factors for obstetric anal sphincter injuries at vaginal birth after caesarean: a retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Vaginal birth after caesarean (VBAC) is associated with an increased risk of obstetric anal sphincter injuries (OASIS). However, specific factors that influence the risk of OASIS at VBAC have not been studied, particularly whether there are specific baseline characteristics of the first delivery which affect the subsequent perineal outcomes. METHODS: Retrospective analysis of prospectively collected data from University of Southampton NHS Foundation Trusts' maternity database. This included secundiparous women with a previous caesarean delivery (CS) who achieved a singleton, term, cephalic vaginal delivery from 2004 to 2014. Univariate analysis compared maternal, intrapartum and neonatal factors of those who suffered OASIS at VBAC with those who did not. A binary logistic regression model calculated the adjusted, independent odds ratio (OR) of OASIS. RESULTS: A total of 1375 women met the inclusion criteria. The OASIS rate was 8.1%, a 1.4-fold increase compared with primiparous women [difference 2.4% (95% CI 1.1, 3.6)]. Those sustaining OASIS at VBAC were older (p = 0.011) and had infants of greater birth weight at initial caesarean (p < 0.001) and VBAC (p = 0.04). Analysis of odds ratios revealed that mediolateral episiotomy (MLE) at VBAC halved the risk of OASIS [37.5% VBAC with OASIS vs. 52.2% VBAC without OASIS (OR 0.51, 95% CI 0.32-0.81)], whereas an urgent CS at initial delivery doubled the risk [52.3% VBAC with OASIS vs. 34.9% VBAC without OASIS (OR 2.05, 95% CI 1.31-3.21)]. CONCLUSIONS: Advanced maternal age, increased infant birth weight and an urgent category of initial CS increase the risk of OASIS at VBAC, whereas MLE is protective

Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders

Purpose: Artificial sweeteners augment bladder contraction. We hypothesized that artificial sweeteners activate sweet taste receptors in the bladder. Thus, we investigated the expression of sweet taste receptors in human and rat bladders. Materials and Methods: Sections of human and rat bladders were cut from paraffin blocks and stained by immunohistochemistry for the expression of T1R2/3 sweet taste receptors. Bladder homogenates were subjected to sodium dodecyl sulfate-polyacrylamide electrophoresis, followed by immunoblotting for T1R2/3 receptor expression. Rat bladder strips with and without urothelium were suspended in organ baths. The contractile response to 10 Hz electrical field stimulation was determined in the absence and presence of saccharin (Sigma-Aldrich®) (10−8 to 10−3 M). Responses to KCl in the absence and presence of saccharin, and saccharin plus zinc were also determined. Results: T1R2/3 sweet taste receptors were expressed in human and rat bladder urothelium. Immunostaining was evident in the plasma membrane of the 3 urothelial cell types, particularly umbrella cells. Immunoblotting revealed bands at expected molecular weights in human and rat bladder homogenates. Saccharin augmented rat bladder smooth muscle contraction due to electrical field stimulation only when urothelium was present in the bladder strip. Zinc blocked the enhancing effect of saccharin on responses to KCl. Conclusions: T1R2/3 sweet taste receptors are expressed in human and rat bladder urothelium. Activation of these receptors by artificial sweeteners may result in augmented bladder contraction

Risk factors for perineal trauma in the primiparous population during non-operative vaginal delivery.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injuries (OASIS) are more common in the primiparous population, especially during operative vaginal delivery (OVD). It would therefore be interesting to establish what factors influence the risk of OASIS when adjusting for the risk bias of OVD. METHODS: Retrospective analysis of prospectively collected data from the maternity database at University of Southampton NHS Foundation Trust of primiparous women sustaining OASIS during a singleton, term, cephalic, non-operative vaginal delivery between 2004 and 2015. A control comparison was made of women with otherwise identical birthing conditions but resulting with intact perinea, delivering between 2014 and 2015. Univariate and multivariate logistic regression compared maternal, intrapartum and neonatal factors of those sustaining OASIS with those with an intact perineum. RESULTS: Seven hundred fifty-six women sustaining an OASI met the criteria, and comparisons were made with a control population of 212. Those sustaining an OASI were significantly older (p < 0.001), more likely to be Asian (4.6-fold, p < 0.001) and had heavier babies, with a 3.6-fold greater proportion over 4 kg (p = 0.001). They were more likely to have delivered post-term and had longer second stages of labour (both p < 0.001). Epidural anaesthesia was associated with a 67% reduction in OASIS. CONCLUSIONS: These findings support previous research regarding risk factors for OASIS. By controlling for bias of risk associated with operative vaginal delivery, this revealed a potential protective effect of the use of regional anaesthesia

Network meta-analysis: development of a three-level hierarchical modeling approach incorporating dose-related constraints

BACKGROUND: Network meta-analysis (NMA) is commonly used in evidence synthesis; however, in situations in which there are a large number of treatment options, which may be subdivided into classes, and relatively few trials, NMAs produce considerable uncertainty in the estimated treatment effects, and consequently, identification of the most beneficial intervention remains inconclusive. OBJECTIVE: To develop and demonstrate the use of evidence synthesis methods to evaluate extensive treatment networks with a limited number of trials, making use of classes. METHODS: Using Bayesian Markov chain Monte Carlo methods, we build on the existing work of a random effects NMA to develop a three-level hierarchical NMA model that accounts for the exchangeability between treatments within the same class as well as for the residual between-study heterogeneity. We demonstrate the application of these methods to a continuous and binary outcome, using a motivating example of overactive bladder. We illustrate methods for incorporating ordering constraints in increasing doses, model selection, and assessing inconsistency between the direct and indirect evidence. RESULTS: The methods were applied to a data set obtained from a systematic literature review of trials for overactive bladder, evaluating the mean reduction in incontinence episodes from baseline and the number of patients reporting one or more adverse events. The data set involved 72 trials comparing 34 interventions that were categorized into nine classes of interventions, including placebo. CONCLUSIONS: Bayesian three-level hierarchical NMAs have the potential to increase the precision in the effect estimates while maintaining the interpretability of the individual interventions for decision making

Surgery for recurrent stress urinary incontinence: the views of surgeons and women

Introduction and hypothesis: The objectives were to explore the views of women with recurrent stress incontinence (SUI) with regard to treatment preferences and the acceptability of randomisation to a future trial, and to survey the views of UK specialists on treatment preferences and equipoise regarding different treatment alternatives. Methods: An online survey of the British Society of Urogynaecology (BSUG) and British Society of Urological Surgeons (BAUS) was carried out. Qualitative semi-structured interviews with a purposive sample of surgeons and women suffering from recurrent SUI from three UK centres. Results: Two hundred fifty-six survey replies were received (176 gynaecology; 80 urology). Comparing the treatments offered, urogynaecologists were more likely to offer pelvic floor exercises (p < 0.05), and repeat midurethral tape (MUT) (p < 0.001). From the Surgical Equipoise Scale (SES) responses, “no preference” was rarely the commonest response. Marked differences for several options existed; midurethral tape dominated responses whenever it appeared. Twenty-one clinicians were interviewed. Treatment preferences were complex, influenced by a range of factors (reason for failure, patient comorbidity, investigations, personal experience, training). A future trial was regarded as important. Eleven women were interviewed. Most had considered more than one option, but felt that decision-making was more a process of elimination rather than a positive process. Randomisation to a study was regarded as unacceptable by most. Conclusions: No consensus exists among surgeons about preferred treatment options for recurrent SUI, and personal experience and training dominate decision-making. For patients, choices were usually based on an elimination of options, including that of a repeat failed procedure. This contrasts with surgeons, who mostly preferred a repeat MUT above other options. Any future comparative study will be challenging

Receptor Isoforms That Mediate Estrogen and Progestagen Action in the Female Lower Urinary Tract

Purpose : Bladder symptoms can be ameliorated by sex steroids but to our knowledge the mechanism of action is unknown. Previous studies of steroid receptor expression in the bladder did not indicate receptor subtype expression. We report the distribution of estrogen and progesterone receptor isoforms in the female lower urinary tract. Materials and Methods : Prospectively recruited women undergoing routine urogynecological or gynecological surgery provided cold cup biopsy samples from the bladder dome, trigone, and proximal and distal urethra. The samples were immediately frozen or fixed in formalin. After RNA extraction transcripts for estrogen receptor α and β, and progesterone receptor A and B were noted on reverse transcriptase-polymerase chain reaction using isoform specific primers. The precise cellular localization of receptor proteins and their relative levels were assessed by immunochemistry in formalin fixed tissue sections with isoform specific antibodies. Results : Nine premenopausal and 10 postmenopausal women were recruited into the study. Two postmenopausal women on hormone replacement therapy. Estrogen receptor α and β, and progesterone receptor A and B transcripts were detected in whole bladder extracts. Nuclear estrogen receptor α immunoreactivity was present in squamous epithelium but absent from transitional epithelium. Estrogen receptor β immunoreactivity was expressed in squamous and transitional cell epithelium. Nuclear progesterone receptor expression was present in urethral squamous epithelium only. Progesterone receptor expression was greater in premenopausal women and in postmenopausal women on estrogen. Conclusions : Estrogen receptor α and β genes are transcribed in bladder tissue but only estrogen receptor β is translated into protein, suggesting that the urothelium responds to endogenous estrogen via estrogen receptor β. Progesterone receptor expression is confined to urethral squamous epithelium and the major isoform is progesterone receptor A

Prediction of miscarriage in women with viable intrauterine pregnancy-A systematic review and diagnostic accuracy meta-analysis.

Both ultrasound and biochemical markers either alone or in combination have been described in the literature for the prediction of miscarriage. We performed this systematic review and meta-analysis to determine the best combination of biochemical, ultrasound and demographic markers to predict miscarriage in women with viable intrauterine pregnancy. The electronic database search included Medline (1946-June 2017), Embase (1980-June 2017), CINAHL (1981-June 2017) and Cochrane library. Key MESH and Boolean terms were used for the search. Data extraction and collection was performed based on the eligibility criteria by two authors independently. Quality assessment of the individual studies was done using QUADAS 2 (Quality Assessment for Diagnostic Accuracy Studies-2: A Revised Tool) and statistical analysis performed using the Cochrane systematic review manager 5.3 and STATA vs.13.0. Due to the diversity of the combinations used for prediction in the included papers it was not possible to perform a meta-analysis on combination markers. Therefore, we proceeded to perform a meta-analysis on ultrasound markers alone to determine the best marker that can help to improve the diagnostic accuracy of predicting miscarriage in women with viable intrauterine pregnancy. The systematic review identified 18 eligible studies for the quantitative meta-analysis with a total of 5584 women. Among the ultrasound scan markers, fetal bradycardia (n=10 studies, n=1762 women) on hierarchical summary receiver operating characteristic showed sensitivity of 68.41%, specificity of 97.84%, positive likelihood ratio of 31.73 (indicating a large effect on increasing the probability of predicting miscarriage) and negative likelihood ratio of 0.32. In studies for women with threatened miscarriage (n=5 studies, n=771 women) fetal bradycardia showed further increase in sensitivity (84.18%) for miscarriage prediction. Although there is gestational age dependent variation in the fetal heart rate, a plot of fetal heart rate cut off level versus log diagnostic odds ratio showed that at ≤110 beat per minutes the diagnostic power to predict miscarriage is higher. Other markers of intra uterine hematoma, crown rump length and yolk sac had significantly decreased predictive value. Therefore in women with threatened miscarriage and presence of fetal bradycardia on ultrasound scan, there is a role for offering repeat ultrasound scan in a week to ten days interval