Complications of Synthetic Midurethral Slings: Is There a Relevant Discrepancy Between Observational Data and Clinical Trials?

CONTEXT: The complications of synthetic midurethral slings (MUSs) in women with stress urinary incontinence (SUI) have become a globally debated issue. OBJECTIVE: To systematically review the short- and long-term complications of mesh slings reported in observational data compared with clinical trial data, to determine whether the complication rates from clinical trials reflects "real-world" observational data. EVIDENCE ACQUISITION: PubMed and Cochrane Library were searched. Methods as detailed in Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane Handbook for Systematic Reviews of Interventions were followed. EVIDENCE SYNTHESIS: Thirty registries/databases including 709 335 MUS procedures (1-22 yr of follow-up) were identified. MUS procedures were associated with intraoperative bladder perforation in 0.86-3.6%, urethral perforation in 0-0.1%, vascular injury in 0.04-0.1%, voiding lower urinary tract symptoms (LUTS) in 1.47-3.5%, vaginal exposure in 0.2-1.9%, and reoperation in up to 9% of cases. Forty-three randomised clinical trials were identified, including 6284 women who underwent MUS procedures and 2177 women who underwent other interventions (1-10 yr of follow-up). MUS procedures were associated with urinary tract perforation in 2.58%, vaginal injury in 1.43%, de novo voiding LUTS in 4.37%, de novo storage LUTS in 5.41%, mesh extrusion/exposure (vaginal/urinary tract) in 2.54%, dyspareunia in 2.26%, pain (pelvic/suprapubic/perineal) in 2.83%, and reoperation for complications required in 1.82% of cases. Meta-analyses of the randomised controlled trials revealed that retropubic MUSs were associated with more events of urinary tract perforation (risk ratio [RR] 9.81, 95% confidence interval [CI] 5.05-19.04, high certainty of evidence [COE]) and voiding LUTS (RR 1.57, 95% CI 1.19-2.07, high COE) than transobturator MUSs. MUSs were associated with more events of pain than mini-slings (RR 1.72, 95% CI 1.04-2.87, moderate COE). CONCLUSIONS: Short- and long-term data on complications of polypropylene mesh used for female SUI are fairly comparable when using outcome data from well-designed clinical trials or from less structured prospective or retrospective registries. Comparisons have to be made with caution since the two systems of data collection are inherently incomparable. This knowledge should be incorporated in the discussion on how to implement polypropylene mesh for female stress incontinence. PATIENT SUMMARY: In order to know whether mesh tapes used for treating stress incontinence work well and are safe, high-quality information is important. It appears that well-designed clinical studies give similar results to large registration databases. These data should be interpreted with caution in view of the different ways the information was collected. These results will help physicians and patients understand the risks of mesh tapes.

The Semon Lectures and the foundation of modern ENT.

BACKGROUND: Sir Felix Semon established the Semon Lecture series in 1913 to advance the specialty of laryngology. The annual lectures continue to the present day (there have been 95 to date). OBJECTIVE: This review illustrates how instrumental these lectures have been in shaping otolaryngology. METHOD: The period 1913-1970 preceded subspecialisation, and so forms the background of laryngology (as well as rhinology and otology) as we know it today. This era forms the focus of the article. RESULTS: Changes came about by a standardisation of practices and research, and in the treatment of conditions. The initial period was crucial. CONCLUSION: Many lectures highlight the specialty's growth. Now, another vital resource, a dedicated website (semonlectures.org), has made this information more accessible to the wider public.

Female Urgency, Trial of Urodynamics as Routine Evaluation (FUTURE study): a superiority randomised clinical trial to evaluate the effectiveness and cost-effectiveness of invasive urodynamic investigations in management of women with refractory overactive bladder symptoms.

BACKGROUND: Overactive bladder (OAB) syndrome is a symptom complex affecting 12-14% of the UK adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. OAB has a negative impact on women's social, physical, and psychological wellbeing. Initial treatment includes lifestyle modifications, bladder retraining, pelvic floor exercises and pharmacological therapy. However, these measures are unsuccessful in 25-40% of women (refractory OAB). Before considering invasive treatments, such as Botulinum toxin injection or sacral neuromodulation, most guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity (DO). However, urodynamics may fail to show evidence of DO in up to 45% of cases, hence the need to evaluate its effectiveness and cost-effectiveness. FUTURE (Female Urgency, Trial of Urodynamics as Routine Evaluation) aims to test the hypothesis that, in women with refractory OAB, urodynamics and comprehensive clinical assessment is associated with superior patient-reported outcomes following treatment and is more cost-effective, compared to comprehensive clinical assessment only. METHODS: FUTURE is a pragmatic, multi-centre, superiority randomised controlled trial. Women aged ≥ 18 years with refractory OAB or urgency predominant mixed urinary incontinence, and who have failed/not tolerated conservative and medical treatment, are considered for trial entry. We aim to recruit 1096 women from approximately 60 secondary/tertiary care hospitals across the UK. All consenting women will complete questionnaires at baseline, 3 months, 6 months and 15 months post-randomisation. The primary outcome is participant-reported success at 15 months post-randomisation measured using the Patient Global Impression of Improvement. The primary economic outcome is incremental cost per quality-adjusted life year gained at 15 months. The secondary outcomes include adverse events, impact on other urinary symptoms and health-related quality of life. Qualitative interviews with participants and clinicians and a health economic evaluation will also be conducted. The statistical analysis of the primary outcome will be by intention-to-treat. Results will be presented as estimates and 95% CIs. DISCUSSION: The FUTURE study will inform patients, clinicians and policy makers whether routine urodynamics improves treatment outcomes in women with refractory OAB and whether it is cost-effective. TRIAL REGISTRATION: ISRCTN63268739 . Registered on 14 September 2017.

Developing and implementing a multi-modality imaging optimization study in paediatric radiology: Experience and recommendations from an IAEA coordinated research project.

Optimization of imaging examinations is a key requirement of both the International and European Basic Safety Standards, and the focus of much international activity. Although methodologies are well established in principle, there continues to be a variety of practical issues both in collecting and interpreting dose and image quality data and in making successful interventions to optimize exposures. A Coordinated Research Project, involving institutes from ten different countries, was established by the IAEA to assess the efficacy of recommended optimization methodologies in the field of paediatric radiology and to derive practical guidance on their implementation. The steps followed in this process were identification of the imaging process to be investigated (abdomen and chest x-rays, micturating cysto-urethrograms, and brain & thorax CT scans); collection of dose and image quality data; evaluation and comparison of the data between institutes and to standards; identification and implementation of interventions for optimization; and re-evaluation of dose and image quality parameters. The project succeeded both in achieving effective interventions for optimization of specific imaging tasks in individual institutes and in identifying key issues with potential to handicap this process. The main area in which problems were encountered was in the collation of reliable dose and image quality data. The reasons for this were explored and a series of recommendations have been made, summarized into 'ten practical tips' for optimization to assist institutes, particularly those in the early stages of addressing optimization issues.

Tadalafil Alone or in Combination with Tamsulosin for the Management for LUTS/BPH and ED.

PURPOSE OF REVIEW: Aim of our systematic review is to evaluate and summarize the efficacy and safety of tadalafil alone or in combination with tamsulosin for the management of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). RECENT FINDINGS: Daily tadalafil, in particular 5 mg, according to retrieved studies, appears to be both safe and effective in treating LUTS/BPH and ED, compared with placebo or tamsulosin. The combination of daily tadalafil 5 mg and tamsulosin 0.4 mg allows a better improvement of LUTS compared with both the monotherapies, even if with an increased, but acceptable and tolerated, adverse events rate. After discontinuation of tamsulosin or tadalafil in patients previously treated with their combination, the improvement of LUTS retains significance compared with baseline. Tadalafil 5 mg should be considered a primary treatment option for patients with LUTS/BPH and ED. Evidence highlight an excellent tolerability, safety, and effectiveness profile, both alone or in combination with tamsulosin 0.4 mg. A better efficacy on LUTS relief has been observed for combination therapy, preserving also sexual function. The further switch to monotherapy allows to preserve LUTS relief, but tadalafil only is able to retain ED improvement. Our results support the evidence for a more and more tailored and modular LUTS treatment.

Effectiveness of splinting for pain and function in people with thumb carpometacarpal osteoarthritis: a systematic review with meta-analysis.

OBJECTIVE: To examine the effectiveness of splinting for reducing pain and improving function and health-related quality of life (HR-QoL) in people with thumb carpometacarpal osteoarthritis (CMC OA). DESIGN: The Cochrane Library, MEDLINE, Embase, CINAHL, ISI Web of Science, Scopus and Google Scholar, 3 trial registries and 4 conference proceedings were systematically searched for randomised and non-randomised controlled trials up to March 17th, 2018. Two reviewers independently applied the inclusion criteria to select potential studies and assess risk of methodologic bias using the Cochrane Collaboration's Risk of Bias Tool. Studies were pooled using the inverse variance method to calculate standardised mean difference (SMD). Sensitivity analyses were conducted and the quality of evidence for each outcome was judged following the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twelve studies were retrieved (n = 1353), 4 comparing a splint to control and 8 to another splint. In the medium-term (3-12 months), low quality evidence showed that splints cause a moderate to large reduction in pain (SMD 0.7 [95% confidence interval (CI) 1.04, 0.35], P < 0.0001) and small to moderate improvement in function (SMD 0.42 [95% CI 0.77, 0.08], P = 0.02). No significant effect was found at short-term or for different types of splints. No studies reported HR-QoL. CONCLUSIONS: Splinting demonstrated a moderate to large effect for pain and small to moderate effect for function in the medium-term but not in the short term. Quality of the evidence is low. Major challenges are the lack of diagnostic criteria and of a gold-standard outcome measure for thumb CMC OA.

Incremental clinical effectiveness and cost effectiveness of providing supervised physiotherapy in addition to usual medical care in patients with osteoarthritis of the hip or knee: 2-year results of the MOA randomised controlled trial.

OBJECTIVE: To investigate the clinical- and cost-effectiveness at 2-year follow-up of providing individual, supervised exercise physiotherapy and/or manual physiotherapy in addition to usual medical care. METHOD: People with hip or knee osteoarthritis meeting the American College of Rheumatology clinical diagnostic criteria were randomised (1:1, concealed, assessor-blinded) to four groups: usual medical care; supervised exercise physiotherapy; manual physiotherapy; or combined exercise and manual physiotherapy. Physiotherapy group participants were provided 10 50-min treatment sessions including booster sessions at 4 and 13 months, in addition to usual care. The primary outcome at 2-year follow-up was incremental cost-utility ratio (ICUR) of each physiotherapy intervention in addition to usual care, compared with usual care alone, from the health system and societal perspectives. To allow interpretation of negative ICURs, we report incremental net benefit (INB). The primary clinical outcome was the Western Ontario and McMaster Osteoarthritis Index (WOMAC). RESULTS: Of 206 patients, 186 (90·3%) were retained at 2-year follow-up. Exercise physiotherapy and manual physiotherapy dominated usual care, demonstrating cost savings; combined therapy did not. Exercise therapy had the highest incremental net benefits (INBs), statistically significant at all willingness-to-pay (base-case: societal New Zealand (NZ)$6,312, 95%CI 334 to 12,279; health system NZ$8,065, 95%CI 136 to 15,994). Clinical improvements were superior to usual care only in the exercise physiotherapy group (-28.2 WOMAC points, 95%CI -49.2 to -7.1). No serious adverse events were recorded. CONCLUSION: Individually supervised exercise therapy is cost-effective and clinically effective in addition to usual medical care at 2-year follow-up, and leads to cost savings for the health system and society. TRIAL REGISTRATION: Prospectively registered with the Australian NZ Clinical Trials Registry, reference ACTRN12608000130369.

Patient radiation doses in paediatric interventional cardiology procedures: a review.

A large number of investigations into the radiation doses from x-ray guided interventional cardiology procedures in children have been carried out in recent years. A review was conducted of these studies, gathering data on kerma area product (P KA), fluoroscopic screening time (FT), air kerma, and estimates of effective dose and organ doses. The majority of studies focus on P KA and FT with no estimation of dose to the patient. A greater than ten-fold variation in average P KA was found between different studies, even where data were stratified by patient age or weight. Typical values of P KA were 0.6-10 Gy · cm2 (<1 year/10 kg), 1.5-30 Gy · cm2 (1-5 years), 2-40 Gy · cm2 (5-10 years), 5-100 Gy · cm2 (10-16 years) and 10-200 Gy · cm2 (>16 years). P KA was lowest for heart biopsy (0.3-10 Gy · cm2 for all ages combined) and atrial septostomy (0.4-4.0 Gy · cm2), and highest for pulmonary artery angioplasty (1.5-35 Gy · cm2) and right ventricular outflow tract dilatation (139 Gy · cm2). Most estimates of patient dose were in the form of effective dose (typically 3-15 mSv) which is of limited usefulness in individualised risk assessment. Few studies estimated organ doses. Despite advances in radiation protection, recent publications have reported surprisingly large doses, as represented by P KA and air kerma. There is little indication of a fall in these dose indicators over the last 15 years. Nor is there much suggestion of a fall in doses associated with the use of flat panel detectors, as opposed to image intensifiers. An assessment of the impact of radiation dose in the context of overall patient outcome is required.

Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM) for diagnosis and management of bladder outlet obstruction in men: study protocol for a randomised controlled trial.

BACKGROUND: Lower urinary tract symptoms (LUTS) comprise storage symptoms, voiding symptoms and post-voiding symptoms. Prevalence and severity of LUTS increase with age and the progressive increase in the aged population group has emphasised the importance to our society of appropriate and effective management of male LUTS. Identification of causal mechanisms is needed to optimise treatment and uroflowmetry is the simplest non-invasive test of voiding function. Invasive urodynamics can evaluate storage function and voiding function; however, there is currently insufficient evidence to support urodynamics becoming part of routine practice in the clinical evaluation of male LUTS. DESIGN: A 2-arm trial, set in urology departments of at least 26 National Health Service (NHS) hospitals in the United Kingdom (UK), randomising men with bothersome LUTS for whom surgeons would consider offering surgery, between a care pathway based on urodynamic tests with invasive multichannel cystometry and a care pathway based on non-invasive routine tests. The aim of the trial is to determine whether a care pathway not including invasive urodynamics is no worse for men in terms of symptom outcome than one in which it is included, at 18 months after randomisation. This primary clinical outcome will be measured with the International Prostate Symptom Score (IPSS). We will also establish whether inclusion of invasive urodynamics reduces rates of bladder outlet surgery as a main secondary outcome. DISCUSSION: The general population has an increased life-expectancy and, as men get older, their prostates enlarge and potentially cause benign prostatic obstruction (BPO) which often requires surgery. Furthermore, voiding symptoms become increasingly prevalent, some of which may not be due to BPO. Therefore, as the population ages, more operations will be considered to relieve BPO, some of which may not actually be appropriate. Hence, there is sustained interest in the diagnostic pathway and this trial could improve the chances of an accurate diagnosis and reduce overall numbers of surgical interventions for BPO in the NHS. The morbidity, and therapy costs, of testing must be weighed against the cost saving of surgery reduction. TRIAL REGISTRATION: Controlled-trials.com - ISRCTN56164274 (confirmed registration: 8 April 2014).

Durable improvements in urinary incontinence and positive treatment response in patients with idiopathic overactive bladder syndrome following long-term onabotulinumtoxinA treatment: Final results of 3.5-year study.

OBJECTIVES: Here we present the final results from an extension study assessing long-term onabotulinumtoxinA treatment (3.5 years) in patients with idiopathic overactive bladder. METHODS: Patients who completed either of 2 Phase III trials were eligible to enter a 3-year extension study in which they received multiple onabotulinumtoxinA (100 U) treatments. Data were analyzed for the overall population of patients who received 100 U in any treatment cycle (n=829) and within discrete subgroups of patients who received exactly 1 (n=105), 2 (n=118), 3 (n=117), 4 (n=83), 5 (n=46), or 6 (n=33) treatments of the 100 U dose throughout the study (n=502). RESULTS: Of the 829 patients enrolled, 51.7 % completed the study. Discontinuations due to AEs/lack of efficacy were low (5.1/5.7 %); other reasons were not treatment-related. Mean reductions from baseline in urinary incontinence (UI) episodes/day (week 12; co-primary endpoint) were consistent among discrete subgroups who received 1 (-3.1), 2 (-2.9, -3.2), 3 (-4.1 to -4.5), 4 (-3.4 to -3.8), 5 (-3.0 to -3.6), or 6 (-3.1 to -4.1) treatments. A consistently high proportion of patients reported improvement/great improvement on the Treatment Benefit Scale (week 12; co-primary endpoint) in the discrete subgroups across all treatments (70.0-93.5 %). Median time to request retreatment was ≤6 months for 34.2 %, >6-≤12 months for 37.2 %, and >12 months for 28.5 % of patients. Most common AE was UTI, with no changes in safety profile over time. CONCLUSION: Long-term onabotulinumtoxinA treatment resulted in consistent reductions in UI and high proportions of patients reporting improvement after each treatment, with no new safety findings.

Nocturia: risk factors and associated comorbidities; findings from the EpiLUTS study.

OBJECTIVE: To evaluate the risk factors and comorbidities associated with nocturia in men and women aged ≥ 40 years. MATERIAL AND METHODS: The EpiLUTS study was an Internet-based cross-sectional, population-representative survey involving 30,000 men and women from the USA, UK and Sweden evaluating lower urinary tract symptoms (LUTS) using the LUTS Tool. A secondary analysis of the EpiLUTS data using participants with nocturia was performed. Descriptive statistics were used to examine the data. Logistic regressions were used to analyse associations of comorbid conditions and risk factors in men and women with nocturia ≥ 2. RESULTS: With a 59% response rate, nocturia ≥ 1 was quite common at 69% in men and 76% in women; 28% men and 34% women had nocturia ≥ 2. Age, body mass index (in women), Hispanic and Black responders, diabetes, high blood pressure, anxiety and depression and a history of bed-wetting were significantly associated with nocturia ≥ 2. Arthritis, asthma, diabetes, heart disease, inflammatory bowel disease, bladder infection, uterine prolapse, hysterectomy and menopausal status were all significantly associated with nocturia ≥ 2 in women. Prostatitis and prostate cancer were significant in men with nocturia ≥ 2. British and Swedish participants had a lesser risk of nocturia ≥ 2. CONCLUSION: Nocturia is a highly prevalent condition associated with various risk factors and comorbidities. Treatment of nocturia should be aimed at these causes in a multidisciplinary fashion. Further studies are needed to look specifically at these conditions in the pathophysiology of nocturia.

[AN EVIDENCE BASED UPDATE ON THE INVESTIGATION AND MANAGEMENT OF MALE LOWER URINARY TRACT SYMPTOMS].

In this review, we aim to summarise the evidence regarding the diagnosis and management of male Lower urinary tract symptoms (LUTS). It is inevitable that with an ageing population the prevalence of male LUTS is likely to increase. Thus symptom prevention and preservation of quality oflife (QoL) feature as high priorities for clinicians and patients alike. There are now a number of different pharmacological options available to men with LUTS which lead to significant improvements in symptom scores, flow rate and QoL. Meta-analyses have shown the benefits for 5-α reductase inhibitors, antimuscarinics, alpha blockers and more recently the phosphodiesterase-5 inhibitors. High level evidence also exists for combinations of all of the above agents with alpha blockers except phosphodiesterase-5 inhibitors and so men with concomitant storage symptoms, prostate volume >30ml/ PSA>1.4 or erectile dysfunction may be considered for combination treatment. The last few years have seen an increase in the data regarding less invasive methods of cystometry. Although these do not provide the same information as cystometry, they may have a role in answering specific questions and counselling men with BPH/LUTS. The key to incorporating these newer techniques in the assessment of men will lie with standardisation and use for specific indications. In an era of personalised medicine, appropriate patient selection is likely to provide the key to the most effective clinical investigative and management strategy.

Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens.

Alpha1 -adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A -adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L -adrenoceptor) is involved in mediating contractions of this tissue. The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [(3) H]tamsulosin binding experiments to identify the α1 -adrenoceptor subtype population present in the human vas deferens. The α1A -adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D -adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A - and α1D -adrenoceptor selective) had a high affinity (pKd = 9.9). [(3) H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [(3) H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively). These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1 -adrenoceptors which have the pharmacological properties of the putative α1L -adrenoceptor, the same functional receptor previously identified in the human prostate.

Femoral nerve infusion after primary total knee arthroplasty: a prospective, double-blind, randomised and placebo-controlled trial.

OBJECTIVES: Effective analgesia after total knee arthroplasty (TKA) improves patient satisfaction, mobility and expedites discharge. This study assessed whether continuous femoral nerve infusion (CFNI) was superior to a single-shot femoral nerve block in primary TKA surgery completed under subarachnoid blockade including morphine. METHODS: We performed an adequately powered, prospective, randomised, placebo-controlled trial comparing CFNI of 0.125% bupivacaine versus normal saline following a single-shot femoral nerve block and subarachnoid anaesthesia with intrathecal morphine for primary TKA. Patients were randomised to either treatment (CFNI 0 ml to 10 ml/h 0.125% bupivacaine) or placebo (CFNI 0 ml to 10 ml/h normal saline). Both groups received a single-shot femoral nerve block (0.25% 20 ml bupivacaine) prior to placement of femoral nerve catheter and subarachnoid anaesthesia with intrathecal morphine. All patients had a standardised analgesic protocol. The primary end point was post-operative visual analogue scale (VAS) pain score over 72 hours post-surgery. Secondary outcomes were morphine equivalent dose, range of movement, side effects, and length of stay. RESULTS: A total of 86 patients were recruited. Treatment and placebo groups were comparable. No significant difference was found in VAS pain scores, total morphine equivalent requirements, side effects, range of movement, motor block, or length of hospital stay. CONCLUSION: No significant advantage was found for CFNI over a single-shot femoral block and subarachnoid anaesthesia after TKA. Cite this article: Bone Joint Res 2015;4:11-16.

Radiation doses from fluoroscopically guided cardiac catheterization procedures in children and young adults in the United Kingdom: a multicentre study.

OBJECTIVE: To gather data on radiation doses from fluoroscopically guided cardiac catheterization procedures in patients aged under 22 years at multiple centres and over a prolonged period in the UK. To evaluate and explain variation in doses. To estimate patient-specific organ doses and allow for possible future epidemiological analysis of associated cancer risks. METHODS: Patient-specific data including kerma area product and screening times from 10,257 procedures carried out on 7726 patients at 3 UK hospitals from 1994 until 2013 were collected. Organ doses were estimated from these data using a dedicated dosimetry system based on Monte Carlo computer simulations. RESULTS: Radiation doses from these procedures have fallen significantly over the past two decades. The organs receiving the highest doses per procedure were the lungs (median across whole cohort, 20.5 mSv), heart (19.7 mSv) and breasts (13.1 mSv). Median cumulative doses, taking into account multiple procedures, were 23.2, 22.2 and 16.7 mSv for these organs, respectively. Bone marrow doses were relatively low (median per procedure, 3.2 mSv; cumulative, 3.6 mSv). CONCLUSION: Most modern cardiac catheterizations in children are moderately low-dose procedures. Technological advances appear to be the single most important factor in the fall in doses. Patients undergoing heart transplants undergo the most procedures. An epidemiological assessment of cancer risks following these procedures may be possible, especially using older data when doses were higher. ADVANCES IN KNOWLEDGE: This is the first large-scale, patient-specific assessment of organ doses from these procedures in a young population.

The effect of mirabegron on patient-related outcomes in patients with overactive bladder: the results of post hoc correlation and responder analyses using pooled data from three randomized Phase III trials.

PURPOSE: To understand how improvements in the symptoms of overactive bladder (OAB) seen with the ß3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect. METHODS: In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (≥50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (≤8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination. RESULTS: Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof. These improvements versus placebo were statistically significant for all double and triple responder analyses and for all single responder analyses except PPBC. PRO measurements showed directional consistency and significant correlations, and there were also significant correlations between objective and subjective measures of efficacy. CONCLUSIONS: The improvements in objective measures seen with mirabegron 50 mg translate into a meaningful clinical benefit as evident by the directional consistency seen in HRQoL measures of benefit.

Nutritional characteristics of camelina meal for 3-week-old broiler chickens.

Limited information on nutritional characteristics on camelina meal for broiler chickens limits its use in diets of broiler chickens. The objectives of this study were to determine the ileal digestible energy (IDE), ME, and MEn contents of 2 different camelina meal (CM1 and CM2) samples for 3-wk-old broiler chickens using the regression method and to determine glucosinolate compounds in the camelina meal samples. The CM1 and CM2 were incorporated into a corn-soybean meal-based reference diet at 3 levels (0, 100, or 200 g/kg) by replacing the energy-yielding ingredients. These 5 diets (reference diet, and 100 and 200 g/kg camelina meal from each of CM1 and CM2) were fed to 320 male Ross 708 broilers from d 21 to 28 post hatching with 8 birds per cage and 8 replicates per treatment in a randomized complete block design. Excreta were collected twice daily from d 25 to 28, and jejunal digesta and ileal digesta from the Meckel's diverticulum to approximately 2 cm proximal to the ileocecal junction were collected on d 28. The total glucosinolate content for CM1 and CM2 were 24.2 and 22.7 nmol/mg, respectively. Jejunal digesta viscosity was linearly increased (P<0.001) from 2.2 to 4.1 cP with increasing dietary camelina meal levels. There were linear effects (P<0.001) of CM1 and CM2 substitution on final weight, weight gain, feed intake, and G:F. The inclusion of CM1 and CM2 linearly decreased (P<0.001) ileal digestibility of DM, energy, and IDE. The supplementation of CM1 and CM2 linearly decreased (P<0.001) the retention of DM, nitrogen, and energy; ME, and MEn. By regressing the CM1 and CM2-associated IDE intake in kilocalories against kilograms of CM1 and CM2 intake, the IDE regression equation was Y=-10+1,429×CM1+2,125×CM2, r2=0.55, which indicates that IDE values were 1,429 kcal/kg of DM for CM1 and 2,125 kcal/kg of DM for CM2. The ME regression was Y=5+882×CM1+925×CM2, r2=0.54, which implies ME values of 882 kcal/kg of DM for CM1 and 925 kcal/kg of DM for CM2. MEn regression was Y=2+795×CM1+844×CM2, r2=0.52, which implies MEn values of 795 kcal/kg of DM for CM1 and 844 kcal/kg of DM for CM2. Based on these results, utilization of energy and nitrogen in camelina meal by broiler chickens is low and the high viscosity observed in jejunal digesta as well as the total glucosinolate in camelina meal may have contributed to the poor energy and nitrogen utilization.

Tissue engineered buccal mucosa for urethroplasty: progress and future directions.

PURPOSE: Autologous buccal mucosa is commonly utilized in the surgical treatment of urethral strictures. Extensive strictures require a larger quantity of tissue, which may lead to donor site morbidity. This review assesses progress in producing tissue engineered buccal mucosa as an alternative graft material. RESULTS: Few clinical studies have introduced cells onto biological or synthetic scaffolds and implanted resulting constructs in patients. The available studies show that buccal mucosa cells on acellular human dermis or on collagen matrix lead to good acute stage tissue integration. Urothelial cells on a synthetic substrate also perform well. However while some patients do well many years post-grafting, others develop stricture recurrence. Acellular biomaterials used to treat long urethral defects in animals commonly lead to fibrosis. CONCLUSIONS: Tissue engineered buccal mucosa shows promise as a substitute for native tissue. The fibrosis which occurs months post-implantation may reflect the underlying disease process recurring in these patients.

Is there a link between overactive bladder and the metabolic syndrome in women? A systematic review of observational studies.

OBJECTIVES: To conduct a systematic review to determine whether there is an association between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) or overactive bladder (OAB) in women. METHODS: We systematically reviewed English language observational studies on the effect of MetS (or component factors) on the presence of OAB or LUTS in women. We searched PubMed, Web of Science and The Cochrane Library with no date restrictions, checked reference lists and undertook citation searches in PubMed and Google Scholar. Studies were assessed for risk of bias. Because of heterogeneity, results were not pooled, but are reported narratively. RESULTS: Of 27 included studies, only three looked at the link between MetS and OAB. The rest looked at links between OAB and components of MetS such as obesity or insulin resistance (n = 10), between MetS and urinary symptoms (n = 3) and between urinary symptoms and components of MetS, such as obesity (n = 14). Evidence is currently limited, but it does suggest that there may be important links between MetS and OAB and components of MetS such as obesity. CONCLUSIONS: The literature on MetS and OAB or LUTS in women is limited, and poor quality. However, the evidence available on obesity appears to support MetS as a contributor and predictor of LUTS in women. Many of the women with LUTS will be overweight and will have features of the MetS, if looked for. This provides not only an opportunity to encourage weight loss as an adjunct to therapy for the OAB symptoms but also a window of opportunity to address cardiovascular risk factors and prevent future cardiovascular morbidity and mortality.