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Uropathogenic Escherichia coli is a major cause of urinary tract infections. Analysis of the innate immune response in immortalized urothelial cells suggests that the bacterial flagellar subunit, flagellin, is key in inducing host defenses. A panel of 48 clinical uro-associated E. coli isolates recovered from either cystitis, pyelonephritis asymptomatic bacteriuria (ABU) or UTI-associated bacteraemia infections were characterized for motility and their ability to induce an innate response in urothelial cells stably transfected with a NF-κB luciferase reporter. Thirty-two isolates (67%) were identified as motile with strains recovered from cystitis patients exhibiting an uneven motility distribution pattern; seven of the cystitis isolates were associated with a  > 5-fold increase in NF-κB signaling. To explore whether the NF-κB signaling response reflected antigenic variation, flagellin was purified from 14 different isolates. Purified flagellin filaments generated comparable NF-κ signaling responses, irrespective of either the source of the isolate or H-serotype. These data argued against any variability between isolates being related to flagellin itself. Investigations also argued that neither TLR4 dependent recognition of bacterial lipopolysaccharide nor growth fitness of the isolates played key roles in leading to the variable host response. To determine the roles, if any, of flagellar abundance in inducing these variable responses, flagellar hook numbers of a range of cystitis and ABU isolates were quantified. Images suggested that up to 60% of the isolate population exhibited flagella with the numbers averaging between 1 and 2 flagella per bacterial cell. These data suggest that selective pressures exist in the urinary tract that allow uro-associated E. coli strains to maintain motility, but exploit population heterogeneity, which together function to prevent host TLR5 recognition and bacterial killing. [ABSTRACT FROM AUTHOR]

Objectives: To develop a nomogram that could predict spontaneous stone passage (SSP) in patients presenting with acute ureteric colic who are suitable for conservative management. Patients and Methods: A 2517 patient dataset was utilised from an international multicentre cohort study (MIMIC, A Multi‐centre Cohort Study Evaluating the role of Inflammatory Markers In Patients Presenting with Acute Ureteric Colic) of patients presenting with acute ureteric colic across 71 secondary care hospitals in the UK, Ireland, Australia, and New Zealand. Inclusion criteria mandated a non‐contrast computed tomography of the kidneys, ureters, and bladder. SSP was defined as the 'absence of the need for intervention'. The model was developed using logistic regression and backwards selection (to achieve lowest Akaike's information criterion) in a subset from 2009–2015 (n = 1728) and temporally validated on a subset from 2016–2017 (n = 789). Results: Of the 2517 patients, 1874 had SSP (74.5%). The mean (SD) age was 47 (14.7) years and 1892 were male (75.2%). At the end of the modelling process, gender: male (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.64–1.01, P = 0.07), neutrophil count (OR 1.03, 95% CI 1.00–1.06, P = 0.08), hydronephrosis (OR 0.79, 95% CI 0.59–1.05, P = 0.1), hydroureter (OR 1.3, 95% CI 0.97–1.75, P = 0.08), stone size >5–7 mm (OR 0.2, 95% CI 0.16–0.25, P < 0.001), stone size >7 mm (OR 0.11, 95% CI 0.08–0.15, P < 0.001), middle ureter stone position (OR 0.59, 95% CI 0.43–0.81, P = 0.001), upper ureter stone position (OR 0.31, 95% CI 0.25–0.39, P < 0.001), medical expulsive therapy use (OR 1.36, 95% CI 1.1–1.67, P = 0.001), oral nonsteroidal anti‐inflammatory drug (NSAID) use (OR 1.3, 95% CI 0.99–1.71, P = 0.06), and rectal NSAID use (OR 1.17, 95% CI 0.9–1.53, P = 0.24) remained. The concordance‐statistic (C‐statistic) was 0.77 (95% CI 0.75–0.80) and a nomogram was developed based on these. Conclusion: The presented nomogram is available to use as an on‐line calculator via www.BURSTurology.com and could allow clinicians and patients to make a more informed decision on pursuing conservative management vs early intervention. [ABSTRACT FROM AUTHOR]

Background: Sexual behavior is associated with human papillomavirus (HPV)–positive head and neck cancer, whereas tobacco and alcohol use are associated with HPV–negative cancer. A case‐control study was designed to investigate additional demographic and behavioral factors independently associated with these distinct oral cancers. Methods: From 2011 to 2014, 249 newly diagnosed oral cavity and oropharyngeal squamous cell carcinoma (OSCC) cases were matched (1:2) on age, gender, and self‐identified race to 498 controls without a cancer history attending the outpatient otolaryngology clinic at The Ohio State University in Columbus. Cases were stratified by detection of high‐risk HPV DNA and RNA in tumors. Demographic and behavioral data were collected using an audio computer‐assisted self‐interview, and associations with HPV–positive versus HPV–negative OSCCs were investigated by use of univariable and multivariable conditional logistic regression models. Results: After adjustment for oral sexual behavior, the odds of HPV–positive cancer decreased with the patient's years of education. Annual income, tobacco smoking, alcohol drinking, marijuana smoking, and poor oral hygiene were not associated with HPV–positive OSCC. In contrast, the odds of HPV–negative OSCC increased independently with decreased annual income, decreased with a high number of marijuana hit‐years, and increased with fewer than annual dental visits after adjustment for lifetime tobacco and alcohol use. Sexual behavior and education were not associated with HPV–negative OSCC. Conclusions: The distinct risk‐factor profiles for HPV–positive and HPV–negative OSCC are confirmed and extended in this case‐control study, thus supporting 2 principal etiological pathways for OSCC development. Lay Summary: Sexually acquired human papillomavirus (HPV) infection is an established cause of tonsil and base of tongue cancers. This study compared and contrasted risk factors for HPV–positive and HPV–negative oral cancers.Low number of years of education and sexual behavior are associated with HPV–positive cancer. In contrast, low annual income, infrequent dental visits, and tobacco and alcohol use are associated with HPV–negative cancers.Long‐term marijuana use appears protective for HPV–negative cancer.Public health efforts to address these modifiable risk factors may prevent oral cancer. The odds of human papillomavirus–positive cancer decrease with years of education after adjustment for lifetime number of oral sex partners. In contrast, the odds of human papillomavirus–negative cancer increase with low annual income and fewer than annual dental visits but decrease with a high number of marijuana hit‐years after adjustment for lifetime tobacco and alcohol use. [ABSTRACT FROM AUTHOR]

Introduction: Renal stones are common, with a lifetime prevalence of 10% in adults. Global incidence is increasing due to increases in obesity and diabetes, with these patient populations being more likely to suffer renal stone disease. Flank pain from stones (renal colic) is the most common cause of emergency admission to UK urology departments. Stones most commonly develop in the lower pole of the kidney (in ~35% of cases) and here are least likely to pass without intervention. Currently there are three technologies available within the UK National Health Service to remove lower pole kidney stones: extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and flexible ureterorenoscopy (FURS) with laser lithotripsy. Current evidence indicates there is uncertainty regarding the management of lower pole stones, and each treatment has advantages and disadvantages. The aim of this trial is to determine the clinical and cost effectiveness of FURS compared with ESWL or PCNL in the treatment of lower pole kidney stones.Methods: The PUrE (PCNL, FURS and ESWL for lower pole kidney stones) trial is a multi-centre, randomised controlled trial (RCT) evaluating FURS versus ESWL or PCNL for lower pole kidney stones. Patients aged ≥16 years with a stone(s) in the lower pole of either kidney confirmed by non-contrast computed tomography of the kidney, ureter and bladder (CTKUB) and requiring treatment for a stone ≤10 mm will be randomised to receive FURS or ESWL (RCT1), and those requiring treatment for a stone >10 mm to ≤25 mm will be randomised to receive FURS or PCNL (RCT2). Participants will undergo follow-up by questionnaires every week up to 12 weeks post-intervention and at 12 months post-randomisation. The primary clinical outcome is health status measured by the area under the curve calculated from multiple measurements of the EuroQol five dimensions five-level version (EQ-5D-5L) questionnaire up to 12 weeks post-intervention. The primary economic outcome is the incremental cost per quality-adjusted life year gained at 12 months post-randomisation.Discussion: The PUrE trial aims to provide robust evidence on health status, quality of life, clinical outcomes and resource use to directly inform choice and National Health Service provision of the three treatment options.Trial Registration: ISRCTN: ISRCTN98970319. Registered on 11 November 2015. [ABSTRACT FROM AUTHOR]

Introduction Lower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care. Methods and analysis PRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool. Ethics and dissemination Ethics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders. [ABSTRACT FROM AUTHOR]

The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic Escherichia coli (UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate, in vitro, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with E.coli flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17β-estradiol (E) for seven days, 50 ng/ml E.coli flagellin (F) for 12 h, or 4 nM 17β-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including DEFβ4A, DEFB103A, LCN2 as well as those associated with keratinisation eg CNFN and SPRR family genes were significantly enhanced (P < 0.05) compared to either E or F treatments alone. Mutation of estrogen responsive elements (EREs) identified in the DEFβ4 gene promoter abolished the augmented gene expression suggesting estrogen functioned directly through a regulatory mechanism involving ESR1/2. Ingenuity pathway analyses also suggested the pro-inflammatory cytokine IL-17A to regulate the vaginal host defences during infection. Pre-treating VK2 E6/E7 cells with estrogen (4 nM) and challenging with 1L-17A & F (12 h) significantly enhanced DEFβ4, DEF103A and S100A7 expression (P < 0.05). Origins of vaginal IL-17 in vivo remain unclear, but patient biopsies support γδ T cells located within the vaginal epithelium. These data suggest that the vaginal antimicrobial response induced by flagellin activation of Toll-like Receptor 5 cell signalling is augmented following topical estrogen application. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharynx cancers has increased substantially in the United States. However, risk stratification tools for the identification of high-risk individuals do not exist. In this study, an individualized risk prediction model was developed and validated for oropharynx cancers in the US population.Methods: A synthetic, US population-based case-control study was conducted. Oropharynx cancer cases diagnosed at Ohio State University (n = 241) were propensity-weighted to represent oropharynx cancers occurring annually in the United States during 2009-2014 (n = 12,656). Controls (n = 9327) included participants in the National Health and Nutrition Examination Survey (2009-2014) and represented the annual US population aged 30 to 69 years (n = 154,532,508). The individualized 1-year absolute risk of oropharynx cancer was estimated with weighted logistic regression.Results: The risk prediction model included age, sex, race, smoking, alcohol use, lifetime sexual partners, and oral oncogenic human papillomavirus (HPV) status. The model had good discrimination and calibration in split-sample validation (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.92-0.97; observed/expected [O/E], 1.01; 95% CI, 0.70-1.32) and external validation (AUC, 0.87; 95% CI, 0.84-0.90; O/E, 1.08; 95% CI, 0.77-1.39). In the US population, 1-year predicted risks of oropharynx cancer were highest for older individuals (21.1/100,000 for 65- to 69-year-olds), men (13.9/100,000), whites (10.4/100,000), smokers (18.0/100,000 for >20 pack-years), heavy alcohol users (18.4/100,000), and those with prevalent oral oncogenic HPV (140.4/100,000). The risk prediction model provided substantial risk stratification, with approximately 77% of all oropharynx cancers and approximately 99% of HPV-positive oropharynx cancers occurring in the 10% of the US population with the highest model-predicted risk.Conclusions: This risk prediction model will enable the efficient design of studies to address the outstanding questions pertaining to the natural history, screening, and secondary prevention of oropharynx cancers. [ABSTRACT FROM AUTHOR]

Background: Recurrent urethral stricture is usually treated with either open urethroplasty or endoscopic urethrotomy. Both of the procedures cause short-term utility loss, which may not be captured by standard utility questionnaires due to the challenges of completing a standard instrument at the time of an acute episode of short duration, especially within a clinical trial setting. We propose to use time trade-off (TTO) methods to estimate these short-term utility losses. Objective: The aim was to compare the use of two alternative TTO methods to elicit patients' short-term utilities following surgical treatments for recurrent urethral stricture. Method: Two variants of TTO (chained and conventional) were used. Six health profiles were developed—three for each procedure. Forty participants took part, with 20 randomly allocated to each TTO method. Results: Thirty-eight participants provided usable data for analysis. Estimated utility values decreased as the severity of the health profiles increased. There was no evidence that utility values differed between elicitation methods or procedures for mild {ranging from 0.79 (standard deviation [SD] 0.17) to 0.83 [SD 0.20]} and moderate (ranging from 0.54 [SD 0.24] to 0.67 [SD 0.21]) health states, although they appeared to differ for severe health states (ranging from 0.29 [SD 0.20] to 0.56 [SD 0.24]). Conclusion: The study demonstrates the feasibility and value of eliciting patients' short-term utilities. Given the small sample size, the study findings are tentative. Further research with a larger sample size is needed to determine the appropriate TTO method to use and how the elicited utilities can be used in combination with standard cost-utility assessments to aid decision making. [ABSTRACT FROM AUTHOR]

Objectives: To assess the relationship of white blood cell count (WBC) and other routinely collected inflammatory and clinical markers including stone size, stone position, and medical expulsive therapy use (MET), with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic, as there are conflicting data on the role of WBC and other inflammatory markers in SSP in patients with acute ureteric colic. Patients and methods: Multicentre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across four countries (UK, Republic of Ireland, Australia, and New Zealand). In all, 4170 patients presented with acute ureteric colic and a computed tomography confirmed single ureteric stone. Our primary outcome measure was SSP, as defined by the absence of need for intervention to assist stone passage (SP). Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results: In all, 2518 patients were discharged with conservative management and had further follow‐up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, neutrophils count, nor C‐reactive protein (CRP) predicted SSP, with an adjusted odds ratio (OR) of 0.97 (95% confidence interval [CI] 0.91–1.04, P = 0.38), 1.06 (95% CI 0.99–1.13, P = 0.1) and 1.00 (95% CI 0.99–1.00, P = 0.17), respectively. MET also did not predict SSP (adjusted OR 1.11, 95% CI 0.76–1.61). However, stone size and stone position were significant predictors. SSP for stones <5 mm was 89% (95% CI 87–90) compared to 49% (95% CI 44–53) for stones ≥5–7 mm, and 29% (95% CI 23–36) for stones >7 mm. For stones in the upper ureter the SSP rate was 52% (95% CI 48–56), middle ureter was 70% (95% CI 64–76), and lower ureter was 83% (95% CI 81–85). Conclusion: In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management neither WBC, neutrophil count, nor CRP, helps determine the likelihood of SSP. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our present findings represent the most comprehensive SP rates for each millimetre increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention. [ABSTRACT FROM AUTHOR]

Background. Oral human papillomavirus (HPV) infection is the principal underlying cause of a dramatic increase in oropharyngeal cancer. Dentistry can play an important role in developing clinical algorithms for secondary prevention. Methods. The authors conducted this cross-sectional pilot study with practices of The National Dental Practice-Based Research Network. The authors evaluated the feasibility and acceptability of screening and testing procedures as judged by practitioners and patients. The authors used tablet devices for patient screening, obtaining consent, and administering a confidential oral HPV risk factor survey. Results. Most patients (85%) were comfortable being asked about their cigarette use and their sexual behavior (69%) and were interested in participating again (79%). More than 90% of practitioners were comfortable with study procedures except the extra time required for patient participation (75% comfortable). There were no problems with oral rinse collection as reported by patients or practitioners. Conclusions. It is feasible in community dental offices to collect oral rinses for HPV detection and to ask patients explicit questions about sexual history when using a tablet device for confidentiality. Practical Implications. Discussing high-risk types of HPV and appropriately assessing that risk are a challenge for oral health care professionals. These results are positive from a research perspective but do not address the advisability of routine HPV screening in dentistry. [ABSTRACT FROM AUTHOR]

Objectives. Recurrent urinary tract infections are associated with uropathogenic Escherichia coli (UPEC) ascending and infecting the urinary tract. Antibiotics provide only symptomatic relief, not prevent recurrence. Clinical evidence suggests that intravesical glycosaminoglycan therapy, such as hyaluronic acid (HA), helps reduce UTI recurrence. This has been investigated here using in vitro systems modelling the urogenital tract tissues. Methods. RT4 bladder cells were preconditioned with high molecular weight HA (> 1500 kDa) at 2 mg mL-1 and challenged with UPEC to analyse barrier protection and bacterial adherence. Untreated and HA-preconditioned VK2 E6/E7 vaginal cells were challenged with E. coli flagellin (50 ng mL-1) to mimic bacterial challenge, and media analysed for lipocalin-2, human β-defensin 2 and interleukin-8 by ELISA. Experiments were repeated after siRNA knockdown of Toll-like receptors 2, 4 and 5, and CD44 to investigate signalling. Results. Microscopic analyses showed reduced bacterial adherence and urothelial disruption with HA, suggesting that HA functions as a barrier protecting the epithelium from bacterial infection. Cells treated with HA and flagellin simultaneously produced more of the host antimicrobial peptide LCN2 and pro-inflammatory IL-8 (P < 0.05) compared to the no HA/flagellin challenges. Increased gene expression of DEFB4 (P < 0.05), but not the hBD2 peptide, was observed in the HA/flagellin-challenged cells. Conclusion. These data suggest that exogenous HA has potential to protect the urogenital epithelia from UPEC infection via a two-pronged approach that involves the physical enhancement of the epithelial barrier and augmentation of its innate immune response. [ABSTRACT FROM AUTHOR]

Background: Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed - a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness.Methods/design: Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to identify problems or need for further treatment.Discussion: A robust examination of the comparative effectiveness of the male synthetic sling will provide high-quality evidence to determine whether or not it should be adopted widely in the NHS.Trial Registration: International Standard Randomised Controlled Trial Registry: Number ISRCTN49212975 . Registered on 22 July 2013. First patient randomised on 29 January 2014. [ABSTRACT FROM AUTHOR]

The article offers information on the British Urology Researchers in Surgical Training (BURST) Research Collaborative which is an international trainee-led research collaborative that aims to produce high-quality research and audit. It mentions information information on the role of Inflammatory Markers In patient's presenting with acute ureteric Colic (MIMIC). It states that BURST assists with ethics approval, statistical considerations, and database design.

Summary Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1) enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease. [ABSTRACT FROM AUTHOR]

Background: Sexual behavior and oral human papillomavirus (HPV) infection are risk factors for oral squamous cell carcinoma (OSCC). The effects of OSCC diagnosis and treatment on subsequent relationship stress and sexual behavior are unknown.Methods: Incident cases of HPV-positive or HPV-negative OSCC in patients who had a partnered relationship and partners of patients with oropharyngeal cancer were eligible for a study in which surveys were administered at diagnosis and at the 6-month follow-up time point to assess relationship distress, HPV transmission and concerns about health consequences, and sexual behavior. The frequency distributions of responses, stratified by tumor HPV status, were compared at baseline and follow-up.Results: In total, 262 patients with OSCC and 81 partners were enrolled. Among the patients, 142 (54.2%) had HPV-positive OSCC, and 120 (45.8%) had HPV-negative OSCC. Relationship distress was infrequently reported, and 69% of patients felt that their relationship had strengthened since the cancer diagnosis. Both HPV-positive patients (25%) and their partners (14%) reported feelings of guilt or responsibility for the diagnosis of an HPV-caused cancer. Concern over sexual, but not nonsexual, HPV transmission to partners was reported by 50%. Significant declines in the frequency of vaginal and oral sexual behaviors were reported at follow-up, regardless of tumor HPV status. From baseline to 6 months, significant increases in abstinence from vaginal sex (from 10% to 34%; P < .01) and oral sex (from 25% to 80%; P < .01) were reported.Conclusions: Diagnosis and treatment of OSCC are associated with significant declines in the frequency of vaginal and oral sex, regardless of tumor HPV status. Sexual behavior is an important quality-of-life outcome to assess within clinical trials. [See related editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:1156-1165. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: This paper proposes a novel perspective on the value of qualitative research for improving trial design and optimising recruitment. We report findings from a qualitative study set within the OPEN trial, a surgical randomised controlled trial (RCT) comparing two interventions for recurrent bulbar urethral stricture, a common cause of urinary problems in men.Methods: Interviews were conducted with men meeting trial eligibility criteria (n = 19) to explore reasons for accepting or declining participation and with operating urologists (n = 15) to explore trial acceptability.Results: Patients expressed various preferences and understood these in the context of relative severity and tolerability of their symptoms. Accounts suggest a common trajectory of worsening symptoms with a particular window within which either treatment arm would be considered acceptable. Interviews with clinician recruiters found that uncertainty varied between general and specialist sites, which reflect clinicians' relative exposure to different proportions of the patient population.Conclusion: Recruitment post referral, at specialist sites, was challenging due to patient (and clinician) expectations. Trial design, particularly where there are fixed points for recruitment along the care pathway, can enable or constrain the possibilities for effective accrual depending on how it aligns with the optimum point of patient equipoise. Qualitative recruitment investigations, often focussed on information provision and patient engagement, may also look to better understand the target patient population in order to optimise the point at which patients are approached.Trial Registration: ISRCTN Registry, ISRCTN98009168 . Registered on 29 November 2012. [ABSTRACT FROM AUTHOR]

To estimate changes in oral human papillomavirus (HPV) prevalence attributable to vaccination vs herd immunity, this national survey study uses National Health and Nutrition Examination Survey data to compare oral HPV prevalence for 4 types targeted by HPV vaccine and 33 nonvaccine types in unvaccinated US adults aged 18 to 59 years from 2009 to 2016. [ABSTRACT FROM AUTHOR]

Objectives To develop a per-patient volume correction for maximum flow rate using multiple home uroflowmetry, and to carry out a pilot study to determine the most prognostically useful volume at which to evaluate this measurement and estimate its relationship with outcome from disobstructive bladder outlet surgery. Methods A total of 30 men carried out home uroflowmetry using a portable device and completed symptom scores before surgery. This was repeated at least 4 months after surgery. For each man's presurgery flow data, voided volume was plotted against maximum flow rate, and a line of best fit with logarithmic form calculated. This allowed maximum flow rate to be corrected for any volume. Percentage reduction in symptom score and increase in mean maximum flow rate were correlated with volume-corrected maximum flow rates. Results Corrected maximum flow rate at all volumes showed the expected negative correlation with both outcome measures. A statistically significant correlation occurred for volumes >190 mL, with the best performance at volumes >300 mL. Conclusions We have devised a novel method allowing estimation of maximum flow rate at any volume, which is a step forward for non-invasive diagnostics. We found this volume-corrected maximum flow rate to correlate significantly with treatment outcome at sufficiently high volumes. [ABSTRACT FROM AUTHOR]

This paper examines issues concerning the protection and management of World Cultural Heritage properties in five countries (China, Spain, Switzerland, United Kingdom and United States) which formed part of a research network funded by the United Kingdom’s Arts and Humanities Research Council during 2013–2015. The themes examined in this context include: legal and administrative measures for protection (including recommendations and guidelines of international organisations), other protection mechanisms (planning policy and regulations), management systems and their efficiency at protecting cultural world heritage properties in ‘the day to day’ administration (tourism, financial resources and sustainable development), as well as unusual situations (development, risk and disaster), and the role of management bodies and representatives, capacity building and monitoring of the properties (practical experiences). These issues are broadly examined from questionnaires responses from the five countries through this paper and set the scene for the development of the themes of the international conference on ‘World Heritage Sites in a National Context: The Implementation of the 1972 UNESCO Convention concerning the Protection of the World Cultural and Natural Heritage’ held at the University of Kent, Canterbury 15–16 January 2015, which are examined in the other papers included in this issue. [ABSTRACT FROM PUBLISHER]

Objectives To investigate the association between detrusor after-contraction and urodynamic parameters in a cohort of patients undergoing urodynamic studies by ambulatory monitoring. Methods All symptomatic adult female patients with non-neurogenic lower urinary tract dysfunction having ambulatory monitoring over the period January 1998 to January 2014 were included. Urodynamic traces were reviewed to identify detrusor after-contraction. Measured urodynamic variables were Qmax (mL/s), Vvoid (mL) and Pdet.Qmax (cmH2O). Student's unpaired t-test was used to compare the mean of the variable in the detrusor after-contraction and non-detrusor after-contraction groups. Results We identified 331 women with a median age of 50 years (range 16-82). Detrusor after-contraction was seen after at least one void in 122 patients giving a prevalence of 37%. A total of 167 (51%) patients had detrusor overactivity. Diagnosis of detrusor overactivity was associated with the presence of detrusor after-contraction ( P < 0.05). Overall, patients with detrusor after-contraction had a statistically higher mean Pdet.Qmax (32 vs 28 cmH2O, P = 0.04) and lower mean voided volume (300 vs 378 mL, P < 0.001). Conclusion These findings suggest a relatively high prevalence of detrusor after-contraction during ambulatory monitoring, and an association between detrusor overactivity, Vvoid, Pdet.Qmax and detrusor after-contraction recorded during ambulatory monitoring. Therefore, a link between detrusor after-contractions and the syndrome of overactive bladder can be postulated. [ABSTRACT FROM AUTHOR]

In this article, we present findings from research conducted as part of a multi-center surgical trial. Bulbar urethral stricture, a narrowing of the middle urethra, is a common cause of urinary problems in men that can have a profound impact on their lives. Semi-structured interviews were conducted with a sample of 19 men seeking treatment for urethral stricture. The findings reveal how men tend to develop routines and tactics to adapt to their symptoms and hide them from others rather than seek help. We argue that this concealment becomes an inseparable part of how the disease is managed and is an additional hidden practical and emotional burden for these men. In addition, we suggest that the patients only sought curative treatments once practices of social concealment are no longer viable. [ABSTRACT FROM AUTHOR]

We describe our experience of using a modified version of the Cochrane risk of bias (RoB) tool for randomised and non-randomised comparative studies. Objectives To assess time to complete RoB assessment, To assess inter-rater agreement, To explore the association between RoB and treatment effect size, Methods Cochrane risk of bias assessment was performed on a sample of full text primary reports included in a systematic review comparing operative techniques for radical prostatectomy. Inter-rater agreement was assessed using the kappa statistic. Results Twenty-four studies were judged as high overall RoB, 13 were judged as low RoB and 11 were unclear. The weighted Kappa value was 0.35 indicating fair agreement. The median (range) time taken to rate each study was 30 min (10-49). The effect estimate for all studies was 0.61 (95% credible interval (CrI) 0.46-0.83) and 0.73 (95% CrI 0.29-1.75) for low risk studies. Conclusions Although the process was time consuming, using a modified version of the RoB tool proved useful for demonstrating conservative effect estimates. That we only achieved a fair agreement between reviewers demonstrates the urgent need for further validation to improve inter-rater agreement. We suggest additional RoB levels could improve inter-rater reliability. © 2013 Crown copyright. [ABSTRACT FROM AUTHOR]

Objectives To develop and externally validate a novel nomogram predicting recurrence risk probability at 12 months in women after an episode of urinary tract infection. Methods The study included 768 women from Santa Maria Annunziata Hospital, Florence, Italy, affected by urinary tract infections from January 2005 to December 2009. Another 373 women with the same criteria enrolled at Santa Chiara Hospital, Trento, Italy, from January 2010 to June 2012 were used to externally validate and calibrate the nomogram. Univariate and multivariate Cox regression models tested the relationship between urinary tract infection recurrence risk, and patient clinical and laboratory characteristics. The nomogram was evaluated by calculating concordance probabilities, as well as testing calibration of predicted urinary tract infection recurrence with observed urinary tract infections. Nomogram variables included: number of partners, bowel function, type of pathogens isolated ( Gram-positive/negative), hormonal status, number of previous urinary tract infection recurrences and previous treatment of asymptomatic bacteriuria. Results Of the original development data, 261 out of 768 women presented at least one episode of recurrence of urinary tract infection (33.9%). The nomogram had a concordance index of 0.85. The nomogram predictions were well calibrated. This model showed high discrimination accuracy and favorable calibration characteristics. In the validation group (373 women), the overall c-index was 0.83 ( P = 0.003, 95% confidence interval 0.51-0.99), whereas the area under the receiver operating characteristic curve was 0.85 (95% confidence interval 0.79-0.91). Conclusions The present nomogram accurately predicts the recurrence risk of urinary tract infection at 12 months, and can assist in identifying women at high risk of symptomatic recurrence that can be suitable candidates for a prophylactic strategy. [ABSTRACT FROM AUTHOR]

We investigated the association of demographic and behavioral factors with oral human papillomavirus (HPV) load for 18 high-risk types among 211 individuals with prevalent high-risk HPV within the National Health and Nutrition Examination Survey 2009-2010. Factors independently associated with HPV load above the median included older age (odds ratio, 1.04 per year increase [95% confidence interval, 1.01-1.07]; P = .004) and intensity of current smoking (P for trend <.001). A marginally greater percentage of men than women had an HPV load above the median (55.7% vs 32.8%; P = .069), and HPV load increased marginally with increasing alcohol use (P for trend = .062). In conclusion, older age and current smoking are associated with a high oral load of high-risk HPV types among individuals with a prevalent infection. [ABSTRACT FROM AUTHOR]

We investigated the association of demographic and behavioral factors with oral human papillomavirus (HPV) load for 18 high-risk types among 211 individuals with prevalent high-risk HPV within the National Health and Nutrition Examination Survey 2009–2010. Factors independently associated with HPV load above the median included older age (odds ratio, 1.04 per year increase [95% confidence interval, 1.01–1.07]; P = .004) and intensity of current smoking (P for trend <.001). A marginally greater percentage of men than women had an HPV load above the median (55.7% vs 32.8%; P = .069), and HPV load increased marginally with increasing alcohol use (P for trend = .062). In conclusion, older age and current smoking are associated with a high oral load of high-risk HPV types among individuals with a prevalent infection. [ABSTRACT FROM PUBLISHER]

Background Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications. Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation. This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. Methods/design The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups. [ABSTRACT FROM AUTHOR]

Objective To report discontinuation rates, inter-injection interval and complication rates after repeated intravesical botulinum toxin type A for the treatment of detrusor overactivity. Method Patients with urodyamically proven detrusor overactivity who had two or more botulinum toxin type A injections in the period 2004-2011 at Freeman Hospital, Newcastle Upon Tyne, UK, were considered for the present study. Discontinuation rates, complication rates and interval between botulinum toxin type A treatments were retrospectively analyzed. Results Overall, 125 patients (median age 53 years, range 19-83 years) were included in the analysis. The female-to-male ratio was 2.4:1 and median follow up was 38 months. A total of 96 patients had idiopathic detrusor overactivity, whereas 29 had neurogenic detrusor overactivity. A total of 667 injections were carried out, with 125 patients receiving two injections, 60 receiving three injections, 28 receiving four injections, 14 receiving five injections, three receiving six injections, three receiving seven injections and two receiving eight injections. The mean interval (±standard deviation) between the first and second injection ( n = 125) was 17.6 months (±10.4), between the second and third ( n = 60) was 15.7 ± 7.4 months, between the third and fourth ( n = 28) was 15.4 ± 8.6 months, and between the fourth and subsequent injections ( n = 22) was 11.6 ± 4.5 months. A total of 26% required intermittent catheterization, and 18% developed recurrent urinary tract infections. There was a discontinuation rate of 25% at 60 months. Conclusion Repeated botulinum toxin type A injections represent a safe and effective method for managing patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity. We have shown that the inter-injection interval remains unchanged up to five injections. [ABSTRACT FROM AUTHOR]

In a contemporary climate in which reconstruction in a historicist style is regarded negatively by heritage specialists as inauthentic, there is a need for better guidance and greater clarity about what reconstruction connotes, when it is admissible to carry it out in a style or form reflecting so far as possible what has been lost, how it should be done, and what authenticity actually means. In this paper, we review the current situation and existing charters and terminology, and suggest ways forward. Experience within the Council of Europe has shown that reconstruction after the wars in the former Yugoslavia will take place whether or not it is approved by the international heritage community. Guidelines are needed and we suggest in an Appendix the form which these might take. [ABSTRACT FROM AUTHOR]

Objective To compare the effectiveness of robot-assisted and standard laparoscopic prostatectomy., Methods A care pathway was described., We performed a systematic literature review based on a search of Medline, Medline in Process, Embase, Biosis, Science Citation Index, Cochrane Controlled Trials Register, Current Controlled Trials, Clinical Trials, WHO International Clinical Trials Registry and NIH Reporter, the Health Technology Assessment databases, the Database of Abstracts of Reviews of Effects, and relevant conference abstracts up to 31st October 2010). Additionally, reference lists were scanned, an expert panel consulted, and websites of manufacturers, professional organisations, and regulatory bodies were checked., We selected randomised controlled trials ( RCTs) and non-randomised comparative studies, published after 1st January 1995, including men with localised prostate cancer undergoing robot-assisted or laparoscopic prostatectomy compared with the other procedure or with open prostatectomy. Studies where at least 90% of included men had clinical tumour stages T1 to T2 and which reported at least one of our specified outcomes were eligible for inclusion., A mixed-treatment comparison meta-analysis was performed to generate comparative statistics on specified outcomes., Results We included data from 19 064 men across one RCT and 57 non-randomised comparative reports., Robotic prostatectomy had a lower risk of major intra-operative harms such as organ injury [0.4% robotic vs 2.9% laparoscopic], odds ratio ([ OR] {95% credible interval [ CrI]} 0.16 [0.03 to 0.76]), and a lower rate of surgical margins positive for cancer [17.6% robotic vs 23.6% laparoscopic], OR [95% CrI] 0.69 [0.51 to 0.96]). There was no evidence of a difference in the proportion of men with urinary incontinence at 12 months ( OR [95% CrI] 0.55 [0.09 to 2.84]). There were insufficient data on sexual dysfunction., Surgeon learning rates for the procedures did not differ, although data were limited., Conclusions Men undergoing robotic prostatectomy appear to have reduced surgical morbidity, and a lower risk of a positive surgical margin, which may reduce rates of cancer recurrence and the need for further treatment, but considerable uncertainty surrounds these results., We found no evidence that men undergoing robotic prostatectomy are disadvantaged in terms of early outcomes., We were unable to determine longer-term relative effectiveness. [ABSTRACT FROM AUTHOR]

Side population (SP) and ABC transporter expression enrich for stem cells in numerous tissues. We explored if this phenotype characterised human bladder cancer stem cells (CSCs) and attempted to identify regulatory mechanisms. Focusing on non-muscle invasive bladder cancer (NMIBC), multiple human cell lines were used to characterise SP and ABC transporter expression. In vitro and in vivo phenotypic and functional assessments of CSC behaviour were undertaken. Expression of putative CSC marker ABCG2 was assessed in clinical NMIBC samples (n = 148), and a role for MAPK signalling, a central mechanism of bladder tumourigenesis, was investigated. Results showed that the ABCG2 transporter was predominantly expressed and was up-regulated in the SP fraction by 3-fold (ABCG2hi) relative to the non-SP (NSP) fraction (ABCG2low). ABCG2hi SP cells displayed enrichment of stem cell markers (Nanog, Notch1 and SOX2) and a three-fold increase in colony forming efficiency (CFE) in comparison to ABCG2low NSP cells. In vivo, ABCG2hi SP cells enriched for tumour growth compared with ABCG2low NSP cells, consistent with CSCs. pERK was constitutively active in ABCG2hi SP cells and MEK inhibition also inhibited the ABCG2hi SP phenotype and significantly suppressed CFE. Furthermore, on examining clinical NMIBC samples, ABCG2 expression correlated with increased recurrence and decreased progression free survival. Additionally, pERK expression also correlated with decreased progression free survival, whilst a positive correlation was further demonstrated between ABCG2 and pERK expression. In conclusion, we confirm ABCG2hi SP enriches for CSCs in human NMIBC and MAPK/ERK pathway is a suitable therapeutic target. [ABSTRACT FROM AUTHOR]

A prolonged catheter duration is a major risk factor for catheter-associated urinary tract infection, with bacteriuria increasing by 5% per day (Gokula et al, 2004). Aim: In this study, the authors explored patients' perceptions of the care process relating to peri-operative catheterisation to identify patient factors that encourage early removal. Method: Semi-structured interviews, incorporating a grounded theory approach, were performed on three men and seven women during 2010. Interviews were transcribed and analysed using constant comparative method and thematic framework analysis. Results: Catheter duration ranged 1-10 days. Main themes elicited included: lack of understanding of the purpose and catheterisation process; loss of patient autonomy and dignity; and impact of environmental factors. Conclusion: Lack of knowledge of the catheterisation process among participants led to fears and concerns that may have contributed to delayed catheter removal. Changes to patient care that are likely to reduce catheter duration include ensuring the provision of pre-operative information, greater patient involvement in catheter removal decisions, and provision of easily accessible toilet facilities. [ABSTRACT FROM AUTHOR]

Background: Urinary biomarkers for bladder cancer detection are constrained by inadequate sensitivity or specificity. Here we evaluate the diagnostic accuracy of Mcm5, a novel cell cycle biomarker of aberrant growth, alone and in combination with NMP22. Methods: 1677 consecutive patients under investigation for urinary tract malignancy were recruited to a prospective blinded observational study. All patients underwent ultrasound, intravenous urography, cystoscopy, urine culture and cytologic analysis. An immunofluorometric assay was used to measure Mcm5 levels in urine cell sediments. NMP22 urinary levels were determined with the FDA-approved NMP22® Test Kit. Results: Genito-urinary tract cancers were identified in 210/1564 (13%) patients with an Mcm5 result and in 195/1396 (14%) patients with an NMP22 result. At the assay cut-point where sensitivity and specificity were equal, the Mcm5 test detected primary and recurrent bladder cancers with 69% sensitivity (95% confidence interval = 62-75%) and 93% negative predictive value (95% CI = 92-95%). The area under the receiver operating characteristic curve for Mcm5 was 0.75 (95% CI = 0.71-0.79) and 0.72 (95% CI = 0.67-0.77) for NMP22. Importantly, Mcm5 combined with NMP22 identified 95% (79/83; 95% CI = 88- 99%) of potentially life threatening diagnoses (i.e. grade 3 or carcinoma in situ or stage ≥pT1) with high specificity (72%, 95% CI = 69-74%). Conclusions: The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways. [ABSTRACT FROM AUTHOR]

Purpose We developed a prototype device using an automatically controlled inflatable penile cuff to measure bladder voiding pressure continuously and non-invasively in men. The purpose of this study was to validate the pressure measurements made by this device by comparison to those during simultaneous invasive PFS. Methods A device was developed to automatically modulate flow rate by controlling pressure in a penile cuff. Men undergoing conventional urodynamics studies were recruited to have an additional fill-void cycle whilst using the new device. We report on 40 men using a standardized protocol. Pressure measured by this device was compared with simultaneous vesical pressure by evaluating maximum pressure during voiding, and calculating the root mean square (RMS) difference between pcuff and pves. Results We recruited 80 men of whom 18 were excluded, 22 were involved in initial development phase and 40 in the standard protocol. Mean (SD) difference between maxima of pcuff and pves (1.3 (15.6) cmH2O) was not significant. In 20 (50%) men, agreement between pcuff and pves throughout the void was moderate or good (RMS difference <20 cmH2O). Causes of unsuccessful measurements were identified. Conclusions Although a prototype device, this technique appears to be promising for continuous non-invasive bladder pressure measurement. From the results of this study a number of improvements have been recommended and implemented. The next generation of this technique will allow assessment of clinical application. Neurourol. Urodynam. 31:557-563, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article determines the prevalence of oral human papillomavirus (HPV) infection in the U.S. from 2009-2010. Results revealed a 6.9 percent prevalence of oral HPV infection among men and women aged 14 to 69 years, and 1.0 percent prevalence of HPV type 16. The researchers observed a bimodal pattern of oral HPV infection with respect to age, with peak prevalence among individuals aged 30-34 and 60-64 years. Women were found to have lower prevalence for any oral HPV infection than men. It appeared that individuals without a history of any type of sexual contact, increased number of sexual partners and cigarettes smoked per day are less likely to have HPV infection.

Purpose: Biofilm infections have a major role in implants or devices placed in the human body. As part of the endourological development, a great variety of foreign bodies have been designed, and with the increasing number of biomaterial devices used in urology, biofilm formation and device infection is an issue of growing importance. Methods: A literature search was performed in the Medline database regarding biofilm formation and the role of biofilms in urogenital infections using the following items in different combinations: 'biofilm,' 'urinary tract infection,' 'bacteriuria,' 'catheter,' 'stent,' and 'encrustation.' The studies were graded using the Oxford Centre for Evidence-based Medicine classification. Results: The authors present an update on the mechanism of biofilm formation in the urinary tract with special emphasis on the role of biofilms in lower and upper urinary tract infections, as well as on biofilm formation on foreign bodies, such as catheters, ureteral stents, stones, implants, and artificial urinary sphincters. The authors also summarize the different methods developed to prevent biofilm formation on urinary foreign bodies. Conclusions: Several different approaches are being investigated for preventing biofilm formation, and some promising results have been obtained. However, an ideal method has not been developed. Future researches have to aim at identifying effective mechanisms for controlling biofilm formation and to develop antimicrobial agents effective against bacteria in biofilms. [ABSTRACT FROM AUTHOR]

Aims Uroflowmetry is a key clinical assessment for men with LUTS. Home uroflowmetry is a convenient way to obtain multiple flow readings and has the potential to combat problems inherent to clinic-based measurements. We reviewed current evidence regarding the technology and value of multiple and home uroflowmetry. Methods We searched PubMed and Embase from January 1988 to February 2011 using a predetermined strategy. Reference lists from retrieved articles were scanned and additional papers screened for relevance. Proceedings of the annual meetings of the International Continence Society since 2008 were also searched. Relevant guidelines were obtained from the UK NHS Evidence repository. Results Eight studies described five simple, low-cost instruments giving multiple representative estimates of Qmax but not a complete flow curve. A further eight studies described home use of four sophisticated, electronic flowmeters similar to clinic-based equipment. The above methods were assessed against ICS recommendations for uroflowmetry and the results of several studies investigating variability of flow parameters such as Qmax were presented. Conclusions Our findings illustrate the gulf between low-cost methods of obtaining average or peak flow measurements and precise, expensive devices with the capabilities of clinic flowmeters. Further studies are required to confirm the statistical benefit of averaging multiple values of Qmax and to investigate the diagnostic and predictive value of flow variables other than Qmax that can be derived from multiple recordings. Neurourol. Urodynam. 31:7-12, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Stem cells accumulate mitochondrial DNA (mtDNA) mutations resulting in an observable respiratory chain defect in their progeny, allowing the mapping of stem cell fate. There is considerable uncertainty in prostate epithelial biology where both basal and luminal stem cells have been described, and in this study the clonal relationships within the human prostate epithelial cell layers were explored by tracing stem cell fate. Fresh-frozen and formalin-fixed histologically-benign prostate samples from 35 patients were studied using sequential cytochrome c oxidase (COX)/succinate dehydrogenase (SDH) enzyme histochemistry and COX subunit I immunofluorescence to identify areas of respiratory chain deficiency; mtDNA mutations were identified by whole mitochondrial genome sequencing of laser-captured areas. We demonstrated that cells with respiratory chain defects due to somatic mtDNA point mutations were present in prostate epithelia and clonally expand in acini. Lineage tracing revealed distinct patterning of stem cell fate with mtDNA mutations spreading throughout the whole acinus or, more commonly, present as mosaic acinar defects. This suggests that individual acini are typically generated from multiple stem cells, and the presence of whole COX-deficient acini suggests that a single stem cell can also generate an entire branching acinar subunit of the gland. Significantly, a common clonal origin for basal, luminal and neuroendocrine cells is demonstrated, helping to resolve a key area of debate in human prostate stem cell biology. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The authors conducted a cross-sectional audit within Newcastle-upon-Tyne Hospitals NHS Foundation Trust to determine the prevalence of urethral catheterisation and documented adherence to relevant NHS standards. An on-line audit questionnaire was completed for all 80 inpatient wards within the Trust on a single day during the third week in June 2009. The tool collected data on prevalence and care requirements detailed in the Department of Health's (DH) Saving Lives High Impact Intervention 6 (2007). Data were analysed using Snap survey software. Overall, 172 of 1187 (14.5%) inpatients were catheterized and all were using a closed drainage system or catheter valve. Evidence of correct continuing catheter care was documented for 168 (98%) patients, while details of catheter insertion were identified in 153 (89%) patient records. Eight (4.5%) patients were being treated for a urinary tract infection. The authors found satisfactory adherence to basic documentation standards with regard to catheter care. This was associated with a low prevalence rate of catheterization and catheter-associated urinary infection within the Trust relative to previously published figures. Details of catheter insertion were missing from 10% of patient records, requiring further development of accessible and transferable documentation tools. Provision of relevant information to patients is also a target for development. [ABSTRACT FROM AUTHOR]

Context: Urodynamic evaluation in the assessment of women complaining of urinary incontinence remains controversial with recent UK National Institute of Health and Clinical Excellence guidance maintaining that it is unnecessary prior to surgery for women with a primarily stress leakage. Other experts contend it should be part of routine preoperative assessment since it establishes a diagnosis, allows more careful patient counseling and predicts surgical outcome. Objectives: To summarize current literature to define the evidence level on which these conflicting opinions are based. Materials and Methods: A systematic literature search was performed and retrieved publications summarized in a narrative evidence review using both original papers and previous reviews. Results: Five hundred and one primary research papers and 65 previous reviews were retrieved. The findings were summarized in a narrative comprising overview, description of methods of bladder and urethral pressure measurement, and a summary of the literature concerning four key questions. Conclusion: The level of evidence was low regarding answering each of the questions posed, preventing firm conclusions. Urodynamic findings do correlate with relevant symptoms and, to some extent, with symptom severity, giving reasonable diagnostic accuracy. There is no reliable evidence that preoperative urodynamic diagnosis improves outcome from surgery for stress incontinence although it is likely to facilitate preoperative discussion. Tests to differentiate sphincter deficiency and urethral hypermobility are not currently recommended due to poor validity and reproducibility. This along with the current use of mid-urethral tapes as the universal primary surgical procedure means differentiation is not a necessity. Preoperative diagnosis of detrusor overactivity does not appear to worsen surgical outcome in women with a primary symptom of stress leakage. Large, well-designed prospective studies are now underway to provide a definitive answer to these questions. [ABSTRACT FROM AUTHOR]

Transurethral incision of the prostate gland (TUIP) is perceived as a less morbid surgical alternative to standard transurethral resection of the prostate gland (TURP) for treatment of symptomatic mild to moderate benign prostate enlargement (BPE). We aimed to evaluate comparative clinical effectiveness of the two procedures. Systematic review and meta-analysis of short- and long-term data from randomised controlled trials comparing TUIP with TURP. This review considered data from 795 randomised participants across 10 RCTs of moderate to poor quality 8 of which stated an upper limit for prostate size. No difference in the degree of symptomatic improvement was seen between the two procedures. Improvement in peak urine flow rate was lower for TUIP compared to TURP whilst the rate of blood transfusion and TUR syndrome was higher after TURP. Urinary retention, urinary tract infection, strictures and incontinence did not differ between the two approaches, although clinically important differences could not be ruled-out. TUIP was associated with a shorter duration of operation and length of hospital stay but a higher re-operation rate. TUIP and TURP appear to offer equivalent symptomatic improvement for men with mild to moderate BPE. Choosing TUIP involves a trade-off between the lower risk of peri-operative morbidity and the higher risk of subsequent re-operation. [ABSTRACT FROM AUTHOR]