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Contains fulltext : 248305.pdf (Publisher’s version ) (Closed access) CONTEXT: Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. OBJECTIVE: This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. EVIDENCE ACQUISITION: A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. EVIDENCE SYNTHESIS: Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. CONCLUSIONS: This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. PATIENT SUMMARY: In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients.

Background: Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom–risk-based algorithm (control). Methods: We did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed. Findings: Patients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n=240) or to the control group(n=61). 28·4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18·5% of patients in the control group (adjusted odds ratio [aOR] 1·71 [95% CI 0·80–3·63]; p=0·17). In the per-protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30·7% of patients) compared with the control group (5·0% of patients; aOR 11·48 [95% CI 1·35–97·83]; p=0·026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose. Interpretation: Biomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low.

Background: understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management.Methods: we reviewed patient choice to follow HCP advice to adjust asthma treatment in a randomised, controlled, single-blind (study participant), multi-centre, parallel group 48-week clinical study comparing biomarker directed treatment adjustment to standard care in severe asthma.Results: of 1572 treatment advisories (301 participants), instructions were followed in 1377 cases (87.6%). Patients were more likely to follow advice to remain on treatment (96.7%) than to either reduce (70.3%) or increase (67.1%) their treatment, with 64% of patients following all treatment advice. Multivariate analysis associated belonging to an ethnic minority group (OR: 3.10; 95% CI: 1.68, 5.73) and prior study medication changes (≥2 OR: 2.77, 95% CI: 1.51, 5.10) with failure to follow treatment advice. In contrast, emergency room attendance in the prior year (OR: 0.54, 95% CI: 0.32, 0.92) was associated with following treatment advice. The largest effect was seen with transition onto or off oral corticosteroids (OR: 29.28; 95% CI: 16.07, 53.36) when compared to those requested to maintain treatment. Centre was also an important determinant regarding the likelihood of patients to follow treatment advice.Conclusions: belonging to an ethnic minority group and multiple prior treatment adjustments were associated with not following HCP treatment advice. Patients also responded differently to HCP advice across UK specialist centres. These findings have implications for generalisability for models of care in severe asthma and require further focussed studies.

Importance: This systematic review summarizes existing studies on dry needling for spasticity and range of motion (ROM) and discusses its potential for use as an occupational therapy intervention. Objective: To examine existing studies on the effects of dry needling on spasticity and ROM. Data Sources: Article citations and abstracts from Scopus, Cochrane Library, PubMed, CINAHL, and a university library search. Study Selection and Data Collection: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in abstracting data. Peer-reviewed journal articles published in English between January 2007 and June 2019 were searched. Of 270 identified studies, 10 met the inclusion criteria. Studies were divided into categories on the basis of outcome measures (Modified Modified Ashworth Scale and ROM). Pain outcome measures were excluded because a systematic review addressing this outcome has recently been completed. Findings: Strong evidence was found to support the use of dry needling to decrease spasticity and increase ROM. Conclusions and Relevance: This systematic review suggests that dry needling is an effective physical agent modality to decrease spasticity and increase ROM, both of which are potentially beneficial to functional outcomes. What This Article Adds: This article provides information that may be helpful in determining the appropriateness of dry needling as an occupational therapy intervention.

International audience; Context: This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). Objective: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. Evidence synthesis: Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non–muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in “fit” patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1–negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/. Conclusions: This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease. Radical cystectomy with urinary diversion remains the mainstay of managing muscle-invasive bladder cancer (MIBC). The use of neoadjuvant chemotherapy (NAC) has improved overall survival rates, but selection of patients who will benefit most from NAC remains challenging. In case bladder-preserving strategies are considered, patient stratification according to their risk profile is imperative and management should be discussed in a multidisciplinary team. As yet, there are no validated prognostic molecular markers to guide the clinical management of MIBC. In a metastatic setting, cisplatin-based chemotherapy remains the first choice in fit patients. In unfit patients, based on interim results from two on-going clinical trials, first-line treatment with pembrolizumab or atezolizumab for urothelial cancer is restricted to Programmed Death Ligand 1-positive patients only.

Coronavirus Disease 19 (COVID-19) can present as an Adult Respiratory Distress Syndrome (ARDS)-like pneumonia Continuous Positive Airway Pressure (CPAP) for ARDS is usually delivered in Intensive Care Units (ICU) Pressure for ICU beds led to Glasgow Royal Infirmary developing a COVID-19 High Dependency Unit (C-HDU) where domiciliary non-invasive ventilators (NIV) (Lumis 150, Resmed) with supplementary oxygen delivered CPAP for respiratory failure due to COVID-19 pneumonia We review the feasibility and efficacy of delivering CPAP outside the ICU setting Method: Retrospective analysis of data from patients receiving CPAP in C-HDU (25th March to 8th May 2020) Results: 58 patients received CPAP in total 46/58 received CPAP only 18/46 improved and were discharged by day 30 12/46 died by day 30 12/46 required mechanical ventilation - of these 6/12 successfully extubated and well at day 30, 3/12 remain in ICU and 3/12 died 4/46 failed CPAP but survived with simple oxygen therapy 12/58 did not tolerate CPAP and were switched to nasal high flow oxygen - of these 8/12 are well at day 30 Conclusions: It is feasible to deliver CPAP using domiciliary NIV machines with supplementary oxygen for COVID-19 pneumonia outwith ICU CPAP has potential to improve patient outcomes, prevent ICU admissions and deliver tangible service efficiencies C-HDU established a multi-disciplinary approach to patient care, incorporating acute medical and respiratory physicians with respiratory physiology support and developed protocols using an iterative learning approach Trials for CPAP in COVID-19 pneumonia are ongoing, but our experience supports its role and the practicality of delivering CPAP using domiciliary NIV equipment

Introduction: Increasing corticosteroids (CS) to control asthma symptoms and exacerbations has potential for inappropriately high and difficult to down-titrate CS doses. Aims and Objectives: We tested whether a T2 biomarker-based strategy (BS) to guide CS reduction (factoring fractional exhaled nitric oxide (FeNO), blood eosinophils, serum periostin) vs. a symptom-based control would see fewer exacerbations and better asthma control and lung function. Methods: In this randomised (4:1/BS:control), single-blind parallel group trial, patients (pts) with severe asthma and FeNO Results: In the intention-to-treat population (240 BS vs. 61 control pts), the proportion of BS pts on lower CS dose at Wk48 was 28.4% vs. 18.5% in the controls (adjusted OR: 1.71; 95%CI 0.80, 3.63; p=0.165). In the per protocol (PP) population (n=121), significantly more pts had lower CS doses at Wk48 in the BS vs. the control group (30.7% vs. 5.0% (OR: 11.48; 95%CI 1.35, 97.83; p=0.026). Failure to follow treatment advice was the main reason for ITT and PP population differences. There was no difference in secondary outcomes between study arms. Conclusion: Biomarker based CS adjustment did not result in a greater proportion of pts reducing CS vs. control, probably because many pts did not follow treatment advice. The biomarker strategy seemed beneficial in pts where symptoms and T2 biomarker profile were discordant.

International audience; CONTEXT: In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and quality of care. OBJECTIVE: A systematic review was performed to evaluate the impact of HV and SV on clinical outcomes. Primary outcomes included in-hospital, 30-d, and 90-d mortality. Secondary outcomes included complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rate. EVIDENCE ACQUISITION: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Comparative studies published after the year of 2000 including patients who underwent RC for bladder cancer were eligible for inclusion. Partial cystectomy was an exclusion criterion. Risk of bias (RoB) assessment was performed according to the ROBINS-1 tool. EVIDENCE SYNTHESIS: After screening of 1190 abstracts, 39 studies recruiting 549 542 patients were included. All studies were retrospective observation cohort studies (level of evidence 3). Twenty-two studies reported on HV only, six studies on SV only, and 12 on both. Higher HV, specifically an HV of >10, was associated with improved primary and secondary outcomes in most studies. In addition, there is some evidence that an HV of >20 improves outcomes. For SV, limited and conflicting data are reported. Most studies had moderate to high RoB. The results were synthesized narratively. CONCLUSIONS: Acknowledging the lower level of evidence, HV is likely associated with in-hospital, 30- and 90-d mortality, as well as the secondary outcomes assessed. Based on this study, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10, and preferably >20, RCs annually or refer the patient to a center that reaches this number. For SV, limited and conflicting data are available. The available evidence suggests HV rather than SV to be the main driver of perioperative outcomes. PATIENT SUMMARY: Current literature suggests that the number of bladder removal operations per hospital per year is associated with postoperative survival as well as the quality of care provided. Copyright

CONTEXT Primary urethral carcinoma (PUC) is a rare cancer accounting for

Metal-on-metal (MoM) total hip arthroplasty (THA) can be associated with adverse metal reactions, including pseudotumors. This case report describes a 58-year-old female with an MoM THA-related pseudotumor that caused unilateral leg edema from compression of her external iliac vein. After thorough preoperative workup to rule out infection and deep vein thrombosis and consultation with a vascular surgeon, the patient underwent revision THA and excision of her pseudotumor. She had complete resolution of her swelling at 4 years after surgery. Review of all available case reports for this rare complication revealed that almost all patients were female. All patients underwent revision THA, with resolution of their symptoms. Literature review demonstrates that women are disproportionally affected by complications associated with MoM THA. We recommend close monitoring of patients with MoM THA, particularly women, for development of adverse metal reactions.

Item does not contain fulltext CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. OBJECTIVE: To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. EVIDENCE ACQUISITION: An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. EVIDENCE SYNTHESIS: Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. CONCLUSIONS: The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. PATIENT SUMMARY: Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.

Context There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Objective To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. Evidence acquisition A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. Evidence synthesis Seven studies compared KSS overall ( n =547) versus RNU ( n =1376). Information on the comparison of SU ( n =586) versus RNU ( n =3692), URS ( n =162) versus RNU ( n =367), and PC ( n =66) versus RNU ( n =114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. Conclusions Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. Patient summary We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours.

Asthma is heterogeneous with different endotypes/phenotypes. Response to corticosteroids is variable and novel biological therapies are proving useful. Biomarkers allow individualization of treatment. This review provides an update on available data regarding asthma biomarkers with focus on their utility for prediction of response to steroidal and new biological therapies.Blood eosinophils are a biomarker with acceptable accuracy as a surrogate for sputum eosinophilia, are associated with relevant outcomes, and are more readily measureable. New evidence supports fraction of exhaled nitric oxide (FENO)-based treatment algorithms for cost-effective maintenance of asthma control/quality of life. Serum and sputum-derived periostin are biomarkers of lung function decline and associated with eosinophilic airway inflammation. Transcriptomics show promise for endotyping; their role in management remains to be determined. Biomarker panels may improve predictive value as shown for the combination of FENO/urinary bromotyrosine in prediction of steroid responsiveness. Novel biological therapies are proving effective in biomarker-selected populations.Biomarkers including blood eosinophils and FENO are proving to have utility for the effective administration of steroidal and novel biological therapies in asthma, allowing individualized treatment. Transcriptomics can discriminate subtypes of asthma and may have a role in delivery of individualized therapy.

Obese asthma is now widely recognized as a phenotype of difficult asthma that is common and less responsive to traditional asthma treatments, so identifying specific treatments is increasingly important.Obesity can lead to asthma through a complex relationship of causes including mechanical, inflammatory, metabolic and genetic factors. Exercise programmes including pulmonary rehabilitation, weight loss via dietary restriction, exercise and bariatric surgery, or combinations of all of these can improve quality of life, symptoms, and exercise capacity, with reductions in medication use and exacerbations, and represent tailored treatment for this phenotype of severe difficult to treat asthmatic patients.Exercise programmes and pulmonary rehabilitation, weight loss programmes targeting 5-10% weight loss and bariatric surgery are effective treatments for the obese asthma phenotype.

This chapter provides a comprehensive overview of how burn rehabilitation should be conducted along the continuum of care. The authors emphasize the importance of early rehabilitative interventions such as positioning, splinting, exercise, and functional mobility in the intensive care unit. They proceed to discuss and illustrate the various modalities practiced in burn rehabilitation, focusing on producing the best functional and cosmetic outcomes at the completion of the rehabilitative process.

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT (n=18) and MCT/CPA3 (mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.

Context The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice. Objective To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. Evidence acquisition The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; ureteroscopy; nephroureterectomy; adjuvant treatment; instillation; recurrence; risk factors; and survival. References were weighted by a panel of experts. Evidence synthesis Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations (ie, grade A). However, the results of recent multicentre studies are now available, and there is a growing number of retrospective articles in UTUC. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification, as well as for radical and conservative treatment; prognostic factors are also discussed. A single postoperative dose of intravesical mitomycin after radical nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumours and two functional kidneys. Conclusions These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours. Patient summary Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis; appropriate diagnosis and management is most important. We present recommendations based on current evidence for optimal management.

Background: Exacerbations are an important cause of morbidity in asthma, particularly in severe disease. Previous studies have identified variables associated with exacerbations, although little is known about risk factors in real-life populations of severe asthma. Methods: We determined the influence of demographics, disease characteristics and biomarkers of inflammation on the frequency of severe exacerbations in 872 adults with refractory asthma recruited to the British Thoracic Society Severe Asthma Registry. Results: 717 (82%) of subjects gave a history of ≥2 severe exacerbations in the last year and almost two-thirds had ≥4. Frequent exacerbations were significantly associated with younger age, higher BMI, higher ACQ score, worse asthma quality-of-life score, higher anxiety and depression score, history of GORD, increased unscheduled GP/emergency visits and hospital admissions in the last year and higher exhaled nitric oxide (FeNO). Preliminary analyses revealed independent variables associated with an increased risk of exacerbations were ACQ score, unscheduled GP/emergency visits in the last year, number of hospital admissions in the last year and FeNO in the total population and blood eosinophils in those not on maintenance oral steroids. Conclusion: Over 80% of a real-life population of adults with severe refractory asthma gave a history of frequent (≥2) severe exacerbations in the last year. Clinical outcomes and inflammatory variables were independent risk factors for severe exacerbations in this population. Further analysis will examine whether combining the independent risk factors in a scoring system can identify those at greatest risk of severe exacerbations.

ObjectiveTo determine the acceptability of using data on medicines dispensed in primary care to inform out-patient treatment of patients with difficult-to-treat asthma. ApproachConsultant respiratory physicians’ access to a summary of all relevant medicines dispensed by community pharmacists to patients with difficult to treat asthma was piloted in 2015 (therapy review (TR)). Dispensed medicine data were collected using the patient’s unique NHS identifier. This information was aggregated monthly for the year before the patient attended their clinic appointment. Patients gave consent and the summary data were used to assess concordance with therapy and inform a discussion about future management. Semi-structured interviews were conducted with eight patients who had received TR and eight respiratory physicians: two with access to the summary. The interviews aimed to highlight the experiences of patients and physicians on the utility of therapy reviews the views of physicians without access to summaries on the prospective use of therapy reviews. With the participant’s consent, interviews were recorded and transcribed. Thematic analysis of grouped responses was conducted using NVivo software. ResultsAll physicians agreed that poor compliance remains a significant concern when treating patients with difficult asthma and supported the use of TR. Physicians with experience of TR identified reliability over current methods of assessing compliance; ability to inform future treatment; and assistance in the discussion of concordance as advantages. The lag of three months in available dispensed data was a disadvantage. Physicians without experience of TR raised concern that use may lead to confrontation: reflected in the experience of one patient who expressed that TR discouraged them from improving compliance. Additional interventions are needed to improve compliance. Opinions from other patients were positive and supported the inclusion of TR as part of a consultation. Physicians with experience of TR found the summary accessible, if access to computers containing specific software to view TR was available. This limitation was considered potentially problematic and physicians without access to TR expressed a preference to accessing TR via NHS Portal - a secure online platform permitting registered users access to patient-level information. ConclusionThis demonstrates the positive impact of using data about primary care dispensed medicine in secondary care to assess medicine concordance and inform individual patient’s ongoing treatment. This supplements other data collected from clinical tests and patient-physician discussion. Development of a more efficient system to access the summary data is required before it is more widely used.

Item does not contain fulltext INTRODUCTION: Different sexual function-preserving surgical techniques aimed at improving voiding and sexual function in patients undergoing radical cystectomy for bladder cancer have been described. The objective of this systematic review is to determine the effect of sexual function-preserving cystectomy (SPC) on functional and oncological outcomes. MATERIALS AND METHODS: Relevant databases were searched covering the time frame 2000 to 2015. All publications presenting data on any type of SPC reporting oncological or functional outcomes with a minimum follow-up of 1 year were identified. Comparative studies including a minimum of 30 patients and single-arm case series with a minimum of 50 patients were selected. No language restrictions were applied. RESULTS: In a total of 8,517 identified abstracts, 12 studies were eligible for inclusion. SPC described included prostate-, capsule-, seminal vesicle, and nerve-sparing techniques. Local recurrence ranged from 1.2% to 61.1% (vs. 16.0%-55.0% in the control group) and metastatic disease from 0% to 33.3% (vs. 33.0%). No differences were found in comparative studies reporting oncological outcomes. Postoperative potency was significantly better in the SPC groups in 6 studies comparing sexual function-preserving cystectomy vs. radical cystectomy (P

Item does not contain fulltext CONTEXT: Pelvic organ-preserving radical cystectomy (POPRC) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical cystectomy (RC). OBJECTIVE: To determine the effect of POPRC on sexual, oncological and urinary outcomes compared with RC in women who undergo standard curative surgery and orthotopic neobladder substitution for bladder cancer. EVIDENCE ACQUISITION: Medline, Embase, Cochrane controlled trials databases and clinicaltrial.gov were systematically searched for all relevant publications. Women with bladder cancer who underwent POPRC or standard RC and orthotopic neobladder substitution with curative intent were included. Prospective and retrospective comparative studies and single-arm case series were included. The primary outcomes were sexual function at 6-12 months after surgery and oncological outcomes including disease recurrence and overall survival (OS) at >2 years. Secondary outcomes included urinary continence at 6-12 months. Risk of bias (RoB) assessment was performed using standard Cochrane review methodology including additional domains based on confounder assessment. EVIDENCE SYNTHESIS: The searches yielded 11 941 discrete articles, of which 15 articles reporting on 15 studies recruiting a total of 874 patients were eligible for inclusion. Three papers had a matched-pair study design and the rest of the studies were mainly small, retrospective case series. Sexual outcomes were reported in seven studies with 167/194 patients (86%) having resumed sexual activity within 6 months postoperatively, with median (range) patients' sexual satisfaction score of 88.5 (80-100)%. Survival outcomes were reported in seven studies on 197 patients, with a mean follow-up of between 12 and 132 months. At 3 and 5 years, cancer-specific survival was 70-100% and OS was 65-100%. In all, 11 studies reported continence outcomes. Overall, the daytime and night-time continence rates were 58-100% and 42-100%, respectively. Overall, the self-catheterisation rate was 9.5-78%. Due to poor reporting and large heterogeneity between studies, instead of subgroup-analysis, a narrative synthesis approach was used. The overall RoB was high across all studies. CONCLUSION: For well-selected patients, POPRC with orthotopic neobladder may potentially be comparable to standard RC for oncological outcomes, whilst improving sexual and urinary function outcomes. However, in women undergoing RC, oncological and functional data regarding POPRC remain immature and require further evaluation in a prospective comparative setting.

Item does not contain fulltext CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

Students do not leave their mental health at the front door when they come to school. From wellness to serious illness, a student’s mental health status is integral to how they think, feel, interact, behave, and learn. Decades of research and experience have laid a solid foundation and framework for effectively providing mental health services in schools that protect student well-being, promote learning, reduce stigma, and improve access. Providing mental health services, ideally in a multitiered system of supports, is good for students, their families, educators, the community, and society at large. Until we take seriously the role of mental health in learning, school reform efforts, largely focused on teacher quality and instruction today, will fall far short of the goal of having all students thrive in school, at home, and in life.

The improved short and long term survival rate of individuals with large burn injuries has made rehabilitation for optimal recovery of the patient increasingly important. Burn injury to the hands worsens the prospect of functional recovery and good quality of life in single events, especially when included in larger burns. The purpose of this paper is to present a narrative review of examination strategies used for children with burn injuries to the hands in the acute, intermediate and long term stages of rehabilitation, and apply these concepts to selected treatments, using a case that is representative of this complex patient population. The model of health described by the World Health Organisation provided the framework for the review, to structure the review in the domains of body structures and body functions, functional activities and participation in life roles. The lack of consensus in the burn literature regarding the most appropriate outcome measures and interventions necessitates futures research and long term outcome studies to identify, predict and prevent the difficulties patients may face over their lifespan.

Asthma in the elderly as well as asthma of adult-onset has been associated with increased morbidity, but little is known specifically about the effects of age on clinical and inflammatory outcomes in severe refractory asthma. The aims of the study were to examine the effects of age [65 versus ≥65 years] and age of onset of asthma [childhood-onset,18 versus adult-onset, ≥18 years] on clinical and inflammatory variables in patients with severe asthma.In 1042 subjects with refractory asthma recruited to the British Thoracic Society Severe Asthma Registry, we compared patient demographics, disease characteristics and biomarkers of inflammation in patients aged65 years (n = 896) versus ≥65 years (n = 146) and onset at age18 years (n = 430) versus ≥18 years (n = 526).Severe asthma patients aged ≥65 years had improved symptom control, better asthma quality of life and in the last year, less emergency visits and rescue oral steroid courses [3 (1-6) versus 5 (2-7), p 0.001] than severe asthmatics aged65 years. Blood eosinophils were lower in the elderly group. Patients with severe adult-onset asthma had similar symptom control, lung function and health-care utilization compared to severe childhood-onset asthma. Adult-onset asthmatics had higher blood eosinophils and were less atopic.Patients with severe refractory asthma aged ≥65 years exhibit better clinical and health care outcomes and have lower blood eosinophils compared to those aged65 years. Severe refractory adult-onset asthma is associated with similar levels of asthma control, higher blood eosinophils and less atopy than severe refractory childhood-onset asthma.

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies.

Resumen Contexto Han surgido nuevos datos sobre el tratamiento del cancer de vejiga con invasion muscular y metastasico (CVIMM) que han llevado a una actualizacion de la Guia Clinica de la Asociacion Europea de Urologia (European Association of Urology [EAU]) del CVIMM. Objetivo Revisar la nueva Guia Clinica de la EAU sobre el CVIMM con un enfoque especifico en el tratamiento. Adquisicion de evidencia La literatura nueva publicada desde la ultima actualizacion de la Guia Clinica de la EAU en 2008 se obtuvo de Medline, la base de datos Cochrane de revisiones sistematicas y listas de referencia en publicaciones y articulos de revision, y se examino exhaustivamente por un grupo de urologos, oncologos y un radiologo designado por la Oficina de Guias Clinicas de la EAU. Tambien se tuvieron en cuenta recomendaciones previas basadas en la literatura anterior sobre este tema. Se anadieron los niveles de evidencia (NE) y grados de recomendacion (GR) basandose en un sistema modificado del Centro de Medicina Basada en la Evidencia de Oxford. Sintesis de evidencia Los datos actuales demuestran que la quimioterapia neoadyuvante junto con la cistectomia radical (CR) es recomendable en ciertas constelaciones de CVIMM. La CR sigue siendo el tratamiento basico de eleccion en enfermedad invasiva localizada para ambos sexos. Se ha intentado definir el grado de cirugia en condiciones estandar en ambos sexos. Se deberia ofrecer un sustituto vesical ortotopico a pacientes, tanto masculinos como femeninos, sin contraindicaciones tales como ausencia de tumor al nivel de la diseccion uretral. En contraste con la quimioterapia neoadyuvante, actualmente se recomienda el uso de quimioterapia adyuvante unicamente en ensayos clinicos. La terapia preservadora de la vejiga multimodalidad en la enfermedad localizada se observa actualmente solo como una alternativa en pacientes seleccionados, bien informados y acatadores para los que la cistectomia no se plantea por razones medicas o personales. En la enfermedad metastasica el tratamiento de primera linea para los pacientes en condiciones suficientes para soportar el cisplatino sigue siendo la poliquimioterapia con cisplatino. Con la llegada de vinflunina, la quimioterapia de segunda linea se ha vuelto disponible. Conclusiones En el tratamiento del cancer de vejiga (CV) invasivo localizado, el tratamiento estandar sigue siendo la extirpacion quirurgica radical de la vejiga dentro de los limites estandar, incluyendo los ganglios linfaticos regionales aun sin especificar. Sin embargo, la adicion de la quimioterapia adyuvante debe ser considerada para ciertos grupos de pacientes especificos. Se ha aprobado y se recomienda un nuevo medicamento para la quimioterapia de segunda linea (vinflunina) en la enfermedad metastasica.

Background and objective: Asthma can be classified as eosinophilic or non-eosinophilic based on the cell profile of induced sputum. This classification can help determine whether corticosteroid treatment is indicated. We assessed the stability of these phenotypes over time and with different treatment regimens. Methods: Clinically stable, non-smoking, asthmatic adults were enrolled in one of two studies. In study one, induced sputum cell counts from 28 subjects were analysed after 4 weeks without corticosteroid treatment and after 6 week treatments with placebo, regular inhaled beta-agonist, inhaled corticosteroid, and combined beta-agonist and corticosteroid. In study two, sputum from 26 subjects with non-eosinophilic asthma was analysed after 12 weeks of placebo and after four 2-week corticosteroid washouts. Sputum with

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Haematuria clinics with same day imaging and flexible cystoscopy are an efficient way for investigating patients with haematuria. The principal role of haematuria clinics with reference to bladder cancer is to determine which patients are ‘normal’ and may be discharged, and which patients are abnormal and should undergo rigid cystoscopy. It is well recognised that CT urography offers a thorough evaluation of the upper urinary tract for stones, renal masses and urothelial neoplasms but the role of CT urography for diagnosing bladder cancer is less certain. The aim of the present study was to evaluate the diagnostic accuracy of CT urography in patients with visible haematuria aged >40 years and to determine if CT urography has a role for diagnosing bladder cancer. This study shows that the optimum diagnostic strategy for investigating patients with visible haematuria aged >40 years with infection excluded is a combined strategy using CT urography and flexible cystoscopy. Patients positive for bladder cancer on CT urography should be referred directly for rigid cystoscopy and so avoid flexible cystoscopy. The number of flexible cystoscopies required therefore may be reduced by 17%. The present study also shows that the diagnostic accuracy of voided urine cytology is too low to justify its continuing use in a haematuria clinic using CT urography and flexible cystoscopy. OBJECTIVES • To evaluate and compare the diagnostic accuracy of computed tomography (CT) urography with flexible cystoscopy and voided urine cytology for diagnosing bladder cancer. • To evaluate diagnostic strategies using CT urography as: (i) an additional test or (ii) a replacement test or (iii) a triage test for diagnosing bladder cancer in patients referred to a hospital haematuria rapid diagnosis clinic. PATIENTS AND METHODS • The clinical cohort consisted of a consecutive series of 778 patients referred to a hospital haematuria rapid diagnosis clinic from 1 March 2004 to 17 December 2007. Criteria for referral were at least one episode of macroscopic haematuria, age >40 years and urinary tract infection excluded. Of the 778 patients, there were 747 with technically adequate CT urography and flexible cystoscopy examinations for analysis. • On the same day, patients underwent examination by a clinical nurse specialist followed by voided urine cytology, CT urography and flexible cystoscopy. Voided urine cytology was scored using a 5-point system. CT urography was reported immediately by a uroradiologist and flexible cystoscopy performed by a urologist. Both examinations were scored using a 3-point system: 1, normal; 2, equivocal; and 3, positive for bladder cancer. • The reference standard consisted of review of the hospital imaging and histopathology databases in December 2009 for all patients and reports from the medical notes for those referred for rigid cystoscopy. Follow-up was for 21–66 months. RESULTS • The prevalence of bladder cancer in the clinical cohort was 20% (156/778). For the diagnostic strategy using CT urography as an additional test for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 1.0 (95% confidence interval [CI] 0.98–1.00), specificity was 0.94 (95% CI 0.91–0.95), the positive predictive value (PPV) was 0.80 (95% CI 0.73–0.85) and the negative predictive value (NPV) was 1.0 (95% CI 0.99–1.00). • For the diagnostic strategy using CT urography as a replacement test for flexible cystoscopy for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.95 (95% CI 0.90–0.97), specificity was 0.83 (95% CI 0.80–0.86), the PPV was 0.58 (95% CI 0.52–0.64), and the NPV was 0.98 (95% CI 0.97–0.99). Similarly using flexible cystoscopy for diagnosing bladder cancer, if scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.98 (95% CI 0.94– 0.99), specificity was 0.94 (95% CI 0.92–0.96), the PPV was 0.80 (95% CI 0.73–0.85) and the NPV was 0.99 (95% CI 0.99–1.0). • For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), patients with a positive CT urography score are referred directly for rigid cystoscopy, and patients with an equivocal or normal score were referred for flexible cystoscopy. Sensitivity was 1.0 (95% CI 0.98–1.0), specificity was 0.94 (95% CI 0.91–0.95), the PPV was 0.80 (95% CI 0.73–0.85), and the NPV was 1.0 (95% CI 0.99–1.0). • For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 2), patients with a positive CT urography score are referred directly for rigid cystoscopy, patients with an equivocal score are referred for flexible cystoscopy and patients with a normal score undergo clinical follow-up. Sensitivity was 0.95 (95% CI 0.90–0.97), specificity was 0.98 (95% CI 0.97–0.99), the PPV was 0.93 (95% CI 0.87–0.96), and the NPV was 0.99 (95% CI 0.97–0.99). • For voided urine cytology, if scores of 0–3 were classified as negative and 4–5 as positive for bladder cancer, sensitivity was 0.38 (95% CI 0.31–0.45), specificity was 0.98 (95% CI 0.97–0.99), the PPV was 0.82 (95% CI 0.72–0.88) and the NPV was 0.84 (95% CI 0.81–0.87). CONCLUSIONS • There is a clear advantage for the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), in which patients with a positive CT urography score for bladder cancer are directly referred for rigid cystoscopy, but all other patients undergo flexible cystoscopy. • Diagnostic accuracy is the same as for the additional test strategy with the advantage of a 17% reduction of the number of flexible cystoscopies performed. • The sensitivity of voided urine cytology is too low to justify its continuing use in a hospital haematuria rapid diagnosis clinic using CT urography and flexible cystoscopy.

Background and objective: Exercise-induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (FENO) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies.We assessed: the efficacy of cromoglycate, formoterol and montelukast in patients with EIW and low FENO ( 35 ppb) group. Methods: Patients had EIW and airway hyperresponsiveness (AHR) to mannitol and/or exercise.Those with low FENO (n = 19) received cromoglycate (20 mg inh. bd + before challenge tests), formoterol (12 mg inh. bd + before challenge tests) and montelukast (10 mg p.o. od), each for 2 weeks. Those with high FENO (n = 20) took inhaled fluticasone (500 mg) daily for 4 weeks. Primary end-points were: 50% reduction in maximumFEV1%fall(clinicalprotection)anddecrease in AHR to mannitol. Results: In patients with low FENO,cromoglycate,formoterol and montelukast significantly decreased AHR to mannitol in 63%, 61% and 47% of patients, respectively.In this group,the magnitude of exercise-induced bronchoconstriction (EIB) was significantly reduced with montelukast and formoterol; between-treatment differences were not significant. Of 6/19 with low FENO and EIB, protection occurred in 67% (cromoglycate), 83% (formoterol) and 50% (montelukast),respectively. In the high FENO group, AHR to mannitol and EIB decreased significantly with fluticasone (P < 0.001, P = 0.005,respectively),and protection occurred in 7/8 (88%) with EIB. Conclusions: In patients with EIW and low FENO, the number of ‘responders’ to cromoglycate, formoterol

Contexto: la aparición de nuevos datos relacionados con el diagnóstico y tratamiento de cáncer vesical músculo-invasivo y metastásico (CaV-MiM) ha obligado a una actualización de las Guías sobre el CaV-MiM de la Asociación Europea de Urología (EAU). Objetivo: revisión de las nuevas guías de la EAU para el CAV-MiM. Evidencia adquirida: un grupo de urólogos, oncólogos y radiólogos designados por el Comité de Guías Clínicas de la EAU ha realizado un exhaustivo trabajo de revisión de la literatura procedente de Medline, el registro central Cochrane de revisiones sistemáticas y las citas bibliográficas de publicaciones y artículos de revisión. Se han tenido en cuenta las recomendaciones basadas en la literatura previa disponible sobre este aspecto. Además, han sido añadidos niveles de evidencia y grados de recomendación, según las modificaciones del Oxford Centre for Evidence-based Medicine. Evidencia sintetizada: el diagnóstico de cáncer vesical músculo-invasivo (CaVMI) se realiza mediante la resección transuretral y el consiguiente estudio histopatológico. Una vez confirmada la existencia de CaVMI es preciso realizar el estadiaje mediante tomografía computarizada toraco-abdómino-pélvica, si se dispone de ella. Actualmente, la quimioterapia adyuvante solamente se recomienda en el contexto de ensayos clínicos. La cistectomía radical es el tratamiento de elección en ambos sexos, y la linfadenectomía debe constituir una parte integral de la misma. Tanto a hombres como a mujeres se les debe ofrecer la sustitución vesical ortotópica siempre que no existan contraindicaciones, tales como la existencia de tumor en el margen uretral. En la actualidad, los tratamientos multimodales para la conservación vesical en casos de enfermedad localizada constituyen un alternativa terapéutica solamente en pacientes seleccionados, adecuadamente informados, y en aquellos en los que se desestima la cistectomía por motivos clínicos o personales. Los protocolos de seguimiento deben diseñarse sobre la base de: a) historia natural de la recurrencia; b) probabilidades de recurrencia; c) deterioro funcional en localizaciones específicas; y d) consideraciones sobre el tratamiento de la recurrencia. En la enfermedad metastásica el tratamiento de primera línea para los pacientes con un estado general adecuado para tolerar el cisplatino es la quimioterapia combinada basada en este fármaco. Actualmente no existe una quimioterapia estandarizada de segunda línea. Conclusiones: estas guías de la EAU constituyen un resumen de la exhaustiva visión de conjunto de las guías recientemente actualizadas del CaV-MiM, publicadas en las guías clínicas de la EAU, también disponibles en la National Guideline Clearinghouse. Context: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. Objective: To review the new EAU guidelines for MiM-BC. Evidence acquisition: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesis: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on: a) natural timing of recurrence; b) probability of disease recurrence; c) functional deterioration at particular sites; and d) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. Conclusions: These EAUguidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

RATIONALE Airway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is conflicting regarding non-eosinophilic asthma (NEA). OBJECTIVES To assess the inflammatory cell phenotypes in asthma after eliminating potentially confounding effects; to compare steroid response in EA versus NEA; and to investigate changes in sputum cells with inhaled corticosteroid (ICS). METHODS Subjects undertook ICS withdrawal until loss of control or 28 days. Those with airway hyper-responsiveness (AHR) took inhaled fluticasone 1000 microg daily for 28+ days. Cut-off points wereor = or2% for sputum eosinophils andor = or61% for neutrophils. RESULTS After steroid withdrawal (n=94), 67% of subjects were eosinophilic, 31% paucigranulocytic and 2% mixed; there were no neutrophilic subjects. With ICS (n=88), 39% were eosinophilic, 46% paucigranulocytic, 3% mixed and 5% neutrophilic. Sputum neutrophils increased from 19.3% to 27.7% (p=0.024). The treatment response was greater in EA for symptoms (p0.001), quality of life (p=0.012), AHR (p=0.036) and exhaled nitric oxide (p=0.007). Lesser but significant changes occurred in NEA (ie, paucigranulocytic asthma). Exhaled nitric oxide was the best predictor of steroid response in NEA for AHR (area under the curve 0.810), with an optimum cut-off point of 33 ppb. CONCLUSIONS After eliminating the effects of ICS and smoking, a neutrophilic phenotype could be identified in patients with moderate stable asthma. ICS use led to phenotype misclassification. Steroid responsiveness was greater in EA, but the absence of eosinophilia did not indicate the absence of a steroid response. In NEA this was best predicted by baseline exhaled nitric oxide.

Contains fulltext : 81147.pdf (Publisher’s version ) (Closed access) CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. CONCLUSIONS: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

The aim was to develop clinical guidelines for multidetector computed tomography urography (CTU) by a group of experts from the European Society of Urogenital Radiology (ESUR). Peer-reviewed papers and reviews were systematically scrutinized. A summary document was produced and discussed at the ESUR 2006 and ECR 2007 meetings with the goal to reach consensus. True evidence-based guidelines could not be formulated, but expert guidelines on indications and CTU examination technique were produced. CTU is justified as a first-line test for patients with macroscopic haematuria, at high-risk for urothelial cancer. Otherwise, CTU may be used as a problem-solving examination. A differential approach using a one-, two- or three-phase protocol is proposed, whereby the clinical indication and the patient population will determine which CTU protocol is employed. Either a combined nephrographic-excretory phase following a split-bolus intravenous injection of contrast medium, or separate nephrographic and excretory phases following a single-bolus injection can be used. Lower dose (CTDIvol 5-6 mGy) is used for benign conditions and normal dose (CTDIvol 9-12 mGy) for potential malignant disease. A low-dose (CTDIvol 2-3 mGy) unenhanced series can be added on indication. The expert-based CTU guidelines provide recommendations to optimize techniques and to unify the radiologist's approach to CTU.

The aim of this cross-sectional survey was to identify a possible relationship between the information-seeking behaviour of patients receiving chemotherapy for breast cancer with source, type, amount and satisfaction of health information accessed. The sample (n = 36) were drawn from the medical oncology department of a large city centre teaching hospital. Participants were recruited through consecutive attendance to the medical oncology department. Eighty-six patients were invited to participate (response rate 42%). An anonymous self-report questionnaire and the Miller Behavioural Style Scale were used to measure attitudes towards 10 different sources of information and identify information-seeking behaviour. The study found that high information-seeking behaviour influenced the type of information sources used to find out about chemotherapy, but did not influence the level of satisfaction with the information sources used. Healthcare professionals were the most frequently used sources of information, but the majority of the sample used a variety of information sources. The Internet was the most frequently used mass media source of information (50% of the sample), especially by those under 50 years old (P = 0.033). Patients' behavioural signature needs to be considered when addressing their information needs. Oncology services need to provide patients with details of recommended high-quality websites to access for information about their chemotherapy.

OBJECTIVE: To evaluate multidetector computed tomography urography (MDCTU) for diagnosing upper urinary tract (UUT) urothelial tumour by comparison with retrograde ureteropyelography (RUP). PATIENTS AND METHODS: MDCTU and RUP were used in a selected series of adult patients presenting with haematuria. Entry criteria were based on findings on intravenous urography and were chosen to ensure a high prevalence of UUT urothelial tumour to allow a valid retrospective comparison of the diagnostic techniques. MDCTU and RUP studies were scored for the presence and absence of UUT urothelial tumour by two radiologists, retrospectively and independently, and while unaware of the demographic and clinical information. The reference standards were the histopathology and clinical follow-up. RESULTS: MDCTU and RUP were used in 106 patients over a 24-month period. RUP was attempted in 151 of 212 UUTs; the corresponding MDCTU for each UUT was reviewed. MDCTU was a true-positive (TP) for urothelial tumour in 31, true-negative (TN) in 111, false-positive (FP) in eight and false-negative (FN) in one UUT, giving a sensitivity of 0.97, a specificity of 0.93, a positive predictive value (PPV) of 0.79 and a negative PV (NPV) of 0.99. RUP was technically successful and diagnostic in 96% of the UUTs (143/151). For diagnosing urothelial tumour, RUP was TP in 26, TN in 112, FP in four and FN in one UUT, giving a sensitivity of 0.97, specificity of 0.93, a PPV of 0.79 and NPV of 0.99. CONCLUSION: This study validates quantitatively the use of MDCTU for diagnosing UUT urothelial tumour.

Multidetector computed tomography (MDCT) is well established for the detection of stones and renal masses, but more recently MDCT urography (MDCTU) is becoming widely used for examination of the entire urinary tract aimed specifically for diagnosing urothelial lesions. Evidence is rapidly accumulating to support the use of MDCTU in this manner. Familiarity with the MDCTU signs of urothelial malignancy is a prerequisite for optimum radiological practice. This article provides a review of the appearances of transitional cell cancer in the upper urinary tract and bladder.

Lack of understanding or knowledge of research among patients participating in randomized clinical trials (RCTs) is common. However, there is a lack of validated measures to assess the extent of the problem. The aim of this study was to develop and pilot a questionnaire to assess knowledge and understanding of RCTs in the cancer setting. A 13-item four-part questionnaire was developed and piloted with three groups: patients with cancer who had no experience of clinical trials (n=26); patients with cancer who had previously participated in an RCT (n=26) and research nurses (n=26). The groups were compared using non-parametric anova techniques which showed a highly statistically significant difference between the nurses and both patient groups (P

Published information on the effectiveness of bronchial thermoplasty (BT) for severe asthma in ‘real life’ patients is limited. We compared safety and efficacy outcomes 12 months post procedure in 10 clinic patients and 15 patients recruited to clinical trials of BT at the same centre. Baseline asthma severity was greater in the clinic group. Adverse events were similar. Clinical improvements occurred in 50% of the clinic patients compared with 73% of the research patients.

The authors present 14 cases from the film interpretation session of the 11th annual meeting of the European Society of Urogenital Radiology presented in September, 2004. The cases demonstrate the imaging findings, differential diagnoses, and clinical relevance of a wide variety of genitourinary tract diseases. The cases include examples of benign and malignant urinary tract neoplasms, inflammatory processes, vascular diseases, traumatic injuries, and congenital anomalies.

Purpose: To evaluate in a prospective study the use of a 4F Rosch inferior mesenteric (RIM) catheter for uterine artery embolisation (UAE). Materials and methods: UAE was performed in 72 women over a 37-month period. A 4F RIM braided J-curve 65-cm catheter was used in combination with an angled hydrophilic 150 cm, 0.035” flexible tip guide-wire to catheterise the horizontal portion of both uterine arteries (UA) from a right common femoral artery (CFA) approach. Technical success was defined as successful catheterisation and embolisation of both uterine arteries. Fluorosocpic and procedure times were recorded. Results: Mean subject age=43.7 years (range=25–57 years). Technical success was 98.6% (n=71/72). A single approach via the right CFA was used in 88.9% (n=64/72) and a bilateral CFA approach in 11.1% (n=8/72). Bilateral uterine artery catheterisation using a single 4F RIM catheter via the right CFA approach was successful in 79.2% (n=57/72). Microcatheters were used in 2.8% of patients (n=2/72). Mean fluoroscopic time=13.6±5.3 min (mean±SD). Mean procedure time=44.2±16.5 min. Conclusion: High technical success rate for UAE is possible using a single 4F RIM catheter via a unilateral right CFA approach, which obviates the need for Waltman loop formation, reversed curve catheters and complex suture-catheter arrangements.

Renal transplant dysfunction: over-reliance on subjective investigations can contribute to diagnostic uncertainty.