Improved mini-Tn7 Delivery Plasmids for Fluorescent Labeling of Stenotrophomonas maltophilia.

Fluorescently labeled bacterial cells have become indispensable for many aspects of microbiological research, including studies on biofilm formation as an important virulence factor of various opportunistic bacteria of environmental origin such as Stenotrophomonas maltophilia. Using a Tn7-based genomic integration system, we report the construction of improved mini-Tn7 delivery plasmids for labeling of S. maltophilia with sfGFP, mCherry, tdTomato and mKate2 by expressing their codon-optimized genes from a strong, constitutive promoter and an optimized ribosomal binding site. Transposition of the mini-Tn7 transposons into single neutral sites located on average 25 nucleotides downstream of the 3'-end of the conserved glmS gene of different S. maltophilia wild-type strains did not have any adverse effects on the fitness of their fluorescently labeled derivatives. This was demonstrated by comparative analyses of growth, resistance profiles against 18 antibiotics of different classes, the ability to form biofilms on abiotic and biotic surfaces, also independent of the fluorescent protein expressed, and virulence in Galleria mellonella. It is also shown that the mini-Tn7 elements remained stably integrated in the genome of S. maltophilia over a prolonged period of time in the absence of antibiotic selection pressure. Overall, we provide evidence that the new improved mini-Tn7 delivery plasmids are valuable tools for generating fluorescently labeled S. maltophilia strains that are indistinguishable in their properties from their parental wild-type strains. IMPORTANCE The bacterium S. maltophilia is an important opportunistic nosocomial pathogen that can cause bacteremia and pneumonia in immunocompromised patients with a high rate of mortality. It is now considered as a clinically relevant and notorious pathogen in cystic fibrosis patients but has also been isolated from lung specimen of healthy donors. The high intrinsic resistance to a wide range of antibiotics complicates treatment and most likely contributes to the increasing incidence of S. maltophilia infections worldwide. One important virulence-related trait of S. maltophilia is the ability to form biofilms on any surface, which may result in the development of increased transient phenotypic resistance to antimicrobials. The significance of our work is to provide a mini-Tn7-based labeling system for S. maltophilia to study the mechanisms of biofilm formation or host-pathogen interactions with live bacteria under non-destructive conditions.

Intervention pathways for low anterior resection syndrome after sphincter-saving rectal cancer surgery: A systematic scoping review.

AIM: Low anterior resection syndrome (LARS) has a large impact on patients' quality of life. Several heterogeneous intervention pathways are suggested in the literature. The steps and timing of the different steps in the pathways are unclear. This systematic scoping review aims to map the range of intervention pathways for LARS after sphincter-saving rectal cancer surgery. METHODS: A search was undertaken on four databases (CINAHL, EMBASE, PubMed, and Web of Science). Any type of paper describing intervention pathways for patients with LARS following sphincter-saving surgery was included. Excluded were patients with a stoma, no full paper, no intervention pathway and not being written in English or Dutch. The review was registered with Open Science Framework (10.17605/OSF.IO/JB5H8). Narrative synthesis of the results was performed by charting and summarising key results. RESULTS: A total of 373 records were screened and 12 papers were included. There was a high variability among the intervention pathways, including which patients should be included. The number of pathway steps ranged from 2-6. Most intervention pathways were treatment-led. Intervention options ranged from conservative measures to a permanent stoma. Pathway flow was highly variable and sometimes not well described, with different or no timings provided for the start, progression, or end of the pathways. Three studies discussed the use of a nurse to coordinate the pathway. CONCLUSION: This systematic scoping review shows that despite similarities in treatment options there are variations in which treatments are included, when treatments should be instigated, and even which patients should be treated.

'He's a surgeon, like I'm not going to waste his time': interviews to determine healthcare needs of people with low anterior resection syndrome after rectal cancer surgery.

AIM: The aim of this study was to determine the views of people on their healthcare needs when managing their bowel symptoms following an anterior resection. METHOD: One-to-one, semi-structured interviews were undertaken, after consent and completion of three questionnaires. Results were analysed using a modified framework analysis and presented narratively. RESULTS: Twenty three participants aged 38-75 years were interviewed; 10 were men. Most had low anterior resection syndrome (LARS) scores indicating 'major LARS', Bowel Function Index scores ranged from 28 to 65. The two most bothersome symptoms were faecal incontinence and unpredictable bowel function. Data were grouped into three broad themes: 'treatment consequences', 'strategies and compromises' and 'healthcare needs.' Each theme had four subthemes, such as 'bowel dysfunction' in the theme 'treatment consequences'. Bowel symptoms were common and persistent. Symptom management often required multiple interventions. Expressed healthcare needs included managing expectations through clinician-led information. Participants needed knowledgeable clinicians to enquire about and assess symptoms, provide and reiterate information as well as making an onward referral to enable symptom management. Peers improved the adaptation process through support and advice. Our findings indicate that participants' needs are not being fully met. CONCLUSION: People with LARS have unmet healthcare requirements needed to meet their individual goals. We propose these are addressed by using the acronym 'LARS': a Learned clinician who Asks and assesses bowel symptoms, Revisiting the topic to address new or persisting symptoms as well as Signposting, advising or referring onwards as needed.

Hernia Active Living Trial (HALT): an exercise intervention in people with a parastomal hernia or bulge.

BACKGROUND: Parastomal hernias are a common consequence of stoma surgery and can occur in up to 50% of patients. They are mangaged either conservatively, through support hosiery, or surgically. A patient feasibility study called the Hernia Active Living Trial (HALT) was designed to examine if a clinical pilates-based exercise programme offers an alternative approach to managing a parastomal hernia or bulge. METHOD: Adults with an ileostomy or colostomy who perceived they had a bulge around their stoma were included in the study. The intervention included up to 12 online sessions of an exercise booklet and videos with an exercise specialist. Interviews were conducted to explore participants' experiences of the intervention. The interview data were analysed systematically and thematically. Participants were also asked to complete patient diaries every week. RESULTS: Twelve of the 13 participants who completed the intervention agreed to be interviewed. Following analysis, three main themes emerged including managing a hernia/bulge, benefits and barriers. Participants talked about the benefits of this programme including: reduction of the size of their hernia, increased abdominal control, body confidence and posture, as well as increased physical activity levels. The barriers described were generally overcome allowing participants to engage in what was perceived to be a positive and potentially life-changing experience. CONCLUSIONS: A clinical pilates-based exercise programme for people with a parastomal hernia can bring both direct and indirect improvements to a patient's hernia management, sense of wellbeing and day-to-day life. Individuals with a hernia should be informed about the need for, and value of, exercise to strengthen core muscles, as part of their non-surgical options for self-management.

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. METHODS: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. INTERPRETATION: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. FUNDING: National Institute for Health Research Health Technology Assessment programme.

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. METHODS: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5-12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0-94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96-1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of -0·040 (95% central range -0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. INTERPRETATION: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Healthcare Professional and Patient Perceptions of Changes in Colorectal Cancer Care Delivery During the COVID-19 Pandemic and Impact on Health Inequalities.

BACKGROUND: The COVID-19 pandemic changed the way in which people were diagnosed and treated for cancer. We explored healthcare professional and patient perceptions of the main changes to colorectal cancer delivery during the COVID-19 pandemic and how they impacted on socioeconomic inequalities in care. METHODS: In 2020, using a qualitative approach, we interviewed patients (n = 15) who accessed primary care with colorectal cancer symptoms and were referred for further investigations. In 2021, we interviewed a wide range of healthcare professionals (n = 30) across the cancer care pathway and gathered national and local documents/guidelines regarding changes in colorectal cancer care. RESULTS: Changes with the potential to exacerbate inequalities in care, included: the move to remote consultations; changes in symptomatic triage, new COVID testing procedures/ways to access healthcare, changes in visitor policies and treatment (e.g., shorter course radiotherapy). Changes that improved patient access/convenience or the diagnostic process have the potential to reduce inequalities in care. DISCUSSION: Changes in healthcare delivery during the COVID-19 pandemic have the ongoing potential to exacerbate existing health inequalities due to changes in how patients are triaged, changes to diagnostic and disease management processes, reduced social support available to patients and potential over-reliance on digital first approaches. We provide several recommendations to help mitigate these harms, whilst harnessing the gains.

Care in Europe after presenting to the emergency department with a seizure; position paper and insights from the European Audit of Seizure Management in Hospitals.

BACKGROUND AND PURPOSE: This position paper makes recommendations following an audit of care provided to people presenting with a seizure to emergency departments (EDs) in Europe. METHODS: Participating countries were asked to include five hospitals agreeing to identify 50 consecutive seizure patients presenting to their ED between 1 August 2016 and 31 August 2017. Anonymous data were collected to a web database. Where quoted, percentages are mean site values and ranges are the 10th-90th centile. RESULTS: Data were collected on 2204 ED visits (47 sites, up to six per country, across 15 countries): 1270 (58%) known epilepsy, 299 (14%) previous blackouts but no epilepsy diagnosis, 634 (29%) with a first seizure. Wide variability was identified for most variables. Of those with known epilepsy, 41.2% (range 26.2%-59.6%) attended the ED in the previous 12 months, but only 64.7% (range 37.2%-79.8%) had seen an epilepsy specialist in the previous 12 months. 67.7% (range 34.0%-100%) were admitted, 53.1% to a neurology ward (range 0.0%-88.9%). Only 37.5% first seizure patients (range 0.0%-71.4%) were given advice about driving. CONCLUSIONS AND RECOMMENDATIONS: It is recommended that in Europe guidance is agreed on the management and onward referral of those presenting to the ED with a seizure; a referral process is created that can be easily implemented; it is ensured that the seizure services receive referrals and see the patients within a short time period; and a simple system is developed and implemented to allow continuous monitoring of key indices of epilepsy care.

Pre-prostatectomy membranous urethral length as a predictive factor of post prostatectomy incontinence requiring surgical intervention with an artificial urinary sphincter or a male sling.

AIMS: To ascertain whether the membranous urethral length (MUL) is predictive of postprostatectomy incontinence (PPI) that requires surgery such as artificial urinary sphincter (AUS) or male sling (MS). METHODS: Men who had undergone AUS or MS for PPI were identified from a prospectively maintained database and compared to a control group of men who were continent at 12 months after radical prostatectomy. MUL in sagittal and coronal planes, sphincter height and width were measured on prebiopsy T2-weighted MRI scans. Sphincter volume was estimated as an ellipsoid cylinder. RESULTS: A total of 95 patients (64 AUS and 31 MS) were compared to 60 continent controls. There was no statistical difference in presenting PSA, prostate volume, and T-stage. The mean MUL in sagittal and coronal planes was 11.31 mm (SD: 2.6, range: 6-17 mm) and 11.43 mm (SD: 2.94, range: 5-17 mm) in patients who had AUS and MS, respectively; 15.23 mm (SD: 4.2, range: 8.25-25 mm) and 15.75 mm (SD: 4.1, range: 8-24 mm) in controls (p < 0.01). No men in the PPI surgery group had an MUL >17 mm compared to 35% (20/57 sagittal, 20/58 coronal) of controls. The odds ratio for requiring surgery for PPI was 13.4 for sagittal MUL <9 mm and 3.2 if the MUL <12 mm. CONCLUSIONS: Patients who had surgery for PPI had a significantly shorter MUL and sphincter volume than continent controls. Men with an MUL >17 mm are unlikely to require surgery for PPI whereas an MUL <12 mm significantly increases the risk of requiring surgery for PPI. MUL should be considered when discussing treatment options for prostate cancer.

Quality of life profiles and their association with clinical and demographic characteristics and physical activity in people with a stoma: a latent profile analysis.

PURPOSE: Quality of life can be negatively impacted by the formation of a stoma and is influenced by a number of factors. Research to date treats people with a stoma as a homogenous group based on their quality of life. We attempted to identify subgroups based upon self-reported quality of life and explored variables associated with group membership. METHODS: The present study is a secondary analysis of a cross-sectional sample of 1419 people with a stoma. Participants completed validated questionnaires for quality of life, physical activity and clinical and demographic characteristics. Latent profile analysis was used to identify the optimal number of subgroups (profiles) and multinomial regression modelling was conducted to identify variables associated with profile membership. RESULTS: The analysis revealed 4 distinct profiles of people with a stoma: 'consistently good quality of life' [N = 891 (62.8%)], 'some quality of life concerns' [N = 184 (13.0%)], 'low quality of life' [N = 181 (12.8%)] and 'financial concerns' [N = 163 (11.5%)]. Modelling revealed that people with a recent stoma (formed < 2 years previously), who have a hernia and are less physically active were more likely to belong to the 'low quality of life' profile. Furthermore, those aged 16-55 were more likely to have financial concerns. CONCLUSION: This study was the first to identify latent profiles within this population and assess whether certain variables are associated with membership. Future research should build upon this to identify additional variables associated with these profiles, which can help to provide the basis for targeting and tailoring future interventions to specific subgroups of people with a stoma.

A systematic review and meta-analysis of the effectiveness of self-management interventions in people with a stoma.

AIMS: Explore the evidence from randomized controlled trials for the effect of self-management interventions on quality of life, self-management skills and self-efficacy, and to explore which intervention characteristics are associated with effectiveness. DESIGN: Systematic review. DATA SOURCES: A search of the literature was conducted in these databases: MEDLINE (OVID), EMBASE (OVID) and PsychINFO (OVID) from January 2000 to February 2020. REVIEW METHODS: Studies were included if participants had a bowel stoma, were over the age of 18 and the design was a randomized controlled trial of a self-management programme. The outcome measures for this review were quality of life, self-management skills and self-efficacy. The Behaviour Change Technique Taxonomy was used to code interventions for underlying components and alongside other intervention characteristics, associations with improvements in outcomes were explored. RESULTS: The search identified 3141 articles, 16 of which were eligible. A meta-analysis of self-efficacy scores from five studies (N = 536) found an improvement in those that received the self-management intervention at follow-up with a 12-point mean difference compared with the usual care group. Effects on quality of life and self-management skills were mixed, and meta-analyses of these data were not possible. Across 13 studies an average of 10 behaviour change techniques were used with, credible source (e.g. nurse, doctor, therapist) (n = 13), instruction on how to perform the behaviour (n = 13), demonstration of the behaviour (n = 12) used most often. The behaviour change technique of self-monitoring was associated with an improvement in quality of life. The involvement of a nurse was associated with higher self-efficacy and self-management skills. CONCLUSION: This review suggests that self-management interventions can increase peoples' self-efficacy for managing their stoma. IMPACT: A standardized approach to the reporting of interventions and the measures used is needed in future studies to better understand the effect on quality of life and self-management skills.

Age-related urologic problems in the complex urologic patient.

PURPOSE: Improved medical care throughout childhood and adolescence has enabled patients with complex urological abnormalities to live longer into adulthood. These patients are now at risk of developing common, age-related, urological conditions. This review aims to review existing data and make recommendations in areas where expert opinion is currently lacking METHODS: This review represents the joint SIU-ICUD (Société Internationale d'Urologie-International Consultation on Urological Disease) consultation on congenital lifelong urology. The results of this analysis were first presented at a joint consultation of the ICUD and SIU at the 2018 SIU annual conference in Seoul, South Korea. RESULTS: BPH may present differently in patients with neurogenic bladder. Thorough assessment of neurological status, bladder and sphincter function is required before offering any bladder outlet surgery. Prostate specific antigen screening should be offered to men aged 50-69 with neurogenic bladders if they have good life expectancy. Multi-parametric MRI and transperineal biopsy would be the investigations of choice if feasible. Surgery for localized disease should only be done by surgeons with the relevant expertise. Bladder cancer in this patient group is more likely to present at a later stage and have a worse prognosis. Parenthood is achievable for most, but often requires assistance with conception. Pregnant women who have had previous urogenital reconstructive surgery should be managed in appropriate obstetric units with the involvement of a reconstructive urologist. CONCLUSIONS: Most evidence regarding complex urogenital abnormalities comes from the pediatric population. Evidence regarding common, age-related urological issues is generally from the 'normal' adult population. As patients with complex congenital urological conditions live longer, more data will become available to assess the long-term benefits of intervention.

Is pre-operative urodynamic bladder function the true predictor of outcome of male sling for post prostatectomy incontinence?

PURPOSE: To investigate pre-operative urodynamic parameters in male sling patients to ascertain whether this might better predict surgical outcomes and facilitate patient selection. METHODS: We performed a retrospective, case notes and video-urodynamics, review of men who underwent AdVanceXP male sling in three London hospitals between 2012 and 2019. Urodynamics were performed in all centres, while retrograde leak point pressure (RLPP) was performed in one centre. RESULTS: Successful outcome was seen in 99/130 (76%) of men who required one pad or less per day. The dry rate was 51%. Pad usage was linked to worse surgical outcomes, mean 2.6 (range 1-6.5) for success vs 3.6 (range 1-10) although the ranges were wide (p = 0.002). 24 h pad weight also reached statistical significance (p = 0.05), with a mean of 181 g for success group versus 475 g for the non-successful group. The incidence of DO in the non-successful group was significantly higher than in successful group (55% versus 29%, p = 0.0009). Bladder capacity less than 250 ml was also associated with worse outcomes (p = 0.003). Reduced compliance was not correlated with outcomes (31% for success groups vs 45% for non-successful group, p = 0.15). Preoperative RLPP was performed in 60/130 patients but did not independently reach statistical significance (p = 0.25). CONCLUSION: Urodynamic parameters related to bladder function-detrusor overactivity and reduced maximum cystometric capacity predict male sling outcomes and may help in patient selection for male sling (or sphincter) surgery; whereas urodynamic parameters of sphincter incompetency (RLPP) were not predictive. Further larger scale studies are required to confirm these findings.

Prevalence of chronic pain following suburethral mesh sling implantation for post-prostatectomy incontinence.

PURPOSE: To evaluate postoperative pain and complications following AdVance™/AdVance™ XP male sling implantation. MATERIALS AND METHODS: A multi-center retrospective medical notes review of patients implanted for bothersome post-prostatectomy incontinence was conducted. All patients were telephoned to provide further information on pain or further complications related to their surgery. Statistical evaluation utilized logistical regression analysis. Additionally, a literature review was conducted reviewing pain outcomes following AdVance™/AdVance™ XP implantation. RESULTS: One-hundred and twenty-seven men were reviewed over an 8-year period. The mean age was 70 years, with mean follow up 52 months. Of those with mild stress urinary incontinence, 45 (79%) had a successful outcome compared to 42 (72%) in the moderate group. Twenty-nine (23%) men reported postoperative pain, with a mean maximal pain score of 6 (range: 0-10). The majority of pain resolved within 4 weeks (19/29 men). A further seven patients resolved by 3 months. Only three men (2.3%) had chronic pain greater than 3 months, which all resolved by 1 year. Men less than 65 years were more likely to suffer pain (p = 0.009). Acute urinary retention occurred in 23 (18%) men and correlated significantly with postoperative pain (p = 0.04). Overactive bladder symptoms, severity of incontinence or radiotherapy were not correlated with postoperative pain. In our cohort, there were no extrusions, divisions, or explantations. CONCLUSION: Approximately a quarter of men experience pain in the early postoperative period. However, the severity and rates of chronic pain (>3 months) are low (2.3%) but all settle within a year.

TAILoR (TelmisArtan and InsuLin Resistance in Human Immunodeficiency Virus [HIV]): An Adaptive-design, Dose-ranging Phase IIb Randomized Trial of Telmisartan for the Reduction of Insulin Resistance in HIV-positive Individuals on Combination Antiretroviral Therapy.

BACKGROUND: Combination antiretroviral therapy results in metabolic abnormalities which increase cardiovascular disease risk. We evaluated whether telmisartan reduces insulin resistance in human immunodeficiency virus (HIV)-positive individuals on antiretrovirals. METHODS: We conducted a multicenter, randomized, open-label, dose-ranging controlled trial of telmisartan. Participants with HIV infection receiving combination antiretroviral therapy were randomized equally to either no intervention (control) or 20, 40, or 80 mg telmisartan once daily. The adaptive design allowed testing of all dose(s) of telmisartan in stage I, with the promising dose(s) being taken into stage II. The primary outcome measure was reduction in homeostasis model assessment of insulin resistance (HOMA-IR) at 24 weeks. RESULTS: A total of 377 patients were recruited. In stage I, 48, 49, 47, and 45 patients were randomized to control and 20, 40, and 80 mg telmisartan, respectively (total n = 189). At the interim analysis, 80 mg telmisartan was taken forward into stage II. At the end of stage II (n = 105, control; 106, 80-mg arm), there were no differences in HOMA-IR (estimated effect, 0.007; SE, 0.106) at 24 weeks between the telmisartan (80 mg) and nonintervention arms. Longitudinal analysis over 48 weeks showed no change in HOMA-IR, lipid or adipokine levels. There were significant (P ≤ .05), but marginal, improvements in revised Quantitative Insulin Sensitivity Check Index (QUICKI) (0.004) and plasma hs-CRP (-0.222 mg/L) and reduction in liver fat content (1.714 mean reduction; P = .005). CONCLUSIONS: No significant effect of telmisartan was demonstrated on the primary outcome (HOMA-IR), but there were marginal improvements with some secondary outcome measures. Further studies in this population are warranted to identify novel strategies for preventing cardiovascular morbidity and mortality. CLINICAL TRIAL REGISTRATION: ISRCTN registry (51069819).

The MIC-KEY button vesicostomy: a superior alternative for suprapubic drainage?

OBJECTIVES: To evaluate the MIC-KEY button vesicostomy as an alternative to indwelling suprapubic catheters (SPCs) for bladder drainage in adults. PATIENTS AND METHODS: Phase II pilot study prospectively evaluating patients with indwelling SPCs that were converted to MIC-KEY buttons, or cystoscopic-guided de novo insertion, between November 2014 and February 2019. In all, 15 patients (14 female, one male) had indwelling SPCs that had conversion or attempted conversion to MIC-KEY button, and one (male) had a cystoscopic-guided de novo insertion with a history of previous suprapubic catheterisation. The mean (range) age was 44.2 (13-73) years. Catheter-related quality-of-life (C-IQoL) questionnaire data were collected at baseline and 3 months. RESULTS: Two patients had attempted conversion but were abandoned perioperatively due to sizing issues and insertion difficulties, respectively. Three patients were subsequently converted back to a SPC; due to button sizing (18 days), leaking (3 months), and recurrent infection (13 months). The remaining 11 patients have remained well with continued drainage via the MIC-KEY button; mean (range) duration since conversion was 34.2 (5-105) months. The C-IQoL score improved 3 months after insertion, from 50.0 to 75.4. Changes were performed dependent on patient's personalised management, typically every 3 months, under local or general anaesthetic. CONCLUSION: The MIC-KEY button is a safe alternative to SPC drainage in adults in the short- to medium-term, in a selected cohort.

Appendix or Ileum-Which is the Best Material for Mitrofanoff Channel Formation in Adults?

PURPOSE: We report long-term data on a large cohort of adults who underwent formation of a continent catheterizable channel for various indications. We examined outcomes according to the tissue used for channel formation. MATERIALS AND METHODS: We retrospectively reviewed the case notes of 176 consecutive adult patients in whom a continent catheterizable channel was created using the Mitrofanoff principle for a broad range of indications a median of 142 months (range 54 to 386) previously. We evaluated outcomes in terms of continued use and continence for each type of material used for channel formation. RESULTS: At the time of this review 165 of the 173 patients (95.4%) included in this study were alive. We included 114 women (65.9%) and 59 men (34.1%) who underwent surgery at a median age of 42 years (range 18 to 73) with a mean followup of 78.6 months (median 60, range 2 to 365). The rate of revision for all causes was higher in the ileal group than in the group with an appendiceal channel (channel stenosis rate 22.7% vs 17.2%, p = 0.39, and channel incontinence rate 36.0% vs 19.5%, p = 0.03). Although 38.7% of patients underwent major surgical revision of the channel at some point, 75.9% of channels continued to be used, of which 90.2% were continent. CONCLUSIONS: This study provides a pragmatic overview of the outcome of these challenging cases. Mitrofanoff channel formation represents a durable technique. Appendix and ileum are each a viable choice for tissue use. Tissue selection depends on availability and individual patient factors.

Smoking, alcohol consumption, diet and physical activity following stoma formation surgery, stoma-related concerns, and desire for lifestyle advice: a United Kingdom survey.

BACKGROUND: Adherence to smoking, alcohol consumption, diet and physical activity (PA) guidelines may improve outcomes for people with a stoma. A better understanding of these behaviours following stoma formation surgery and their experiences and attitudes towards receiving lifestyle advice, could help identify specific gaps and inform interventions going forward. The aim of this study was to describe changes in current lifestyle following stoma formation and to explore concerns, desire for lifestyle information, advice and support among people who have or have had a stoma. METHODS: A sample of adults who currently had or in the past had a stoma for treatment for any medical condition was recruited online through relevant charities and companies, and invited to complete a cross-sectional, online survey. Consenting participants (n = 425) provided demographic information and completed brief, validated questionnaires about their lifestyle, alongside questions around their concerns regarding permanent stoma and experiences of lifestyle information and advice. Responses were summarised using descriptive statistics, and associations between reported concerns about stoma and changes in health behaviours were explored. RESULTS: Most respondents (93%) still had a stoma at the time of completing the survey. The majority (80%) had not consumed at least 5 portions of fruit and vegetables on the previous day and 20% reported they had not participated in at least 30 min of physical activity on any day in the previous week. Most respondents were non-smokers (84%) and did not exceed recommendations for alcohol intake (60%). Most (56%) felt their PA had decreased following stoma formation. Frequencies of concerns about a permanent stoma were high, and appeared to be associated with reported decreases in PA. Of those reporting nausea, 40% felt their diet had worsened since having their stoma. A large proportion of respondents had not received PA (42%) or dietary (30%) advice, and of these > 90% would have liked guidance. CONCLUSIONS: Few respondents to this survey were eating the recommended amount of fruit and vegetables, and most reported a decrease in their PA following stoma surgery. Lifestyle advice would be welcomed by this population, which professionals should take into account when addressing stoma- related concerns.

Experiences of wearing support garments by people living with a urostomy.

BACKGROUND: support garments are commonly worn by people with a urostomy but there are no published data about their experiences of doing so. AIMS: to identify the views of people living with a urostomy on the role of support garments. METHODS: a cross-sectional survey of the stoma population's experiences of support garments was conducted in 2018. Recruitment was by social media. The free-text responses provided by a sub-sample of 58 people out of 103 respondents with a urostomy, were analysed. FINDINGS: thematic analysis revealed four themes: physical self-management; psychosocial self-management; lifestyle; and healthcare advice and support. There were mixed feelings about the value of support garments. Many cited a sense of reassurance and confidence and being able to be more sociable and active; others reported discomfort and uncertainty about their value. CONCLUSION: these findings add new understanding of experiences of support garments and provide novel theoretical insights about life with a urostomy.

Persistence with mirabegron therapy for overactive bladder: A real life experience.

AIMS: To evaluate persistence rates of patients receiving mirabegron therapy for overactive bladder (OAB) within our institution over a 6 month period, identify determinants of early discontinuation of therapy, and assess overall patient satisfaction with treatment. METHODS: Hospital prescription data were analyzed in order to identify all patients who had been prescribed mirabegron in our institution. Case notes were retrospectively reviewed to obtain demographic data, previous treatments for OAB, reasons for discontinuation of previous treatments, and duration of treatment with mirabegron. Overall satisfaction with treatment was assessed using the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q). RESULTS: One hundred and ninety-seven patients were prescribed mirabegron. Of these, 81% previously discontinued anticholinergic therapy, 14% had previously received intravesical botulinum toxin A therapy, and 19% were prescribed mirabegron first-line. At 3 months 69% persisted with treatment which fell to 48% by 6 months. The commonest reason for discontinuation was lack of efficacy, followed by adverse effects. Overall 32% of patients preferred mirabegron over previous treatments and only 39% were satisfied with mirabegron therapy. CONCLUSION: Persistence rates with mirabegron in this group of patients for OAB are satisfactory. The commonest reasons for discontinuation are unmet treatment expectations and adverse effects. We had very few treatment-naïve patients and so further studies are required to assess mirabegron persistence rates with longer-term follow up, as first-line treatment and in different groups of OAB severity. Neurourol. Neurourol. Urodynam. 36:404-408, 2017. © 2015 Wiley Periodicals, Inc.