Adjustable continence therapy (proACT) for the treatment of male stress urinary incontinence post-prostatectomy: a systematic review and meta-analysis (2023 update).

PURPOSE: Stress urinary incontinence (SUI) is a key factor for post-prostatectomy (RP) quality of life. Current international guidelines struggle to find the adequate place for each kind of surgeries. The aim of this systematic review and meta-analysis considering updated evidence is to assess the efficacy and safety of proACT in treating male patients with post-RP SUI. METHODS: A review of the literature was performed by searching the PubMed database. We narrowed included studies with adult male patients with SUI; outcomes included pads or pad weight per day and quality of life (QOL) questionnaires, as well as safety outcomes. RESULTS: 18 studies involving 1570 patients mean age of 68.8 (EC 2.1) were included. The mean follow-up reported was 34.7 months (EC 17.7; median 38.5; range 1-128 months). An average of 60.7% (EC 27) and 40.4% of patients suffered from mild-to-moderate and severe incontinence, respectively. The overall dryness rate was 55.1% (EC 19.3) while respecting the definition of 0-1 pads per day, and the mean dryness rate was 53% (EC 0.2). The mean overall complication rate was 31.2% (EC 18.3%), including an explantation rate of 26.5% (EC 15.3) and a reoperation rate of 22.7% (EC 8.7). The methodological quality of the 18 studies was very heterogeneous. CONCLUSION: Implantation of proACT adjustable balloons is a minimally invasive technique that provides medium outcomes (53%) with a strict definition of dryness (0-1 PPD) and important complication rate (31.2%). Past of irradiation is a negative predictive factor for incontinence.

Melatonin may slow disease progression in amyotrophic lateral sclerosis: Findings from the Pooled Resource Open-Access ALS Clinic Trials database.

INTRODUCTION: We utilized the Pooled Resource Open-Access Clinical Trials (PRO-ACT) database to investigate whether melatonin use among patients with amyotrophic lateral sclerosis (ALS) was associated with slower disease progression and prolonged survival. METHODS: This retrospective analysis of the PRO-ACT database addresses the impact of melatonin on progression and overall survival of ALS. A Cox proportional hazards ratio model was performed to investigate the effect that melatonin had on time to death. For secondary outcome measures, linear mixed effects regression models were used to ascertain the effect of melatonin on change in standardized ALS Functional Rating Scale (sALSFRS) and percentage predicted forced vital capacity (FVC) scores. RESULTS: Melatonin users had a significantly decreased annualized hazard death rate compared with the non-melatonin users (hazard ratio, 0.241; 95% confidence interval, 0.088-0.659; P = .0056). The melatonin users also had a slower rate of decline in sALSFRS score (t = 2.71; P = .0069) and change in percent predicted FVC score (t = 2.94; P = .0035) compared with the non-melatonin users. DISCUSSION: Our findings suggest that melatonin may be beneficial for patients with ALS. Due to the nature of this database, our results are solely intended to be hypothesis-generating and no strong associations can be made. Given the low cost and favorable safety profile of melatonin, the hypotheses generated warrant further investigation.

Relative effects of forced vital capacity and ALSFRS-R on survival in ALS.

INTRODUCTION/AIM: Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular disease with marked clinical heterogeneity. This heterogeneity can be partly captured by clinical measures, such as the forced vital capacity (FVC) and ALS Functional Rating Scale-Revised (ALSFRS-R). We aimed to further characterize the performance of these clinical measures, including their independence and additivity, in predicting mortality. METHODS: We leveraged the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT ALS) database, which includes data from 23 clinical trials (n = 2050). The primary exposures were baseline FVC and ALSFRS-R. The primary outcome was 1-y mortality. We performed correlation analyses, survival analyses and assessed classification performance using receiver operator characteristic (ROC) curves. RESULTS: FVC and ALSFRS-R were weakly correlated (r = 0.31, p < .001). A 1-SD increase in FVC (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.59-0.74) and ALSFRS-R (HR: 0.75; 95% CI: 0.68-0.82) were associated with reduced risk of 1-y mortality. ROC analyses showed optimal predictive cutoffs at 80% for FVC (area under the curve [AUC]: 0.69) and 38 for ALSFRS-R (AUC: 0.67). After stratifying patients based on these cutoffs, we found a marked reduction (HR: 0.25; 95% CI: 0.19-0.33) in incident mortality for patients in the high FVC and high ALSFRS-R group relative to the low FVC and low ALSFRS-R group. DISCUSSION: ALSFRS-R and FVC are comparable predictors of survival that are only weakly correlated. When considered together, they synergistically predict survival. As such, consideration of both measures should be a routine part of prognostication in care of patients with ALS.

What if artificial urinary sphincter is not possible? Feasibility and effectiveness of ProACT for patients with persistent stress urinary incontinence after radical prostatectomy treated by sling.

BACKGROUND: Stress urinary incontinence (SUI) is a major component of the post radical prostatectomy (RP) trifecta. Surgical treatments are sub-urethral slings, artificial urinary sphincter (AUS) and adjustable peri-urethral balloons (PUB) ProACT. All options are imperfect at best and persistent SUI is challenging when AUS is not manageable. AIMS: This study analyzed the cumulate experience of our 2 centers with offering PUB implantation for SUI post RP in patients with insufficient improvement from slings. MATERIALS & METHODS: This retrospective study reviewed all patients implanted with second line ProACT. The primary endpoint was continence, defined as 0 pads per day (PPD). The secondary endpoints were 50% decrease in PPD and increases in the Incontinence Quality of Life score (IQOL). Refilling and complications were reported. RESULTS: Between 2007 and 2016, 26 patients were implanted. Five patients have had adjuvant radiotherapy (18%). The mean follow-up was 36 months (±20; min 14-max 128). All patient presented with persistent SUI, using 2.3 PPD (±1; min 1-max 6), and only one sling was removed due to infection. After ProACT with an average 3 mL refilling (±1.2 min 2-max 6), 18 patients (66.7%) were continent. Eight of the remaining patients (29.6%) were improved; their number of PPD decreased from 2.6 to 1. The average IQOL score of those 8 patients increased by 20 points, from 53.4 up to 74.2 (P = .005). Overall 26 patients (96.3%) were improved. The remaining patient was not implanted because of an intraoperative urethral injury and is considered a failed case (3.7%). He had instead an AUS implantation. Three patients (14.8%) needed PUB replacement. CONCLUSION: The limited population of patients from both our centers who presented with persistent SUI after RP, despite sling placement, improved with PUB ProACT implantations without significant complications.

Long-term results of ProACT primary and repeat implantation for treatment of stress urinary incontinence in men.

INTRODUCTION: Urinary incontinence in men after radical prostatectomy affects strongly quality of life. If conservative treatment fails, surgical treatment consists of implantable devices. If the requirement of manual dexterity in the artificial sphincter is to be avoided, the ProACT system offers a readjustable system, which shows good continence, but also high revision rates. Aim of our single-centre, single-surgeon study was to evaluate the success and revision rates of ProACT over long-term follow-up and if repeat ProACT implantation after failure would be a reasonable strategy. MATERIALS AND METHODS: In May 2017, follow-up of all patients who underwent ProACT implantation between 2003 and 2013 was obtained. Parameters were numbers of pads used, filling volume of balloons, and patient-reported satisfaction. Furthermore, revisions were noted. RESULTS: Between 2003 and 2013, 134 patients were implanted a ProACT system. Median age was 71 years; median follow-up was 118 months. 112 implantations were successful (82.6%) and the number of pads used decreased significantly (p < 0.005). 63 patients were revised and 49 were successful (77.8%). No differences in success rate, pads used, or filling volume were seen (all p > 0.8). In a second revision, again, no differences in success rate or pads used were noted (all p > 0.7). Patients' personal satisfaction was high despite the high revision rate. CONCLUSION: In the hands of an experienced surgeon, ProACT is a safe and effective therapy for post-prostatectomy incontinence especially if mayor surgery is to be avoided. Revision rates are high, but the results of ProACT reimplantation are comparable to the results after the first implantation.

[Pro-ACT™ device implantation efficiency in second line treatment of post-radical prostatectomy urinary incontinence after sub-urethral male sling failure]. / Efficacité des ballons Pro-ACT™ dans le traitement de seconde ligne de l'incontinence urinaire d'effort post-prostatectomie après échec des bandelettes sous-urétrales.

INTRODUCTION AND OBJECTIVES: The periurethral adjustable balloons (PUAB) Pro-ACT™ are less invasive technique to treat non-severe forms of post-radical prostatectomy urinary incontinence (pRP-UI), like sub-urethral trans-obturator male sling. Few data of efficiency are available for their use in second line treatment after male sling failure. OBJECTIVE: To evaluate the efficiency of PUAB Pro-ACT™ (Uromedica, Inc., MN, USA) in the second line treatment for non-severe pRP-UI after male sling failure. MATERIALS AND METHODS: Single center retrospective study of patients treated with male sling (17 Advance™, 1 TOMS™) between 2009 and 2015. The continence results were evaluated by the number of pad per day and the quality of life assessment by the I-QOL questionnaire. The "cure" was defined as no pad and "improved" as decreased more than 50 % of pads use. RESULTS: Eighteen patients were included with median follow-up of 21.5 [14-44] months. Two patients (11.1 %) had a past history of pelvic radiotherapy. The median pads per day used was 2 [1-3] after male sling insertion and before Pro-ACT™ device insertion. After Pro-ACT™ device insertion, the median pads per day used was 0 [0-1], with 77.7 % of patients cured and 22.2 % improved. The median quality of life score I-QOL, was 52.2 [23.3-62.6] and 83 [31.8-97.7], respectively before and after Pro-ACT™ device insertion (P<0.001). Nine (60 %) patients rated their incontinence severity as mild, four (26.6 %) as middle and two (13.3 %) as severe, after balloon insertion. The median volume of adjustment was 3 [2-6] mL. CONCLUSIONS: The PUAB Pro-ACT™ have a significant efficiency for use after male sling failure and can be used in second line therapy. LEVEL OF EVIDENCE: 3.

Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open-Access ALS clinical trials database.

INTRODUCTION: Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. METHODS: Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. RESULTS: After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P < 0.01). DISCUSSION: Our pooled analysis provides further support for urate as a prognostic factor for survival in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 57: 430-434, 2018.

Using an onset-anchored Bayesian hierarchical model to improve predictions for amyotrophic lateral sclerosis disease progression.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a rare disease with extreme between-subject variability, especially with respect to rate of disease progression. This makes modelling a subject's disease progression, which is measured by the ALS Functional Rating Scale (ALSFRS), very difficult. Consider the problem of predicting a subject's ALSFRS score at 9 or 12 months after a given time-point. METHODS: We obtained ALS subject data from the Pooled Resource Open-Access ALS Clinical Trials Database, a collection of data from various ALS clinical trials. Due to the typical linearity of the ALSFRS, we consider several Bayesian hierarchical linear models. These include a mixture model (to account for the two potential classes of "fast" and "slow" ALS progressors) as well as an onset-anchored model, in which an additional artificial data-point, using time of disease onset, is utilized to improve predictive performance. RESULTS: The onset-anchored model had a drastically reduced posterior predictive mean-square-error distributions, when compared to the Bayesian hierarchical linear model or the mixture model under a cross-validation approach. No covariates, other than time of disease onset, consistently improved predictive performance in either the Bayesian hierarchical linear model or the onset-anchored model. CONCLUSIONS: Augmenting patient data with an additional artificial data-point, or onset anchor, can drastically improve predictive modelling in ALS by reducing the variability of estimated parameters at the cost of a slight increase in bias. This onset-anchored model is extremely useful if predictions are desired directly after a single baseline measure (such as at the first day of a clinical trial), a feat that would be very difficult without the onset-anchor. This approach could be useful in modelling other diseases that have bounded progression scales (e.g. Parkinson's disease, Huntington's disease, or inclusion-body myositis). It is our hope that this model can be used by clinicians and statisticians to improve the efficacy of clinical trials and aid in finding treatments for ALS.

Sequential treatment with ProACT™ device implantation after male sling failure for male urinary incontinence.

OBJECTIVES: There is no strong evidence for second line therapy after male sling failure for post-prostatectomy urinary incontinence (PPUI). We report the outcomes after periurethral balloons implantation for persistence or recurrence of mild PPI symptoms after male sling implantation. METHODS: All patients implanted of a ProACT™ device (Uromedica, Inc., MN, USA) following I-STOP transobturator male sling (TOMS) failure, in a tertiary reference center between 2009 and 2016, were included. Patients were evaluated by 24-hour pad-test before and after implantation, and after each balloon repressurizing procedure. PGI-I and Likert scale patient satisfaction were estimated during a telephone interview conducted in 2016. Objective and subjective cure of urinary incontinence were defined by a 24-hour pad-test<8g and the use of zero or one pad per day, respectively. RESULTS: Fourteen patients were included. Median follow-up was 34months [4-89]. Objective and subjective cure were 29% (n=4) and 57% (n=8), respectively. Median pad-test decreased from 95g [IQR: 130] to 34g [IQR: 83] (P=0.022). ProACT™ significantly decreased median pad-test by a factor 2.73 [1.19-6.29]. Eighty-eight percent patients were feeling a little better, much better or very much better and 77% were satisfied or very satisfied at the end of follow-up. Reoperation rate was 28% (n=4): 3 balloons were changed for caudally migration (n=2) or deflation (n=1) and 1 had a urinary sphincter implanted for severe UI. CONCLUSIONS: ProACT™ is a safe and efficient treatment that can be used in second line therapy after TOMS failure for PPUI. LEVEL OF EVIDENCE: 4.

Alignment of site versus adjudication committee-based diagnosis with patient outcomes: Insights from the Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3 trial.

BACKGROUND: Adjudication by an adjudication committee in clinical trials plays an important role in the assessment of outcomes. Controversy exists regarding the utility of adjudication committee versus site-based assessments and their relationship to subsequent clinical events. METHODS: This study is a secondary analysis of the Providing Rapid Out of Hospital Acute Cardiovascular Treatment-3 trial, which randomized patients with chest pain or shortness of breath for biomarker testing in the ambulance. The emergency department physician diagnosis at the time of emergency department disposition was compared with an adjudicated diagnosis assigned by an adjudication committee. The level of agreement between emergency department and adjudication committee diagnosis was evaluated using kappa coefficient and compared to clinical outcomes (30-day re-hospitalization, 30-day and 1-year mortality). RESULTS: Of the 477 patients, 49.3% were male with a median age of 70 years; hospital admission rate was 31.2%. The emergency department physicians and the adjudication committee disagreed in 55 cases (11.5%) with a kappa of 0.71 (95% confidence interval: 0.64, 0.78). The 30-day re-hospitalization, 30-day mortality, and 1-year mortality were 22%, 1.9%, and 9.4%, respectively. Although there were similar rates of re-hospitalization irrespective of adjudication, in cases of disagreement compared to agreement between adjudication committee and emergency department diagnosis, there was a higher 30-day (7.3% vs 1.2%, p = 0.002) and 1-year mortality (27.3% vs 7.1%, p < 0.001). CONCLUSION: Despite substantial agreement between the diagnosis of emergency department physicians and adjudication committee, in the subgroup of patients where there was disagreement, there was significantly worse short-term and long-term mortality.

A case study using the PrOACT-URL and BRAT frameworks for structured benefit risk assessment.

While benefit-risk assessment is a key component of the drug development and maintenance process, it is often described in a narrative. In contrast, structured benefit-risk assessment builds on established ideas from decision analysis and comprises a qualitative framework and quantitative methodology. We compare two such frameworks, applying multi-criteria decision-analysis (MCDA) within the PrOACT-URL framework and weighted net clinical benefit (wNCB), within the BRAT framework. These are applied to a case study of natalizumab for the treatment of relapsing remitting multiple sclerosis. We focus on the practical considerations of applying these methods and give recommendations for visual presentation of results. In the case study, we found structured benefit-risk analysis to be a useful tool for structuring, quantifying, and communicating the relative benefit and safety profiles of drugs in a transparent, rational and consistent way. The two frameworks were similar. MCDA is a generic and flexible methodology that can be used to perform a structured benefit-risk in any common context. wNCB is a special case of MCDA and is shown to be equivalent to an extension of the number needed to treat (NNT) principle. It is simpler to apply and understand than MCDA and can be applied when all outcomes are measured on a binary scale.

[Functional results and treatment of functional dysfunctions after radical prostatectomy]. / Résultats fonctionnels et prise en charge des troubles fonctionnels après prostatectomie totale.

OBJECTIVE: To describe the functional results and treatment of functional dysfunctions after radical prostatectomy for localized prostate cancer. MATERIAL AND METHOD: Bibliography search was performed from the database Medline (National Library of Medicine, Pubmed) selected according to the scientific relevance. The research was focused on continence, potency, les dyserections, couple sexuality, incontinence, treatments of postoperative incontinence, dysrection and trifecta. RESULTS: Radical prostatectomy is an elaborate and challenging procedure when carcinological risk balances with functional results. Despite recent developments in surgical techniques, post-radical prostatectomy urinary incontinence (pRP-UI) continues to be one of the most devastating complications, which affects 9-16% of patients. Sphincter injury and bladder dysfunction are the most common causes or pRP-UI. The assessment of severity of pRP-UI that affects the choice of treatment is still not well standardized but should include at least a pad test and self-administered questionnaires. The implantation of an artificial urinary sphincter AMS800 remains the gold standard treatment for patients with moderate to severe pRP-UI. The development of less invasive techniques such as the male sling of Pro-ACT balloons has provided alternative therapeutic options for moderate and slight forms of pRP-UI. Most groups now consider the bulbo-urethral compressive sling as the treatment of choice for patients with non-severe pRP-UI. The most appropriate second-line therapeutic strategy is not clearly determined. Recent therapies such as adjustable artificial urinary sphincters and sling and stem cells injections have been investigated. Maintenance of a satisfying sex life is a major concern of a majority of men facing prostate cancer and its treatments. It is essential to assess the couple's sexuality before treating prostate cancer in order to deliver comprehensive information and consider early therapeutic solutions adapted to the couple's expectations. Active pharmacological erectile rehabilitation (intracavernous injections or phosphodiesterase type 5 inhibitors [PDE5i] on demand, during in the month following surgery) or passive (daily PDE5i after surgery) might improve the quality of erections especially in response to PDE5i. Unimpaired aspects of sexual response (orgasm) may, when the erection is not yet recovered, represent an alternative allowing the couple to preserve intimacy and complicity. Androgen blockade is a major barrier to maintain or return to a satisfying sex. Trifecta is a simple tool to present in one way the results of radical prostatectomy: in case of bilateral neurovascular preservation, Trifecta is 60% whatever the surgical approach. CONCLUSION: Radical prostatectomy is an elaborate and challenging procedure when carcinological risk balances with functional results. Various treatments of postoperative incontinence and dysrections exist. Functional disorders after surgery have to be treated to ameliorate quality of life of patients.

ALSFRS-R decline rate prior to baseline is not useful for stratifying subsequent progression of functional decline.

OBJECTIVE: One of the difficulties in developing a novel drug for patients with amyotrophic lateral sclerosis (ALS) is the significant variation in the clinical course. To control this variation, a 12-week run-in period is used in some clinical trials. Based on the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) change during the run-in period, only moderate progressors are selected in some clinical trials. Some reports showed that the ALSFRS-R progression rate was associated with survival. However, it is unclear whether the ALSFRS-R change in the run-in period is a useful prognostic factor of the ALSFRS-R change from baseline. In addition, we explore the inclusion criteria that could control the variability in ALS-function progression without setting a run-in period. METHODS: We utilized the Japanese and US ALS registry databases (JaCALS and PRO-ACT). Patients were classified into three populations (rapid, moderate, and slow progressors) based on the ALSFRS-R change prior to baseline. We also classified patients into three prognostic populations based on the ALSFRS-R change from baseline. We confirmed whether each of the three populations were matched with their respective three prognostic populations. RESULTS: Our data showed that the three groups classified by the ALSFRS-R change during the 12 weeks prior to baseline or by the rate of progression from onset to baseline did not accord with the three prognostic groups. CONCLUSIONS: Our results showed that the ALSFRS-R change in the run-in period or from onset to baseline is not useful for stratifying subsequent progression of functional decline in clinical trials.

Comparison of Demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data.

OBJECTIVE: To characterize the participant demographics in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database compared with the web-portal National Amyotrophic Lateral Sclerosis (ALS) Registry (the Registry). METHODS: Demographics and ALS symptom information were compared between the self-reported registrant data in the Registry web portal (2010-2021) and the latest available PRO-ACT data (updated August 2022), which is a collection of clinical trials data. RESULTS: Greater percentages of younger (≤ 59 years old) but smaller percentages of older (60 + years old) participants were represented in PRO-ACT compared to Registry. Enrollment for minority race groups was greater in the Registry portal data, but race information was largely missing/unknown in PRO-ACT database. Median age at the time of diagnosis and age at the time of symptom onset were significantly higher for Registry enrollees compared to the participants of PRO-ACT. Symptom onset sites were similarly reported, but duration between self-noted symptom onset and diagnosis was slight, but significantly longer for the Registry enrollees (11 vs. 9 months). Hispanic were as likely as non-Hispanic to participate in research studies, based on the Registry data. CONCLUSION: There was a notable difference in the age distribution and minority representation of enrollees between the PRO-ACT and Registry study populations. Age distribution in the PRO-ACT database skewed to a younger and less diverse cohort. Despite the clinical heterogeneity and complex disease mechanism of ALS, identifying the underrepresented demographic niche in the PRO-ACT and Registry study populations can help improve patient participation and criteria for patient selection to enhance generalizability.

Secondary placement of adjustable continence therapy (ProACT™) using open perineal technique: Case report of ProACT placement in a man with a devastated urethra following pelvic trauma and multiple AUS erosions.

Adjustable continence therapy (ProACT) is an underutilized treatment option in men with stress urinary incontinence. The device is placed using a perineal percutaneous tunneled approach. We demonstrate a salvage technique for ProACT placement in a man with a devastated urethra following pelvic trauma and multiple artificial urinary sphincter (AUS) erosions who failed a tunneled approach. Our novel technique has utility in those at high risk for intra-operative trocar injury to the urinary tract with a tunneled approach. An open approach may also be a viable option in high-risk patients who have failed a conventional ProACT approach, male sling, or AUS.

Warfarin faring better: vitamin K antagonists beat rivaroxaban and apixaban in the INVICTUS and PROACT Xa trials.

Although guidelines give preference to direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF), DOACs are not recommended in those with rheumatic heart disease or mechanical heart valves. The results of the INVICTUS trial (Investigation of Rheumatic AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies), which compared rivaroxaban with a VKA in patients with rheumatic heart disease-associated AF, and the PROACT Xa trial (A Trial to Determine if Participants with an On-X Aortic Valve Can be Maintained Safely on Apixaban), which compared apixaban with warfarin in patients with an On-X valve in the aortic position, support the use of VKAs for these indications. In this paper, we review the results of these trials, provide perspective on why VKAs were superior to DOACs, and discuss future directions for anticoagulation in these disorders.

ProACT in the management of stress urinary incontinence after radical prostatectomy. What happens after 8 years of follow up? monocentric analysis in 42 patients.

OBJECTIVES: Stress urinary incontinence is defined by a complaint of any involuntary loss of urine on effort or physical exertion or on sneezing or coughing and represents a major complication after radical prostatectomy. According to surgical technique, incidence of post-prostatectomy incontinence varies from open (7-39.5%), laparoscopic (5-33.3%) or robotic-assisted (4-31%) approaches. The ProACT® device (Uromedica, Inc., MN) is a possible surgical option for the treatment of this condition. METHODS: We retrospectively analyzed surgical records of consecutive patients underwent ProACT® implantation in our department between January 2006 to November 2010. We collected data at 6 and 12 months after surgical approach about the daily pad use, International Prostatic Symptoms Score and its quality of life domain. RESULTS: 42 patients were included in the final analysis. Most patients (92.9%) received minimally invasive surgery for treating prostate cancer. During the follow up after 6 and 12 months, the daily pad, International Prostatic Symptom Score and its quality of life domain significantly improved compared to preoperative outcomes. The logistic regression analysis found that presence of comorbidities was the only predictive factor of low satisfaction rate (PGE-I > 2) in patients who underwent ProACT® implant. CONCLUSIONS: ProACT® implant represents an effective and safe treatment for post-prostatectomy stress urinary incontinence with a high satisfaction degree and a low rate of complications.

Surgical Management of Male Stress Incontinence: Techniques, Indications, and Pearls for Success.

Purpose: Male stress urinary incontinence (SUI) has detrimental and long-lasting effects on patients. Management of this condition is an evolving field with multiple options for surgical treatment. We sought to review the pre-operative evaluation, intra-operative considerations, post-operative care, and future directions for treatment of male SUI. Methods: A literature review was performed using the PubMed platform to identify peer-reviewed, English-language articles published within the last 5 years pertaining to management of male stress urinary incontinence with an emphasis on devices currently on the market in the United States including the artificial urinary sphincter (AUS), male urethral slings, and the ProACTTM system. Patient selection criteria, success rates, and complications were compared between the studies. Results: Twenty articles were included in the final contemporary review. Pre-operative workup most commonly included demonstration of incontinence, PPD, and cystoscopy. Definition of success varied by study; the most common definition used was social continence (0-1 pads per day). Reported rates of success were higher for the AUS than for male urethral slings (73-93% vs 70-90%, respectively). Complications for these procedures include urinary retention, erosions, infections, and device malfunction. Newer treatment options including adjustable balloon systems and adjustable slings show promise but lack long-term follow-up. Conclusion: Patient selection remains the primary consideration for surgical decision-making for management of male SUI. The AUS continues to be the gold standard for moderate-to-severe male SUI but comes with inherent risk of need for revision. Male slings may be a superior option for appropriately selected men with mild incontinence but are inferior to the AUS for moderate and severe incontinence. Ongoing research will shed light on long-term results for newer options such as the ProACT and REMEEX systems.

Safety and efficacy of the feed additive consisting of protease produced by Bacillus licheniformis DSM 33099 (ProAct 360) for use in poultry species for fattening or reared for laying/breeding (DSM Nutritional Products Ltd).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a protease (ProAct 360) produced by a genetically modified strain of Bacillus licheniformis (DSM 33099) as a zootechnical feed additive for poultry species for fattening or reared for laying/breeding. The production strain and its recombinant DNA were not detected in an intermediate concentrated product representative of the final formulation. The final product did not trigger a safety concern with regard to the genetic modification. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that ProAct 360 is considered safe for all growing poultry species at the recommended inclusion level of 30,000 NFP/kg complete feed. The use ProAct 360 as a feed additive did not give rise to concerns for the consumers or the environment. The additive is not an eye or a dermal irritant but should be considered a respiratory sensitiser. In the absence of data, no conclusions could be reached on the skin sensitisation potential of the additive. The FEEDAP Panel concluded that the additive has the potential to be efficacious at 30,000 NFP/kg complete feed for all poultry species for fattening or reared for laying/breeding.

Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery.

iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24 weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.