Latest insights into the pathophysiology of bladder pain syndrome/interstitial cystitis.

PURPOSE OF REVIEW: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a common medical problem in both sexes affecting people of all ages. Patients might report overactive bladder symptoms with additional bladder pain at maximum bladder filling, during and after micturition. This review aims to highlight pathophysiological mechanisms associated with this disease. RECENT FINDINGS: Latest literature exposes different pathophysiological mechanisms such as impaired urothelial barrier function, alteration of urothelial factors and cytokines, chronic inflammation, vascular lesions, neurogenic inflammation and processes in the central nervous system leading to central sensitization. According to the involved mechanisms, BPS/IC may be arranged in clusters according to the clinical phenotype thus helping in clinical decision-making and treatment. Moreover, patients with BPS/IC suffer from other comorbidities such as fibromyalgia, irritable bowel syndrome, chronic pain and functional syndromes and psychosomatic diseases making the management challenging for medical professionals. SUMMARY: Bladder pain syndrome/interstitial cystitis is a complex heterogeneous medical condition involving different pathomechanisms leading to bladder pain and dysfunction, consequently, impairing quality-of-life in affected individuals. However, these mechanisms are still not fully understood, so that patient treatments often remain unsatisfactory. For this reason, continuing research is important to understand the underlying pathomechanisms to discover biomarkers and treatment targets eventually improving diagnostic and therapeutic measures of BPS/IC.

Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials.

Transcutaneous tibial nerve stimulation (TTNS) is a promising treatment for neurogenic lower urinary tract symptoms. However, the evidence is limited due to a general lack of randomised controlled trials (RCTs) and, also, inconsistency in the sham and blinding conditions. In the context of much-needed RCTs, we aimed to develop a suitable sham-control protocol for a clinical setting to maintain blinding but avoid meaningful stimulation of the tibial nerve. Three potential electrode positions (lateral malleolus/5th metatarsal/plantar calcaneus) and two electrode sizes (diameter: 2.5 cm/3.2 cm) were tested to determine which combination provided the optimal sham configuration for a TTNS approach, based on a visible motor response. Sixteen healthy volunteers underwent sensory and motor assessments for each sham configuration. Eight out of them came back for an extra TTNS visit. Sensory thresholds were present for all sham configurations, with linear regression models revealing a significant effect regarding electrode position (highest at plantar calcaneus) but not size. In addition, motor thresholds varied with the position-lowest for the 5th metatarsal. Only using this position and 3.2 cm electrodes attained a 100% response rate. Compared to TTNS, sensory and motor thresholds were generally higher for the sham configurations; meanwhile, perceived pain was only higher at the lateral malleolus. In conclusion, using the 5th metatarsal position and 3.2 cm electrodes proved to be the most suitable sham configuration. Implemented as a four-electrode setup with standardized procedures, this appears to be a suitable RCT protocol for maintaining blinding and controlling for nonspecific TTNS effects in a clinical setting.

Urodynamics Are Essential to Predict the Risk for Upper Urinary Tract Damage after Acute Spinal Cord Injury.

We used clinical parameters to develop a prediction model for the occurrence of urodynamic risk factors for upper urinary tract (UUT) damage during the first year after acute spinal cord injury (SCI). A total of 97 patients underwent urodynamic investigation at 1, 3, 6, and 12 months after acute SCI, within the framework of a population-based longitudinal study at a single university SCI center. Candidate predictors included demographic characteristics and neurological and functional statuses 1 month after SCI. Outcomes included urodynamic risk factors for UUT damage: detrusor overactivity combined with detrusor sphincter dyssynergia, maximum storage detrusor pressure (pDetmax) ≥ 40 cmH2O, bladder compliance < 20 mL/cmH2O, and vesicoureteral reflux. Multivariable logistic regression was used for the prediction model development and internal validation, using the area under the receiver operating curve (aROC) to assess model discrimination. Two models showed fair discrimination for pDetmax ≥ 40 cmH2O: (i) upper extremity motor score and sex, aROC 0.79 (95% CI: 0.69-0.89), C-statistic 0.78 (95% CI: 0.69-0.87), and (ii) neurological level, American Spinal Injury Association Impairment Scale grade, and sex, aROC 0.78 (95% CI: 0.68-0.89), C-statistic 0.76 (95% CI: 0.68-0.85). We identified two models that provided fair predictive values for urodynamic risk factors of UUT damage during the first year after SCI. Pending external validation, these models may be useful for clinical trial planning, although less so for individual-level patient management. Therefore, urodynamics remains essential for reliably identifying patients at risk of UUT damage.

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction.

OBJECTIVE: To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS: bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS: A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.

Temporal development of unfavourable urodynamic parameters during the first year after spinal cord injury.

OBJECTIVES: To describe the temporal development of and risk factors for the occurrence of unfavourable urodynamic parameters during the first year after spinal cord injury (SCI). PATIENTS AND METHODS: This population-based longitudinal study used data from 97 adult patients with a single-event traumatic or ischaemic SCI who underwent video-urodynamic investigation (UDI) at a university SCI centre. The first occurrences of unfavourable urodynamic parameters (detrusor overactivity combined with detrusor sphincter dyssynergia [DO-DSD], maximum storage detrusor pressure ≥40 cmH2 O, bladder compliance <20 mL/cmH2 O, vesico-ureteric reflux [VUR] and any unfavourable parameter [composite outcome]) were evaluated using time-to-event analysis. RESULTS: The majority of the population (87/97 [90%]) had at least one unfavourable urodynamic parameter. Most unfavourable urodynamic parameters were initially identified during the 1- or 3-month UDI, including 92% of the DO-DSD (78/85), 82% of the maximum storage pressure ≥40 cmH2 O (31/38), and 100% of the VUR (seven of seven) observations. No low bladder compliance was observed. The risk of DO-DSD was elevated in patients with thoracic SCI compared to those with lumbar SCI (adjusted hazard ratio [aHR] 2.38, 95% confidence interval [CI] 1.16-4.89). Risk of maximum storage detrusor pressure ≥40 cmH2 O was higher in males than females (aHR 8.33, 95% CI 2.51-27.66), in patients with a cervical SCI compared to those with lumbar SCI (aHR 14.89, 95% CI 3.28-67.55), and in patients with AIS Grade B or C compared to AIS Grade D SCI (aHR 6.17, 95% CI 1.78-21.39). No risk factors were identified for the composite outcome of any unfavourable urodynamic parameter. CONCLUSIONS: The first UDI should take place within 3 months after SCI as to facilitate early diagnosis of unfavourable urodynamic parameters and timely treatment. Neuro-urological guidelines and individualised management strategies for patients with SCI may be strengthened by considering sex and SCI characteristics in the scheduling of UDIs.

Neurogenic Lower Urinary Tract Dysfunction in the First Year After Spinal Cord Injury: A Descriptive Study of Urodynamic Findings.

PURPOSE: We aimed to provide a real-world description of neurogenic lower urinary tract dysfunction within the first year after spinal cord injury with a focus on unfavorable urodynamic parameters that are associated with urological morbidity. MATERIALS AND METHODS: Urodynamic investigations from 97 patients with traumatic or ischemic acute spinal cord injury and managed according to the European Association of Urology Guidelines on Neuro-Urology were analyzed at a single university spinal cord injury center at 1 month, 3 months, 6 months, and 12 months after injury. Unfavorable urodynamic parameters were defined as detrusor overactivity in combination with detrusor sphincter dyssynergia, maximum storage detrusor pressure of 40 cm H2O or higher, bladder compliance less than 20 mL/cm H2O, and vesicoureteral reflux of any grade. RESULTS: One or more unfavorable urodynamic parameter was observed in 87 out of 97 patients (90%) within the first year after spinal cord injury. Eighty-eight percent of the patients showed detrusor overactivity with detrusor sphincter dyssynergia, 39% a maximum storage detrusor pressure of 40 cm H2O or higher, and 7% vesicoureteral reflux. No patient developed a low-compliance bladder. CONCLUSIONS: Using a standardized urodynamic follow-up schedule, we found unfavorable urodynamic parameters in a majority of the population within the first year after spinal cord injury. As early treatment based on urodynamic findings might reduce the risk of deterioration of upper and lower urinary tract function, thereby improving long-term outcomes, there is need for further research regarding recommendations for a urodynamic follow-up schedule during the first year after spinal cord injury.

Myofascial Pelvic Pain: Best Orientation and Clinical Practice. Position of the European Association of Urology Guidelines Panel on Chronic Pelvic Pain.

CONTEXT: Despite the high prevalence of a myofascial pain component in chronic pelvic pain (CPP) syndromes, awareness and management of this component are lacking among health care providers. OBJECTIVE: To summarize the current state of the art for the management of myofascial pain in chronic primary pelvic pain syndromes (CPPPS) according to scientific research and input from experts from the European Association of Urology (EAU) guidelines panel on CPP. EVIDENCE ACQUISITION: A narrative review was undertaken using three sources: (1) information in the EAU guidelines on CPP; (2) information retrieved from the literature on research published in the past 3 yr on myofascial pelvic pain; and (3) expert opinion from panel members. EVIDENCE SYNTHESIS: Studies confirm a high prevalence of a myofascial pain component in CPPPS. Examination of the pelvic floor muscles should follow published recommendations to standardize findings and disseminate the procedure. Treatment of pelvic floor muscle dysfunction and pain in the context of CPP was found to contribute to CPP control and is feasible via different physiotherapy techniques. A multidisciplinary approach is the most effective. CONCLUSIONS: Despite its high prevalence, the myofascial component of CPP has been underevaluated and undertreated to date. Myofascial pain must be assessed in all patients with CPPPS. Treatment of the myofascial pain component is relevant for global treatment success. Further studies are imperative to reinforce and better define the role of each physiotherapy technique in CPPPS. PATIENT SUMMARY: Pain and inflammation of the body's muscle and soft tissues (myofascial pain) frequently occurs in pelvic pain syndromes. Its presence must be evaluated to optimize management for each patient. If diagnosed, myofascial pain should be treated.

Sacral Neuromodulation for Neurogenic Lower Urinary Tract Dysfunction.

BACKGROUND: Neurogenic lower urinary tract dysfunction (NLUTD) is a highly prevalent and disabling condition; nevertheless, standard treatments often remain unsatisfactory. Sacral neuromodulation (SNM) is a well-established therapy for non-NLUTD, but there is a lack of randomized controlled trials to show benefit in patients with NLUTD. METHODS: For this sham-controlled, double-blind, multicenter trial, patients with refractory NLUTD (and intended SNM) were recruited at four Swiss SNM referral centers. After lead placement into the sacral foramina S3 (rarely, S4), all participants underwent SNM testing. If successful (≥50% improvement in key bladder diary variables), the neurostimulator was implanted for permanent stimulation. For 2 months, neuromodulation was optimized using subsensory stimulation with individually adjusted parameters. Thereafter, the neurostimulator remained on or was switched off (1:1 random allocation to group SNM ON or SNM OFF, respectively) for 2 months, followed by a neurourologic reevaluation. The primary outcome was success, as defined above, of SNM compared with baseline. RESULTS: Of 124 patients undergoing SNM testing, 65 (52%) had successfully improved lower urinary tract function. Of these, 60 patients (median age, 49.5 years; 43 women) were randomly assigned to the intervention. After 2 months of intervention, the SNM ON group demonstrated a success rate of 76%. In the SNM OFF group, 42% of patients showed sustained SNM effects despite their neurostimulator being switched off during the last 2 months (odds ratio, 4.35; 95% confidence interval, 1.43 to 13.21; P=0.009). During the entire study period, there were 11 adverse events (6 dropouts; no dropouts during the intervention phase). CONCLUSIONS: SNM effectively corrected refractory NLUTD in the short term in well-selected neurologic patients. (Funded by the Swiss National Science Foundation, Vontobel­Stiftung, Gottfried und Julia Bangerter­Rhyner Stiftung, Dr. Urs Mühlebach, and the Swiss Continence Foundation; ClinicalTrials.gov number, NCT02165774.)

The Challenge of Asymptomatic Bacteriuria and Symptomatic Urinary Tract Infections in Patients with Neurogenic Lower Urinary Tract Dysfunction.

PURPOSE: We investigated the prevalence of asymptomatic bacteriuria and the incidence of symptomatic urinary tract infections in patients with neurogenic lower urinary tract dysfunction undergoing urodynamics. We also assessed predictors of symptomatic urinary tract infections. MATERIALS AND METHODS: We evaluated a prospective consecutive series of 317 patients, including 106 women and 211 men, with neurogenic lower urinary tract dysfunction. Of the patients 111 (35%) voided spontaneously, 141 (44%) relied on intermittent self-catheterization and 65 (21%) relied on an indwelling catheter. Before urodynamics the urine samples were collected by sterile catheterization for dipstick testing and urine culture. We assessed the association of patient characteristics with symptomatic urinary tract infections after urodynamics in patients with asymptomatic bacteriuria and developed a prediction model based on the most important risk factors. RESULTS: Before urodynamics urine cultures were negative in 123 patients (39%) and positive in 194 (61%). Escherichia coli and Klebsiella pneumoniae were the most frequent bacteria, found in 32% and 18% of patients, respectively. Of 194 patients with a positive culture 35 (18%) had at least 1 symptomatic urinary tract infection. In patients with a history of previous urinary tract infections the overall estimated probability of a symptomatic urinary tract infection was 45% regardless of the underlying neurological disorder. CONCLUSIONS: A symptomatic urinary tract infection will develop in the followup year in about 1 of 5 patients with asymptomatic bacteriuria. This rather low overall probability precludes routine antibiotic prophylaxis or treatment in patients with neurogenic lower urinary tract dysfunction who have asymptomatic bacteriuria since 4 of 5 would be overtreated. However, in patients with a history of previous symptomatic urinary tract infections antibiotic prescription might be justified.

Transcutaneous Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Pilot Study for an International Multicenter Randomized Controlled Trial.

BACKGROUND: Tibial nerve stimulation (TNS) is an effective and safe treatment for idiopathic lower urinary tract dysfunction (LUTD), but its value in neurological patients is unclear. OBJECTIVE: To test the feasibility, acceptability, and safety of a randomized, sham-controlled, double-blind transcutaneous TNS (TTNS) setup for treating neurogenic LUTD. DESIGN, SETTING, AND PARTICIPANTS: A pilot study including nine patients with refractory neurogenic LUTD investigated prospectively at a university neuro-urology department. INTERVENTION: Randomized, sham-controlled, double-blind verum and sham TTNS was performed for 30min twice a week, for 6 wks. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were feasibility, acceptability, and safety of the TTNS protocol. Secondarily, potential efficacy was investigated. Descriptive statistics were used. RESULTS AND LIMITATIONS: All procedures were feasible and well tolerated by all nine patients. Using verum TTNS, a motor response could be triggered in all patients and a sensory response in all but one. At the beginning and end of treatment, seven and six (78% and 67%) patients believed to receive verum TTNS, and five and six (56% and 67%) correctly guessed their group allocation, respectively. No treatment-related adverse events occurred. A comparison of baseline versus 6 wks of verum and sham TTNS led to relevant symptom and functional changes in only a limited number of piloted patients. CONCLUSIONS: Verum and sham TTNS combined with the blinding procedures proved feasible and safe. Both interventions and procedures, as well as the randomization process, were well accepted by the patients. While the subsensory threshold TTNS approach in combination with the sham condition is advantageous for patients' blinding, the clinical findings raised some doubt regarding sufficient TNS. Hence, relevant methodological adjustments concerning the adequate stimulation current and corresponding sham condition are needed before starting randomized controlled trials to clarify the value and role of TTNS in neuro-urology. PATIENT SUMMARY: Transcutaneous tibial nerve stimulation is a promising treatment option for neurogenic lower urinary tract dysfunction, but methodological adjustments in treatment application are required before further prospective studies can be initiated.

Urethral pressure profile assessment after artificial urinary sphincter implantation (FlowSecure™ and AMS-800™): A case series.

The AMS-800™ artificial urinary sphincter has become the 'gold standard' in the treatment of male stress urinary incontinence. In 2006, the novel artificial urinary sphincter FlowSecure™ containing a stress relief balloon providing low cuff pressures at rest with conditional pressure elevation during periods of stress has been launched. We assessed the intraurethral pressure in the cuff area of the AMS-800 and the FlowSecure by urethral pressure profile in four patients each. Urethral pressure profile was performed at rest and during coughing. In addition, continence situation and patient satisfaction after artificial urinary sphincter implantation was assessed. At rest, median pressure in the cuff region was 74 (38-117, FlowSecure) cm H2O and 102 (95-110, AMS-800) cm H2O. During coughing, pressure peaks rose to 135 (54-162, FlowSecure) cm H2O and 202 (128-216, AMS-800) cm H2O. Median pad usage before artificial urinary sphincter implantation in the FlowSecure and the AMS-800 group was 4 (3-4) and 4.5 (2-6) pads/24 h, respectively. At the time of urodynamic investigation, median pad usage declined to 1.5 (0-4) pads/24 h in the FlowSecure and to 1 (1-2) pads/24 h in the AMS-800 group. Seven of eight patients reported on a satisfactory quality of life, and one patient remained unhappy after FlowSecure implantation. It remains unclear if the trade-off in favour of lower cuff pressures, and consecutively lower intraurethral pressures, holds truly long-term benefits regarding device revision, explantation and patient satisfaction.

Alpha-blockers for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review and meta-analysis. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: We aimed to systematically assess the evidence on the efficacy and safety of alpha-blockers in patients with multiple sclerosis (MS) suffering from neurogenic lower urinary tract dysfunction (NLUTD). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to perform this systematic review. An electronic search of Cochrane register, Embase, Medline, Scopus (last search 3 March 2018) and screening of reference lists as well as reviews were used to identify the studies. Articles were included if they reported on efficacy/safety of alpha-blockers for the treatment of NLUTD in patients with MS. RESULTS: After screening of 7'015 abstracts, three studies enrolling a total of 50 patients were included: one randomized, placebo-controlled, single-blind trial and two prospective cohort studies. Alpha-blocker treatment was successful in 50% to 96% of the patients. Pooling data from the three included studies, the relative risk for successful alpha-blocker treatment was 3.89 (95% confidence interval 2.7-7.0). The general safety profile of alpha-blockers was favorable with 8% of the patients reporting adverse events. CONCLUSIONS: Alpha-blockers may be effective and safe for treating NLUTD in female and male patients with MS but the studies were small and the overall quality of evidence was low. To make definitive conclusions, well designed randomized controlled trials are highly warranted.

Catheterization for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: To systematically assess all available evidence on efficacy and safety of catheterization for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Embase, Medline, Scopus, Cochrane register (last search March 3, 2018) and by screening of reference lists and reviews. RESULTS: After screening 7'015 articles, we included four studies (one prospective and two retrospective cohort studies, one retrospective cross-sectional study), in which a total of 445 patients were enrolled. No randomized controlled trial was available. Catheterization substantially increased quality of life, post void residual, and incontinence episodes in all included studies. Pooling of data for meta-analysis was not possible due to the heterogeneity of reported outcomes. Adverse events were reported in two studies only. Risk of bias and confounding was intermediate. CONCLUSIONS: Preliminary data suggests beneficial effects of catheterization on the urological outcome in patients with MS. However, although intermittent and indwelling catheterization is used frequently in daily clinical practice in the MS population, the evidence base is very limited and well-designed, properly sampled, and powered studies are urgently needed.

The Management of Lower Urinary Tract Dysfunction in Multiple Sclerosis.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is the most frequent neuroinflammatory disease of the central nervous system and is commonly associated with lower urinary tract (LUT) dysfunction. As a consequence, health-related quality of life is often impaired and the upper urinary tract might be at risk for damage. The aim of this review is to give an overview of current treatment options for LUT dysfunction in patients with MS. RECENT FINDINGS: The treatment is tailored to the type of dysfunction-storage or voiding dysfunction-beginning with conservative treatment options and ending with invasive therapies and surgery. Additionally, alternative options, e.g., different intravesical therapies or cannabinoids, have been evaluated in recent years with promising results. Current available therapies offer different possible treatments for LUT dysfunction in patients with MS. They address either voiding or storage dysfunction and therefore ameliorate LUT symptoms improve quality of life and protect the upper urinary tract.

Detrusor Acontractility after Acute Spinal Cord Injury-Myth or Reality?

PURPOSE: We assessed urodynamic parameters within the first 40 days after spinal cord injury to investigate whether the detrusor is acontractile during the acute phase of spinal cord injury. MATERIALS AND METHODS: We performed a prospective cohort study in 54 patients with neurogenic lower urinary tract dysfunction due to acute spinal cord injury who underwent urodynamic investigation within the first 40 days after injury at a single university spinal cord injury center. RESULTS: Urodynamic investigation revealed an acontractile detrusor in only 20 of the 54 patients (37%) but unfavorable urodynamic parameters in 34 (63%). We found detrusor overactivity in 32 patients, detrusor-sphincter dyssynergia in 25, maximum storage detrusor pressure greater than 40 cm H2O in 17, vesicoureteral reflux in 3 and low bladder compliance (less than 20 ml/cm H2O) in 1. More than 1 unfavorable urodynamic parameter per patient was possible. CONCLUSIONS: In contrast to the common notion of an acontractile detrusor during acute spinal cord injury, almost two-thirds of our patients showed unfavorable urodynamic parameters within the first 40 days after spinal cord injury. Considering that early treatment of neurogenic lower urinary tract dysfunction in patients with acute spinal cord injury might improve the long-term urological outcome, urodynamic investigation should be performed timely to optimize patient tailored therapy.

Antibiotic prophylaxis may not be necessary in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections for neurogenic detrusor overactivity.

Many of the patients undergoing intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity (NDO) present with chronic bacteriuria. In these patients, antibiotic prophylaxis has been widely recommended since bacteriuria might impair treatment efficacy and cause urinary tract infections (UTI) but the evidence is limited. The aim of this study was to evaluate if an antibiotic prophylaxis is needed in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections. Between 06/2012 and 12/2014, a consecutive series of 154 patients undergoing a total of 273 treatment cycles were prospectively evaluated. Before treatment urine samples were collected, patients with no clinical signs for UTI underwent onabotulinumtoxinA injections, no antibiotic prophylaxis was given. Asymptomatic bacteriuria was found in 73% (200/273 treatments). Following treatment, UTI occurred in 5% (9/200) and 7% (5/73) of patients with and without bacteriuria, respectively. Intradetrusor onabotulinumtoxinA injections were clinically and urodynamically successful in 70% (192/273). There was no association between bacteriuria and treatment-related adverse events (odds ratio 0.64, 95% CI 0.23-1.81, p = 0.4) nor between bacteriuria and therapy failure (odds ratio 0.78, 95% CI 0.43-1.43, p = 0.4). Thus, we conclude that antibiotic prophylaxis needs to be critically reconsidered in patients undergoing intradetrusor onabotulinumtoxinA injections, especially taking into account the alarming antibiotic resistance worldwide.

More Than 15 Years of Experience with Intradetrusor OnabotulinumtoxinA Injections for Treating Refractory Neurogenic Detrusor Overactivity: Lessons to Be Learned.

BACKGROUND: Intradetrusor onabotulinumtoxinA (BoNT-ONA) injections have become a well-established therapy for refractory neurogenic detrusor overactivity (NDO). However, little is known about long-term outcome and patients' adherence to this treatment. OBJECTIVE: To assess long-term outcomes of intradetrusor BoNT-ONA injections and patients' adherence to treatment. DESIGN, SETTING, AND PARTICIPANTS: A consecutive series of 52 patients who underwent first intradetrusor BoNT-ONA injections for refractory NDO >10 yr ago were evaluated retrospectively and prospectively at a single university spinal cord injury (SCI) centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was current neuro-urologic treatment. Secondary outcomes were urodynamic parameters. For data comparison, the paired/unpaired t test, chi-square test, and McNemar test were used. RESULTS AND LIMITATIONS: Mean duration since first intradetrusor BoNT-ONA injections was 12±2 yr. Most patients (61% [32 of 52]) suffered from SCI, 15% (8 of 52) from spina bifida, 14% (7 of 52) from multiple sclerosis (MS), and the remaining (10% [5 of 52]) from other neurologic disorders. Almost 60% (31 of 52) of all patients are continuing with intradetrusor BoNT-ONA injections but only 14% (1 of 7) of the patients with MS. Lack of clinical and/or urodynamic response (21% [11 of 52]) and switching to another treatment (antimuscarinics and/or neuromodulation) despite appropriate BoNT-ONA efficacy (19% [10 of 52]) were the reasons for discontinuation. In patients continuing BoNT-ONA treatment, the positive effect was sustained after repeat injections (p<0.05). CONCLUSIONS: Although intradetrusor BoNT-ONA injections are a highly effective therapy for refractory NDO, approximately 40% of the patients discontinue treatment over time. All prospective neurologic patients should be given this information, and it needs to be considered in the treatment decision-making process. PATIENT SUMMARY: Approximately 60% of the patients treated with intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity continue this therapy long term with good therapeutic effects. STUDY REGISTRATION NUMBER: NCT01293110.

Severe mitral regurgitation in an adult patient with cor triatriatum.

A 52-year-old female patient who presented with a history of increasing shortness of breath and fatigue was diagnosed with a combination of cor triatriatum and myxomatous mitral valve disease. Transesophageal echocardiography revealed cor triatriatum and severe mitral regurgitation (MR) due to myxomatous degeneration. The patient underwent a successful removal of the left atrial membrane and repair of the mitral valve. This combination of cor triatriatum and myxomatous mitral valve disease is exceedingly rare; in the present patient the symptoms caused by MR led to the discovery of a left atrial membrane.

Sleep patterns in high school and university students: a longitudinal study.

We performed a longitudinal study to investigate whether changes in social zeitgebers and age alter sleep patterns in students during the transition from high school to university. Actimetry was performed on 24 high-school students (mean age+/-SD: 18.4+/-0.9 yrs; 12 females) for two weeks. Recordings were repeated in the same subjects 5 yrs later when they were university students. The sleep period duration and its center, the mid-sleep time, and total sleep time were estimated by actimetry. Actigraphic total sleep time was similar when in high school and at the university on school days (6.31+/-0.47 vs. 6.45+/-0.80 h, p = ns) and longer on leisure days by 1.10+/-1.10 h (p < 0.0001 vs. school days) when in high school, but not at the university. Compared to the high school situation, the mid-sleep time was delayed when at the university on school days (03:11+/-0.6 vs. 03:55+/-0.7 h, p < 0.0001), but not on leisure days. Individual mid-sleep times on school and leisure days when in high school were significantly correlated with the corresponding values 5 yrs later when at the university (r = 0.58 and r = 0.55, p < 0.05, respectively). The large differences in total sleep time between school and leisure days when students attended high school and the delayed mid-sleep time on school days when students attended university are consistent with a circadian phase shift due to changes in class schedules, other zeitgebers, and lifestyle preferences. Age-related changes may also have occurred, although some individuality of the sleep pattern was maintained during the 5 yr study span. These findings have important implications for optimizing school and work schedules in students of different age and level of education.