[Intravesical oxybutynin treatment for neurogenic detrusor overactivity : Efficacy and safety data from clinical practice with the first intravesical oxybutynin treatment authorized in Germany]. / Intravesikale Oxybutynin-Behandlung der neurogenen Detrusorüberaktivität : Wirksamkeits- und Sicherheitsdaten aus der Praxis der ersten in Deutschland zugelassenen intravesikalen Oxybutynin-Behandlung.

Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cm H2O ± 26.12 standard deviation (SD) to 21.07 cm H2O ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects.

The NeuroSAFE frozen section technique during radical prostatectomy - Implementation and optimization of technical aspects in a routine pathology workflow.

BACKGROUND AND AIMS: In prostate cancer patients, application of the NeuroSAFE frozen section technique during radical prostatectomy has been shown to increase the rate of nerve sparing surgery and to improve functional outcome for the patients. The aim of this study is to report on technical and organizational optimization opportunities of the procedure. MATERIAL AND METHODS: All patients submitted to bilateral intraoperative frozen section from January 2018 until December 2020 (n = 452) were retrospectively analyzed and parameters such as turnaround time, staff situation in the laboratory and histologic properties of the tumors were assessed. RESULTS: The median turnaround time per case was 40.3 ( ± 10.5) min. In 2020 the average time needed from accessioning to diagnosis was 38.1 min. Multivariate linear regression suggested that the number of technical assistants/cryotomes (46.1 min vs. 39.13 min; p < 0.001), the place of microscopic examination (43.0 min vs. 38.7 min; p < 0.001) and the presence of a positive margin (38.0 vs. 44.0 min; p < 0.001) were significant influential factors. The turnaround time was independent of the uropathological expertize of the consultant (39.84 min vs. 40.7 min; p = 0.09), the tumor grade (42.3 vs 39.8 min; p = 0.493) and the presence of extraprostatic extension (44.0 vs 39.8 min; p = 0.099). CONCLUSION: The implementation of simple optimization measures in the workflow as well as structured training of all pathology staff involved in the examination leads to a significant increase in the efficiency of the examination while maintaining the same level of resources. The results could thus be a contribution to the broader application of the procedure.

Daily fluctuations in occupation with and worry about COVID-19.

In the first week after the first COVID-19 patient was reported in the Netherlands, we conducted a pre-registered momentary assessment study (7 surveys per day, 50 participants, 7 days) to study the dynamic relationship between individuals' occupation with and worries about COVID-19 in daily life, and the moderating role of neuroticism in this relationship. At the group level, higher scores on occupation and worry co-occurred, and occupation predicted worry 1 h later, but not vice versa. There were substantial individual differences in the magnitudes and directions of the effects. For instance, occupation with COVID-19 was related to increases in worry for some but decreases in worry for others. Neuroticism did not predict any of these individual differences in the links between worry and occupation. This study suggests that it is important to go beyond group-level analyses and to account for individual differences in responses to COVID-19.

[Use of synthetic slings and mesh implants in the treatment of female stress urinary incontinence and prolapse : Statement of the Working Group on Urological Functional Diagnostics and Female Urology of the Academy of the German Society of Urology]. / Einsatz von synthetischen Band- und Netzimplantaten bei der Behandlung von Belastungsinkontinenz und Descensus genitalis der Frau : Stellungnahme des Arbeitskreises Urologische Funktionsdiagnostik und Urologie der Frau der Akademie der Deutschen Gesellschaft für Urologie.

Due to a safety alert issued by the US Food and Drug Administration (FDA) in 2011 for transvaginal mesh implants to treat female prolapse as a result of numerous reports of complications such as infection, chronic pain, dyspareunia, vaginal erosion, shrinkage and erosion into other organs nearly all industrial products have been withdrawn from the market in the meantime. The United Kingdom, Australia, and New Zealand extended warnings and prohibitions even on the implantation of midurethral slings (TVT, TOT). In view of these current international controversies regarding the use of implanted materials for the treatment of stress incontinence and prolapse and the lack of clear guidelines for the use of biomaterials, the opinion of the Working Group on Urological Functional Diagnostics and Female Urology should provide clarity. The Opinion is based on the SCENIHR Report of the "European Commission's Scientific Committee on Emerging and Newly Identified Health Risks", the "Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence" and in compliance with relevant EAU and national guidelines and the opinion of the Association for Urogynaecology and Plastic Pelvic Floor Reconstruction (AGUB eV). In addition, recommendations are given for the future handling of implants of slings and meshes for the treatment of stress incontinence and prolapse from a urologic viewpoint.

[Lower urinary tract dysfunction in Guillain-Barre syndrome]. / Harntraktfunktionsstörungen bei Guillain-Barré-Syndrom.

BACKGROUND: Guillain-Barré syndrome (GBS) as acute inflammatory demyelinating polyradiculoneuropathy frequently leads to lower urinary tract dysfunction. The available knowledge in the medical literature is limited and good recommendations for diagnosis and therapy are rare. MATERIALS AND METHODS: In this study, 189 patients with GBS were screened for lower urinary tract dysfunction. In symptomatic patients, a urodynamic study was performed. Detrusor contractility, post-void residual, and changes of the symptoms over time were studied. Overall Barthel index and urinary control Barthel index as well as the relationship of time after onset of the disease and post-void residual were studied as possible screening criteria for urodynamic assessment. RESULTS: According to the urinary control Barthel index (BI), 115 of 189 patients (61%) presented lower urinary tract symptoms sometime during the course of disease. In 28 patients, these symptoms were temporary during the acute phase. At the time of urological assessment, 87 patients had lower urinary tract symptoms. At the end of rehabilitation, 37 had no symptoms anymore (BI 10), 20 were able to control micturition to a certain extent (BI 5), and 30 had no lower urinary tract control (BI 0). There was a significant negative correlation between post-void residual volume and overall BI (ρ -0.5823, p < 0.0001) and BI for urinary tract control (ρ -0.6430, p < 0.0001). CONCLUSIONS: Overall BI and BI for urinary tract control are suitable screening criteria for urodynamic assessment.

[Enuresis and pediatric urinary incontinence : Diagnostics and therapy]. / Enuresis und Harninkontinenz bei Kindern : Diagnostik und Therapie.

Differentiated non-invasive diagnostic procedures allow a discrimination between nocturnal enuresis and behavior-linked urinary incontinence in children with daytime symptoms, which are different entities of a pathological pediatric micturition syndrome. The article describes the diagnostic procedure as well as the therapeutic approach to all forms of micturition disorders in childhood. All behavioral, medical and biofeedback therapeutic methods according to the recently published S2k guidelines from the Association of the Scientific Medical Societies in Germany (AWMF) on enuresis and non-organic (functional) incontinence in children and adolescents are mentioned and discussed.

[Urethral Syndrome and Urethral Pain: Do we Treat People or Diagnoses?]. / Das Urethralsyndrom und urethrale Schmerzen - behandeln wir den Menschen oder die Diagnose?

The urethral syndrome with urethral pain and bladder voiding disorders is a diagnosis of exclusion. Possible aetiologies are diverse and include organic, functional and inflammatory pathologies of the urethra. Infections, inflammation of the paraurethral glands, spasms of the sphincter muscle and/or of the pelvic floor muscles, oestrogen deficiency, trauma, neuropathies, hypersensitivity and psychosomatic issues have been investigated as possible causes.Patients with urethral syndrome must be viewed, evaluated and treated holistically. They need a lot of time and attention during their evaluation and treatment. It is now well known that psychosocial aspects are involved in the development of many somatic conditions and may have a crucial impact on the course of a disease. This needs to be taken into consideration during the treatment process.

[The ice water test and bladder cooling reflex. Physiology, pathophysiology and clinical importance]. / Eiswassertest und Bladder-cooling-Reflex. Physiologie, Pathophysiologie und klinische Bedeutung.

BACKGROUND: Urodynamic studies are utilised for identification and follow-up of functional disorders of the lower urinary tract. Provocation tests are used to determine disorders which could not be revealed in standard cystometry. The ice water test is a simple test to identify neurogenic bladder dysfunction and to screen the integrity of the upper motor neuron in neurogenic bladder dysfunction. OBJECTIVES: Development and significance of the ice water test is presented in this review against the background of physiology and pathophysiology of the lower urinary tract. MATERIALS AND METHODS: A systematic review of PubMed and ScienceDirect databases was performed in April 2015. No language or time limitation was applied. The following key words and Medical Subject Heading terms were used to identify relevant studies: "ice water test", "bladder cooling reflex", "micturition" and "neuronal control". Review articles and bibliographies of other relevant studies identified were hand searched to find additional studies. RESULTS: The ice water test is performed by rapid instillation of 4-8 °C cold fluid into the urinary bladder. Hereby, afferent C fibers are activated by cold receptors in the bladder leading to the bladder cooling reflex. It is a spinal reflex which causes an involuntarily contraction of the urinary bladder. The test is normally positive in young infants during the first 4 years of life and become negative with maturation of the central nervous system afterwards by inhibition of the reflex. The damage of the upper motor neuron causes the recurrence of the reflex in the adulthood and indicates spinal and cerebral lesions. DISCUSSION: The ice water test is utilised to identify lesions of the upper motor neuron. However, in the case of detrusor acontractility the test will always be negative and can not be utilized to distinguish between neurogenic or muscular causes. Furthermore, the test is also positive in a small percentage of cases of non-neurogenic diseases, e.g. in prostate-related bladder outlet obstruction or idiopathic overactive bladder. Although no clear explanation exists, a positive ice water test could be the first sign of an otherwise asymptomatic neurological disease. CONCLUSIONS: Due to the simple procedure, the ice water test is a reliable possibility to identify neurologic bladder hyperactivity subsequent to standard cystometry.

[Use of botulinum toxin type A in non-neurogenic overactive bladder. Recommendations of the Working Group Urological Functional Diagnostics and Urology in Women]. / Botulinumtoxin Typ A bei der nicht-neurogenen überaktiven Blase. Empfehlungen des Arbeitskreises "Urologische Funktionsdiagnostik und Urologie der Frau".

The use of botulinum toxin for the treatment of neurogenic detrusor overactivity was first described in 2000 and thereafter botulinum toxin has also been used in non-neurogenic overactive bladder. In current guidelines intravesical injection of onabotulinumtoxin A in refractory patients is recommended. Our aim is to provide some clinically relevant recommendations from the Working Group Urologische Funktionsdiagnostik und Urologie der Frau for diagnostics and treatment with onabotulinumtoxin A of patients with non-neurogenic overactive bladder.

Impact of stress on different components of impulsivity in borderline personality disorder.

BACKGROUND: Previous research on impulsivity in borderline personality disorder (BPD) has revealed inconsistent findings. Impulsive behaviour is often observed during states of emotional distress and might be exaggerated by current attention deficit hyperactivity disorder (ADHD) symptoms in individuals with BPD. We aimed to investigate different components of impulsivity dependent on stress induction controlling for self-reported ADHD symptoms in BPD. METHOD. A total of 31 unmedicated women with BPD and 30 healthy women (healthy controls; HCs), matched for age, education and intelligence, completed self-reports and behavioural tasks measuring response inhibition (go/stop task) and feedback-driven decision making (Iowa Gambling Task) under resting conditions and after experimental stress induction. ADHD symptoms were included as a covariate in the analyses of behavioural impulsivity. Additionally, self-reported emotion-regulation capacities were assessed. RESULTS: BPD patients reported higher impulsive traits than HCs. During stress conditions - compared with resting conditions - self-reported impulsivity was elevated in both groups. Patients with BPD reported higher state impulsivity under both conditions and a significantly stronger stress-dependent increase in state impulsivity. On the behavioural level, BPD patients showed significantly impaired performance on the go/stop task under stress conditions, even when considering ADHD symptoms as a covariate, but not under resting conditions. No group differences on the Iowa Gambling Task were observed. Correlations between impulsivity measures and emotion-regulation capacities were observed in BPD patients. CONCLUSIONS: Findings suggest a significant impact of stress on self-perceived state impulsivity and on response disinhibition (even when considering current ADHD symptoms) in females with BPD.

[Age-related aspects in neurourology]. / Altersbezogene Aspekte in der Neurourologie.

This review highlights age-related aspects of neurogenic lower urinary tract dysfunction. The changing needs and requirements of elderly long-term paraplegics and of elderly people affected from acute spinal cord injury or neurological diseases are discussed. Complications and delayed damage in the urinary tract must be recognized in time to be treated successfully. For uro-oncological early recognition examinations and the assessment of screening parameters, disease and paralysis-associated aspects as well as the individual social situation must be considered. Urologists involved in the long-term treatment of elderly paraplegic patients should take the increased cardiovascular morbidity and mortality into consideration. If paraplegia or a neurodegenerative disease occurs in elderly persons, constellations are often present which stretch the established neurourological concepts of diagnostics, therapy and long-term care to their limits. Knowledge compiled over decades of neurourological care of younger paraplegic patients can be adapted to the needs of elderly patients and new approaches can sometimes be tried.

[Urodynamic testing of the lower urinary tract]. / Urodynamische Funktionsdiagnostik des unteren Harntrakts.

Based on the measurement of simple physiological parameters urodynamic testing can reproduce clinical symptoms in a quantitative way, associates changes in physiological parameters to pathophysiological conditions and helps to establish a diagnosis in numerous lower urinary tract dysfunctions. Furthermore, urodynamic testing allows lower urinary tract dysfunctions to be classified as storage failure, voiding failure or combined storage and voiding failure. Therapeutic decision-making is based on this classification.

[Systematic approach for dysfunctional analysis in radiotherapy]. / Démarche systématique d'analyse dysfonctionnelle en radiothérapie.

PURPOSE: We previously presented a systematic and structured approach to acquire an accurate functional model of the patient's process in radiotherapy. This approach relied on new functional structuring patterns, derived from system engineering and knowledge engineering. Additionally, we propose a complementary methodical process for the dysfunctional analysis of the obtained functional model. MATERIALS AND METHODS: The procedure is based on joint implementation of two qualitative methods named "Failure modes and effects analysis" (FMEA) and "Hazard and operability" (HazOp). RESULTS: All the technical, the human and the organizational dimensions of the patient's process are pooled in a unique, exhaustive and detailed dysfunctional analysis. The application of this systematic approach within a particular institution can precisely identify the risks incurred by patients in care, but also highlight the logical sequence between precursor events and incidents. CONCLUSION: The dysfunctional analysis presented in this document will be used for the development still in process of quantified risk models.

[Functional modeling for risk analysis in radiotherapy]. / Modélisation fonctionnelle adaptée à l'analyse des risques en radiothérapie.

PURPOSE: This document presents a systematic and structured approach for functional modeling for risk analysis in radiotherapy, aiming to reconcile the need, on one hand, for a method that can be applied generally and, on the other hand, for a method that provides a highly precise model. MATERIALS AND METHODS: The approach relies on new functional structuring patterns and flux analysis, derived from system engineering and knowledge engineering. RESULTS: The method affords strong support for the development of detailed models of the patient's process through a department of radiotherapy. Lack of structure of the actual process in a particular department may be easily identified leading to the development of specific procedures for the improvement of security. CONCLUSION: Modeling approach derived from engineering may be used for functional modeling for risk analysis in radiotherapy.

Mephedrone ("bath salt") pharmacology: insights from invertebrates.

Psychoactive bath salts (also called meph, drone, meow meow, m-CAT, bounce, bubbles, mad cow, etc.) contain a substance called mephedrone (4-methylcathinone) that may share psychostimulant properties with amphetamine and cocaine. However, there are only limited studies of the neuropharmacological profile of mephedrone. The present study used an established invertebrate (planarian) assay to test the hypothesis that acute and repeated mephedrone exposure produces psychostimulant-like behavioral effects. Acute mephedrone administration (50-1000 µM) produced stereotyped movements that were attenuated by a dopamine receptor antagonist (SCH 23390) (0.3 µM). Spontaneous discontinuation of mephedrone exposure (1, 10 µM) (60 min) resulted in an abstinence-induced withdrawal response (i.e. reduced motility). In place conditioning experiments, planarians in which mephedrone (100, 500 µM) was paired with the non-preferred environment during conditioning displayed a shift in preference upon subsequent testing. These results suggest that mephedrone produces three behavioral effects associated with psychostimulant drugs, namely dopamine-sensitive stereotyped movements, abstinence-induced withdrawal, and environmental place conditioning.

[Neuromuscular dysfunction of the lower urinary tract dysfunction beyond spinal cord injury and multiple sclerosis. A challenge for urologists]. / Neuromuskuläre Funktionsstörungen des unteren Harntraktes jenseits von Querschnittlähmung und multipler Sklerose. Eine Herausforderung für den Urologen.

Neurogenic bladder subsequent to paraplegia serves as a paradigm when classifying the type of disorder analogous to the level of paralysis. In cases of multiple sclerosis micturition symptoms already present a manifold picture that changes in the clinical course. Rarer neurological disorders, on the other hand, such as infantile cerebral palsy, Parkinson's disease, multisystem atrophy, Alzheimer's disease, cerebrovascular disorders, Guillain-Barré syndrome, AIDS, herpes zoster, systemic lupus erythematosus, and herniated lumbar disc, often cause uncertainty with regard to necessary diagnostic tests and treatment.This review considers the available knowledge about voiding disorders and urinary incontinence associated with specific neurologic and neuromuscular diseases and provides recommendations for diagnostic work-up and pragmatic therapy.

[Conservative treatment of male stress incontinence]. / Konservative Therapie der männlichen Belastungsinkontinenz.

The majority of male patients affected by stress incontinence developed this disturbance after radical prostatectomy or less frequently after TURP. Urodynamic evaluation shows sphincter insufficiency in more than 90% of the patients. The conservative therapy of postprostatectomy stress incontinence relies on physical methods, namely, pelvic floor muscle training with or without electrical or magnetic stimulation. However, evidence in favor of one or the other approach is limited. Since publication of the positive results with duloxetine in women, interest in medical therapy for men reporting postoperative stress incontinence has increased. Conclusive evidence in favor of duloxetine for prostatectomy-associated incontinence however is still missing.

[Overactive bladder syndrome. Are there indications for surgical therapy?]. / Uberaktive Blase. Gibt es Indikationen für eine operative Therapie?

Conservative therapeutic options are considered the gold standard in therapy of overactive bladder syndrome. However, surgery may be beneficial in selected cases. Neuromodulation is well established in clinical practice. If conservative or minimally invasive therapy fails, augmentation techniques or urinary diversion may be considered. This review presents the current knowledge about surgical treatment options for idiopathic overactive bladder.

Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics.

PURPOSE: In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. MATERIALS AND METHODS: A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. RESULTS: Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. CONCLUSIONS: Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.