The effect of tolterodine 4 and 8mg on the heart rate variability in healthy subjects

Purpose: To investigate the potential effect of tolterodine on the human heart rate variability (HRV). Oral antimuscarinic treatment for overactive bladder might significantly alter HRV, which is an important predictor for cardiac and all-cause mortality. Yet, little information exists regarding the influence of oral antimuscarinics on the HRV. Methods: Healthy female volunteers were randomly assigned to either placebo, tolterodine extended release (ER) 4 or 8mg. Before and 4h post treatment, a 10min electrocardiogram (ECG) was recorded in supine position. Frequency domain and time domain analysis of both ECG measurements resulted in very low frequency (VLF), low frequency (LF), and high frequency (HF) data, the root mean square of differences of successive NN (=normal to normal, i.e. interval between two R-peaks) intervals (RMSSD), and the standard deviation of the NN intervals (SDNN). Results: Thirty subjects (mean age: 23.7±2.3years) were investigated. Placebo caused no significant HRV changes. Tolterodine 4mg significantly increased heart rate (HR) and significantly decreased VLF. Tolterodine 8mg significantly decreased HF, VLF, RMSSD and SDNN and significantly increased HR and LF/HF ratio. The changes observed with 4mg were not significantly different versus placebo, but 8mg significantly increased LF/HF as compared to placebo. Conclusions: A single dose of 8mg tolterodine ER, but not 4mg seems to reduce resting HRV versus placebo in young healthy subjects. This might be particular relevant for patients with pre-existing cardiac conditions on daily overactive bladder drug treatment and should be further investigated in larger trial

The facilitatory effect of duloxetine combined with pelvic floor muscle training on the excitability of urethral sphincter motor neurons

Introduction and hypothesis: Aim of this study was to investigate the excitability of sphincter motor neurons under the influence of pelvic floor muscle training (PFMT) and duloxetine. Due to their mechanisms of action, there might be a synergistic effect of duloxetine and PFMT in regard to the facilitation of spinal reflexes controlling urethral sphincter contractions and hence continence. Methods: In ten healthy female subjects, clitoral electric stimulation (CES) and transcranial magnetic stimulation (TMS) were used to determine individual motor thresholds for external urethral sphincter (EUS) contractions before and after PFMT, duloxetine, and PFMT + duloxetine. Results: PFMT and duloxetine alone significantly decreased the motor thresholds for EUS contractions during CES and TMS. However, the combined treatment reduced the motor threshold for EUS contractions significantly stronger compared to PFMT or duloxetine alone. Conclusions: The results are suggestive for a synergistic facilitatory effect of PFMT and duloxetine on sphincter motor neuron activatio

Potreba za psihosocijalnom rehabilitacijom oboljelih od raka

In addition to the healing and alleviation of primary somatic cancer symptoms, the comprehensive psycho oncological treatment of cancer patients is an important and fundamental component of oncological rehabilitation in Germany. Rehabilitation treatment encompasses medical, physiotherapeutic, psychological, and creative therapeutic methods, as well as psycho-educational interventions within the framework of an individualized therapy plan. Psycho-oncological interventions within rehabilitation are governed less by individual therapeutic schools of thought, and more by a supportive, patient-centered approach that integrates various psychotherapeutic methods. Adapted methods and techniques from various psychotherapeutic approaches (behavioral therapy, psychoanalytical psychotherapies, systemic family therapy, or hypnotherapy) are currently used in the treatment of cancer patients. A total of N=116 patients of the Paracelsus Clinic am See in Bad Gandersheim were able to be included in the study. In summary, this study shows that about two thirds of the patients admitted to the oncological rehabilitation clinic exhibit middle to high degrees of distress in the areas of anxiety and/or depression. Moreover, it appears to be particularly important to assess not only the mental distress of cancer patients but also their degree of information with regard to psycho-oncological treatment when performing screening for psycho-oncological treatment outside of the rehabilitation clinic setting. Here it is particularly important to accommodate for a differing need for differing forms of treatment (need for counseling, care, or treatment).Sveobuhvatno psiho-onkološko liječenje bolesnika s rakom važan je prilog u liječenju i ublažavanju primarnih somatskih simptoma te temeljna komponenta onkološke rehabilitacije u Saveznoj Republici Njemačkoj. Ova vrsta rehabilitacije obuhvaća medicinske, fizioterapijske, psihološke te kreativno terapijske pristupe, ali i psihoedukacijske intervencije u okviru individualiziranih terapijskih programa. Psiho-onkološki rehabilitacijski postupci manje su određeni kognitivnim psihoterapijskim metodma, a više potpornim, pacijentu usmjerenim pristupima koji obuhvaćaju različite psihoterapijske tehnike. Prilagođene metode i tehnike iz različitih psihoterapijskih pristupa (bihevioralna terapija, psihoanalitička psihoterapija, sistemska obiteljska terapija ili hipnoterapija) predstavljaju suvremeni koncept u liječenju onkoloških bolesnika. Ova studija provedena je na uzorku od 116 pacijenata Paracelsus Clinic am See u Bad Gandersheimu. Rezultati studije pokazali su da dvije trećine pacijenata uključenih u onkološku rehabilitaciju pokazuje srednji do visok stupanj poremećaja u području anksioznosti i/ili depresije. Osim toga, osobito je važno da se u uvjetima definiranja psiho-onkološkog liječenja u izvankliničkim uvjetima ne procjenjuje samo vrsta i stupanj psihičkog poremećaja, već također i razina informiranosti o psiho-onkološkom liječenju. U tom smislu posebno je važno različite oblike liječenja prilagoditi različitim osobnim potrebamabolesnika (npr. potreba za savjetovanjem, njegom, liječenjem)

Potreba za psihosocijalnom rehabilitacijom oboljelih od raka

In addition to the healing and alleviation of primary somatic cancer symptoms, the comprehensive psycho oncological treatment of cancer patients is an important and fundamental component of oncological rehabilitation in Germany. Rehabilitation treatment encompasses medical, physiotherapeutic, psychological, and creative therapeutic methods, as well as psycho-educational interventions within the framework of an individualized therapy plan. Psycho-oncological interventions within rehabilitation are governed less by individual therapeutic schools of thought, and more by a supportive, patient-centered approach that integrates various psychotherapeutic methods. Adapted methods and techniques from various psychotherapeutic approaches (behavioral therapy, psychoanalytical psychotherapies, systemic family therapy, or hypnotherapy) are currently used in the treatment of cancer patients. A total of N=116 patients of the Paracelsus Clinic am See in Bad Gandersheim were able to be included in the study. In summary, this study shows that about two thirds of the patients admitted to the oncological rehabilitation clinic exhibit middle to high degrees of distress in the areas of anxiety and/or depression. Moreover, it appears to be particularly important to assess not only the mental distress of cancer patients but also their degree of information with regard to psycho-oncological treatment when performing screening for psycho-oncological treatment outside of the rehabilitation clinic setting. Here it is particularly important to accommodate for a differing need for differing forms of treatment (need for counseling, care, or treatment).Sveobuhvatno psiho-onkološko liječenje bolesnika s rakom važan je prilog u liječenju i ublažavanju primarnih somatskih simptoma te temeljna komponenta onkološke rehabilitacije u Saveznoj Republici Njemačkoj. Ova vrsta rehabilitacije obuhvaća medicinske, fizioterapijske, psihološke te kreativno terapijske pristupe, ali i psihoedukacijske intervencije u okviru individualiziranih terapijskih programa. Psiho-onkološki rehabilitacijski postupci manje su određeni kognitivnim psihoterapijskim metodma, a više potpornim, pacijentu usmjerenim pristupima koji obuhvaćaju različite psihoterapijske tehnike. Prilagođene metode i tehnike iz različitih psihoterapijskih pristupa (bihevioralna terapija, psihoanalitička psihoterapija, sistemska obiteljska terapija ili hipnoterapija) predstavljaju suvremeni koncept u liječenju onkoloških bolesnika. Ova studija provedena je na uzorku od 116 pacijenata Paracelsus Clinic am See u Bad Gandersheimu. Rezultati studije pokazali su da dvije trećine pacijenata uključenih u onkološku rehabilitaciju pokazuje srednji do visok stupanj poremećaja u području anksioznosti i/ili depresije. Osim toga, osobito je važno da se u uvjetima definiranja psiho-onkološkog liječenja u izvankliničkim uvjetima ne procjenjuje samo vrsta i stupanj psihičkog poremećaja, već također i razina informiranosti o psiho-onkološkom liječenju. U tom smislu posebno je važno različite oblike liječenja prilagoditi različitim osobnim potrebamabolesnika (npr. potreba za savjetovanjem, njegom, liječenjem)

A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging

Objectives: Although botulinum neurotoxin type A (BoNT/A) intradetrusor injections are a recommended therapy for neurogenic detrusor overactivity (NDO), refractory to antimuscarinic drugs, a standardisation of injection technique is missing. Furthermore, some basic questions are still unanswered, as where the toxin solution exactly spreads after injection. Therefore, we investigated the distribution of the toxin solution after injection into the bladder wall, using magnet resonance imaging (MRI). Methods: Six patients with NDO were recruited. Three of six patients received 300U of BoNT/A+contrast agent distributed over 30 injection sites (group 1). The other three patients received 300U of BoNT/A+contrast agent distributed over 10 injection sites (group 2). Immediately after injection, MRI of the pelvis was performed. The volume of the detrusor and the total volume of contrast medium inside and outside the bladder wall were calculated. Results: In all patients, a small volume (mean 17.6%) was found at the lateral aspects of the bladder dome in the extraperitoneal fat tissue, whereas 82.4% of the injected volume reached the target area (detrusor). In both groups there was a similar distribution of the contrast medium in the target area. A mean of 33.3 and 25.3% of the total detrusor volume was covered in group 1 and 2, respectively. Six weeks after injection, five of six patients were continent and showed no detrusor overactivity in the urodynamic follow-up. No systemic side effects were observed. Conclusions: Our results provide morphological arguments that the currently used injection techniques are appropriate and saf

Abnormal Resting-State Network Presence in Females with Overactive Bladder

Overactive bladder (OAB) is a global problem reducing the quality of life of patients and increasing the costs of any healthcare system. The etiology of OAB is understudied but likely involves supraspinal network alterations. Here, we characterized supraspinal resting-state functional connectivity in 12 OAB patients and 12 healthy controls (HC) who were younger than 60 years. Independent component analysis showed that OAB patients had a weaker presence of the salience (Cohen's d = 0.9) and default mode network (Cohen's d = 1.1) and weaker directed connectivity between the fronto-parietal network and salience network with a longer lag time compared to HC. A region of interest analysis demonstrated weaker connectivity in OAB compared to HC (Cohen's d > 1.6 or 1.9). The degree of deviation in supraspinal connectivity in OAB patients (relative to HC) appears to be an indicator of the severity of the lower urinary tract symptoms and an indication that such symptoms are directly related to functional supraspinal alterations. Thus, future OAB therapy options should also consider supraspinal targets, while neuroimaging techniques should be given more consideration in the quest for better phenotyping of OAB

Supraspinal Control of Urine Storage and Micturition in Men—An fMRI Study

Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showed less robust activation during initiation of micturition, with activity in the forebrain and brainstem particularly lacking. Our findings suggest that micturition is controlled by a specific supraspinal network which is essential for the voluntary initiation of micturition. Once this network triggers the bulbospinal micturition reflex via brainstem centers, micturition continues automatically without further supraspinal input. Unsuccessful micturition is characterized by a failure to activate the periaqueductal gray and pons during initiatio

Urodynamic investigations in patients with spinal cord injury: should the ice water test follow or precede the standard filling cystometry?

OBJECTIVES To evaluate whether the ice water test (IWT) should be performed before or after the standard urodynamic investigation (UDI). PATIENTS AND METHODS Two cohorts of patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) were matched by lesion level and age. The patients of cohort A (n=55, retrospective cohort) underwent the IWT before and the patients of cohort B (n=110, prospective cohort) after standard UDI. The IWT effect on urodynamic parameters has been compared between the two groups using the Mann-Whitney U-test for independent samples. UDI was performed according to good urodynamic practices recommended by the International Continence Society. RESULTS The mean age of both cohorts was 49 years. Performing the IWT before versus after standard UDI resulted in a significantly lower maximum cystometric bladder capacity (P=0.01), lower incidence of detrusor overactivity (P=0.017) and lower maximum detrusor pressure during IWT (P=0.04). All other urodynamic parameters assessed demonstrated no significant difference (P>0.05). CONCLUSIONS Our results are in line with findings from animal studies demonstrating a bladder cooling-induced gating effect on the micturition reflex volume threshold on the level of sacral interneurons. Since the IWT is an unphysiological investigation that might significantly bias subsequent urodynamics, we suggest that the IWT should not precede more physiological standard UDI.Spinal Cord advance online publication, 22 September 2015; doi:10.1038/sc.2015.152

Lower urinary tract electrical sensory assessment: A systematic review and meta-analysis

OBJECTIVE To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs). The applied methods will be discussed in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics. METHODS The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched upon October 13, 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk-of-bias (RoB) as well as confounding. RESULTS After screening 9925 articles, 80 studies (5 randomized controlled trials (RCTs) and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects. 61 studies investigated exclusively CPTs and 19 studies reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and -SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in healthy subjects and patients. LUTESA demonstrated significant differences in LUT sensitivity between healthy subjects and neurological patients as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses revealed that several stimulation parameters (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies. CONCLUSIONS Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complement already established diagnostics such as urodynamics, allowing for a more comprehensive patient workup. The high RoB and confounding rate was rather related to inconsistency and inaccuracy in reporting than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool