Transcutaneous Electrical Stimulation of the Abdomen, Ear, and Tibial Nerve Modulates Bladder Contraction in a Rat Detrusor Overactivity Model: A Pilot Study.

PURPOSE: The global prevalence of overactive bladder (OAB) is estimated at 11.8%. Despite existing treatment options such as sacral neuromodulation, a substantial number of patients remain untreated. One potential alternative is noninvasive transcutaneous electrical stimulation. This form of stimulation does not necessitate the implantation of an electrode, thereby eliminating the need for highly skilled surgeons, expensive implantable devices, or regular hospital visits. We hypothesized that alternative neural pathways can impact bladder contraction. METHODS: In this pilot study, we conducted transcutaneous electrical stimulation of the abdominal wall (T6-L1), the ear (vagus nerve), and the ankle (tibial nerve) of 3 anesthetized female Sprague-Dawley rats. Stimulation was administered within a range of 20 Hz to 20 kHz, and its impact on intravesical pressure was measured. We focused on 3 primary outcomes related to intravesical pressure: (1) the pressure change from the onset of a contraction to its peak, (2) the average duration of contraction, and (3) the number of contractions within a specified timeframe. These measurements were taken while the bladder was filled with either saline or acetic acid (serving as a model for OAB). RESULTS: Transcutaneous stimulation of the abdominal wall, ear, and ankle at a frequency of 20 Hz decreased the number of bladder contractions during infusion with acetic acid. As revealed by a comparison of various stimulation frequencies of the tibial nerve during bladder infusion with acetic acid, the duration of contraction was significantly shorter during stimulation at 1 kHz and 3 kHz relative to stimulation at 20 Hz (P = 0.025 and P = 0.044, respectively). CONCLUSION: The application of transcutaneous electrical stimulation to the abdominal wall, ear, and tibial nerve could provide less invasive and more cost-effective treatment options for OAB relative to percutaneous tibial nerve stimulation and sacral neuromodulation. A follow-up study involving a larger sample size is recommended.

Variation of diagnosis and treatment of catheter-associated urinary tract infections: an online survey among caretakers involved.

Background: The diagnosis of a clinically significant catheter-associated urinary tract infection (CAUTI) in patients performing clean intermittent catheterization (CIC) or with an indwelling catheter (IC) can be challenging. Objective: To get an insight into the variation of the used definition, diagnosis and management of CAUTIs by relevant healthcare workers in the Netherlands. Design: An online clinical scenario-based survey. Methods: The survey was built in Limesurvey and distributed to healthcare workers from randomly selected urology departments, rehabilitation departments/centres and general practice offices between January and May 2022. Questions regarding their field of experience, management strategies, used guidelines and two hypothetical cases with clinical scenarios of a possible CAUTI were included. Results: A total of 172 individuals participated, of which 112 completed the survey. In all, 32 individuals who completed the survey partially were also included. Participants consisted of 68 [44 urologists, 22 rehabilitation doctors (RDs) and 2 general practitioners (GPs)] doctors, 60 nurses (46 from the urology department and 14 from rehabilitation centres/departments) and 16 medical assistants (13 from urology department and 3 from GP offices). The majority consulted patients with an IC or on CIC on a daily/weekly or monthly basis. In all, 35 urologists (79.5%), 9 RDs (40.9%), 21 (45.7%) nurses in the urology department and 6 (42.9%) nurses from a rehabilitation department/centre indicated bladder irrigation as a treatment option for prevention/treatment of CAUTIs, treatment of symptoms or treatment of blockage of the catheter. In the clinical scenarios presented, treatment discrepancies were seen between subspecialties and healthcare workers. Various guidelines were named for the definition of CAUTIs. Conclusion: A considerable variation in diagnoses and management of CAUTIs between the healthcare workers involved was seen. Uniformity in diagnosing and managing CAUTIs, to prevent overtreatment and possible resistance to antibiotics, is advised. Suitable multidisciplinary guidelines are preferred.

Androgen receptors in the forebrain: A study in adult male cats.

Androgens and their receptors are present throughout the body. Various structures such as muscles, genitals, and prostate express androgen receptors. The central nervous system also expresses androgen receptors. Androgens cross the blood-brain barrier to reach these central areas. In the central nervous system, androgens are involved in multiple functions. The current study investigated in which forebrain areas androgens are expressed in the male cat. Androgen receptor immunoreactive (AR-IR) nuclei were plotted and the results were quantified with a Heidelberg Topaz II + scanner and Linocolor 5.0 software. The density and intensity of the labeled cells were the main outcomes of interest. The analysis revealed a dense distribution of AR-IR nuclei in the preoptic area, periventricular complex of the hypothalamus, posterior hypothalamic area, ventromedial hypothalamic, parvocellular hypothalamic, infundibular, and supramammillary nucleus. Numerous AR-IR cells were also observed in the dorsal division of the anterior olfactory nucleus, lateral septal nucleus, medial and lateral divisions of the bed nucleus of the stria terminalis, lateral olfactory tract nucleus, anterior amygdaloid area, and the central and medial amygdaloid nuclei. AR-IR nuclei were predominantly observed in areas involved in autonomic and neuroendocrinergic responses which are important for many physiological processes and behaviors.

Two-Staged Sacral Neuromodulation for the Treatment of Nonobstructive Urinary Retention: A Multicenter Study Assessing Predictors of Success.

OBJECTIVES: The aims of this study were to 1) determine the success rate of the tined lead test phase in patients with nonobstructive urinary retention (NOUR), 2) determine predictive factors of a successful test phase in patients with NOUR, and 3) determine long-term treatment efficacy and satisfaction in patients with NOUR. MATERIALS AND METHODS: The first part was a multicenter retrospective study at two centers in The Netherlands. Patients with NOUR received a four-week tined lead test phase. Success was defined as a ≥50% reduction of clean intermittent catheterization frequency or postvoid residual. We analyzed possible predictors of success with multivariable logistic regression. Second, all patients received a questionnaire to assess efficacy, perceived health (Patient Global Impression of Improvement), and treatment satisfaction. RESULTS: This study included 215 consecutive patients (82 men and 133 women) who underwent a tined lead test phase for the treatment of NOUR. The success rate in women was significantly higher than in men, respectively 62% (83/133) and 22% (18/82, p < 0.001). In women, age per ten years (odds ratio [OR] 0.74, 95% CI: 0.59-0.93) and a history of psychiatric illness (OR 3.92, 95% CI: 1.51-10.2), including posttraumatic stress disorder (PTSD), significantly predicted first stage sacral neuromodulation (SNM) success. In men, age per ten years (OR 0.43, 95% CI: 0.25-0.72) and previous transurethral resection of the prostate and/or bladder neck incision (OR 7.71, 95% CI: 1.43-41.5) were significant predictors of success. Conversely, inability to void during a urodynamic study (for women, OR 0.79, 95% CI: 0.35-1.78; for men, OR 3.06, 95% CI: 0.83-11.3) was not predictive of success. Of the patients with a successful first stage, 75% (76/101) responded to the questionnaire at a median follow-up of three years. Of these patients, 87% (66/76) continued to use their SNM system, and 92% (70/76) would recommend SNM to other patients. CONCLUSIONS: A history of psychiatric illness, including PTSD, in women with NOUR increased the odds of first stage SNM success 3.92 times. A previous transurethral resection of the prostate and/or bladder neck incision in men increased the odds of success 7.71 times. In addition, a ten-year age increase was associated with an OR of 0.43 in men and 0.74 in women, indicating a 2.3- and 1.3-times decreased odds of success, respectively.

Kilohertz alternating current neuromodulation of the pudendal nerves: effects on the anal canal and anal sphincter in rats.

The first two objectives were to establish which stimulation parameters of kilohertz frequency alternating current (KHFAC) neuromodulation influence the effectiveness of pudendal nerve block and its safety. The third aim was to determine whether KHFAC neuromodulation of the pudendal nerve can relax the pelvic musculature, including the anal sphincter. Simulation experiments were conducted to establish which parameters can be adjusted to improve the effectiveness and safety of the nerve block. The outcome measures were block threshold (measure of effectiveness) and block threshold charge per phase (measure of safety). In vivo, the pudendal nerves in 11 male and 2 female anesthetized Sprague Dawley rats were stimulated in the range of 10 Hz to 40 kHz, and the effect on anal pressure was measured. The simulations showed that block threshold and block threshold charge per phase depend on waveform, interphase delay, electrode-to-axon distance, interpolar distance, and electrode array orientation. In vivo, the average anal pressure during unilateral KHFAC stimulation was significantly lower than the average peak anal pressure during low-frequency stimulation (p < 0.001). Stimulation with 20 kHz and 40 kHz (square wave, 10 V amplitude, 50% duty cycle, no interphase delay) induced the largest anal pressure decrease during both unilateral and bilateral stimulation. However, no statistically significant differences were detected between the different frequencies. This study showed that waveform, interphase delay and the alignment of the electrode along the nerve affect the effectiveness and safety of KHFAC stimulation. Additionally, we showed that KHFAC neuromodulation of the pudendal nerves with an electrode array effectively reduces anal pressure in rats.

Androgen receptors in areas of the spinal cord and brainstem: A study in adult male cats.

Sex hormones, including androgens and estrogens, play an important role in autonomic, reproductive and sexual behavior. The areas that are important in these behaviors lie within the spinal cord and brainstem. Relevant dysfunctional behavior in patients with altered androgen availability or androgen receptor sensitivity might be explained by the distribution of androgens and their receptors in the central nervous system. We hypothesize that autonomic dysfunction is correlated with the androgen sensitivity of spinal cord and brainstem areas responsible for autonomic functions. In this study, androgen receptor immunoreactive (AR-IR) nuclei in the spinal cord and brainstem were studied using the androgen receptor antibody PG21 in four uncastrated young adult male cats. A dense distribution of AR-IR nuclei was detected in the superior layers of the dorsal horn, including lamina I. Intensely stained nuclei, but less densely distributed, were found in lamina X and preganglionic sympathetic and parasympathetic cells of the intermediolateral cell column. Areas in the caudal brainstem showing a high density of AR-IR nuclei included the area postrema, the dorsal motor vagus nucleus and the retrotrapezoid nucleus. More cranially, the central linear nucleus in the pons contained a dense distribution of AR-IR nuclei. The mesencephalic periaqueductal gray (PAG) showed a dense distribution of AR-IR nuclei apart from the most central part of the PAG directly adjacent to the ependymal lining. Other areas in the mesencephalon with a dense distribution of AR-IR nuclei were the dorsal raphe nucleus, the retrorubral nucleus, the substantia nigra and the ventral tegmental area of Tsai. It is concluded that AR-IR nuclei are located in specific areas of the central nervous system that are involved in the control of sensory function and autonomic behavior. Furthermore, damage of these AR-IR areas might explain related dysfunction in humans.

Transcutaneous Electrical Nerve Stimulation and Percutaneous Tibial Nerve Stimulation to Treat Idiopathic Nonobstructive Urinary Retention: A Systematic Review.

CONTEXT: Transcutaneous electrical nerve stimulation (TENS) and percutaneous tibial nerve stimulation (PTNS) provide minimally invasive ways to treat idiopathic nonobstructive urinary retention (NOUR). OBJECTIVE: To assess the efficacy of TENS and PTNS for treating idiopathic NOUR. EVIDENCE ACQUISITION: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Embase, Medline, Web of Science Core Collection, and the Cochrane CENTRAL register of trials were searched for all relevant publications until April 2020. EVIDENCE SYNTHESIS: A total of 3307 records were screened based on the title and abstract. Eight studies met the inclusion criteria and none of the exclusion criteria. Five studies, all from the same group, reported the efficacy of PTNS and two that of TENS in adults with idiopathic NOUR. One study reported the efficacy of TENS in children with idiopathic NOUR. Objective success was defined as a ≥50% decrease in the number of catheterizations per 24 h or in the total catheterized volume in 24 h. The objective success rate of PTNS ranged from 25% to 41%. Subjective success was defined as the patient's request for continued chronic treatment with PTNS, and ranged from 46.7% to 59%. Eighty percent of women who underwent transvaginal stimulation reported an improvement such as a stronger stream when voiding. TENS in children reduced postvoid residual and urinary tract infections. CONCLUSIONS: The efficacy of TENS and PTNS in the treatment of idiopathic NOUR is limited and should be verified in larger randomized studies before application in clinical practice. PATIENT SUMMARY: The outcomes of transcutaneous electrical nerve stimulation and percutaneous tibial nerve stimulation for the treatment of urinary retention of unknown origin were reviewed. Whether these treatments are superior to other treatments could not be established.

Recent advances in neuroimaging of bladder, bowel and sexual function.

PURPOSE OF REVIEW: In this review, we summarize recent advances in the understanding of the neural control of the bladder, bowel and sexual function, in both men and women. RECENT FINDINGS: Evidence of supraspinal areas controlling the storage of urine and micturition in animals, such as the pontine micturition centre, emerged in the early 20th century. Neurological stimulation and lesion studies in humans provided additional indirect evidence for additional bladder-related brain areas. Thereafter, functional neuroimaging in humans with PET and fMRI provided more direct evidence of the involvement of these brain areas. The areas involved in the storage and expulsion of urine also seem to be involved in the central control of storage and expulsion of feces. Furthermore, most knowledge on the brain control of sexual function is obtained from dynamic imaging in human volunteers. Relatively little is known about the dysfunctional central circuits in patients with pelvic organ dysfunction. SUMMARY: fMRI has been the most widely used functional neuroimaging technique in the last decade to study the central control of bladder function, anorectal function and sexual function. The studies described in this review show which sensory and motor areas are involved, including cortical and subcortical areas. We propose the existence of a switch-like phenomenon located in the pons controlling micturition, defecation and orgasm.

Frequent atrial extrasystolic beats predict atrial fibrillation in patients with congenital heart defects.

Aims: Atrial fibrillation (AF) is increasingly observed in patients with congenital heart defects (CHDs) who survive nowadays into adulthood. Yet, predictors of AF are scarce in this high-risk population. This study therefore examined the predictive ability of atrial extrasystole (AES) for development of AF in CHD patients. Methods and results: Adult CHD patients who had a 24 h Holter registration were followed to determine who developed AF. A total of 573 patients (49% male, mean age 35 ± 12 years) were included; they had a simple/complete repaired CHD (n = 279), complex repaired CHD (n = 251), or univentricular heart (UVH, n = 43). Ageing (P < 0.0001), female gender (P = 0.028), UVH (P = 0.0010), and left atrial dilatation (P = 0.0025) were associated with the number of AES. During a median follow-up of 51.6 months (interquartile range 22.8-85.7), 29 patients (5%) developed de novo AF. An one-point increase in the number of logtotal-AES was associated with a two-fold higher risk of AF development (hazard ratio 1.95; 95% confidence interval 1.21-3.13; P = 0.016). C-statistic for left atrial dilatation, complexity, and age had a good discriminative ability for the incidence of AF with a C-statistic of 84.5%. The addition of the total number of AES/24 h to this model increased C-statistic to 88.4%. Conclusion: Atrial extrasystole occur relatively frequent in adult CHD patients compared with patients with other cardiac diseases. This is the first study that showed an association between an increased AES frequency and a higher risk of AF development in CHD patients.