A Prospective Observational Study of Posterior Tibial Nerve Stimulation in Multiple Sclerosis.

INTRODUCTION AND HYPOTHESIS: The objective was to examine the outcomes of posterior tibial nerve stimulation (PTNS) on bladder, bowel, and sexual health-related quality of life among a cohort of patients with multiple sclerosis (MS) with refractory lower urinary tract symptoms (LUTS). METHODS: Patients with MS and refractory LUTS were recruited for a prospective, observational study using PTNS to treat their symptoms. Patients underwent 12 weekly 30-min PTNS sessions and bladder, bowel, and sexual symptoms were evaluated at baseline, 3, 12, and 24 months with voiding diaries, visual analog scales (VAS), and validated patient-reported questionnaires, including the American Urological Association Symptom Score (AUA-SS), Neurogenic Bladder Symptom Score (NBSS), Michigan Incontinence Symptom Index (M-ISI), Health Status Questionnaire, Sexual Satisfaction Scale, and Bowel Control Scale. RESULTS: A total of 23 patients were recruited: 18 started PTNS and 14 completed 3 months of PTNS. Of the 18 who started PTNS, the mean age was 52 years (SD 12), 61% were female, 83% were white, and most patients had relapsing remitting (39%) MS. Baseline (n=18) and 3-month voiding (n=11) outcomes showed no significant change in number of voids or incontinence episodes. The median VAS symptom improvement was 49 (IQR 26.5, 26) and 9 (53%) patients elected for monthly maintenance PTNS. On paired analysis, there was a significant improvement in median change in NBSS, AUA-SS, and M-ISI. There was no significant change in bowel or sexual dysfunction. CONCLUSIONS: This prospective, observational study of PTNS in patients with MS with refractory LUTS shows improvement in patient-reported bladder outcomes, but not in number of voids per day or bowel or bladder function.

Feasibility and effectiveness of a distance-adapted physical activity intervention in adolescents with obesity during the COVID-19 pandemic.

BACKGROUND: Pediatric obesity represents one of the most important public health challenges and its prevalence significantly increased during the COVID-19 pandemic. Our prospective study aimed to assess the feasibility of a remote adapted physical activity (PA) intervention and its effectiveness in improving anthropometric indices, metabolic health parameters, as well as cardiopulmonary function and fitness in adolescents with obesity. METHODS: A PA intervention involving synchronous online lessons combined with asynchronous sessions and promotion of independent PA and "active breaks" to interrupt prolonged sedentary behaviors was proposed to 20 adolescents aged 11-17 years with obesity over a 4-month period. Clinical and anthropometric parameters (weight, height, waist, body composition, blood pressure), metabolic parameters (glycemia, insulinemia, glycated hemoglobin, oral glucose tolerance test [OGTT], lipid profile, presence of hepatic steatosis), cardiopulmonary function and fitness indices (VO2max, six-minute walking test [6MWT], upper and lower limb strength test) were evaluated before and after the intervention. RESULTS: Twenty adolescents with obesity were enrolled (11 male [55%], aged 14.1±1.5 years, BMI SDS 3.1±0.5). Eighteen participants (90%) successfully completed the project, and no adverse events were reported. We observed an increase in cardiovascular and muscle fitness [higher VO2peak, maximal workload, better performance at limb strength and 6MWT (all P<0.05)], increased lean body mass (P=0.005), and an improvement of glucose metabolism response with a reduction of insulin concentrations during OGTT (P=0.043). CONCLUSIONS: Participation in the training program was feasible and effective in improving cardiovascular fitness, glucose metabolism, body composition, strength, and endurance in adolescents with obesity during the COVID-19 pandemic.

Short-Term Dorsal Genital Nerve Stimulation Increases Subjective Arousal in Women With and Without Spinal Cord Injury: A Preliminary Investigation.

OBJECTIVES: Female sexual dysfunction (FSD) affects an estimated 40% of women. Unfortunately, FSD is understudied, leading to limited treatment options for FSD. Neuromodulation has shown some success in alleviating FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD. MATERIALS AND METHODS: This study comprises a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations. RESULTS: We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations. CONCLUSIONS: To our knowledge, this is the first study to measure sexual arousal in response to short-term neuromodulation in women. This study indicates that short-term DGNS but not TNS can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for FSD.

Integrating Patient Preferences with Guideline-Based Care in Neurogenic Lower Urinary Tract Dysfunction After Spinal Cord Injury.

Individual and social factors are important for clinical decision-making in patients with neurogenic bladder secondary to spinal cord injury (SCI). These factors include the availability of caregivers, social infrastructure, and personal preferences, which all can drive bladder management decisions. These elements can be overlooked in clinical decision-making; therefore, there is a need to elicit and prioritize patient preferences and values into neurogenic bladder care to facilitate personalized bladder management choices. For the purposes of this article, we review the role of guideline-based care and shared decision-making in the SCI population with neurogenic lower urinary tract dysfunction.

Patient and physician decision-making dynamics in overactive bladder care: A mixed methods study.

AIMS: Overactive bladder management includes multiple therapeutic options with comparable efficacy but a range of administration modalities and side effects, creating an ideal setting for shared decision-making. This study investigates patient and physician health beliefs surrounding decision-making and expectations for overactive bladder with the aim of better understanding and ultimately improving decision-making in overactive bladder care. METHODS: Patient and physician participants completed a questionnaire followed by a semi-structured interview to assess health beliefs surrounding decision making and expectations for overactive bladder treatment. The semi-structured interview guide, developed in an iterative fashion by the authors, probed qualities of overactive bladder therapies patients and physicians valued, their process of treatment selection, and their experiences with therapies. RESULTS: Patients (n = 20) frequently cited treatment invasiveness, efficacy, and safety as the most important qualities that influenced their decision when selecting overactive bladder therapy. Physicians (n = 12) frequently cited safety/contraindications, convenience, cost/insurance, and patient preference as the most important qualities. In our integration analysis, we identified four key themes associated with decision making in overactive bladder care: frustration with inaccessibility of overactive bladder treatments, discordant perception of patient education, diverging acceptability of expected outcomes, and lack of insight into other parties' decisional priorities and control preferences. CONCLUSIONS: While both patients and physicians desire to engage in a shared decision-making process when selecting therapies for overactive bladder, this process is challenged by significant divergence between patient and physician viewpoint across key domains.

Vacuum-assisted Mini-percutaneous Nephrolithotomy for 2-3-cm Renal Stones: A Comparative Study with Retrograde Intra-renal Surgery.

PURPOSE: To compare vacuum-assisted percutaneous nephrolithotomy (VAmini-PCNL) with retrograde intra-renal surgery (RIRS) for the treatment of renal stones measuring 2-3 cm in diameter. MATERIAL AND METHODS: This retrospective study included children receiving treatment for pyelocalyceal stones of 2-3 cm in diameter from November 2018 to September 2022. Consecutive patients undergoing VAmini-PCNL after 2020 were compared with a historically matched group undergoing RIRS. VAmini-PCNL was performed using a 12-Ch nephroscope through a 16-Ch vacuum ClearPetra access sheet. RIRS was performed using a flexible ureteroscope through a ureteral sheath. The endpoints included the need for pre-stenting, duration of surgery, complications, stone-free rate (SFR), and need for secondary procedures. RESULTS: The patients were grouped into two with 15 patients for each group. VAmini-PCNL group was not different from the RIRS one for age at surgery [median (range) 6.6 (1-12)years vs. 7.7 (1.5-14)years], and stone diameter [median (range) 2.4 (2.0-2.9)cm vs. 2.3 (2.1-2.8)cm] and density [median (range) 577.5 (421-1068) vs. 541.5 (462-927) Hunsfield Units]. Pre-stenting was necessary in five RIRS patients (33 %). The median duration of surgery was 85.3 (76-112)min for VAmini-PCNL vs. 150.6 (132-167)min for RIRS, p = 0.00001. No major complications were observed. The SFR was 100 % after VAmini-PCNL and 60 % after RIRS, p = 0.02. All residual fragments were removed with a second RIRS. CONCLUSION: VAmini-PCNL was feasible and safe in children aged >1 year. It allowed for a significantly higher SFR despite a significantly shorter operative time than RIRS, which also requires pre-stenting in one-third of patients and a second RIRS in 40 % of cases. LEVEL OF EVIDENCE: III.

Perceived vs Actual Shared Decision-Making Behavior Among Urologists: A Convergent, Parallel, Mixed-Methods Study of Self-Reported Practice.

OBJECTIVE: To evaluate the association between self-perceived use of shared decision-making among urologists with use of validated prediction tools and self-described surgical decision-making. METHODS: This is a convergent mixed methods study of these parallel data from two modules (Shared Decision Making and Validated Prediction tools) within the 2019 American Urological Association (AUA) Annual Census. The shared decision-making (SDM) module queried aspects of SDM that urologists regularly used. The validated prediction tools module queried whether urologists regularly used, trusted, and found prediction tools helpful. Selected respondents to the 2019 AUA Annual Census underwent qualitative interviews on their surgical decision-making. RESULTS: In the weight sampled of 12,312 practicing urologists, most (77%) reported routine use of SDM, whereas only 30% noted regular use of validated prediction tools. On multivariable analysis, users of prediction tools were not associated with regular SDM use (31% vs 28%, P = .006) though was associated with use of decision aids f (32% vs 26%, P < .001). Shared decision-making emerged thematically with respect to matching treatment options, prioritizing goals, and navigating challenging decisions. However, the six specific components of shared decision-making ranged in their mentions within qualitative interviews. CONCLUSION: Most urologists report performing SDM as supported by its thematic presence in surgical decision-making. However, only a minority use validated prediction tools and urologists infrequently mention specific SDM components. This discrepancy provides an opportunity to explore how urologists perform SDM and can be used to support integrated strategies to implement SDM more effectively in clinical practice.

Antibiotic use, best practice statement adherence, and UTI rate for intradetrusor onabotulinumtoxin-A injection for overactive bladder: A multi-institutional collaboration from the SUFU Research Network (SURN).

INTRODUCTION: Onabotulinumtoxin A (BTX-A) is a well-established treatment for overactive bladder (OAB). The American Urological Association (AUA) 2008 Antibiotic Best Practice Statement (BPS) recommended trimethoprim-sulfamethoxazole or fluoroquinolone for cystoscopy with manipulation. The aim of the study was to evaluate concordance with antibiotic best practices at the time of BTX-A injection and urinary tract infection (UTI) rates based on antibiotic regimen. METHODS: Men and women undergoing first-time BTX-A injection for idiopathic OAB with 100 units in 2016, within the SUFU Research Network (SURN) multi-institutional retrospective database were included. Patients on suppressive antibiotics were excluded. The primary outcome was concordance of periprocedural antibiotic use with the AUA 2008 BPS antimicrobials of choice for "cystoscopy with manipulation." As a secondary outcome we compared the incidence of UTI among women within 30 days after BTX-A administration. Each outcome was further stratified by procedure setting (office vs. operating room; OR). RESULTS: Of the cohort of 216 subjects (175 women, 41 men) undergoing BTX-A, 24 different periprocedural antibiotic regimens were utilized, and 98 (45%) underwent BTX-A injections in the OR setting while 118 (55%) underwent BTX-A injection in the office. Antibiotics were given to 86% of patients in the OR versus 77% in office, and 8.3% of subjects received BPS concordant antibiotics in the OR versus 82% in office. UTI rates did not vary significantly among the 141 subjects who received antibiotics and had 30-day follow-up (8% BPS-concordant vs. 16% BPS-discordant, CI -2.4% to 19%, p = 0.13). A sensitivity analysis of UTI rates based on procedure setting (office vs. OR) did not demonstrate any difference in UTI rates (p = 0.14). CONCLUSIONS: This retrospective multi-institutional study demonstrates that antibiotic regimens and adherence to the 2008 AUA BPS were highly variable among providers with lower rates of BPS concordant antibiotic use in the OR setting. UTI rates at 30 days following BTX-A did not vary significantly based on concordance with the BPS or procedure setting.

Percutaneous tibial nerve stimulation in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients: a historically controlled study.

Background: Percutaneous tibial nerve stimulation (PTNS) is widely used in the treatment of neurogenic detrusor overactivity (NDO) in multiple sclerosis (MS); however, controlled studies are still lacking.Objective:: To assess effectiveness of PTNS in MS patients with NDO unresponsive to pharmacological and behavioural therapies. Methods: MS patients with NDO were enrolled. Inclusion criteria were NDO not responding to pharmacological and behavioural therapies. Exclusion criteria were the presence of relevant comorbidities and urinary tract infections. Patients were evaluated using 3-day bladder diaries and validated questionnaires at baseline, after 4 weeks of educational therapy and after 12 PTNS sessions. The primary outcome measure was the percentage of patients considered responders after the behavioural therapy and after the PTNS in a historical controlled fashion (definition of 'responder' was reduction ⩾50% of urgency episodes). Results: A total of 33 patients (26 women, 7 men) were enrolled. Two patients dropped out for reasons not related to the protocol. Two out of 31 patients (6.5%) and 21/29 (72.4%) were considered responders at visits 1 and 2, respectively. In PTNS responders, a statistically significant improvement in both bladder diary results and standardized questionnaire scores was recorded, compared with that obtained with behavioural therapy alone. No serious adverse events were reported. Conclusion: This historically controlled study suggests that PTNS may be effective in improving NDO in MS patients.

Acute dorsal genital nerve stimulation increases subjective arousal in women with and without spinal cord injury: a preliminary investigation.

Introduction: Female sexual dysfunction (FSD) impacts an estimated 40% of women. Unfortunately, female sexual function is understudied, leading to limited treatment options for FSD. Neuromodulation has demonstrated some success in improving FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD. Methods: This study consists of a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations. Results: We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations. Discussion: This is the first study to measure sexual arousal in response to acute neuromodulation in women. This study demonstrates that acute DGNS, but not TNS, can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for female sexual dysfunction.

Neuron-selective toxicity of tau peptide in a cell culture model of neurodegenerative tauopathy: essential role for aggregation in neurotoxicity.

Intracellular aggregation of tau is a pathological hallmark in Alzheimer's disease and other tauopathies. The mechanisms underlying tau aggregation and the role that these aggregates play in neuronal death have remained controversial. To study these issues, we established a cell culture model of tauopathy using a hexameric peptide with the sequence (306)VQIVYK(311) located within the third microtubule-binding repeat of tau, rendered cell-permeable by a tag of nine arginine residues (R(9)). This peptide (VQIVYK-R(9)), designated as T-peptide, self-assembles in vitro into paired helical filament-like aggregates. Primary neuronal cells treated with T-peptide die within 24 hr. Neurodegeneration correlates with the ability of the peptide to aggregate. Two peptides with mutations in the hexameric core, K-peptide (VQIVKK) and VV-peptide (VQVVVK), that are incapable of aggregating are not toxic, whereas two other mutant peptides, V-peptide (VQVVYK) and F-peptide (VQIVFK), which aggregate, are also neurotoxic. Two other peptides that aggregate in vitro, but are not derived from tau, are not neurotoxic suggesting sequence dependence. Although localizing to the nucleus, T-peptide induces aggregation of cellular proteins in the cytoplasm. These aggregates are not caused by disruption of endogenous tau localization, although endogenous tau is reduced in neurons exposed to T-peptide. Interestingly, nonneuronal cells are less sensitive to T-peptide toxicity, recapitulating in part the selective loss of neurons in tauopathies. Moreover, T-peptide treatment leads to mitochondrial dysfunction, a common feature of neurodegenerative disorders. The model system described here represents a convenient paradigm for studying the mechanisms underlying tau aggregation and neurotoxicity and for identifying compounds that can prevent these effects.