Efficacy of sacral transcutaneous electrical nerve stimulation in patients with overactive bladder refractory to anticholinergic treatment: a prospective multi-center study. / Eficacia de la electroestimulación transcutánea sacra en pacientes con vejiga hiperactiva refractarios a fármacos anticolinérgicos. Estudio prospectivo y multicéntrico.

OBJECTIVE: To determine whether sacral transcutaneous electrical nerve stimulation (S-TENS) is an effective treatment in patients refractory to anticholinergic drugs (Achs). MATERIALS AND METHODS: A prospective multi-center study of patients with overactive bladder (OB) refractory to Achs treated with S-TENS from 2018 to 2021 was carried out. S-TENS was applied over 3 months. Symptom progression was assessed using the voiding calendar and the Pediatric Lower Urinary Tract Symptoms Score (PLUTSS), excluding questions 3 and 4 -referring to enuresis- so that progression of daytime symptoms only (LUTS variable) was analyzed. RESULTS: 66 patients -50% of whom were female- were included, with a mean age of 9.5 years (range: 5-15). S-TENS significantly lowered PLUTSS (19.1 baseline vs. 9.5 final, p< 0.001) and LUTS (13.1 baseline vs. 4.8 final, p< 0.001). It also reduced the number of mictions (8.5 baseline vs. 6.4 final, p< 0.001), while increasing urine volume in the voiding records (214 ml baseline vs. 258 ml final, p< 0.001). Enuresis was the only variable refractory to S-TENS. Complication rate was 3% (2 patients with dermatitis in the S-TENS application area). CONCLUSIONS: S-TENS is effective and safe in the short-term in patients with OB refractory to Achs. Further studies assessing long-term efficacy and potential relapses are required.

OBJETIVOS: Determinar si la electroterapia nerviosa transcutánea a nivel sacro (TENS-S) es un tratamiento efectivo en pacientes refractarios a fármacos anticolinérgicos (Ach). MATERIAL Y METODOS: Estudio prospectivo y multicéntrico: pacientes con VH refractaria a Ach tratados con TENS-S entre 2018-2021. El TENS-S se aplicó durante 3 meses. La evolución sintomática fue evaluada utilizando el calendario miccional y el cuestionario PLUTSS (Pediatric Lower Urinary Tract Symptoms Score), pero excluyendo sus preguntas 3 y 4 (referidas a la enuresis) para analizar solamente la evolución de la sintomatología diurna (variable LUTS). RESULTADOS: Fueron incluidos 66 pacientes (50% niñas), con una edad media de 9,5 años (rango: 5-15). El TENS-S disminuyó significativamente el PLUTSS (19,1 inicial vs 9,5 final, p< 0,001) y el LUTS (13,1 inicial vs 4,8 final, p< 0,001). Además, redujo el número de micciones (8,5 inicial vs 6,4 final, p< 0,001) y aumentó el volumen de orina en los registros miccionales (214 ml inicial vs 258 ml final, p< 0,001). La enuresis fue la única variable refractaria al TENS-S. La tasa de complicaciones fue del 3% (2 pacientes, dermatitis en el área de aplicación del TENS-S). CONCLUSIONES: El TENS-S es efectivo y seguro a corto plazo en pacientes con VH refractarios a los Ach. Deben realizarse estudios para evaluar la eficacia a largo plazo y posibles recaídas.

Transcutaneous electrical nerve stimulation as add-on therapy in children receiving anticholinergics and/or mirabegron for refractory daytime urinary incontinence: A retrospective cohort study.

AIMS: To investigate if children with daytime urinary incontinence (DUI) and overactive bladder (OAB) refractory to standard urotherapy and medicinal treatment, would experience improvement in symptoms after add-on treatment with transcutaneous electrical nerve stimulation (TENS). METHODS: Children were retrospectively enrolled from tertiary referral centers at Aarhus and Aalborg University Hospitals. All data were retrieved from the patients' journals. All children were prescribed TENS as an add-on treatment to the highest-tolerable dose of medicinal treatment in a standardized regime of 2 h a day for around 3 months. Primary endpoints were the number of wet days per week (WDPW) and incontinence episodes per day. Effect of treatment was defined as greater or equal to 50% reduction in the frequency of DUI episodes. Secondary endpoints were to establish predictive factors for the effect of treatment using logistic regression. RESULTS: Seventy-six children diagnosed with DUI and OAB refractory to treatment with standard urotherapy and pharmacological treatment, at the age of 5-16 years were included from February 2017 to February 2020. A reduction in WDPW (from 6.31 [5.86-6.61] to 4.27 [3.45-4.90], p < 0.05) and incontinence episodes per day (from 2.45 [1.98-2.91] to 1.43 [1.07-1.80], p < 0.05) was observed. Twelve patients became completely dry. At 6 months follow-up, seven of the 12 complete responders had relapsed while five remained dry. A history of constipation before TENS was a predictor of poor treatment response (p = 0.016). CONCLUSIONS: TENS as add-on to anticholinergic treatment seems effective in a number of children with treatment-refractory DUI.

The efficacy and safety of electrostimulation of the posterior tibial nerve and antimuscarinic drugs in the treatment of overactive bladder: a meta-analysis and systemic review / 中华泌尿外科杂志

Objective:To systematically review the efficacy and safety of electrostimulation of the posterior tibial nerve and antimuscarinic drugs in the treatment of overactive bladder.Methods:The literature search was conducted using the PubMed, The Cochrane Library, EMbase, Medline, CNKI, CQVIP, Wanfang databases.The retrieval period was from the establishment of the database to February 2021. Literature was screened and evaluated independently by two investigators to compare the safety and efficacy of electrostimulation of the posterior tibial nerve and antimuscarinic drugs in the treatment of overactive bladder. Meta-analysis was performed using Review Manager 5.4 software.Results:A total of 11 clinical trials, including 10 randomized controlled trials and 1 cross-over study were included, involving 605 patients, including 309 in the experimental group (nerve stimulation group) and 296 in the control group(antimuscarinic drugs group). The results of meta-analysis showed as follow. For patients with non-neurogenetic overactive bladder, there was no statistically significant differences between electrostimulation of the posterior tibial nerve therapy and antimuscarinic drugs in the improvement of 24h urination frequency( MD=-0.06, 95% CI -1.67-1.54, P>0.05), 24h urge incontinence frequency( MD=0.04, 95% CI -0.46-0.54, P>0.05), symptoms scores of OAB-q questionnaire( MD=0.37, 95% CI -0.02-0.76, P>0.05)and quality of life scores( SMD=0.32, 95% CI-0.06-0.69, P>0.05). However, compared with antimuscarinic drugs, posterior tibial nerve stimulation had better efficacy satisfaction rate ( OR=1.97, 95% CI 1.16-3.36, P<0.05) and lower side effect rate ( OR=0.24, 95% CI 0.12-0.48, P<0.0001). And the results have significant statistical differences. Conclusions:Electrostimulation of the posterior tibial nerve was almost as effective as antimuscarinic drugs in improving symptoms and quality of life in patients with non-neurogenic OAB. However, compared with antimuscarinic drugs, electrostimulation of the posterior tibial nerve had a higher efficacy satisfaction rate and a lower incidence of side effects. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.

Comparative associations between anticholinergic burden and emergency department visits for anticholinergic adverse events in older Korean adults: a nested case-control study using national claims data for validation of a novel country-specific scale.

BACKGROUND: Considering the limited generalizability of previous anticholinergic burden scales, the Korean Anticholinergic Burden Scale (KABS) as a scale specific to the Korean population was developed. We aimed to validate the KABS by detecting the associations between high anticholinergic burden, measured with the KABS, and emergency department (ED) visits compared to the pre-existing validated scales in older Korean adults. METHODS: A nested case-control study was conducted using national claims data. The cases included the first anticholinergic ED visits between July 1 and December 31, 2016. Anticholinergic ED visits were defined as ED visits with a primary diagnosis of constipation, delirium, dizziness, fall, fracture, or urinary retention. Propensity score-matched controls were identified. Average daily AB scores during 30 days before the index date were measured. Multivariate logistic regression analyses were performed. RESULTS: In total, 461,034 were included. The highest proportion of those with high AB was identified with KABS (5.0%). Compared with those who had a KABS score of 0, older adults with a score ≥ 3 were at higher risk for overall anticholinergic ED visits (aOR, 1.62, 95% CI, 1.53-1.72), as well as visits for falls/fractures (aOR: 1.54, 95% CI: 1.40-1.69), dizziness (aOR: 1.44, 95% CI: 1.30-1.59), delirium (aOR: 2.96, 95% CI: 2.28-3.83), constipation (aOR: 1.84, 95% CI: 1.68-2.02), and urinary retention (aOR: 2.13, 95% CI: 1.79-2.55). High AB by KABS showed a stronger association with overall anticholinergic ED visits and visits due to delirium and urinary retention than those by other scales. CONCLUSIONS: In conclusion, KABS is superior to pre-existing scales in identifying patients with high AB and predicting high AB-related ED visits in older Korean adults.

Intracerebroventricular microinjection of kaempferol on memory retention of passive avoidance learning in rats: involvement of cholinergic mechanism(s).

Purpose of the study: Kaempferol (KM) is a flavonoid found in plant-derived foods and medicinal plants. Recently, it is well established that KM plays a protective role to develop Alzheimer's disease. The current study aimed at evaluating the effect of intracerebroventricular micro-injection of KM on memory retention of passive avoidance learning (MRPAM) and identifying the potentially related cholinergic mechanisms (ChMs) in rats. Materials and methods: In the current study, male Wistar rats randomly divided into control, vehicle and KM (10, 20 and 40 µg/rat) groups. Moreover, MRPAM was evaluated by shuttle box test. The role of ChM was studied using non-selective and selective acetylcholine antagonists (scopolamine [SCN], 4-DAMP and methoctramine [MN], respectively) as well as pirenzepine (PZ) in combination with KM. Results: The employment of KM (40 µg/rat) improved the SCN-induced memory impairment in MRPAM. Co-treatment with KM (40 µg/rat) plus 4-DAMP significantly increased the step-through latency (STL, P < 0.05; 167 ± 28 s) and decreased the total dark chamber (TDC, P < 0.05; 121 ± 31 s) compared with those of the 4-DAMP group (STL: 75 ± 13 s; TDC: 178 ± 46 s). Co-treatment with KM (40 µg/rat) plus PZ attenuated STL, and also increased TDC (P < 0.01; 220 ± 28 s) compared with those of the PZ group. Co-treatment with KM (10 and 20 µg/rat) and MN increased STL (P < 0.05), and deceased TDC compared with those of the MN group (P < 0.01). Conclusions: Totally, the results of the present study showed that cholinergic system may be involved in improving effect of KM on SCN-induced memory impairment.

Do Patients Discontinue Overactive Bladder Medications after Sacral Neuromodulation?

PURPOSE: Overactive bladder medications often have poor tolerability or lack of efficacy with many patients progressing to third line therapy such as sacral neuromodulation. Those treated with sacral neuromodulation may avoid the potential side effects of overactive bladder medications while achieving symptom improvement. We evaluated the postoperative rate of discontinuing overactive bladder medications in patients who underwent sacral neuromodulation of refractory overactive bladder. MATERIALS AND METHODS: We queried a prospectively collected, institutional review board approved database for patients who underwent sacral neuromodulation. Patients were excluded from analysis if the surgical indication was urinary retention or a sacral neuromodulation device was removed 1 year or less postoperatively. We assessed clinical characteristics, urodynamic parameters and filled overactive bladder medications using an external prescription database. Patient perceived postoperative outcomes were examined. Groups were compared by the Student t-test and the chi-square test. RESULTS: Of the 78 patients who met inclusion criteria 82.1% stopped and never restarted overactive bladder medications (the sacral neuromodulation only group). Of the patients 14.1% consecutively continued filling overactive bladder medications 1 year or more following surgery (the concurrent group). There was no difference between the groups in body mass index, gender, sacral neuromodulation revision, urodynamic parameters, the PGI-I (Patient Global Impression of Improvement) or patient perceived percent improvement. However, concurrent patients were significantly older than those who received sacral neuromodulation only (p = 0.002). CONCLUSIONS: More than 80% of patients who progressed to sacral neuromodulation discontinued overactive bladder medications and received sacral neuromodulation as the sole treatment. A small portion of patients concurrently used overactive bladder medications following sacral neuromodulation for 1 year or more. However, outcomes were similar in the 2 groups. Sacral neuromodulation is a strategy to provide a successful outcome in refractory cases and yet avoid the potentially detrimental side effects related to overactive bladder medications.

Predictors of short-term LAMA ineffectiveness in treatment naïve patients with moderate to severe COPD.

BACKGROUND: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients. METHODS: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6­min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV1), and as single components. RESULTS: Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (p = 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p < 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV1 with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (p < 0.001). CONCLUSION: Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD.

Treatment of uncommon sites of focal primary hyperhidrosis: experience with pharmacological therapy using oxybutynin

OBJECTIVES: Primary hyperhidrosis usually affects the hands, armpits, feet and cranio-facial region. Sweating in other areas is common in secondary hyperhidrosis (after surgery or in specific clinical conditions). Oxybutynin has provided good results and is an alternative for treating hyperhidrosis at common sites. Our aim was to evaluate the efficacy of oxybutynin as a treatment for primary sweating at uncommon sites (e.g., the back and groin). METHODS: This retrospective study analyzed 20 patients (10 females) who received oxybutynin for primary focal hyperhidrosis at uncommon sites. The subjects were evaluated to determine quality of life before beginning oxybutynin and six weeks afterward and they were assigned grades (on a scale from 0 to 10) to measure their improvement at each site of excessive sweating after six weeks and at the last consult. RESULTS: The median follow-up time with oxybutynin was 385 days (133-1526 days). The most common sites were the back (n = 7) and groin (n = 5). After six weeks, the quality of life improved in 85% of the subjects. Dry mouth was very common and was reported by 16 patients, 12 of whom reported moderate/severe dry mouth. Five patients stopped treatment (two: unbearable dry mouth, two: excessive somnolence and one: palpitations). At the last visit, 80% of patients presented with moderate/great improvement at the main sites of sweating. CONCLUSION: After six weeks, more than 80% of the patients presented with improvements in their overall quality of life and at the most important site of sweating. Side effects were common (80% reported at least one side effect) and caused 25% of the patients to discontinue treatment. Oxybutynin is effective for treating bothersome hyperhidrosis, even at atypical locations and most patients cope well with the side effects. .

Tolterodine to Relieve Urinary Symptoms Following Transurethral Resection of the Prostate: A Double-Blind Placebo-Controlled Randomized Clinical Trial

PURPOSE: To evaluate the effect of tolterodine on early storage symptoms following transurethral resection of the prostate. MATERIALS AND METHODS: Seventy patients over 55 years of age who underwent transurethral resection of the prostate owing to benign prostatic hyperplasia were randomly assigned to receive either 2 mg of tolterodine twice daily (treatment group) or matched placebo during a 1-month study period. Before and 1 month after the procedure, they were asked to complete the International Prostate Symptom Score (IPSS) questionnaire and quality of life subscale to assess their symptoms. Also, analgesic use and adverse drug events were determined at follow-up. RESULTS: Of 70 allocated patients, 64 patients (91.4%), including 33 in the treatment group and 31 in the placebo group, completed the study. The mean age of the patients was 67 years. None of the patients' basic clinical characteristics were significantly different. At the end of the follow-up period, the total IPSS and quality of life score had significantly improved in the patients receiving tolterodine compared with those receiving placebo (p=0.001 and p=0.036, respectively). The treatment group compared with placebo demonstrated significant improvements in frequency and urgency but not in nocturia. The amount of consumed painkiller was also significantly lower in the tolterodine group than in the placebo group (p=0.0001). The rate of side effects was not significantly different between the groups. CONCLUSIONS: Administering 2 mg of tolterodine twice daily is an effective and well-tolerated regimen to relieve early storage symptoms, quality of life, and the amount of analgesic consumption following transurethral resection of the prostate.