N-acetylcysteine decreases dopamine transporter availability in the non-lesioned striatum of the 6-OHDA hemiparkinsonian rat.

This study aimed to explore the beneficial effects of the antioxidant N-acetylcysteine (NAC) on the degenerated dopamine system. The short- and long-term regulatory mechanisms of NAC on the 6-OHDA hemiparkinsonian rat model were longitudinally investigated by performing positron emission tomography (PET) imaging using the specific dopamine transporter (DAT) radioligand [18F]FE-PE2I. The results demonstrate that after a unilateral dopamine insult NAC has a strong influence on the non-lesioned hemisphere by decreasing the levels of DAT in the striatum early after the lesion. We interpret this early and short-term decrease of DAT in the healthy striatum of NAC-treated animals as a beneficial compensatory effect induced by NAC.

[Neurogenic overactive bladder: focus on cognitive function].

BACKGROUND: An overactive bladder and cognitive impairment are two medical and social problems, which have an outmost importance, affecting the quality of life. Both disorders are common in the practice of a urologist, neurologist, internist, and other physicians. Parkinsons disease and multiple sclerosis are the most common neurological diseases, which often manifest by pelvic dysfunction and cognitive dysfunction. The clinician needs to understand the pathogenesis of the underlying disease and the pharmacologic properties of drugs, which can be used both in neurology and urology, as well as in other related specialties. AIM: To evaluate cognitive functions in patients with neurogenic overactive bladder treated with trospium chloride. MATERIALS AND METHODS: A total of 45 patients with neurological disease (28 with Parkinsons disease [group 1] and 17 with multiple sclerosis [group 2]) were included in the study. All patients had symptoms of an overactive bladder. Trospium chloride was administered in an individually adjusted dose for 12 weeks. Cognitive functions were assessed using the international Montreal Cognitive Assessment (MoCA) before and after the therapy. A change of total scores over time was assessed using the paired Wilcoxon test. The level of significance of <0.05 was used (confidence level of 95%). RESULTS: A significant decrease in all studied parameters of an overactive bladder in both groups was seen. The baseline evaluation of the total score on the MoCA scale prior to the start of taking trospium chloride revealed the presence of moderate cognitive impairment (21.3+/-2.9 points) in patients of the group 1. After 12 weeks of therapy, no significant change in cognitive functions was observed (21.7+/-3.1 points; p>0.05). In group 2, moderate cognitive impairment (MoCA 22.5+/-3.7 points) was found at baseline. After taking trospium chloride, no significant changes were noted (MoCA 22.9+/-4.1 points) (p>0.05). No central nervous system side effects were reported in any group. CONCLUSION: Trospium chloride is an effective drug, which does not affect cognitive functions in patients with neurogenic overactive bladder. This drug is safe to use in both Parkinsons disease and multiple sclerosis, considering the low risk of cognitive impairment in polypharmacy.

Hyoscyamus albus nortropane alkaloids reduce hyperglycemia and hyperinsulinemia induced in HepG2 cells through the regulation of SIRT1/NF-kB/JNK pathway.

BACKGROUND: Chronic superphysiological glucose and insulin concentrations are known to trigger several tissue and organ failures, including insulin resistance, oxidative stress and chronic low-grade inflammation. Hence, the screening for molecules that may counteract such conditions is essential in current existing therapeutic strategies, thereby the use of medicinal plant derivatives represents a promising axis in this regard. METHODS: In this study, the effect of a selected traditional medicinal plant, Hyoscyamus albus from which, calystegines have been isolated, was investigated in an experimental model of hyperinsulinemia and hyperglycemia induced on HepG2 cells. The mRNA and protein expression levels of different insulin signaling, gluconeogenic and inflammatory pathway- related molecules were examined. Additionally, cell viability and apoptosis, oxidative stress extent and mitochondrial dysfunctions were assayed using flow cytometric and qRT-PCR techniques. RESULTS: Treatment of IR HepG2 cells with calystegines strongly protected the injured cells from apoptosis, oxidative stress and mitochondrial integrity loss. Interestingly, nortropane alkaloids efficiently regulated the impaired glucose metabolism in IR HepG2 cells, through the stimulation of glucose uptake and the modulation of SIRT1/Foxo1/G6PC/mTOR pathway, which is governing the hepatic gluconeogenesis. Furthermore, the alkaloidal extract restored the defective insulin signaling pathway, mainly by promoting the expression of Insr at the mRNA and protein levels. What is more, treated cells exhibited significant mitigated inflammatory response, as evidenced by the modulation and the regulation of the NF- κB/JNK/TLR4 axis and the downstream proinflammatory cytokines recruitment. CONCLUSION: Overall, the present investigation demonstrates that calystegines from Hyoscyamus albus provide cytoprotection to the HepG2 cells against insulin/glucose induced insulin resistance and apoptosis due to the regulation of SIRT1/Foxo1/G6PC/mTOR and NF-κB/JNK/TLR4 signaling pathways. Video Abstract.

The relationship between lower urinary tract function and 123ioflupane scintigraphy in drug-naïve Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) is the most common degenerative cause of movement disorder, and autonomic dysfunction has been recognized in this disorder. PD patients' lower urinary tract (LUT) function is not established. We investigated LUT function in PD by single-photon emission computerized tomography (SPECT) imaging of the dopamine transporter with 123I-ioflupane and clinical-urodynamic observations. PATIENTS AND METHODS: We retrospectively analyzed the cases of 30 patients diagnosed with PD based on published criteria who completed a systematized lower urinary tract symptoms (LUTS) questionnaire and a urodynamics examination irrespective of the presence of LUTS. None of the patients were taking anti-parkinsonian medication during the study. RESULTS: The questionnaire revealed that all 30 patients had LUTS: night-time urinary frequency (in 70%), urinary incontinence (40%), and daytime urinary frequency (80%). A urodynamic study revealed a mean volume at the first sensation at 92.3 ml, bladder capacity at 200.9 ml, and detrusor overactivity in 50%. Sphincter electromyography revealed neurogenic change in 13.6% of those for whom the test was performed. The average SBR showed a significant correlation with bladder capacity (Spearman's correlation coefficient p = 0.0076) and Hoehn Yahr motor stage (Spearman's correlation coefficient p = 0.012). CONCLUSION: Our findings demonstrate that the striatum is relevant to the higher control of storage in micturition function in PD.

Fahr's syndrome due to hypoparathyroidism revisited: A case of parkinsonism and a review of all published cases.

INTRODUCTION: Fahr's syndrome due to hypoparathyroidism refers to bilateral basal ganglia (BG) calcifications and manifests with movement disorders, seizures, cognitive and behavioral symptoms. CASE PRESENTATION: We report a case of a 74-year-old woman, who presented with parkinsonism due to post-surgical hypoparathyroidism and normal DaT scan, despite extensive calcifications of the BG, periventricular white matter, and cerebellum. METHODS: A comprehensive literature review of all reported cases of Fahr's syndrome due to hypoparathyroidism was conducted in the electronic databases PubMed and Web of science. Moreover, demographic and clinical characteristics of the patients overall were calculated and associated with radiological findings. RESULTS: We reviewed a total of 223 cases with Fahr's syndrome due to hypoparathyroidism (124 female, 99 male). Mean age on presentation was 44.6 ± 17.7 years. Thirty nine percent of patients had idiopathic hypoparathyroidism, 35.4 % acquired and 25.6 % pseudohypoparathyroidism. Almost half of the patients had tetany, seizures or a movement disorder and approximately 40 % neuropsychiatric symptoms. The patients with a movement disorder had a 2.23 likelihood of having neuropsychiatric symptoms as well (OR 2.23, 95 % CI 1.29-3.87). Moreover, there was a statistically significant association between the phenotype severity (i.e. the presence of more than one symptom) and the extent of brain calcifications (χ2 = 32.383, p = 0.009). CONCLUSION: Fahr's syndrome is a rare disorder, which nonetheless manifests with several neurological symptoms. A head CT should be considered for patients with hypoparathyroidism and neurological symptoms. More studies using DaT scan are needed to elucidate the effects of calcifications on the dopaminergic function of the BG.

Sensory satellite glial Gq-GPCR activation alleviates inflammatory pain via peripheral adenosine 1 receptor activation.

Glial fibrillary acidic protein expressing (GFAP+) glia modulate nociceptive neuronal activity in both the peripheral nervous system (PNS) and the central nervous system (CNS). Resident GFAP+ glia in dorsal root ganglia (DRG) known as satellite glial cells (SGCs) potentiate neuronal activity by releasing pro-inflammatory cytokines and neuroactive compounds. In this study, we tested the hypothesis that SGC Gq-coupled receptor (Gq-GPCR) signaling modulates pain sensitivity in vivo using Gfap-hM3Dq mice. Complete Freund's adjuvant (CFA) was used to induce inflammatory pain, and mechanical sensitivity and thermal sensitivity were used to assess the neuromodulatory effect of glial Gq-GPCR activation in awake mice. Pharmacogenetic activation of Gq-GPCR signaling in sensory SGCs decreased heat-induced nociceptive responses and reversed inflammation-induced mechanical allodynia via peripheral adenosine A1 receptor activation. These data reveal a previously unexplored role of sensory SGCs in decreasing afferent excitability. The identified molecular mechanism underlying the analgesic role of SGCs offers new approaches for reversing peripheral nociceptive sensitization.

Efficacy of trospium for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study.

BACKGROUND: Catheter-related bladder discomfort (CRBD) is a frequent complaint after awakening from anesthesia in patients receiving perioperative bladder catheterization. Overactive bladder (OAB) and CRBD show similar symptoms; thus, drugs used for the management of OAB influence symptoms of CRBD. Trospium chloride has been found effective in managing resistant cases of OAB. We evaluated the efficacy of oral trospium on CRBD in the postoperative period. METHODS: Sixty-four male and female adult patients, with planned spinal surgery and requiring urinary bladder catheterization, were randomly divided into two groups of 32 each. Group T patients received 60 mg extended-release oral trospium (extended-release) 1 h before induction of anesthesia and Group C patients received a similar-looking placebo. The anesthetic technique was identical in both groups. The CRBD score was evaluated in the postoperative ward using a 4-point scale (1 = no discomfort, 2 = mild, 3 = moderate, 4 = severe). Readings were recorded on arrival (0 h), and 1 h, 2 h, and 6 h postoperatively. All patients received fentanyl for postoperative pain relief. RESULTS: The incidence of CRBD was significantly higher in group C than in group T at 0 h (66% vs 22%, P=0.001) and 1 h postoperatively (72% vs 28%, P=0.001). The incidence of moderate to severe CRBD was higher in group C at postoperative 2 h (82% vs 14%, P=0.004). There was no significant difference in postoperative fentanyl requirements. CONCLUSIONS: Pretreatment with 60 mg ER trospium reduced the incidence and severity of CRBD in the early postoperative period.

Nortropane alkaloids as pharmacological chaperones in the rescue of equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome through mitochondrial potentiation, endoplasmic reticulum stress mitigation and insulin resistance alleviation.

OBJECTIVES: Equine metabolic syndrome (EMS) refers to a cluster of associated abnormalities and metabolic disorders, including insulin resistance and adiposity. The numerous biological properties of mesenchymal stem cells (MSCs), including self-renewal and multipotency, have been the subject of many in-depth studies, for the management of EMS; however, it has been shown that this cell type may be affected by the condition, impairing thus seriously their therapeutic potential. Therefore, an attempt to rescue EMS adipose-derived stem cells (ASCs) with calystegines (polyhydroxylated alkaloids) that are endowed with strong antioxidant and antidiabetic abilities was performed. METHODS: ASCs isolated from EMS horses were subsequently treated with various concentrations of total calystegines. Different parameters were then assessed using flow cytometry, confocal as well as SE microscopy, and RT-qPCR. RESULTS: Our results clearly demonstrated that calystegines could improve EqASC viability and proliferation and significantly reduce apoptosis, via improvement of mitochondrial potentiation and functionality, regulation of pro- and anti-apoptotic pathways, and suppression of ER stress. Furthermore, nortropanes positively upregulated GLUT4 and IRS transcripts, indicating a possible sensitizing or mimetic effect to insulin. Most interesting finding in this investigation lies in the modulatory effect of autophagy, a process that allows the maintenance of cellular homeostasis; calystegines acted as pharmacological chaperones to promote cell survival. CONCLUSION: Obtained data open new perspectives in the development of new drugs, which may improve the metabolic dynamics of cells challenged by MS.

Overactive bladder - pharmacological treatment

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

MORPHOLOGICAL ASSESSMENT OF NO-SYNTHASE DISTRIBUTION IN OVERACTIVE BLADDER AND STRESS URINE INCONTINENCE IN ANIMAL MODELS ADMINISTERED WITH EXPERIMENTAL PHARMACOCORRECTION REGIMENS.

The objective of the study was immunohistochemical evaluation of distribution of various NO synthase fractions in the structural elements of the bladder wall under stress urinary incontinence and its overactivity prior and post Mirabegron, Spasmex, Quercetin therapies and their combinations with Testosterone and Estradiol. Using the immunohistochemical method, we studied the expression of the main fractions of NO synthase in experimental models of hyperactive bladder (OAB) and stress urinary incontinence (SUI). We found that OAB and SUI were characterized by emergence of expression of the inducible fraction (iNOS) predominantly in the interstitial cells of the muscular layer of the bladder and reduced expression of endothelial (eNOS) and neuronal (nNOs) NO synthase fractions. In contrast to Spasmex, Mirabegron and Quercetin in combination with Testosterone and Estradiol contributed to stabilization of eNOS and nNOs expression already at early observation phases, and reduced the level of iNOS expression with its further disappearance in the later observation period.

Transcutaneous posterior tibial nerve electrostimulation with low dose trospium chloride: Could it be used as a second line treatment of overactive bladder in females.

AIM: To evaluate the effect of adding low dose trospium chloride with transcutaneous posterior tibial nerve stimulation (TPTNS) in the treatment of overactive bladder (OAB) in females after failure of behavioral therapy. METHODS: We randomized 30 women with OAB, in two groups: G I received 30 min TPTNS, three times a week; GII received TPTNS plus 20 mg trospium chloride daily. OAB Symptom Score questionnaire (OABSS), Incontinence Impact Questionnaire-short form 7 (IIQ-7), 3 day voiding diary and urodynamics at weeks 0 and 8 were evaluated. RESULTS: The groups were similar before treatment. Eight weeks after treatment, the mean OABSS decreased significantly to 8.53 ± 1.30 for group II vs 10.0 ± 2.0 for GI (P < 0.024). The mean IIQ-7 score decreased significantly to 51.86 ± 17.26 in group I vs 31.99 ± 9.26 in group II (P < 0.001). Before treatment, 11 (73.3%) and 4 (26.7%) patients in each group had moderate and poor quality of life (QoL), respectively. After treatment, 6 (40%) and 14 (93.3%) had good QoL, 7 (46.7%) and 1 (6.7%) had moderate QoL in GI and GII, respectively. Two (13.3%) patients in GI had poor QoL. The mean frequency was reduced to 8.60 ± 0.83 vs 10.60 ± 2.32 for GII and GI respectively (P = 0.006). The cystometric capacity increased from 263.40 ± 50.45 to 377.80 ± 112.92 mL (P = 0.001) for GII vs 250.13 ± 56.24 to 296.40 ± 99.0 mL (P = 0.026) for GI. CONCLUSION: TPTNS combined with low dose trospium chloride proved to be more effective than TPTNS alone in the treatment of OAB in females.

[Urodynamic studies prior to urinary incontinence surgery : What is useful?] / Urodynamik vor operativer Inkontinenztherapie : Was ist sinnvoll?

Surgery is often necessary after failure of conservative therapy for urinary incontinence. Guidelines recommend urodynamic studies before surgery. A distinction is made between non-invasive (uroflowmetry) and invasive methods (cystometry and pressure-flow study, if necessary as combined videourodynamics, as well as urethral pressure profile). All examinations serve to objectify and quantify the symptoms, to correctly assign symptoms to the pathophysiology and anatomy as well as to identify risk factors, which often have a significant influence on the success of surgical therapy. Given appropriate experience, complications and often significant sequelae of bladder dysfunction affecting the patient's quality of life and life expectancy can be recognized. Urodynamic studies are performed to help narrow down potential diagnoses, to develop therapeutic strategies, and to obtain prognostic parameters. The following article is intended to provide some support.

Does combination therapy with tamsulosin and trospium chloride improve lower urinary tract symptoms after SEEDS brachytherapy for prostate cancer compared with tamsulosin alone? : A prospective, randomized, controlled trial.

OBJECTIVE: To compare the efficacy of combination therapy with an alpha-blocker and an anticholinergic to monotherapy with an alpha blocker on lower urinary tract symptoms (LUTS) following brachytherapy in prostate cancer patients. MATERIAL AND METHODS: A total of 124 patients that had been clinically diagnosed with localized prostate cancer and underwent prostate brachytherapy were enrolled in the present study. Patients were randomized and allocated to two groups, including 60 to the combination group (tamsulosin 0.2 mg/day and trospium chloride 20 mg twice daily) and 64 to the monotherapy group (tamsulosin 0.2 mg/day). Treatment began 1 day after brachytherapy and continued for 6 months. LUTS were compared between the two groups using the total International Prostate Symptom Score (IPSS), storage and voiding IPSS subscores, quality of life (QoL) scores, maximum flow rate (Qmax), and postvoid residual (PVR) urine volume at 1, 3, 6, and 12 months after implantation. RESULTS: In all, 111 patients were ultimately analyzed in the study. Compared with pretreatment scores, a significant increase in total IPSS was found at 1, 3, and 6 months in both groups, but no statistically significant differences were observed between the two groups. The combination therapy group showed a greater decrease in the IPSS storage score compared with the monotherapy group at 1, 3, and 6 months (p = 0.031, 0.030 and 0.042, respectively). Patients receiving tamsulosin plus trospium chloride also showed significant improvements in QoL at 1 and 3 months compared with tamsulosin alone (P = 0.039, P = 0.047). Between the two groups, there was no significant difference in IPSS voiding score, Qmax, and PVR from baseline to each point of the study period. CONCLUSIONS: Combination therapy with tamsulosin and trospium chloride helped to improve IPSS storage symptoms and Qol scores in prostate brachytherapy patients with LUTS compared with tamsulosin monotherapy.

Availability of dopamine transporters in heroin-dependent subjects: A 18F-FECNT PET imaging study.

This study was to reconfirm the reduced dopamine transporter (DAT) availability in heroin-dependent subjects and validate the use of 2ß-carbomethoxy-3ß-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (18F-FECNT) as a PET radiotracer to assess the changes of striatal DAT in drug addicted subjects. Herein, we assessed DAT standardized uptake values (SUV) of 18F-FECNT in the striatum and cerebellum of 20 heroin-dependent subjects and 10 healthy controls and analyzed the correlation between DAT availability and heroin withdrawal symptom scores and anxiety/depression rating scales in heroin-dependent subjects, as well as the relationship between the withdrawal symptoms scores and age. The striatal DAT availability in heroin-dependent subjects was significantly lower (by ~15.7-17.6%) than that in healthy controls. Age was positively related to heroin withdrawal symptom scores. The withdrawal symptom scores in older patients (Age: 49.5±2.5) were significantly higher (by ~20%) than those in younger patients (Age: 30.9±4.8). These results confirm that chronic heroin use induces striatal DAT reduction, suggesting that 18F-FECNT could be used as an alternative PET imaging radioligand for in vivo imaging of DAT in drug addicted subjects. Moreover, older patients might suffer more severe withdrawal symptoms than younger patients, suggesting that older patients with heroin withdrawal could be given more medication.

Clinical validity of presynaptic dopaminergic imaging with 123I-ioflupane and noradrenergic imaging with 123I-MIBG in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies in the context of a structured 5-phase development framework.

The use of biomarkers (BMs) for accurate diagnosis of Alzheimer's disease (AD) has been proposed by recent diagnostic criteria; however, their maturity is not sufficient to grant implementation in the clinical routine. A proper diagnostic process requires not only confirmation of the disease but also the exclusion of similar disorders entering differential diagnosis, like dementia with Lewy bodies (DLB). This review is aimed at evaluating the clinical validity of 123I-ioflupane brain single photon emission tomography and 123I-MIBG cardiac scintigraphy as imaging BMs for DLB. For this purpose, we used an adapted version of the 5-phase oncology framework for BMs development. A review of the literature was conducted using homogenous search criteria with other BMs addressed in parallel reviews. Results of our literature search showed that the rationale for the use of both BMs in the differential diagnosis of DLB and AD is strong (phase 1) and that they allow a good discrimination ability (phase 2), but studies investigating BMs distribution antemortem and postmortem on pathology are lacking. Moreover, thresholds for test positivity have not been defined for 123I-MIBG. The 2 BMs have not been yet assessed in early phases of DLB and AD (phase 3). No phase 4 and phase 5 studies have so far been carried out. This review highlights the priorities to address in future investigations to enable the proper use of 123I-ioflupane and 123I-MIBG for the differential diagnosis of dementia.

The effective tool for self-assessment of adherence to treatment in patients with benign prostatic obstruction and overactive bladder symptoms.

PURPOSE: Study of validity of the Medication Adherence Self-Report Inventory (MASRI) for use in clinical practice to treat patients with benign prostatic obstruction (BPO) accompanied with overactive bladder (OAB) symptoms. METHODS: During 12 weeks of the randomized study, 452 patients with BPO and OAB symptoms (mean age of 61.3 (12.7)) were studied for adherence to the treatment with Tamsulosin, Solifenacin and Trospium using the MASRI. External monitoring instruments included the Brief Medication Questionnaire (BMQ) and the visual remaining pill count. The state of the prostate gland and the lower urinary tract was monitored using questionnaires I-PSS, OAB Awareness Tool, uroflowmetry and voiding diaries. RESULT: Correlation between the percentage of men non-adherent to treatment (MASRI) and the percentage of patients having a belief barrier on the screen of the BMQ was r = 0.89, p ≤0.05, r = 0.92, p ≤0.01, r = 0.85, p ≤0.05, a number of missed doses on the Regimen Screen of the BMQ was r = 0.79; p ≤0.05; r = 0.81; p ≤0.05; r = 0.75, p ≤0.05, a number of non-adherent patients according to the BMQ was r = 0.83 (p ≤0.05), r = 0.88 (p ≤0.05), r = 0.79, p ≤0.05, the results of the pill count were r = 0.65-0.76; p ≤0.05-0.01. These data confirm high validity of the MASRI. CONCLUSION: The MASRI is a valid tool for rapid assessment of adherence to treatment of patients with BPO and OAB receiving Tamsulosin and antimuscarinic drugs and may be recommended for use in clinical practice.

Randomized, double-blind, placebo-controlled trial to compare solifenacin versus trospium chloride in the relief of double-J stent-related symptoms.

PURPOSE: We aimed to compare the safety and efficacy of solifenacin versus trospium chloride and compare each drug versus placebo regarding the relief of stent-related symptoms following uncomplicated ureteroscopic lithotripsy (URSL). METHODS: In a prospective, randomized, double-blind study, 210 eligible patients who underwent URSL with double-J stent insertion were recruited and randomly assigned to either the first group, receiving solifenacin (10 mg), second group, receiving trospium chloride (60 mg), or the third group, receiving placebo (one tablet). All patients were kept on study medication once daily during the entire 2-week postoperative period. All subjects were asked to complete a brief-form questionnaire to assess the lower urinary symptoms, stent-related body pain and hematuria, preoperatively and 2 weeks postoperatively. RESULTS: There were no statistically significant differences among the study groups in terms of mean age, gender, anthropometric measurements, stone and stent criteria. The overall symptom score, urgency, urge incontinence, flank pain, urethral pain and gross hematuria scores were significantly lower in solifenacin group compared to trospium chloride and placebo groups (p < 0.001). Concerning frequency and nocturia, there was no significant difference in mean scores across all groups. Drug-related side effects, particularly constipation, were higher in trospium group than in solifenacin one. CONCLUSIONS: Solifenacin treatment showed significant improvement in almost all domains of stent-related symptoms than trospium. In terms of safety and tolerance, both drugs were comparable. Future studies should be designed to address the impact of combined drugs and lower doses in the management of DJ stent-related symptoms.

Effect of Trospium Chloride on Cognitive Function in Women Aged 50 and Older: A Randomized Trial.

OBJECTIVES: This study aimed to investigate the effect of trospium chloride on cognitive function in postmenopausal women treated for overactive bladder (OAB). METHODS: Randomized double-blind placebo-controlled trial conducted from April 2013 to April 2015. Women aged 50 years or older seeking treatment for OAB were randomized to either trospium chloride XR 60 mg daily or placebo. Baseline cognitive function was assessed via Hopkins Verbal Learning Test-Revised (HVLT-R), Mini Mental Status Exam, Mini Mental Status X, Digit Span, Trails A, Trails B, and Epworth Sleepiness Scale. Cognitive function was reassessed at week 1 and week 4. A priori power analysis determined that 21 subjects were needed per group. RESULTS: Although 59 women were enrolled and randomized (28 trospium and 31 placebo), 45 completed assessment (21 trospium and 24 placebo). Mean age was 68 years, 78% were white, and 44% had previously taken OAB medication. For the primary outcome, there was no difference in HVLT-R total score between trospium and placebo groups at week 4 (P = 0.29). There were also no differences based on the other cognitive tests. There was a correlation between age and the following week-4 tests: HVLT-R total score (r = -0.3, P = 0.02), HVLT-R total recall subscale (r = -0.4, P = 0.007), Trails A (r = 0.4, P = 0.002), and Trails B (r = 0.4, P = 0.004). A linear regression model found that HVLT-R total score decreased by 0.372 points for each increased year of age. CONCLUSIONS: In women aged 50 years and older, there were no changes in cognitive function between those taking trospium and placebo. Cognitive function was correlated with age.

Combined low-dose antimuscarinics for refractory detrusor overactivity in children.

INTRODUCTION AND AIMS: Behavioral therapy and bowel management are the initial and mainstay treatments for overactive bladder (OAB). Antimuscarinic agents are initiated if these measures fail or symptoms are severe. This study reported the results of treatment with a high dosage of a single drug in children with refractory detrusor overactivity (DO). After the children maintained their previous antimuscarinic medication, a second antimuscarinic drug (trospium chloride) was added as a combination therapy. MATERIALS AND METHOD: Seventy-two children with DO were enrolled in this prospective study (Figure). They had persistent urgency and urgency urinary incontinence (UUI), even with behavioral bowel therapy, and used an optimized dosage of oxybutynine. All patients demonstrated DO at urodynamic study and started on oxybutynin and trospium chloride at the lowest weight-adjusted dose (10-20 mg/day for trospium chloride). A bladder diary was recorded for 3 days, and urodynamic studies were repeated at 3 and 6 months. RESULTS: Sixteen children (22.2%) became dry. Thirty-three children (45.8%) attained a significant decrease in incontinence from an average of 5 to 1.3 episodes per day. A statistically significant increase of mean cystometeric bladder capacity (P = 0.006) was also observed at the 6-month follow-up. The overall success rate was 68%, since 23 children (32%) discontinued combined treatment due to persistent symptoms and/or intolerable side effects. A total of 41 children (57%) reported no side effects, 25 (34.7%) reported mild side effects, six (8.3%) reported moderate side effects, and two withdrew from the study due to their side effects. CONCLUSIONS: The addition of low-dose trospium chloride to oxybutynine seemed to be an effective and safe treatment approach for children with DO who were refractory to high-dosage monotherapy. Different combinations with different antimuscarinics drugs could be evaluated in the future.