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INTRODUCTION AND HYPOTHESIS: The aim of this study is to compare the effectiveness of transcutaneous tibial nerve stimulation (TTNS) on quality of life (QoL) and clinical parameters related to incontinence in pharmacological agents (PhAs) naive and refractory women with idiopathic overactive bladder (iOAB). METHODS: In this prospective nonrandomized clinical trial, women with resistance to PhAs were included in the first group (n=21), PhA-naive women were included in the second group (n=21). TTNS was performed 2 days a week, a total of 12 sessions for 6 weeks. Every session lasted 30 min. Women were evaluated for the severity of incontinence (Pad test), 3-day voiding diary (voiding frequency, nocturia, incontinence episodes, and number of pads), symptom severity (Overactive Bladder Questionnaire-V8), quality of life (Incontinence Impact Questionnaire-7), treatment satisfaction, positive response, and cure-improvement rates. RESULTS: A statistically significant improvement was found in all parameters for each group at the 6th week compared with the baseline values (p<0.05). It was found that the severity of incontinence, incontinence episodes, symptom severity, treatment satisfaction, and QoL parameters were significantly improved in PhA-naive group compared with the PhA-resistant group at the 6th week (p<0.05). There were no statistically significant differences in the frequency of voiding, nocturia, and number of pads between the two groups (p>0.05). Positive response rates, the primary outcome measure, were statistically significantly higher in the PhA-naive group than in the PhA-resistant group. CONCLUSIONS: Although TTNS is more effective in PhA-naive women with iOAB, it appears to be an effective therapy that can also be used in the management of PhA-resistant women with iOAB.
Subject(s)
Nocturia , Transcutaneous Electric Nerve Stimulation , Urinary Bladder, Overactive , Urinary Incontinence , Humans , Female , Urinary Bladder, Overactive/drug therapy , Quality of Life , Prospective Studies , Treatment Outcome , Tibial Nerve , Urinary Incontinence/therapyABSTRACT
AIM: Antimuscarinics and the ß3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α1 -adrenoreceptor antagonists (α1 -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α1 -blocker plus mirabegron with an α1 -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations. METHODS: Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α1 -blocker plus OAB agent with an α1 -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Qmax ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis. RESULTS: Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α1 -blocker plus mirabegron and α1 -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α1 -blocker plus mirabegron group compared with the α1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Qmax . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α1 -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation. CONCLUSION: This systematic review and meta-analysis showed that an α1 -blocker plus mirabegron and an α1 -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.
Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Thiazoles , Urinary Bladder, Overactive , Urinary Retention , Humans , Male , Female , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/etiology , Urinary Bladder, Overactive/diagnosis , Muscarinic Antagonists/adverse effects , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/drug therapy , Urinary Retention/complications , Bayes Theorem , Network Meta-Analysis , Treatment Outcome , Drug Therapy, Combination , Acetanilides/adverse effects , Lower Urinary Tract Symptoms/drug therapy , Lower Urinary Tract Symptoms/etiology , Adrenergic beta-3 Receptor Agonists/adverse effects , Randomized Controlled Trials as TopicABSTRACT
AIMS: The management of overactive bladder (OAB) involves lifestyle changes and conservative measures in the first instance with the use of liquid/dietary advice, weight loss, and bladder training. Thereafter oral pharmacotherapy is instigated in symptomatic patients. Antimuscarinics and beta 3 agonists form the main classes of drug therapy in this field. Views on what is the best first line OAB treatment is changing based on recent evidence and adverse event profiles of these medications. METHODS: At the ICI-RS meeting 2023, Bristol, UK this topic was discussed and debated as a proposal. The following article summarizes the concepts presented that day as well as the interactive discussion that took place thereafter. RESULTS: OAB guidelines are moving in many circumstances to an either antimuscarinic or beta 3 agonist approach based on patient factors. Several studies have raised concerns on the long-term impact of antimuscarinics, in relation to cognition, dementia, cardiovascular events, and mortality all related to antimuscarinic load. Neither antimuscarinics nor beta 3 agonists have good persistence and adherence rates in the medium to long term. Several barriers also exist to prescribing including guidelines recommending utilizing drugs with the lowest acquisition cost and "step therapy." A newer approach to managing OAB is personalized therapy in view of the many possible etiological factors and phenotypes. These concepts are highlighted in this article. CONCLUSIONS: Current oral pharmacotherapy in managing OAB is limited by adverse events, adherence and persistence problems. Both antimuscarinics and beta 3 agonists are efficacious but most clinical trials demonstrate significant placebo effects in this field. Personalizing treatment to the individual seems a logical approach to OAB. There is a need for better treatments and further studies are required of existing treatments with high quality longer term outcomes.
Subject(s)
Adrenergic beta-3 Receptor Agonists , Muscarinic Antagonists , Urinary Bladder, Overactive , Humans , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/physiopathology , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Administration, Oral , Adrenergic beta-3 Receptor Agonists/adverse effects , Adrenergic beta-3 Receptor Agonists/therapeutic use , Adrenergic beta-3 Receptor Agonists/administration & dosageABSTRACT
OBJECTIVE: To evaluate the evidence regarding the therapeutic benefits and safety of oral detrusor relaxing agents (DRAs) in treating neurogenic detrusor overactivity (NDO). METHODS: A comprehensive search was performed on 1 September 2022. Two authors independently reviewed the articles to extract data using a pre-designed form. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A common-effect or random-effects model was used based on the heterogeneity among studies. Bayesian network meta-analysis (NMA) was further performed to make indirect comparisons of antimuscarinics and mirabegron. RESULTS: A total of 23 randomised controlled trials (RCTs) comprising 1697 patients were included in our analysis. Compared to placebo, the clinical benefits of oral DRAs, along with more adverse events (AEs), were demonstrated in the treatment of NDO. In the subgroup analysis, antimuscarinics significantly improved both urodynamic and bladder diary outcomes (including urinary incontinence episodes, urinary frequency, and residual volume), with a higher rate of AEs, such as xerostomia. Mirabegron improved some of the parameters and had fewer bothersome side-effects in patients with NDO. The NMA showed that none of the antimuscarinics or mirabegron was superior or inferior to the other. CONCLUSIONS: Detrusor relaxing agents are associated with improved outcomes in patients with NDO and our analysis has added new evidence regarding antimuscarinics. Evidence concerning mirabegron as first-line therapy for NDO is still limited. Well-designed RCTs are still required in this specific population.
Subject(s)
Botulinum Toxins, Type A , Urinary Bladder, Neurogenic , Urinary Bladder, Overactive , Humans , Urinary Bladder, Neurogenic/drug therapy , Muscarinic Antagonists/therapeutic use , Network Meta-Analysis , Botulinum Toxins, Type A/adverse effects , Treatment Outcome , Urinary Bladder, Overactive/drug therapy , Urodynamics , Randomized Controlled Trials as TopicABSTRACT
Objective: We conducted a meta-analysis to assess the efficacy and safety of mirabegron (50 mg/day) and antimuscarinics in treating ureteral stent-related symptoms (SRSs). Methods: All randomized controlled trials (RCTs) were identified by searching PubMed, Embase, Web of Science, and Cochrane Library. The RevMan version 5.3.0 software was used for statistical analysis. Results: This meta-analysis included five RCTs involving 317 patients. A fixed effects model revealed that mirabegron was superior to antimuscarinics in treating urinary symptoms (MD -1.39, 95% CI -2.63 to -0.15, p = 0.03) and general health (MD -1.65, 95% CI -2.60 to -0.69, p = 0.0007) 1 week after treatment initiation. We observed no significant differences in body pain (MD 0.05, 95% CI -1.06 to 1.15, p = 0.94), work performance (MD -0.86, 95% CI -1.77 to 0.06, p = 0.07), and sexual matters (MD 0.03, 95% CI -0.77 to 0.83, p = 0.94). Two weeks after treatment initiation, the ureteral stent symptom questionnaire (USSQ) revealed no significant differences between the two groups. The mirabegron group demonstrated a significant improvement in the quality of life (QoL) (MD -0.18, 95% CI -0.34 to -0.01, p = 0.03), while the International Prostate Symptom Score did not reveal a significant difference between the two groups (MD -0.74, 95% CI -1.79 to 0.32, p = 0.17). Regarding safety, a pooled data analysis presented that the incidence of constipation was lower in the mirabegron group (OR 0.10, 95% CI 0.01 to 0.77, p = 0.03). The mirabegron and antimuscarinics groups did not differ significantly concerning the risk of dry mouth (OR 0.15, 95% CI 0.02 to 1.27, p = 0.08). Conclusion: Mirabegron is superior to antimuscarinics in alleviating ureteral SRSs and improving QoL. Additionally, mirabegron 50 mg/day presented safety with a lower incidence of constipation.
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Major depressive disorder is one of the most severe mental disorders. It strongly impairs daily functioning, and, in extreme cases, it can lead to suicide. Although different treatment options are available for patients with depression, there is an ongoing search for novel therapeutic agents, such as scopolamine (also known as hyoscine), that would offer higher efficacy, a more rapid onset of action, and a more favorable safety profile. The aim of our study was to review the current clinical evidence regarding the use of scopolamine, a promising therapeutic option in the treatment of depression. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases up to 5 June 2023. We included randomized placebo-controlled or head-to-head clinical trials that compared the clinical efficacy and safety of scopolamine in the treatment of major depressive disorder. Two reviewers independently conducted the search and study selection and rated the risk of bias for each study. Four randomized controlled trials were identified in the systematic review. The included studies investigated the use of scopolamine administered as an oral, intramuscular, or intravenous drug, alone or in combination with other antidepressants. The results indicated that scopolamine exerts antidepressant effects of varying intensity. We show that not all studies confirmed a statistically and clinically significant reduction of depressive symptoms vs. placebo. A broader perspective on scopolamine use in antidepressant treatment should be confirmed in subsequent large randomized controlled trials assessing both effectiveness and safety. Therefore, studies directly comparing the effectiveness of scopolamine depending on the route of administration are required.
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BACKGROUND: Patients with overactive bladder may cycle through different antimuscarinic medications even though there is limited evidence to support this approach. OBJECTIVE: To describe treatment patterns and the associated health care resource utilisation (HCRU) according to antimuscarinic cycling groups. DESIGN, SETTING, AND PARTICIPANTS: The CYCLe AntiMuscarinics in ENgland (CYCLAMEN) study was a retrospective observational investigation that used primary care records from the Clinical Practice Research Datalink GOLD database linked to Hospital Episode Statistics secondary care data. Eligible patients (≥18 yr) were prescribed their first antimuscarinic between January 2014 and December 2017. Patients were categorised into groups prescribed one, two, or three or more (groups 1-3) consecutive unique antimuscarinics over 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The HCRU rate and costs were calculated for the period of continuous antimuscarinic therapy (first antimuscarinic treatment episode) and the 18-mo follow-up period. Treatment sequence patterns were displayed using sunburst plots and Kaplan-Meier analysis was used to assess time on treatment. RESULTS AND LIMITATIONS: Overall, 35 369 patients were included, of whom 31 760 (89.8%) received one antimuscarinic (group 1), 3182 (9.0%) received two (group 2), and 427 (1.2%) received three or more (group 3). The most common initial antimuscarinics were solifenacin (13 628 patients, 42.9%) in group 1, and oxybutynin in group 2 (1267 patients, 39.8%) and group 3 (200 patients, 46.8%). The median duration of the first antimuscarinic treatment episode was 57 d and <20% of patients were receiving any antimuscarinic after 18 mo. The number of primary care visits and mean costs increased across groups. The reasons for cycling could not be identified in this study. CONCLUSIONS: Approximately 10% of patients underwent sequential cycling with two or more antimuscarinics. Furthermore, as the majority discontinued treatment within 18 mo, there is a need to improve the management of these patients in the clinical care setting. PATIENT SUMMARY: We investigated treatment patterns and health care use for patients with overactive bladder who were prescribed at least one antimuscarinic drug (AMD), which are drugs that reduce some of the impulses passing from the bladder to the brain. Around 10% of patients accessing primary health care in England received more than one sequential AMD. Most patients discontinued treatment, which may indicate inadequate management of their condition. Prescription of a higher number of AMDs was associated with higher health care costs.
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Overactive bladder prevalence increases in older adults often complicating the management of other comorbidities. The theoretical antagonism between the parasympathetic-blocking anticholinergic agent and the parasympathetic stimulatory agents concomitantly used by patients is only recently being explored. The primary aim was to determine the frequency of the annual use of acetylcholinesterase inhibitors, overactive bladder anticholinergics, and the use of both agents in the same year. The secondary aim was measurement of the association between annual hospitalization and same-year use of both acetylcholinesterase inhibitors and anticholinergics. The US nationally representative MarketScan® Medicare databases were analyzed. In the Medicare enrollees, there were 122 020, 141 920, and 15 639 users of acetylcholinesterase inhibitors, anticholinergics, and both agents, respectively. The percentage of acetylcholinesterase inhibitor users who also used anticholinergics was 12.8%. Comparing users of both acetylcholinesterase inhibitors and anticholinergics to those using AChEI alone, 5 608 of the former experienced a hospitalization (35.9%) compared to 33 182 of the latter (31.2%). There was an increased risk of hospitalization for those using both acetylcholinesterase inhibitors and anticholinergics in the same year, with an odds ratio (OR) of 1.23 (95% CI, 1.19, 1.28). Clinicians should consider improved monitoring of the usage of both medications and clarify alternative regimens that avoid anticholinergics in at-risk older adults.
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BACKGROUND: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD. OBJECTIVES: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD. METHODS: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods. RESULTS: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses. CONCLUSIONS: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.
Subject(s)
Parkinson Disease , Urinary Bladder, Overactive , Urological Agents , Humans , Aged , United States , Muscarinic Antagonists/adverse effects , Urinary Bladder, Overactive/diagnosis , Cohort Studies , Prospective Studies , Parkinson Disease/complications , Parkinson Disease/drug therapy , Medicare , Acetanilides/therapeutic use , Cholinergic Antagonists/adverse effects , Treatment Outcome , Urological Agents/therapeutic useABSTRACT
The carbamate pyridostigmine bromide (PB) is the only fielded pharmacological prophylaxis for military use against nerve agents. Previous studies have shown differences in the PB-pretreatment efficacy for various nerve agents and in the influence of post-exposure treatment with common antidotes. In the present study, the aim was to evaluate the possibility of using an ex vivo rat precision-cut lung slice model to determine the impact of PB pretreatment on VX-induced bronchoconstriction. In addition, the efficacy of post-exposure treatment with atropine sulfate following PB-prophylaxis was investigated.Bronchoconstriction was induced by electric-field stimulation and was significantly aggravated by 10 µM PB. Airway recovery was decreased by both 1 and 10 µM PB. Evaluation of acetylcholineesterese inhibition by PB showed that the lower concentration met the clinical criteria of residual enzyme activity while the higher concentration completely inhibited the activity. Exposure to VX with or without pretreatment demonstrated similar contractions. However, VX-incubation following pretreatment caused decreased airway relaxation compared to pretreatment alone. Atropine treatment following PB- and VX-exposure significantly decreased the maximum airway contraction and increased the relaxation.In conclusion, no beneficial effect of PB-prophylaxis on VX-induced contractions was observed. The atropine efficacy to relax airways was significant demonstrating the importance of efficient post-exposure therapeutics to protect against the life-threatening respiratory contractions.
Subject(s)
Nerve Agents , Pyridostigmine Bromide , Rats , Animals , Pyridostigmine Bromide/pharmacology , Nerve Agents/toxicity , Atropine/pharmacology , Lung , Cholinesterase Inhibitors/toxicityABSTRACT
INTRODUCTION: There are publications about the impact of a new coronavirus infection (COVID) on the lower urinary tract, including the development of overactive bladder (OAB) or COVID-associated cystitis. The cause of dysuria in patients with COVID is not fully understood. MATERIAL AND METHODS: A total of 14 consecutive patients after COVID with complaints of frequent urination with urgency were included in the study. The main inclusion criterion was the development or worsening of OAB symptoms after resolution of COVID, confirmed by the eradication of SARS-CoV-2 by a polymerase chain reaction. The severity of OAB was assessed using the International Scale of Symptoms (Overactive Bladder Symptom Score, OABSS). RESULTS: Three (21.4%) out of fourteen patients had OAB symptoms prior to COVID, while in 11 (78.6%) patients OAB symptoms developed in post-COVID period. In 4 patients (28.6% of the entire cohort and 36.4% of patients in de novo group) urge urinary incontinence and urgency developed. The average score on the OABSS scale in patients with baseline OAB was 6.7+/-0.8, which corresponded to the moderate severity. In this group, one patient developed urge urinary incontinence and urgency, which were not present prior to COVID. In a retrospective evaluation of symptoms before the COVID, their average score on the OABSS scale was 5.2 +/- 0.7, i.e., past COVID led to an increase in OAB symptoms by 1.5 points. In patients with OAB de novo, the symptoms were less pronounced, with a score of 5.1+/-0.6 points, that is between mild and moderate OAB. At the same time, urinalysis in 9 patients did not have signs of inflammation: in 5 cases, 5-7 white blood cells per field of view was seen only once. A follow-up urine test was normal, suggesting contamination. None of the cases revealed bacteriuria over 102 CFU/ml. All patients were prescribed trospium chloride at a dose of 30 mg per day. The choice of the drug was due to the absence of a negative effect on the central nervous system, which is very important both during COVID and in post-COVID period, since the neurotoxicity of SARS-CoV-2 has been proven. CONCLUSION: A past history of COVID led to an increase in OAB symptoms by 1.5 points in patients who had OAB prior to infection. In 11 patients, after the treatment of COVID, the moderate symptoms of OAB developed de novo. Our small study showed the importance of focusing the attention of internists and infectious disease doctors on urination disorders in patients with COVID and timely referral to a urologist. For the treatment of post-COVID OAB, trospium chloride is the drug of choice, as it does not aggravate the potential neurotoxicity of SARS-CoV-2.
Subject(s)
COVID-19 , Urinary Bladder, Overactive , Urinary Incontinence , Humans , Urinary Bladder , Urinary Bladder, Overactive/drug therapy , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , COVID-19/complicationsABSTRACT
PURPOSE: To assess the prescribing practices for overactive bladder (OAB) pharmacotherapy based on the prescription trend analysis across different specialties of India. METHOD: s: IQVIA (Quintiles and IMS Health) secondary sales audit (SSA), as well as a prescription audit for antimuscarinics and beta-3 adrenoceptor agonists (mirabegron) from 2014 to 2021, were analyzed. The data includes SSA data of various antimuscarinics like solifenacin, oxybutynin, tolterodine, darifenacin, trospium and mirabegron change in the prescription trend of antimuscarinics and mirabegron across different specialties; prescribers overlap analysis for solifenacin and mirabegron among Indian urologists were also analyzed. RESULTS: Urologists prescription rates of OAB drugs were 65% in 2016 and 54% in 2021. The rate of OAB medication prescription by non-urologist was highest from the surgeon (11%), followed by gynecologists (9%) and consultant physicians (8%) in 2021. In addition, among OAB medication prescription rates for antimuscarinics were 100% in 2016 and 58% in 2021 whereas for mirabegron, it was 0% in 2016 and 42% in 2021. Solifenacin was most frequently prescribed anticholinergics, followed by oxybutynin, tolterodine, darifenacin, and trospium. The proportion of prescribers of OAB medication among urologists was 38% in 2016 and 33% in 2021. Exclusive prescribers of solifenacin were 748 in 2018 and 739 in 2021 at the urologist, whereas for mirabegron, it was 961 in 2018 and 934 in 2021. The compound annual growth rate for prescription of the last 6 years (from 2016-2021) for solifenacin and mirabegron was -3% and 8% respectively. CONCLUSIONS: Urology remained a top prescribing specialty for OAB drugs, although prescription share increased at surgeon and consultant physician. OAB medicines prescriptions by urologists are shifting from leading antimuscarinic solifenacin to beta-agonist mirabegron. Data from this study will ultimately lead to the OAB medication preference by the specialist that could lead to more advanced OAB management.
Subject(s)
Urinary Bladder, Overactive , Urological Agents , Humans , Urinary Bladder, Overactive/drug therapy , Muscarinic Antagonists/therapeutic use , Solifenacin Succinate/therapeutic use , Tolterodine Tartrate/therapeutic use , Acetanilides/therapeutic use , Prescriptions , Urological Agents/therapeutic useABSTRACT
Abstract Objective To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). Data Source Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence. Data Collection RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence. Data Synthesis We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]. Conclusion Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.
Resumo Objetivo Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH). Fonte de Dados Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão. Coleta de Dados RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. Síntese dos Dados Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,89-0,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,48-0,68); 9.375 pacientes; RR: 0,44 (0,35-0,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,98-1,00)]. Conclusão Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.
Subject(s)
Humans , Muscarinic Antagonists , Urinary Bladder, Overactive/therapyABSTRACT
Overactive bladder (OAB) is a common and distressing condition which is known to have a significant effect on Health-Related Quality of Life (HRQoL). Whilst all patients complaining of overactive bladder symptoms will, in theory, initially benefit from conservative measures, many will require pharmacological therapy. Antimuscarinics currently remain the most commonly used drugs to treat OAB although compliance and persistence can be poor due to concerns regarding adverse events and lack of efficacy. This review will explore the common management strategies for OAB with a particular focus on patient adherence to therapy including compliance and persistence. The role of antimuscarinics and the B3-agonist, mirabegron, will be considered along with barriers to their efficacy and adoption. For those patients in whom conservative and pharmacological treatment proves ineffective or is unsuitable, the management of refractory OAB will also be considered. In addition, the role of current and future developments will be examined.
ABSTRACT
PURPOSE: We aimed to outline the existing information and the underlying mechanisms of risk of falls associated with the use of urinary antimuscarinics for overactive bladder (OAB) or alpha-blockers for benign prostatic hyperplasia (BPH) in older adults. In addition, we aimed to provide assistance to clinicians in decision-making about (de-)prescribing these drugs in older adults. METHODOLOGY: Based on a literature search in PubMed and Google Scholar, we reviewed the literature, and identified additional relevant articles from reference lists, with an emphasis on the most commonly prescribed drugs in OAB and BPH in older patients. We discussed the use of bladder antimuscarinics and alpha-blockers, their potential side effects related to falls, and the deprescribing of these drugs in older adults. RESULTS: Urinary urgency or incontinence and lower urinary tract symptoms due to untreated OAB and BPH contribute to fall risk. On the other hand, the use of bladder antimuscarinics and alpha-blockers is also related to fall risk. They contribute to (or cause) falling through dizziness, somnolence, visual impairment, and orthostatic hypotension while they differ in their side-effect profiles regarding these problems. Falls are common and can cause a remarkable amount of morbidity and mortality. Thus, preventive measures should be taken to lower the risk. If the clinical condition allows, withdrawal of bladder antimuscarinics and alpha-blockers is recommended in fall-prone older adults. There are practical resources and algorithms that guide and assist clinicians in deprescribing these drug groups. CONCLUSIONS: The decision to prescribe or deprescribe these treatments in patients at high risk of falls should be individualized. In addition to explicit tools that are helpful for clinical decision-making in (de-)prescribing these drugs, STOPPFall (a recently developed expert-based decision aid specifically aiming to prevent falls) is present to assist prescribers in attaining decisions.
Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Urinary Bladder, Overactive , Male , Humans , Aged , Muscarinic Antagonists/adverse effects , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/complications , Accidental Falls/prevention & control , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/complications , Lower Urinary Tract Symptoms/complications , Lower Urinary Tract Symptoms/drug therapy , Adrenergic alpha-Antagonists/adverse effectsABSTRACT
OBJECTIVES: Epidemiological studies have reported an association between antimuscarinics and reduced risk of cancer, including lung cancer (LC). However, the potential association between antimuscarinic use and LC prognosis has not previously been assessed. In a large population-based cohort, we aimed to investigate the association between the use of antimuscarinics and LC-specific survival. MATERIALS AND METHODS: Norwegian residents, aged ≥ 50 years, and diagnosed with LC between 2005 and 2018, were identified in the Cancer Registry of Norway, and information on filled prescriptions was obtained from the Norwegian Prescription Database. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association between peri-diagnostic and post-diagnostic use of antimuscarinics and LC-specific survival. RESULTS: We included 26,693 patients with incident primary invasive LC. Of these, 466 (1.7 %) were peri-diagnostic users, and 877 (3.3 %) were post-diagnostic users of antimuscarinics, respectively. During a median follow-up of nine months, 18,088 (67.8 %) patients died due to LC. In the overall LC population, the HRs for the association between the use of antimuscarinics, compared to no use, were estimated at 1.01 (95 %CI: 0.90-1.12) for peri-diagnostic use, and 0.84 (95 %CI: 0.77-0.92) for post-diagnostic use. The association with post-diagnostic use was observed in many subgroups defined by sex, age, smoking status, histopathology, and stage, except for patients with unspecified or other histopathology than small cell LC and non-small cell LC, and for patients with local disease. The association was observed in patients treated with chemotherapy (HR = 0.75, 95 %CI: 0.64-0.88), but not in those not treated with chemotherapy (HR = 1.00, 95 %CI: 0.86-1.17; p for interaction: 0.007). CONCLUSION: Our results suggest a possible association between use of antimuscarinics and longer LC-specific survival. More studies are warranted to investigate the use of antimuscarinics to possibly prolong LC prognosis.
Subject(s)
Lung Neoplasms , Muscarinic Antagonists , Humans , Cohort Studies , Muscarinic Antagonists/adverse effects , Lung Neoplasms/drug therapy , Proportional Hazards Models , NorwayABSTRACT
OBJECTIVE: To assess the economic impact associated with overactive bladder (OAB) patients, treated with mirabegron or antimuscarinics (AM) in Spain, over a 12-month period. METHODS: A probabilistic model (second-order Monte Carlo simulation) was used in a hypothetical cohort of 1000 patients with OAB and a time horizon of 12 months. The use of resources was obtained from the retrospective observational study MIRACAT that included 3330 patients with OAB. The analysis was carried out from the perspective of the National Health System (NHS) including that of society with the indirect cost of abseenteism in a sensitivity analysis. Unit costs were obtained from Spanish public healthcare prices ( 2021) and from previously published Spanish studies. RESULTS: The annual average savings for the NHS for each patient with OAB treated with mirabegron would be 1135 (95%confidence interval (CI) 390; 2421) compared with a patient treated with AM. Annual average savings were maintained in all the sensitivity analyses carried out, ranging from a minimum of 299 to a maximum of 3381 per patient. The substitution of 25% of the AM treatments (for 81534 patients) to mirabegron would generate, within 1 year, savings for the NHS of 92 million (95% CI 31; 197 million). CONCLUSIONS: According to the present model, the treatment of OAB with mirabegron would generate savings compared with treatment with AM in all scenarios and sensitivity analysis performed, and for the NHS and for society perspectives.
Subject(s)
Urinary Bladder, Overactive , Humans , Urinary Bladder, Overactive/drug therapy , Muscarinic Antagonists/therapeutic use , Spain , Acetanilides/therapeutic use , Treatment OutcomeABSTRACT
Objectives: To compare the therapeutic efficacy, adverse events (AEs), and patient preference in elderly patients with overactive bladder (OAB) receiving different combinations of mirabegron and solifenacin. Materials and Methods: Elderly OAB patients received mirabegron 25 mg (M25) daily for 1 month (1M) followed by randomization to receive M25 (Group 1), mirabegron 50 mg (M50, Group 2), solifenacin 5 mg (S5, group 3); or M25 plus S5 (Group 4) for further 2 months. Efficacy and AEs were evaluated. At the end of 3M, patients' preferred option for future treatment was investigated. Results: A total of 168 patients were enrolled, and 100 completed 3-month treatment. At 1M, all parameters improved significantly except postvoid residual (PVR), 23 (13.7%) patients had no symptom, 16 (9.5%) had no improvement, and 10 (6.0%) withdrew from the trial. Compared parameters at 3M with 1M revealed that quality of life, Patient's Perception of Bladder Condition scores, and voided volume improved significantly in group 1; the OAB Symptom Score (OABSS) increased in group 2; mean PVR and Global Response Assessment (GRA) deteriorated in group 3; and the OABSS and GRA improved in group 4. At 3M, the AEs prevalence increased significantly in group 3. Only 38.1% in group 4 preferred long-term usage of combination therapy. Conclusion: M25 daily is effective and safe in treating elderly OAB patients. Dose escalation to 50 mg or shifting to S5 does not increase the therapeutic efficacy. Combining M25 with S5 provides better treatment efficacy but is associated with lower patient compliance than M25 alone.
ABSTRACT
INTRODUCTION AND HYPOTHESIS: This study aims to compare the effectiveness of intravaginal electrical stimulation (IVES) with regard to quality of life (QoL) and clinical parameters related to incontinence in women with idiopathic overactive bladder (iOAB) naive or refractory to treatment with pharmacological agents (PhA). METHODS: In this prospective trial, PhA-naive women were included in Group 1 (n = 24) and women with PhA-resistant iOAB were included in Group 2 (n = 24). IVES was performed 3 days a week, with a total of 24 sessions for 8 weeks. Every session lasted 20 minutes. Women were evaluated for the severity of incontinence (24-hour pad test), pelvic floor muscle (PFM) strength (perineometer), 3-day voiding diary (frequency of voiding, nocturia, incontinence episodes, and the number of pads), symptom severity (OAB-V8), quality of life (IIQ-7), treatment success (positive response rate), cure/improvement rate, and treatment satisfaction. RESULTS: A statistically significant improvement was found in all parameters for each group at the 8th week compared to the baseline values (p < 0.05). At the 8th week, there were no statistically significant differences in the severity of incontinence, PFM strength, incontinence episodes, nocturia, number of pads, QoL, treatment satisfaction, cure-improvement, or positive response rates between the two groups (p > 0.05). It was found that the frequency of voiding and symptom severity parameters were significantly more improved in Group 1 than in Group 2 (p < 0.05). CONCLUSIONS: Although IVES was more effective in PhA-naive women with iOAB, it also appears to be an effective treatment in the management of women with PhA-resistant iOAB. CLINICAL TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov under no. NCT05416450.
Subject(s)
Nocturia , Urinary Bladder, Overactive , Urinary Incontinence , Female , Humans , Electric Stimulation , Pelvic Floor , Prospective Studies , Quality of Life , Treatment Outcome , Urinary Bladder, Overactive/drug therapy , Urinary Incontinence/therapyABSTRACT
A radical prostatectomy is frequently used as the first-line treatment for men with prostate cancer. Persistent urinary incontinence after surgery is one of the most severe adverse events. We report the results of a comprehensive literature search focused on post-prostatectomy urinary incontinence (PPI), performed by a panel of experts on non-neurogenic lower urinary tract symptoms. The data on the prevalence and timing of PPI are very heterogeneous. The etiology of PPI can be multifactorial and mainly dependent on patient characteristics, lower urinary tract function or surgical issues. The medical history with a physical examination, the use of validated questionnaires with a voiding diary and pad tests are determinants in identifying the contributing factors and choosing the right treatment. Lifestyle intervention and urinary containment are the most frequently used strategies for the conservative management of PPI, while antimuscarinics, beta-3 agonists and duloxetine (off-label) are drugs indicated to manage PPI with a concomitant overactive bladder. Surgical therapies for the management of post-prostatectomy SUI include non-adjustable trans-obturator slings in men with mild-to-moderate incontinence and an artificial urinary sphincter in men with moderate-to-severe incontinence.