Effectiveness and Safety of Intradetrusor OnabotulinumtoxinA Injection for Neurogenic Detrusor Overactivity and Overactive Bladder Patients in Taiwan—A Phase IV Prospective,Interventional, Multiple-Center Study (Restore Study)

We conducted a phase IV, pre/post multi-center study to evaluate the efficacy and safety of intradetrusor onabotulinumtoxinA injection in patients with neurogenic detrusor overactivity (NDO, n = 119) or overactive bladder (OAB, n = 215). Patients received either 200U (i.e., NDO) and 100U (i.e., OAB) of onabotulinumtoxinA injection into the bladder, respectively. The primary endpoint for all patients was the change in the PPBC questionnaire score at week 4 and week 12 post-treatment compared with baseline. The secondary endpoints were the changes in subjective measures (i.e., questionnaires: NBSS for patients with NDO and OABSS for those with OAB) at week 4 and week 12 post-treatment compared with baseline. Adverse events included symptomatic UTI, de novo AUR, gross hematuria and PVR > 350mL were recorded. The results showed that compared with baseline, PPBC (3.4 versus 2.4 and 2.1, p < 0.001) and NBSS (35.4 versus 20.4 and 18.1, p < 0.001) were significantly improved at 4 weeks and 12 weeks in NDO patients. In addition, compared with baseline, PPBC (3.5 versus 2.3 and 2.0, p < 0.001) and OABSS (9.1 versus 6.2 and 5.7, p < 0.001) were significantly improved at 4 weeks and 12 weeks in OAB patients. Eight (6.7%) had symptomatic UTI and 5 (4.2%) had de novo AUR in NDO patients. Twenty (9.3%) had symptomatic UTI but no de novo AUR in OAB patients. In conclusion, we found that intradetrusor onabotulinumtoxinA injections were safe and improved subjective measures related to NDO or OAB in our cohort.     

Long-Term Efficacy and Safety of Repeated Intravescial OnabotulinumtoxinA Injections Plus Hydrodistention in the Treatment of Interstitial Cystitis/Bladder Pain Syndrome

Intravesical onabotulinumtoxinA (BoNT-A) injection can relieve symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks sustainability. Repeated injections have been shown to provide a superior outcome to a single injection, but data on long-term efficacy and safety is limited. In this prospective study, we enrolled patients with refractory IC/BPS, and treated them with 100 U of BoNT-A injection plus hydrodistention followed by repeated injections every six months for up to two years or until the patient wished to discontinue. A “top-up” dose was offered after the fourth injection. Of these 104 participants, 56.7% completed four BoNT-A injections and 34% voluntarily received the fifth injection due to exacerbated IC symptoms. With a follow-up period of up to 79 months, O’Leary-Sant symptom and problem indexes (ICSI, ICPI, OSS), pain visual analogue scale (VAS) functional bladder capacity, frequency episodes, and global response assessment (GRA) all showed significant improvement (p < 0.0001). Those who received repeated injections had a better success rate during the long-term follow-up period. The incidence of adverse events did not rise with the increasing number of BoNT-A injections. A higher pre-treatment ICSI and ICPI score was predictive for successful response to repeated intravesical BoNT-A injections plus hydrodistention.     

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action,Efficacy and Safety

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.     

Satisfaction with Detrusor OnabotulinumtoxinA Injections and Conversion to Other Bladder Management in Patients with Chronic Spinal Cord Injury

This study investigated the satisfaction with continued detrusor Botox injections for urinary incontinence and conversion to other surgical procedures and bladder management procedures for neurogenic detrusor overactivity (NDO) in patients with chronic spinal cord injury (SCI). A total of 223 patients with chronic SCI underwent detrusor Botox 200U for urodynamically confirmed NDO and urinary incontinence. After initial detrusor Botox injections, patients opted to either continue detrusor Botox injections every six to nine months and on clean intermittent catheterization (CIC), switch to other bladder management procedures, or receive surgical procedures to improve their urinary incontinence, correct emergent complications, or have better voiding conditions without CIC. Urinary incontinence improvement rates and satisfaction with bladder management were assessed and compared between different subgroups, urodynamic parameters, and bladder management procedures. Finally, a total of 154 male and 69 female patients were included, among whom 56 (25.1%), 81 (36.3%), 51 (22.9%), and 35 (15.7%) showed a marked, moderate, mild, and no reduction in urinary incontinence, respectively. However, only 48.4% of the patients continued detrusor Botox injections over the mean follow-up period of seven years. Patients with cervical or thoracic SCI had fair incontinence improvement rates. The presence of high detrusor pressure and higher-grade bladder outlet resistance also predicted a decrease in incontinence. Although more than 50% of the patients switched to other bladder management procedures or received surgical treatment, 69.1% expressed satisfaction with their current status. This large cohort of patients with chronic SCI who received initial detrusor Botox injections revealed that only 48.4% continued with Botox injections. Those who received surgical procedures due to urological complications or demanded change in bladder management could achieve high satisfaction rates.     

Pharmacological treatments available for the management of underactive bladder in neurological conditions

Introduction: Underactive bladder (UAB) is a common cause of lower urinary tract dysfunction which has an increasing incidence with aging. It is characterized as an incompetent detrusor contraction with reduced strength and/or duration to completely empty the bladder. UAB is observed in both men and women. The exact definition, classification, and pathophysiological mechanism responsible for UAB is still debatable, however neurologic, myogenic, and iatrogenic causes are explained. The symptom complex related to UAB includes hesitancy, diminished sensation of bladder filling, a slow urinary stream, increased post-void residue, and etc.

Areas covered: We reviewed the current understanding of UAB with special focus on pharmacological treatments and potential pharmacotherapy options particularly in neurological conditions. Also, the definition, etiology, symptoms, diagnosis and management of UAB were discussed in this review.

Expert commentary: The underlying mechanism of UAB is not clear yet. Therefore; the lack of efficient pharmacotherapies is evident in such patients. Prior to any decision for pharmacological or surgical interventions, the underlying causes of UAB and detrusor impairment in each patient should be distinguished. Future researches need to address the exact dynamics of detrusor contraction and the muscular and neurological contributors to UAB.     

Clean intermittent catheterization rates after initial and subsequent treatments with onabotulinumtoxinA for non-neurogenic overactive bladder in real-world clinical settings

Objective: Previous randomized controlled trials have reported a 6.1–6.9% incidence of clean intermittent catheterization (CIC) following treatment with onabotulinumtoxinA in non-neurogenic overactive bladder (OAB) patients who were inadequately managed by ≥1 anticholinergic. A multi-center retrospective chart review assessed the real-world rate of voiding dysfunction requiring catheterization.

Methods: Patients received onabotulinumtoxinA 100?U (approved dose) administered by experienced injectors between January 2013 and June 2015. Patients using CIC or an indwelling catheter for ≥24?hours for voiding dysfunction prior to onabotulinumtoxinA injections were excluded. The primary outcome was post-treatment CIC (lasting >24?hours; per individual physician’s clinical judgment considering patient’s voiding symptoms, post-void residual [PVR] urine volumes and patient bother). Potential baseline predictors of CIC (history of pelvic prolapse, cystocele, diabetes, PVR urine volume and age) were assessed using multivariable logistic regression.

Results: Overall, 299 patients received their first treatment with onabotulinumtoxinA 100?U. Mean age was 66.4 years; 98.3% were female. The incidence of CIC was 2.7% in the total study population after the first treatment with onabotulinumtoxinA. The de novo CIC rate in treatments 2 and 3 combined was similarly low (3.2%). None of the evaluated baseline characteristics were significant predictors of CIC initiation due to the low CIC incidence.

Conclusions: This real-world study of non-neurogenic OAB patients treated with onabotulinumtoxinA suggests that the CIC rate is lower than the rates reported in previous studies. There were no significant correlations between baseline predictors and CIC initiation, although statistical significance may not have been reached because of the low incidence of CIC.     

Tolterodine for the treatment of overactive bladder

Background: The overactive bladder syndrome is a common condition affecting ～ 12% of men and women. It is extremely disturbing with a great impact on quality of life. Its treatment involves a combination of behavioural and pharmacological therapy. The latter includes antimuscarinic drugs such as tolterodine. Objective: To review the safety and efficacy of tolterodine in the treatment of overactive bladder in comparison with other available antimuscarinic agents. Methods: A Pubmed search was carried out differentiating randomised, clinical trials; longitudinal, retrospective studies; and metanalysis on the use of tolterodine for overactive bladder treatment. In the comparison with other antimuscarinic agents, only randomised, clinical trials were considered. Results/conclusion: Tolterodine is available as immediate- or extended-release formulations. It has been extensively evaluated with long-term, randomised trials for safety and efficacy showing a significant improvement in overactive bladder symptoms with an excellent tolerability profile.     

The emerging role of solifenacin in the treatment of overactive bladder

Although antimuscarinic drug therapy has been proven to be effective in the management of patients with symptoms of the overactive bladder syndrome, compliance with medication is often affected by the antimuscarinic adverse effects of dry mouth, constipation, somnolence and blurred vision. The development of bladder-selective M₃-specific antagonists offers the possibility of increasing efficacy whilst minimising adverse effects. At present there are no M₃-specific antagonists currently available although solifenacin and darifenacin are both under development and are due to be launched in 2004. The purpose of this article is to review the pharmacology and clinical trial data available for solifenacin, in addition to examining its role in the treatment of the overactive bladder syndrome.     

Real-World Data Regarding Satisfaction to Botulinum Toxin A Injection into the Urethral Sphincter and Further Bladder Management for Voiding Dysfunction among Patients with Spinal Cord Injury and Voiding Dysfunction

Purpose: This study aimed to investigate improvement in voiding condition after the initial botulinum toxin A (BoNT-A) injection into the urethral sphincter among patients with chronic spinal cord injury (SCI) and voiding dysfunction. Moreover, subsequent surgical procedures and bladder management were evaluated. Materials and Methods: From 2011 to 2020, 118 patients with SCI and dysuria who wanted to void spontaneously received their first BoNT-A injection at a dose of 100 U into the urethral sphincter. Improvement in voiding and bladder conditions after BoNT-A treatment were assessed. Next, patients were encouraged to continually receive BoNT-A injections into the urethral sphincter, convert to other bladder managements, or undergo surgery. After undergoing bladder management and surgical procedures, the patients were requested to report improvement in voiding condition and overall satisfaction to bladder conditions. Then, data were compared. Results: In total, 94 male and 24 female participants were included in this analysis. Among them, 51 presented with cervical, 43 with thoracic, and 24 with lumbosacral SCI. After BoNT-A injections into the urethral sphincter, 71 (60.2%) patients, including 18 (15.3%) with excellent, and 53 (44.9%) with moderate improvement, had significant improvement in voiding condition. Patients with cervical SCI (66.6%), detrusor overactivity and detrusor sphincter dyssynergia (72.0%), partial hand function (80.0%), and incomplete SCI (68.4%) had a better improvement rate than the other subgroups. Only 42 (35.6%) patients continually received treatment with BoNT-A injections into the urethral sphincter. Meanwhile, more than 60% of patients who converted their treatment to augmentation enterocystoplasty (n = 5), bladder outlet surgery (n = 25), BoNT-A injections into the detrusor muscle (n = 20), and medical treatment (n = 55) had moderate and marked improvement in voiding dysfunction and overall satisfaction. Discussion: Although BoNT-A injections into the urethral sphincter could improve voiding condition, only patients with SCI who presented with voiding dysfunction were commonly satisfied. Those whose treatments were converted to other bladder managements, which can promote urinary continence, or to surgical procedures, which can facilitate spontaneous voiding, had favorable treatment outcomes.     

膀胱癌术后膀胱内灌注化疗药物的护理体会

目的探讨膀胱癌术后膀胱内灌注化疗药物的护理。方法回顾我院36例膀胱癌术后病人,于术后第2周开始行膀胱内灌注吡柔比星化疗药物,与患者进行详细的心理沟通与疏导,详细讲解灌注治疗在预防肿瘤复发中的重要性。结果36例患者心态良好,坚持治疗,其中2例患者出现膀胱刺激征、发热、尿道狭窄、骨髓抑制。结论膀胱内灌注式化疗,方法简单、方便、全身毒副作用小,生存率高,局部复发率低,在护理工作中,需密切观察化疗反应。     

心脉隆注射液对慢性心力衰竭患者的疗效和安全性研究

探讨心脉隆注射液治疗慢性心力衰竭患者的治疗有效性和安全性.选取该院心内科于2017年6月至2019年6月期间收治的64 例慢性心力衰竭患者作为本次研究的对象,将其随机均分为治疗组(n=32)和安慰剂组(n=32).心脉隆注射液组在标准治疗的基础上加入心脉隆注射液治疗(5 mg/kg,静脉滴注).对照组采用标准治疗加等量...     

索利那新和托特罗定治疗膀胱过度活动症的疗效及安全性的Meta分析

目的系统评价索利那新和托特罗定对照治疗膀胱过度活动症(OAB)的疗效及安全性。方法搜集运用索利那新和托特罗定对比治疗OAB的随机对照试验中英文文献,并追查已纳入文献的参考文献。使用统计软件Rev Man5.0完成Meta分析。结果共纳入8个研究,总样本量约832例进行Meta分析,其基线经检验一致。通过比较用药后5项判效指标及不良反应。Meta分析发现索利那新和托特罗定在改善OAB 24 h尿急次数、24 h尿失禁次数及24 h夜尿次数方面差异无统计学意义;但索利那新在改善24 h排尿次数及每次尿量方面优于托特罗定,差异有统计学意义(P<0.05)。不良反应与托特罗定相比,索利那新口干发生率低50%,差异有统计学意义;便秘、视物模糊及消化不良方面,二者差异无统计学意义。结论索利那新和托特罗定均可改善OAB症状,但在改善24 h排尿次数及每次尿量、口干方面索利那新优于托特罗定。本研究纳入文献和样本量有限,建议进行大样本、长期随访的高质量临床试验,提供更佳循证证据。     

Safety and efficacy of tramadol in the treatment of idiopathic detrusor overactivity: a double-blind, placebo-controlled, randomized study

AIM: To evaluate the efficacy and safety of tramadol in patients with idiopathic detrusor overactivity (IDO). METHODS: A total of 76 patients 18 years or older with IDO were randomly assigned to receive 100 mg tramadol sustained release (group 1, n = 38) or placebo (group 2, n = 38) every 12 h for 12 weeks. Clinical evaluation was performed at baseline and every 2 weeks during treatment. All patients underwent urodynamics and ice water test at baseline and 12-week treatment. Main outcome measures were number of voids per 24 h, urine volume per void and episodes of urge incontinence per 24 h on a frequency volume chart and detailed recording of adverse effect. RESULTS: After 12 weeks of treatment mean number of voids per 24 h +/- SD decreased from 9.3 +/- 3.2 to 5.1 +/- 2.1 (P < 0.001 vs. placebo) [95% confidence interval (CI) -5.1--0.4]. At that time mean urine volume per void increased from 158 +/- 32 to 198 +/- 76 ml (P < 0.001 vs. placebo) (95% CI 8-22), while mean number of incontinence episodes per 24 h decreased from 3.2 +/- 3.3 to 1.6 +/- 2.8 (P < 0.001 vs. placebo) (95% CI -2-0.3). Tramadol induced significant improvements in urodynamic parameters. More adverse effects were associated with tramadol treatment than with placebo (P < 0.05). The main adverse event with tramadol was nausea. CONCLUSIONS: In patients with non-neurogenic IDO tramadol provided beneficial clinical and urodynamic results. Further studies are required to draw final conclusions on the efficacy of this drug in IDO.     

尼莫同联合依达拉奉注射液治疗缺血性脑卒中患者的临床疗效及安全性

目的:评价尼莫同与依达拉奉注射液联合治疗缺血性脑卒中患者的临床疗效及安全性。方法:选取在某院接受缺血性脑卒中治疗的患者100例,按照治疗方法的不同,将其均分为单一治疗组和联合治疗组两个组别,比较两组治疗的临床疗效、治疗前后的神经功能缺损情况。结果:联合治疗组治疗的总有效率显著高于单一治疗组(P<0.05),治疗后7d、14d联合治疗组的神经功能缺损评分的改善情况显著优于单一治疗组(P<0.05),且联合治疗组患者的不良反应率显著低于单一治疗组(P<0.05)。结论:尼莫地平注射液和依达拉奉注射液联合治疗缺血性脑卒中具有更好的临床疗效,且不良反应率低,值得推广。     

2型糖尿病伴陈旧性脑梗死患者餐后注射门冬胰岛素的疗效观察

目的评价门冬胰岛素（InsulinAspart,IASP）餐后注射与餐前注射治疗2型糖尿病合并脑梗死患者的疗效及安全性。方法以32例因口服磺脲类药物继发失效已使用预混胰岛素治疗12周以上且血糖控制不佳的2型糖尿病合并陈旧性脑梗死患者为研究对象．随机分为2组,停用原降糖方案,在联合睡前甘精胰岛素的基础上,分别以IASP餐后（A组）及餐前（B组）注射12周,比较2组空腹及餐后2h血糖、糖化血红蛋白（HbAle）、低血糖发生频率、神经功能缺损评分（ChinaStrokeScale,CSS）情况。结果2组治疗后空腹血糖、餐后2h血糖、HbAle均较治疗前显著下降,组间疗效比较无显著性差异。A组低血糖发生频率明显低于B组（6．25％vs37．50％,P〈0．05）。治疗后12周A组CSS评分明显低于B组（19．2±8．7vs24．3±9．5,P〈0．05）。结论与IASP餐前注射相比,餐后注射同样能够有效控制血糖,且低血糖发生率显著减少,可改善神经功能缺损症状,安全性更好。     

Treatment Outcomes of Intravesical Botulinum Toxin A Injections on Patients with Interstitial Cystitis/Bladder Pain Syndrome

Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS patients receiving intravesical BoNT-A injections. This retrospective study included IC/BPS patients who had 100U BoNT-A intravesical injections in the past 20 years. The treatment outcomes at 6 months following the BoNT-A treatment were evaluated using the global response assessment (GRA) scale. The treatment outcomes according to the GRA scale include clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urinary biomarkers, and it was these predictive factors for achieving satisfactory outcomes which were investigated. Among the 220 enrolled patients (180 women, 40 men) receiving BoNT-A injections, only 87 (40%) had significantly satisfactory treatment outcomes. The satisfactory group showed significantly larger voided volumes, and lower levels of both the urinary inflammatory protein MCP-1 and the oxidative stress biomarker 8-isoprostane in comparison to the unsatisfactory group. The IC severity and detrusor pressure are predictive factors of BoNT-A treatment outcomes. IC/BPS patients with less bladder inflammation showed satisfactory outcomes with intravesical BoNT-A injections. Patients with severe bladder inflammation might require more intravesical BoNT-A injections to achieve a satisfactory outcome.     

The medical treatment of overactive bladder,including current and future treatments

Introduction: Oveactive bladder (OAB) is a common condition that affects patients' quality of life. The role of antimuscarinics and future treatments in the management of this bothersome condition is reviewed.

Areas covered: The current literature on the efficacy, suitability and safety of current and future treatments is reviewed based on a search of Medline/Pubmed for relevant articles published in English between 1980 and 2010.

Expert opinion: Currently, antimuscarinic drugs are the cornerstone of OAB treatment; clinically recommended doses of these agents decrease the ability of the bladder to contract during the storage phase and so increase cystometric bladder capacity. In general, these agents are safe and have mild adverse effects. There is also evidence that, despite having different tolerability profiles, available drugs are well tolerated compared with placebo. Antimuscarinic agents, as a class, have similar efficacy. They offer substantial help in the alleviation of OAB symptoms, providing significant improvement to quality of life. Investigation to provide pharmacological alternatives whenever antimuscarinic drugs do not provide symptomatic relief or cause intolerable side effects is intense. Beta-adrenergic agents may be the next pharmacologic agents for OAB. However, many other areas of research may soon provide new pharmacological agents for OAB treatment.     

索利那新联合生物反馈治疗女性膀胱过度活动症的疗效

目的 观察索利那新(抗排尿功能障碍药)联合生物反馈治疗女性膀胱过度活动症(OAB)的疗效.方法 31例女性OAB患者,口服索利那新(28天,5mg/24 h )联合生物反馈(20天)进行治疗,3个月后评价疗效并追踪观察.结果 31例女性OAB患者中,治愈17例(58.1%),有效10例(32.3%),无效4例(12.9%),总有效率达87.1%.治疗后有效随访26例,3个月无复发.结论 索利那新联合生物反馈是治疗女性OAB的一种有效方法.     

双氯芬酸钠利多卡因用于胸外科开胸术后镇痛的临床研究

目的：观察和评价双氯芬酸钠利多卡因用于胸外科开胸手术术后镇痛治疗的临床疗效和安全性。方法：以舒芬太尼为对照药,选择胸外科开胸手术患者160例,随机分为两组（n=80）;观察组给药剂量为每次1支,75mg／支,肌内注射,每日2次;对照组给药为静脉自控镇痛,剂量为：舒芬太尼1.0mg＋托烷司琼5mg·（200mL）^-1。观察记录术后4、8、12、24、36、48、72各时点镇痛评分（VAS）和镇静评分（SS）及其间的不良反应情况。结果：两组镇痛评分（VAS）无显著的统计学差异（P〉0.05）,镇静评分（SS）有显著的统计学差异（P〈0.05）,试验组镇静效果及恶心、呕吐等不良反应明显低于对照组。结论：双氯芬酸钠利多卡因用于胸外科开胸术后镇痛治疗的效果优良,不良反应少,是一种安全、有效的术后镇痛方法。