onabotulinumtoxinA Injections Research Articles

Migraine With Comorbid Depression: Pathogenesis, Clinical Implications, and Treatment.

Migraine is a neurological disorder that strongly relates to psychiatric conditions like depression. Lately, the increased prevalence of depression in migraineurs has come to attention. This article compiled various literature to explore the association between migraine and depression. Genetic overlap of various gene segments was studied, and heritability patterns were explored. Shared mechanisms such as serotonergic dysfunction, methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and hormonal effects were investigated, and commonalities like comorbidities, stress, and environmental factors were analyzed. Migraine with comorbid depression (MID) affects various aspects of life and its clinical impact on migraine disability, quality of life (QOL), progression, and medication overuse was investigated. We further inspected several types of research in order to provide options on various treatment modalities. Pharmacotherapy such as antidepressants and anti-Calcitonin Gene-Related Peptide (CGRP) monoclonal antibodies like fremanezumab were studied. Alternative treatment options such as onabotulinumtoxinA (OBTA) injections, cognitive behavioral therapy (CBT), and vagal nerve stimulations (VNS) were also appraised and the efficacies of each were compared.

Adverse events after different forms of botulinum neurotoxin A injections in children with cerebral palsy: An 8-year retrospective study.

To compare the risks of adverse events 3 months after Onabotulinumtoxin-A and Lanbotulinumtoxin-A injections in children with cerebral palsy (CP) and to identify risk factors and associations. A total of 1037 children (682 males, 355 females; mean age 5 years 2 months [SD 3 years]; age range 2 years-17 years 10 months) with CP underwent 1013 Onabotulinumtoxin-A injections and 418 Lanbotulinumtoxin-A injections from 2012 to 2021. Information was recorded in a purpose-built database. The adverse event rates of Onabotulinumtoxin-A and Lanbotulinumtoxin-A were reported as 13.92% and 11.96% respectively. Most adverse events were mild and self-limiting. Children in Gross Motor Function Classification System (GMFCS) levels IV to V had a higher risk of adverse events than those in GMFCS levels I to III (odds ratio [OR] [95% confidence interval {CI}]=3.65 [1.56, 5.40], p < 0.01). The history of recent illness and higher dose increased the likelihood of adverse events (OR [95% CI]=2.00 [1.55, 3.00] and 2.20 [1.53, 3.07] respectively, p < 0.01). Sex, age, and the number of injections had no significant effect on adverse event rates (p > 0.05). The incidence of upper respiratory tract infection and lower respiratory tract infection after injections was weakly correlated with the incidence before injections (r=0.36 and r=0.27 respectively, p < 0.01). Occurrence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with CP. Dose, GMFCS level, and health background were risk factors. The prevalence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with cerebral palsy (CP). The prevalence of adverse events increased with the severity of CP and the injected dose. Sex, age, and number of injections had no significant effect on the prevalence of adverse events.

Urinary tract infection following intradetrusor onabotulinumtoxina injection for non-neurogenic urgency incontinence: single- vs. multi-dose prophylactic antibiotic treatment regimens.

Urinary tract infection is one of the most common adverse events following onabotulinumtoxinA injection for urgency incontinence. Our hypothesis was that those undergoing injection for urgency incontinence who received more than one dose of prophylactic antibiotics have lower post-procedure urinary tract infection rates compared to those who receive a single dose. We conducted a multi-center retrospective cohort study in females who underwent onabotulinumtoxinA injection for non-neurogenic urgency incontinence to evaluate the effect of single- vs. multi-dose prophylactic antibiotic regimens on the risk of post-procedure urinary tract infection. The primary outcome was the rate of urinary tract infection within 30 days of injection. Our sample size calculation required 136 subjects per group. Two hundred eighty-one patients were included from four centers. The single-dose cohort included 145 patients (51.6%), and the multi-dose cohort included 136 patients (48.4%). The mean age was 65 years, and patients were primarily Caucasian (81.4%). There was no difference in the rate of urinary tract infections diagnosed within 30 days of injection between the cohorts (single dose 13.8% vs. multi-dose 10.3%, p = 0.369). Those with a positive urine culture within 30 days of injection had a 15.2 times greater odds of having a post-procedure infection than those who did not (95% CI 3.19-72.53). There was no significant difference between the two cohorts in terms of adverse health events following injection. In females with non-neurogenic urgency incontinence undergoing onabotulinumtoxinA injection, multi-dose prophylactic antibiotic regimens were not associated with lower post-procedure urinary tract infection rates.

Glabellar Botulinum Toxin Injection Improves Depression Scores: A Systematic Review and Meta-Analysis.

Depression is a leading cause of disability worldwide. Preliminary evidence suggests that glabellar onabotulinumtoxinA injections improve depression scores with few side effects compared to current first-line antidepressant medications. The authors' review reports on these studies, hypothesizing that glabellar onabotulinumtoxinA injections can be an alternative safe and effective treatment for depression. A systematic review and meta-analysis of the relevant literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Cochrane Library, Embase, and Scopus databases were searched in August of 2020 using the keywords ["botox" OR "botulinum"] AND ["mood" OR "depression"] for articles published between 1980 and 2020. Prospective studies and randomized controlled trials on the use of glabellar onabotulinumtoxinA injections for the primary purpose of treating depression were considered. The primary endpoint for the meta-analysis was the mean difference in primary depression scores after treatment, along with a second endpoint of the standardized mean difference in depression scores among treated patients including all nine studies. Of the 499 reviewed articles, nine studies were included that reported improvement in mean depression scores from baseline. All five randomized controlled trials reported an improvement in mean depression scores at 6 weeks after treatment, with a weighted average change of -8.39 points ( p < 0.0001). The aggregate standardized mean difference from baseline to the primary endpoint across all nine prospective studies was -1.61 SD ( p < 0.0001). Meta-analysis and systematic review of the included studies provide support for an antidepressant effect of glabellar onabotulinumtoxinA injections.

Impact of Duration of Antibiotic Prophylaxis on Incidence of UTI after OnabotulinumtoxinA Injection

ObjectiveTo assess the impact of duration of antibiotic prophylaxis on incidence of urinary tract infection (UTI) after intravesical OnabotulinumtoxinA (BTX) injection. MethodsA retrospective cohort study of patients with overactive bladder who underwent office BTX injections from 2014 to 2020. UTI incidence within 30 days of BTX was compared between 3 durations of antibiotic prophylaxis: no antibiotic, single day, or multiple day course. Association of UTI with units of BTX, body mass index, history of diabetes, immunosuppression, neurogenic overactive bladder, chronic catheter, or recurrent UTI were investigated. ResultsTwo hundred ninety patients and 896 cycles of BTX injections were included: 877 injections (97.7%) were women, with mean age 61.4 years (range 20-96; SD 13.3). No antibiotic prophylaxis was given to 112 (12.5%) patients, 595 (66%) received a single day, and 189 (21%) received a multiple day regimen (3-7 days). Overall incidence of UTI within 30 days was 11.4%. On multivariable logistic regression, use of any antibiotic prophylaxis was associated with a lower incidence of UTI (single odds ratio [OR] 0.34; 95% confidence interval [CI] 0.19-0.61; P < .001; multiple OR 0.47; 95% CI 0.24-0.92; P = .029), with no difference between single and multiple day regimens (OR 1.38; 95% CI 0.80-2.38; P = .249). History of recurrent UTI (OR 3.77; 95% CI 2.23-6.39; P < .001) and chronic suprapubic catheter (OR 2.88; 95% CI 1.04-7.95; P = .041) were additional predictors. ConclusionA multiple day regimen of antibiotic prophylaxis was not more effective than a single day in preventing UTI for intravesical BTX injection. Use of any antibiotic prophylaxis was associated with a significantly lower incidence of UTI compared to no antibiotic.

Oral phenazopyridine vs intravesical lidocaine for bladder onabotulinumtoxinA analgesia: a randomized controlled trial

The efficacy of intradetrusor onabotulinumtoxinA injections for the management of idiopathic overactive bladder has been well-established. The injections are typically performed in the office setting using local analgesia, most commonly a 20 to 30-minute intravesical instillation of lidocaine. There are limited data evaluating alternative bladder analgesics. To compare pain scores with preprocedure oral phenazopyridine vs intravesical lidocaine in women undergoing intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder. Nonpregnant adult females with idiopathic overactive bladder, scheduled for office injection of 100 units of intradetrusor onabotulinumtoxinA were randomized to either 200 mg of oral phenazopyridine taken 1 to 2 hours preprocedure or a 20-minute preprocedure intravesical instillation of 50 mL of 2% lidocaine. We excluded participants with neurogenic bladders, and those who had received intradetrusor onabotulinumtoxinA injections in the previous 12 months. The primary outcome was pain measured by a 100-mm visual analog scale. Demographic characteristics and overall satisfaction with the procedure were also recorded. Providers answered questions about cystoscopic visualization, ease of procedure, and perception of participant comfort. Prespecified noninferiority margin was set to equal the anticipated minimum clinically important difference of 14 mm. A planned sample of 100 participants, 50 in each treatment arm, provided 80% power to detect noninferiority at a significance level of.05. We performed a modified intention-to-treat analysis and compared variables with the t test or the Fisher exact test. A total of 111 participants were enrolled, and complete data were obtained for 100 participants; 47 participants were randomized to phenazopyridine and 53 to lidocaine. Baseline characteristics did not differ between groups. There were 19.6% and 20.8% of participants in the phenazopyridine and lidocaine groups, respectively, who previously underwent intradetrusor onabotulinumtoxinA injections. The mean postprocedure pain was 2.7 mm lower in the phenazopyridine group than in the lidocaine group (95% confidence interval,-11.3 to 10.7), demonstrating noninferiority. More than 90% of participants in both groups stated that the pain was tolerable. Slightly more participants reported being "very satisfied" in the lidocaine group, although this was not statistically significant (50.0% vs 40.4%; P=.34). Providers reported clear visualization in 89.4% of participants in the phenazopyridine group and in 100% of participants in the lidocaine group (P=.02). Provider perception of participant comfort and overall ease of procedure were not different between groups. Length of time in the exam room was significantly shorter in the phenazopyridine than in the lidocaine group (44.4 vs 57.5 minutes; P=.0003). In women receiving intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder, oral phenazopyridine was noninferior to intravesical lidocaine for procedural pain control. Phenazopyridine is well-tolerated by participants, allows for the procedure to be performed with similar ease, and is associated with shorter appointment times.

Evaluating and understanding combination therapy decision drivers for the treatment of overactive bladder in the United States.

ObjectiveTo understand factors guiding overactive bladder (OAB) therapy selection and experience with combination therapy (antimuscarinics and beta-3 agonists).MethodsCross-sectional surveys of OAB patients and OAB-treating physicians in the USA were conducted. Patients receiving monotherapy with antimuscarinics were categorized by OAB treatment history: monotherapy only; third-line procedures (e.g., onabotulinumtoxinA injections) and combination therapy; third-line therapy only; and combination therapy only. The patient survey assessed therapy choice drivers and barriers, treatment satisfaction and sociodemographic/clinical characteristics. The physician survey assessed drivers of and barriers to OAB treatment choices.ResultsOf 200 patients, 86.5% reported involvement in treatment decision-making; doctor’s recommendation was the most frequently considered factor (84.4%). Most patients (71%) were unaware of combination therapy. The primary reason why those patients aware of combination therapy had not used it (N = 43/200; 21%) was physician recommendation of other treatments (69.8%). For physicians (N = 50), the most frequently considered factors when prescribing OAB treatment were effectiveness (92.0%) and side effects (84.0%); 70% prescribed combination therapy, primarily for symptom severity (82.9%). The main reasons for not prescribing combination therapy were cost/insurance coverage (80%) and lack of information (53.3%).ConclusionsShared decision-making guided treatment decisions; the main considerations were treatment safety and efficacy.

Study of botulinum toxin type A for the treatment of ultraviolet B-induced hyperpigmentation: A prospective, randomized, controlled trial.

Botulinum toxin type A (BTX-A) has been used experimentally under various dermatological conditions. Recent studies have revealed a preventive effect of BTX-A against ultraviolet B (UVB)-induced skin hyperpigmentation. We examined the effect of BTX-A for the treatment of UVB-induced hyperpigmentation in humans. A prospective, double-blind, randomized controlled trial was conducted. UVB irradiation induced five separate hyperpigmented squares on the abdomen. Seven days after irradiation, all squares were randomly assigned to five intervention groups: control, 0.9% normal saline injection, 12 units (1:2.5), 6 units (1:5), and 4 units (1:7.5) of onabotulinum toxin injections. The lightness index (L*), hyperpigmentation improvement score rated by a blinded physician, and participant satisfaction scores were obtained at 14, 21, and 28days after injection. Fifteen participants (mean age 36.9years, Fitzpatrick skin types III-IV) completed the study. The BTX-A (1:2.5)-treated site had a lower degree of hyperpigmentation at all time points, as measured by mean L* and hyperpigmentation improvement scores. However, there were no statistically significant differences between the groups. Participants were most satisfied with the control site. Intradermal BTX-A injection had no therapeutic effect on UVB-induced hyperpigmentation. However, the role of BTX-A injections in the treatment of other hyperpigmentary conditions requires further elucidation.

Treatment of idiopathic overactive bladder with botulinum toxin: real-life results and patients' expectations.

Overactive bladder (OAB) is a prevalent syndrome affecting 11% to 16% of the adult population. When first-line pharmacological therapy is not effective, intradetrusorial injections of onabotulinumtoxinA (BTX-A) might have an important role in controlling symptoms. The main aim of this study was to access both the efficacy and safety of intradetrusor injections of 100U BTX-A in real clinical practice, among women with idiopathic OAB (iOAB). Retrospective study, based on clinical diaries in 136 iOAB female patients, with or without urinary incontinence, submitted to BTX-A injections, between 2005 and 2018 in a tertiary university hospital. Positive response was considered only when the patient mentioned she had great improvement after the injection, otherwise, it was considered negative. A positive response was obtained in 90 patients (66%) after the first injection. Women with a positive response after the first treatment had 7.5 times more chances to improve with the second (P = .01). Discontinuation of the therapy after the first injection was neither dependent on the presence of incontinence at baseline (P = .73) nor it was related to age (P = .6). On univariate analyses, none of the parameters evaluated was useful of predicting successful response, although there was a trend in women who had had a previous midurethral sling surgery for stress urinary incontinence, to have a lower chance of having a positive response after the first injection (P = .06).Thirty-nine women (29%) had at least 1 adverse event, urinary tract infection, and straining to void were the most frequent. Women above 65 years old had less risk of developing a urinary tract infection (P = .04). In real clinical practice, BTX-A injection is an effective (66%) and safe treatment, capable of improving quality of life. Moreover, responding to the first injection seems to predict good clinical outcomes in the second treatment. This procedure can be done with minimal restrictions.

Editorial Comment

This prospective study of OnabotulinumtoxinA injection (BTX-A) bladder injections in patients with neurogenic bladder specifically from congenital spinal dysraphism (CSD), adds to the literature by assessing both patient-reported and more traditional urodynamic measurements, but also by taking an important look at the “high risk” population. This cohort of patients with characteristics worrisome for eventual bladder deterioration and kidney damage is small and heterogeneous as expected in CSD especially by the time they reach a transitional urologist, but is still meaningful.

Reduced versus standard intradetrusor onabotulinumtoxina injections for treatment of overactive bladder

Reduced versus standard intradetrusor onabotulinumtoxina injections for treatment of overactive bladder

Oral phenazopyridine versus intravesical lidocaine for office onabotulinumtoxina analgesia: a randomized controlled trial

To compare pain scores in women undergoing intradetrusor onabotulinumtoxinA for idiopathic overactive bladder (OAB) between women randomized to pre-procedure oral phenazopyridine versus intravesical lidocaine. Non-pregnant adult females scheduled for office injection of 100 units intradetrusor onabotulinumtoxinA were randomized to either 200mg of oral phenazopyridine taken 1-2 hours preprocedure versus a 20 minute preprocedure intravesical instillation of 50mL 2% lidocaine. We excluded patients with neurogenic bladder, and those who had received intradetrusor onabotulinumtoxinA injections in the previous 12 months. The primary outcome was pain measured by a 100mm visual analog scale (VAS). Demographic characteristics and overall satisfaction with the procedure were also collected. Providers answered questions about cystoscopic visualization, ease of procedure, and perception of patient comfort. In order to detect a difference of 14 (SD 25) or greater on the VAS with 80% power and a significance level of .05, we planned to obtain complete data for 100 patients, 50 in each treatment arm. We performed an intention to treat analysis and compared variables by T-test or Fisher’s exact test. 111 patients were enrolled; complete data was obtained for 100 participants. 47 patients were randomized to phenazopyridine and 53 to lidocaine. Baseline characteristics did not differ between groups. 19.6% and 20.8% in the phenazopyridine and lidocaine groups, respectively, had previously undergone intradetrusor onabotulinumtoxinA injections. Pre-procedure pain scores did not differ between groups. The mean post-procedure pain score was not significantly different between groups, with a mean of 24 (28) in the phenazopyridine group compared to 28 (31) in the lidocaine group (p=0.52). A post-hoc power analysis with 47 and 53 patients per treatment arm showed similar power. Greater than 90% of patients in both groups stated the pain was tolerable. Slightly more patients reported being “very satisfied” in the lidocaine group, although this was not statistically different (50.0% vs 40.4%, p = 0.34). Providers reported clear visualization in 89.4% of patients in the phenazopyridine group versus 100% in the lidocaine group (p=0.02). Provider perception of patient comfort and overall ease of procedure was not different between groups. Length of time in the exam room was significantly shorter in the phenazopyridine versus the lidocaine group (44.4 vs 57.5 minutes, p=0.0003). In women receiving intradetrusor onabotulinumtoxinA injections for idiopathic OAB, there was no difference in pain scores when comparing oral phenazopyridine versus intravesical lidocaine. Phenazopyridine is well-tolerated by patients, allows for the procedure to be performed with similar ease, and is associated with shorter appointment times.

Complications of Cosmetic Botulinum Toxin A Injections to the Upper Face: A Systematic Review and Meta-Analysis.

BackgroundBotulinum toxin A (BoNT-A) injections are a popular non-surgical procedure for facial rejuvenation. Its increase in popularity and utilization is met with limited regulations, potentially posing a significant risk to patient safety and public health.ObjectivesThe authors sought to assess the safety profile of cosmetic glabellar and forehead BoNT-A injections and evaluate BoNT-A type on complication rate.MethodsA systematic search of MEDLINE and EMBASE was performed for studies reporting complications after cosmetic BoNT-A in the glabellar or in the forehead region in the glabellar or in the forehead region. A random effects meta-analysis was carried out to assess complication rate. Where there were sufficient randomized-controlled trials, a network meta-analysis was performed.ResultsOf 556 identified articles, 24 were included in the final quantitative analysis, with 4268 BoNT-A injection sessions and 1234 placebos. Frequently observed treatment-related complications in the BoNT-A intervention group included headache, local skin reactions, and facial neuromuscular symptoms. The overall BoNT-A complication rate was 16%. The odds ratio of developing complications from abobotulinum toxin injections compared with placebo was 1.62 (1.15, 2.27; P > 0.05) and that from onabotulinum toxin injections compared with placebo was 1.34 (0.52, 3.48; P > 0.05). In 30% of the studies, the injectors were doctors, whereas the training status of the practitioner was not reported in the remaining 70%.ConclusionsCosmetic BoNT-A injections in the glabellar and forehead region appear to be safe, and most complications are mild and transient. Nevertheless, the literature demonstrates heterogeneous reporting of complications and a lack of consistency of the definition of treatment-related complications.Level of Evidence: 2

Commentary on: Hyaluronic Acid Compound Filling Plus Mesotherapy vs Botulinum Toxin A for the Treatment of Horizontal Neck Lines: A Multicenter, Randomized, Evaluator-Blinded, Prospective Study in Chinese Subjects.

See the Original Article here. We read with interest the article entitled “Hyaluronic Acid Compound Filling Plus Mesotherapy vs Botulinum Toxin A for the Treatment of Horizontal Neck Lines: A Multicenter, Randomized, Evaluator-Blinded, Prospective Study in Chinese Subjects.” 1 We enjoyed reading this study, and we appreciate the opportunity to provide our comments. In this article, the authors take a novel approach to the treatment of “horizontal neck lines” that involves a combination technique for hyaluronic acid (HA) filler injection: linear threading within the horizontal rhytids, combined with intradermal field injection with mesotherapy needles. They compared the outcomes of this technique (HA filling plus mesotherapy) with targeted intradermal injection of onabotulinum toxin A (BTX-A; Botox, Allergan, Irvine, CA), and concluded that HA filling plus mesotherapy is superior. We did not find any major flaws in this study, and the authors should be commended for organizing a prospective, multicenter, randomized,...

Ultra-Long-Term Therapy of Benign Essential Blepharospasm with Botulinumtoxin A-30 Years of Experience in a Tertiary Care Center.

Aim of this study was to investigate the long-term results of botulinum toxin A (BoNT-A) injections for the treatment of benign essential blepharospasm (BEB) and to report our experience with (ultra-)long-term treatment with onabotulinumtoxin-A. We conducted a retrospective cross-sectional analysis at a university hospital. Patients with BEB and BoNT-A treatment were assigned to the Total Blepharospasm Group, patients with ≥21 onabotulinumtoxin-A injections to the Ona Long-Term Group. The Total Blepharospasm Group (n = 1940) included 33,933 BoNT-A injections. The age of patients at symptom onset was (mean ± SD) 58.0 ± 13.1 years, and 70.4% were female. The Ona long-term group (n = 234) included 10,632 onabotulinumtoxin-A injections. In this group, patients received 45.4 ± 22.9 injections with a mean dose of 22.2 IU ± 0.5. The duration of treatment was 12.6 ± 5.4 years, ranging from 2.9 to 30.0 years. The effect–duration–dose quotient did not change during long-term treatment. The observed side effects were comparable in type and frequency to other studies, even with the (ultra-)long treatment with onabotulinumtoxin-A. Our results, based on one of the largest patient populations and a treatment duration of up to 30 years, impressively demonstrate that onabotulinumtoxin-A is a safe and effective therapy for essential blepharospasm, even in the ultra-long term.

Machine learning provides an accurate prognostication model for refractory overactive bladder treatment response and is noninferior to human experts.

The increasing wealth of clinical data may become unmanageable for a physician to assimilate into optimal decision-making without assistance. Utilizing a novel machine learning (ML) approach, we sought to develop algorithms to predict patient outcomes following the overactive bladder treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM). ROSETTA datasets for overactive bladder patients randomized to OBTX-A or SNM were obtained. Novel ML algorithms, using reproducing kernel techniques were developed and tasked to predict outcomes including treatment response and decrease in urge urinary incontinence episodes in both the OBTX-A and SNM cohorts, in validation and test sets. Blinded expert urologists also predicted outcomes. Receiver operating characteristic curves were generated and AUCs calculated for comparison to lines of ignorance and the expert urologists' predictions. Trained algorithms demonstrated outstanding accuracy in predicting treatment response (OBTX-A: AUC 0.95; SNM: 0.88). Algorithms accurately predicted mean decrease in urge urinary incontinence episodes (MSE < 0.15) in OBTX-A and SNM. Algorithms were superior to human experts in response prediction for OBTX-A, and noninferior to human experts in response prediction for SNM. Novel ML algorithms were accurate, superior to expert urologists in predicting OBTX-A outcomes, and noninferior to expert urologists in predicting SNM outcomes. Some aspects of the physician-patient interaction are subtle and uncomputable, and thus ML may complement, but not supplant, a physician's judgment.

BoNT/A1 Secondary Failure for the Treatment of Neurogenic Detrusor Overactivity: An Ex Vivo Functional Study.

Management of neurogenic detrusor overactivity (NDO) remains a clinical priority to improve patients’ quality of life and prevent dramatic urological complications. Intradetrusor injection of onabotulinumtoxinA (BoNT/A1, botulinum neurotoxin A1) is approved as second therapeutic line in these patients, demonstrating a good efficacy. However, a loss of its efficacy over time has been described, with no clear understanding of the underlying mechanisms. This paper aims at shedding new light on BoNT/A1 secondary failure in NDO through functional and structural analysis. Three groups of patients (either non-NDO, NDO with no toxin history or toxin secondary failure) were investigated using an ex vivo bladder strip assay. Detrusor strips were tensed in organ baths and submitted to electrical field stimulation to generate contractions. Recombinant BoNT/A1 was then added at various concentrations and contractions recorded for 4 h. Histology exploring BoNT/A1 targets, fibrosis and neuronal markers was also used. Detrusor strips from patients with BoNT/A1 secondary failure displayed a smaller sensitivity to toxin ex vivo at 3 nM compared to the other groups. Histological evaluation demonstrated the presence of cleaved Synaptosomal-Associated Protein, 25 kDa (c-SNAP25) in the detrusor from the toxin-secondary failure population, indicating some remaining in vivo sensitivity to BoNT/A1 despite the therapeutic escape. Moreover, residual c-SNAP25 did not affect parasympathetic-driven contractions observed ex vivo. This study confirms the slightly lower efficacy of BoNT/A1 in the BoNT/A1 secondary failure NDO group, suggesting that the escape from BoNT/A1 efficacy in NDO occurs at least at the parasympathetic level and could imply compensatory mechanisms for detrusor contraction.

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.

Concomitant therapy of surgical shave excision and intralesional injections for ear keloids: Early results from a retrospective cohort study.

IntroductionKeloids are hypertrophic scars that commonly arise in the ear region. The authors’ objectives were to (1) evaluate effectiveness of surgical shave excision followed by intralesional triamcinolone acetonide and onabotulinumtoxinA injections; and (2) evaluate safety and patient satisfaction.Methods and MaterialsThis study was a retrospective chart review of patients who received treatment of extralesional surgical shave excision followed by intralesional triamcinolone acetonide and onabotulinumtoxinA injections to treat ear keloids at a single outpatient dermatology clinic. A prospective patient questionnaire was administered to the same patient population to collect recurrence and patient satisfaction.ResultsA total of 45 patients were included, consisting of 84.4% females (n = 38) and 15.6% males (n = 7) with a mean age of 25.5 years. Through retrospective chart review, early recurrence was seen in 6.7% of patients (n = 3), and via the prospective patient questionnaire, 11.1% of patients noted early keloid recurrence (n = 5). Of the patients who expressed their level of satisfaction in-clinic, 96.0% (n = 24) reported being satisfied or very satisfied and 4.0% (n = 1) were dissatisfied. Satisfaction was also assessed through the prospective patient questionnaire; of those who consented to the questionnaire, 100.0% (n = 24) were satisfied or very satisfied. Only 20.0% (n = 9) of all patients reported experiencing side effects, consisting of pruritus (11.1%; n = 5), tenderness (4.4%; n = 2), pain (2.2%; n = 1), and mild atrophy (2.2%; n = 1).ConclusionExtralesional surgical shave excision followed by intralesional triamcinolone acetonide and onabotulinumtoxinA injections may represent a promising treatment option for ear keloids.Evidence Level: 3 retrospective cohort study.Lay SummaryKeloids are a type of raised scar, which can be painful and itchy for patients. Keloids can occur on various part of the body, including on the ear. They are challenging to treat and tend to come back. There are many treatment options, however, there is not one universal best treatment for keloids on the ear. We hoped to discover if shave excision followed by intralesional triamcinolone acetonide and onabotulinumtoxinA injections is effective at treating keloids on the ear. In order to answer this we completed a chart review of clinic patients, who have already completed the following combination treatment for keloids on the ear. The keloids were treated first by physically removing the bulk of the keloid with a scalpel, which is called shave excision. After the removal, triamcinolone acetonide and onabotulinumtoxinA were injected directly into the keloid. The rate of patient satisfaction and the rate of the keloid returning were collected during in-clinic visits and an optional post-clinic patient questionnaire. The treatment effectiveness and side effects experienced were reported during in-clinic visits. This indicated that with the low rate of side effects, high patient satisfaction, and low rate of keloid return, this treatment combination should be considered as an option for keloids on the ear. However, since this review was completed at one clinic with a small population of patients, it is not fully known if this treatment combination will work for all patients.

Reduced Reflex Autonomic Responses Following Intradetrusor OnabotulinumtoxinA Injections: A Pre-/Post-study in Individuals With Cervical and Upper Thoracic Spinal Cord Injury.

Urodynamic studies (UDS) can provoke autonomic dysreflexia (AD) in individuals with spinal cord injury (SCI) at and above the sixth thoracic spinal segment potentially leading to profound vagally mediated heart rate (HR) reductions. In this study,1 we test the hypothesis that intradetrusor onabotulinumtoxinA injections will improve HR and its variability (HRV) responses to UDS in individuals with cervical and thoracic SCI. A total of 19 participants with chronic SCI (5 women, mean age 42.5 ± 7.9 years) with confirmed neurogenic detrusor overactivity underwent UDS before (i.e., baseline) and 1 month after intradetrusor onabotulinumtoxinA (200 U) injections (post-treatment). Continuous electrocardiography and blood pressure (BP) recordings were used to assess RR-interval, time, and frequency domain metrics of HRV (a surrogate marker of autonomic nervous system activity), and AD pre- and post-treatment. UDS pre-treatment resulted in increased RR-interval as well as time and frequency domain metrics of HRV. Vagally mediated increases in high-frequency (HF) power during UDS were larger in participants with cervical compared to upper thoracic SCI. Post-treatment, UDS had no effect on RR-interval and significantly reduced instances of bradycardia. Furthermore, intradetrusor onabotulinumtoxinA injections significantly reduced time domain metrics of HRV and HF power responses to UDS across all participants. Changes in HRV during UDS could be a potential indicator of improved autonomic cardiovascular function following interventions such as intradetrusor onabotulinumtoxinA injections.