Antibiotic use, best practice statement adherence, and UTI rate for intradetrusor onabotulinumtoxin-A injection for overactive bladder: A multi-institutional collaboration from the SUFU Research Network (SURN).

INTRODUCTION: Onabotulinumtoxin A (BTX-A) is a well-established treatment for overactive bladder (OAB). The American Urological Association (AUA) 2008 Antibiotic Best Practice Statement (BPS) recommended trimethoprim-sulfamethoxazole or fluoroquinolone for cystoscopy with manipulation. The aim of the study was to evaluate concordance with antibiotic best practices at the time of BTX-A injection and urinary tract infection (UTI) rates based on antibiotic regimen. METHODS: Men and women undergoing first-time BTX-A injection for idiopathic OAB with 100 units in 2016, within the SUFU Research Network (SURN) multi-institutional retrospective database were included. Patients on suppressive antibiotics were excluded. The primary outcome was concordance of periprocedural antibiotic use with the AUA 2008 BPS antimicrobials of choice for "cystoscopy with manipulation." As a secondary outcome we compared the incidence of UTI among women within 30 days after BTX-A administration. Each outcome was further stratified by procedure setting (office vs. operating room; OR). RESULTS: Of the cohort of 216 subjects (175 women, 41 men) undergoing BTX-A, 24 different periprocedural antibiotic regimens were utilized, and 98 (45%) underwent BTX-A injections in the OR setting while 118 (55%) underwent BTX-A injection in the office. Antibiotics were given to 86% of patients in the OR versus 77% in office, and 8.3% of subjects received BPS concordant antibiotics in the OR versus 82% in office. UTI rates did not vary significantly among the 141 subjects who received antibiotics and had 30-day follow-up (8% BPS-concordant vs. 16% BPS-discordant, CI -2.4% to 19%, p = 0.13). A sensitivity analysis of UTI rates based on procedure setting (office vs. OR) did not demonstrate any difference in UTI rates (p = 0.14). CONCLUSIONS: This retrospective multi-institutional study demonstrates that antibiotic regimens and adherence to the 2008 AUA BPS were highly variable among providers with lower rates of BPS concordant antibiotic use in the OR setting. UTI rates at 30 days following BTX-A did not vary significantly based on concordance with the BPS or procedure setting.

Psychopathological variables in chronic migraine patients with different therapeutic approach: psychological profile differences and impact on therapeutic efficacy in real life.

BACKGROUND: Migraine is a debilitating neurological condition linked to various psychological comorbidities. The aims of our study are: 1) to evaluate potential psychopathological differences between patients in treatment with anti-CGRP monoclonal antibodies (SPECIFIC group) and those with onabotulinumtoxin-A/oral pharmacotherapy (Group NON-SPECIFIC), 2) to compare treatment efficacy over time between groups, and examined whether psychopathological comorbidities can influence it. METHODS: This is a post-hoc ambispective study: a retrospective analysis of patient-level real-life data prospectively collected for clinical evaluation. We enrolled 102 patients with chronic migraine (CM), 64 in treatment with erenumab or galcanezumab, and 38 with botulinum toxin or oral pharmacotherapies. Psychopathological variables are assessed at baseline, whereas clinical factors over time. RESULTS: The NON-SPECIFIC group showed more pronounced emotion regulation difficulties (DERS, p = 0.001), alexithymia (TAS-20, p = 0.012), and impulsiveness (BIS-11, p = 0.002) with respect to the SPECIFIC group. Moreover, treatment efficacy overtime was more pronounced in the group with anti-CGRP treatment with a reduction of migraine frequency overtime, pain intensity, and improved quality of life up to six months post-treatment. Psychopathological comorbidity did not influence treatment efficacy. CONCLUSIONS: Our study highlighted more pronounced psychopathological comorbidities in patients in treatment with NON-SPECIFIC therapies in terms of impulsivity, alexithymia, and emotion regulation. Moreover, treatment efficacy overtime was more pronounced and stable over time in the SPECIFIC group, and psychopathological comorbidity did not influence it.

The impact of postinjection urinary tract infection on efficacy of intravesical onabotulinumtoxinA-A secondary analysis.

OBJECTIVES: To compare treatment response in women who did and did not develop a urinary tract infection (UTI) within 14 days after intravesical onabotulinumtoxinA injections for treatment of refractory urgency urinary incontinence (UUI). METHODS: This is a secondary analysis of women who received Onabotulinumtoxin A in the Refractory Overactive Bladder: Sacral Neuromodulation vs Botulinum Toxin Assessment (ROSETTA) Trial. Participants were grouped by presence or absence of UTI within 14 days of injection. UTI was defined as symptomatic with positive urine culture per the primary ROSETTA protocol. Our primary outcome was change from baseline in mean number of UUI episodes based on monthly 3-day bladder diaries averaged over 6 months. We performed t tests and chi-square/Fisher's exact for continuous and categorical variables. A p value of <0.05 was considered statistically significant. RESULTS: Of 187 participants in the onabotulinumtoxinA arm, 10 (5.3%) experienced UTI within 14 days of injection, and 177 (94.7%) did not. At baseline, groups did not differ in demographics, mean UUI episodes per day (no UTI [5.37 ± 2.65] vs. UTI [6.40 ± 3.02], p = 0.24), or other diary parameters. For our primary outcome, groups did not differ in the change in mean daily UUI episodes at 1 month (no UTI [-4.29 ± 2.75] vs. UTI [-3.74 ± 2.01]; mean difference [95% confidence interval, CI] -0.55 [-2.39 to 1.28], p: 0.55) or 6 months (no UTI [-3.63 ± 2.89] vs. UTI [-2.15 ± 3.18]; mean difference [95% CI] -1.48 [-3.44 to 0.48], p: 0.14). CONCLUSIONS: UTI within 14 days after intravesical injection of onabotulinumtoxinA for refractory UUI was not significantly associated with inferior treatment response at 1 or 6 months.

Antibiotic regimen and route of administration do not alter rates of urinary tract infection after intravesical botulinum toxin injection for overactive bladder.

INTRODUCTION AND HYPOTHESIS: Guidelines vary on antibiotic prophylaxis for onabotulinumtoxinA (Botox) treatment for overactive bladder (OAB). Our primary objective was to determine whether any prophylactic regimen is more effective in preventing urinary tract infection (UTI) after Botox. The secondary objective was to identify prophylactic practice patterns among female pelvic medicine and reconstructive surgery (FPMRS) providers of different training backgrounds as well as general urologists. METHODS: This was a secondary analysis of a retrospective cohort study on urinary retention after Botox injection in women with and without diabetes mellitus and OAB. Women > 18 years old who underwent Botox injection for OAB between January 2013 and September 2018 were included. Exclusion criteria were history of urinary retention and neuromuscular bladder dysfunction. RESULTS: A total of 565 patients were included. Two hundred eighty (49.6%) were treated by OB-GYN FPMRS, 209 (37.0%) by urology FPMRS and 76 (13.5%) by general urologists. The majority (92.9%) received antibiotic prophylaxis: 44.4% received intravenous (IV) only, 8.9% received oral (PO) only, and 39.7% received combination IV and PO prophylaxis. Urology FPMRS used antibiotic prophylaxis less frequently (p = 0.003). Within 3 months, 171 patients developed UTI (30.4%). There was no difference in post-procedural UTI for any antibiotic regimen compared to no prophylaxis. No route of antibiotic administration was superior at preventing UTI. CONCLUSIONS: In this cohort, no route of antibiotic administration was more effective in the prevention of UTI. Antibiotic prophylaxis did not lower the rate of post-procedural UTI compared to no antibiotics.

Botulinum Toxin Can Abolish and/or Quiet Tinnitus Associated with Chronic Migraine: Serendipidous Observations.

INTRODUCTION: It is well established that treatment of head and neck myofascial dysfunction can alleviate both tinnitus and chronic migraine (CM). Onabotulinumtoxin A (OnaA) has become a standard treatment for CM. In a recent systematic study a subject reported tinnitus improvement. This prompted a survey of the tinnitus in all study participants. METHODS: Fifty-seven patients with CM at a tertiary headache referral center received intramuscular Onabotulinumtoxin A (OnaA) injections into craniocervical muscles using the "follow-the-pain" protocol for headache. Effectiveness of OnaA was assessed by changes in (i) tinnitus loudness and (ii) number of headache days. RESULTS: Of the five patients with pre-existing tinnitus OnaA abolished the tinnitus in two, including one whose tinnitus of ten years' duration resolved permanently with one treatment. The tinnitus loudness of the other four was attenuated between 70 to 100 percent for about three months, which paralleled their headaches response. All were women who had (i) a significant improvement of their CM and (ii) headaches located fronto-temporally. None of the CM non-responders reported tinnitus. Analysis of injection sites revealed that the temporalis muscle injections were likely accounting for the tinnitus attenuation. CONCLUSION: Tinnitus associated with chronic migraine is abolished/quieted by intramuscular craniocervical Onabotulinumtoxin A injections. These results are consistent with the dorsal cochlear nucleus hypothesis for craniocervical somatic tinnitus, as well as the association between migraine and tinnitus. This serendipitous result warrants further study of botulinum toxin for tinnitus.

Onabotulinumtoxin A (ONA-BoNT/A) in the treatment of chronic migraine.

Migraine is a common primary headache disease, which reduces quality of life. About 8% of migraineurs suffer from chronic migraine (CM), which is the most severe and troublesome type. It has been proven that onabotulinumtoxinA (ONA-BoNT/A) significantly improves CM, presumably inhibiting the release of calcitonin gene-related peptide (CGRP) and other neurotransmitters from c-fibres endings, and thus decreasing activation of nociceptive pathways and transmission of pain. The aim of this position paper was to assess the place of ONA-BoNT/A for the prophylaxis of CM in adults. The authors have compared the efficacy, safety and tolerance of the toxin to those of classical oral preventive therapies as well as to recently introduced anti-CGRP-pathway monoclonal antibodies. The results of randomised controlled studies of ONA-BoNT/A have been compared to open label (real world practice) trials.

Are 200 units of onabotulinumtoxin A sufficient for the suppression of neurogenic detrusor overactivity in individuals with established 300-unit botulinum toxin treatment? A retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To investigate the effects of 200-unit onabotulinumtoxin A detrusor injections on neurogenic detrusor overactivity (NDO) in patients who have previously been treated with 300-unit injections. SETTING: Tertiary urologic referral center in Switzerland. METHODS: The patient database was screened for patients with NDO as a result of chronic (≥ 12 months) spinal cord injury (SCI), who had been treated with 300- followed by 200-unit onabotulinumtoxin A detrusor injections. Patient characteristics, bladder management data and concurrent bladder medication as well as urodynamic data were collected. The percent changes in the urodynamic parameters from the 300- to the 200-unit treatment phase were calculated to test for non-inferiority of the 200-unit treatment. RESULTS: The data of 61 individuals with a mean age of 44 ± 15 years (range 18-73 years) and a mean 13.2 ± 9.5 years (range 2-43 years) since SCI were analyzed. The 200-unit treatment was not inferior regarding the urodynamic parameters compared to the 300-unit treatment. Furthermore, the proportion of patients with urinary incontinence was similar for both doses. There was no significant difference in the number of daily bladder evacuations (p = 0.13) or used incontinence pads (p = 0.43) between the two dosage phases. Moreover, there was no significant (p = 0.19) increase in the use of concurrent NDO medication (antimuscarinics or mirabegron) during the 200-unit treatment. CONCLUSIONS: The treatment of NDO with 200 units of onabotulinumtoxin A was not inferior to a 300-unit treatment regarding urodynamic parameters in patients with chronic SCI.

Onabotulinumtoxin A (Botox): A reasonable alternative for refractory neurogenic bladder dysfunction in children and young adults.

AIMS: We aimed to describe the effectiveness of Onabotulinumtoxin A (Botox) in children with neurogenic bladder (NGB) unresponsive to medical therapy to determine urodynamic parameters predictive of success. METHODS: Children receiving Botox for refractory NGB, between 2008 and 2019, from a single academic center, were included in this study. Botox success was defined as improvement of incontinence and/or urodynamic parameters. RESULTS: Of 34 patients who received Botox, 13 (38.2%) had a positive response from their first injection, with improvement in capacity by a median of 35% of expected capacity for age compared to only a 9% increase in those who did not respond clinically. When patients were divided into groups by baseline urodynamic parameters, high-pressure (Pdetmax > 20 cm H2 O) patients had significantly greater improvement in compliance compared with low-pressure patients (p = 0.017). Low compliance patients (<10 ml/cm H2 O) had a dramatic improvement of 3.08 ml/cm H2 O in their compliance compared with minimal change in the high compliance group (p = 0.003). Finally, low-capacity (<50% of expected CC) patients had significant improvement in capacity and compliance when compared with high-capacity patients (p = 0.004 and p = 0.036, respectively). Improvement in detrusor overactivity (DO) was noted in both the clinical responders and non-responders. CONCLUSION: In our series, 38% had clinical success with intradetrusor Botox injections for refractory neurogenic bladder. When successful, improvement in capacity and compliance, DO, and/or incontinence was consistent with prior literature. While we could not determine which parameters predicted success, subdividing patients into categories based on baseline urodynamic parameters identified who would benefit from Botox treatment based on differential improvements in capacity and compliance. At least 1 injection of Botox should be considered for a subset of children with refractory NGB, before undertaking more invasive treatments.

Influence of headache pain intensity and frequency on migraine-related disability in chronic migraine patients treated with OnabotulinumtoxinA.

BACKGROUND: There is a need to establish which are the more relevant headache-related outcomes that have an impact on our patient's lives to accurately evaluate treatment response in daily clinical practice. OBJECTIVE: The aim of this study was to evaluate the relevance of clinical trial endpoints in clinical real-life disability improvement in response to migraine preventive treatment with OnabotulinumtoxinA. METHODS: This is an observational prospective study. We included patients with chronic migraine fulfilling ICHD-3beta/3 criteria. We prospectively collected data of 8 headache-related and acute medication use endpoints recommended by the Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine. We evaluated their impact on disability improvement after 6 months of treatment with OnabotulinumtoxinA. We defined as a responder in disability, patients with ≥50% MIDAS score reduction after 2 cycles of treatment following PREEMPT protocol. We performed an analysis to measure the impact of improvement in the evaluated outcome measures according to perceived disability in clinical practice. RESULTS: We included 395 patients (85.1% women, mean age 46.7 ± 12.6 years). Mean headache frequency at baseline was 26.5 ± 5.2 headache days/month. After 6 months, 49.1% of patients were headache-related disability responders. From all outcome measures collected, variables independently associated to disability improvement were headache days reduction (p = 0.02) and ≥ 50% pain intensity reduction (p = 0.04). A ≥ 50% reduction in headache frequency or pain intensity showed similar influence on disability improvement after treatment. CONCLUSIONS: Headache pain intensity is as important as frequency when evaluating the clinical response and impact on patient headache-related disability after migraine preventive treatment with OnabotulinumtoxinA.

A randomized, double-blind, placebo-controlled trial of onabotulinumtoxin A trigger point injections for myofascial pelvic pain.

BACKGROUND: Pelvic pain is estimated to effect 15% of women, and onabotulinumtoxin A is used to treat a variety of pain disorders. However, the data on the use of onabotulinumtoxin A for the treatment of women with myofascial pelvic pain are limited. OBJECTIVE: The objective of the study was to compare the effect of onabotulinumtoxin A vs placebo injections to the pelvic floor muscles in women with myofascial pelvic pain. STUDY DESIGN: This was a double-blind, randomized, placebo-controlled trial in women with myofascial pelvic pain. Women ≥18 years were eligible if they reported pain ≥6 on a 10 point visual analog scale ≥50% of the time and had pain on palpation ≥6 on the visual analog scale in ≥1 of 6 pelvic floor muscle groups. Participants were randomly allocated to a pelvic floor injection of 200 units of onabotulinumtoxin A or 20 mL of saline. All participants started 8 weeks of physical therapy 4 weeks after the injection. Participants completed validated questionnaires at baseline, 2, 4, and 12 weeks after injection. At each visit, a urogynecologist who was blinded to treatment arm performed a clinical examination with palpation of the left and right sides of 6 pelvic floor muscle groups. The primary outcome was change in participant-reported pain on palpation of the most painful pelvic floor muscle at 2 weeks. Analyses were intention to treat. RESULTS: We consented 60 women. One participant was lost to follow-up after she was consented; therefore, we randomized 59 women. The groups had similar demographic and clinical characteristics. With regard to the primary outcome, there was no significant difference between the intervention and placebo groups in the change in participant-reported pain on palpation of the most painful pelvic floor muscle at 2 weeks. There were no significant differences in participant-reported pain on palpation for any muscle group at 4 or 12 weeks. At 4 and 12 weeks, participants in the intervention group reported greater declines in overall pelvic pain on the visual analog scale compared with the placebo group, although these differences were not statistically significant (both P = .16). Using the Patient Global Impression of Improvement index, participants in the intervention group were more likely to report their symptoms were improved at 4 and 12 weeks compared with the placebo group, although this difference was significant only at 4 weeks (P = .03 and P = .10, respectively). At 2 weeks, the placebo group had a significant improvement in the Pelvic Floor Distress Inventory score compared with the intervention group (P = .01); however, this difference did not persist at 4 (P = .19) or 12 weeks (P = .11). At 2 weeks, the most common adverse event was constipation in the intervention and placebo groups, with 10.1% reporting de novo constipation. This was followed by urinary incontinence in the intervention group (22%) and urinary tract infection (9%) in the placebo group. CONCLUSION: Pelvic floor onabotulinumtoxin A injections for myofascial pelvic pain were not more effective than saline injections at decreasing muscle pain on palpation. Despite this, participants who received onabotulinumtoxin A were more likely than those who received saline to report improvement, albeit not statistically significant, in their overall pelvic floor pain at 4 and 12 weeks.

Onabotulinumtoxin-A in Chronic Migraine: Should Timing and Definition of Non-Responder Status Be Revised? Suggestions From a Real-Life Italian Multicenter Experience.

OBJECTIVE: To clarify whether the clinical response after the first 2 cycles with Onabotulinumtoxin A can accurately predict the long-term response. BACKGROUND: Onabotulinumtoxin-A (OBT-A) is an approved preventive treatment option for chronic migraine (CM). Nowadays, it remains to be clarified if the treatment has to be prolonged for at least an entire year (4 injections every 3 months - ie, quarterly, as proposed in the PREEMPT trials) or it can be halted after the second or third injection if not clinically effective. DESIGN AND METHODS: We conducted a multicenter observational cohort study based on real-life data on the usage of OBT-A in CM patients from 2 Italian headache centers, Roma Campus Bio-Medico and Milano Besta, adopting the whole 4-injections protocol. We performed a retrospective analysis of medical records of consecutive patients treated in the 2 centers. The main statistical analysis aimed to evaluate longitudinal measures related to headache (monthly headache frequency, monthly number of analgesic drugs, MIDAS). We hypothesized from our clinical practice with OBT-A that only 2 cycles of treatment were not enough to actually define the non-responder status to botulinum toxin A and that probably a longer time of treatment is needed to get the condition of long-term (delayed) responder. RESULTS: We considered 115 patients from the 2 centers: 53 in Roma and 62 in Milano. Regarding the main analysis, a clear improvement in each measure was obtained at the 6 months assessment and maintained up to 12 months. Comparing patients with <30% and ≥30% reduction in headache frequency between T0 and T2 or T4 (respectively, "Non-Responders" and "Responders"), we found that the agreement between the classification Responders/Non-Responders at T2 and T4 was not very high (79/104 = 76.0%, with a "moderate" Cohen's Kappa of 0.51), suggesting that the status at T4 is not fully predictable by the status at T2 (λ = 0.47). Responders for headache frequency at T4 were 54.8%. Among Responders at T2, Responders at T4 were 47/62 = 75.8% (95% CI: 64.5%, 85.5%), while among Non-Responders at T2, Responders at T4 were 10/42 = 23.8% (95% CI: 11.9%, 38.1%). Similarly, even when considering the 50% reduction in painkillers consumption or in MIDAS total score between T0 and T2 as possible prognostic factors, the changes occurring at T4 are not strongly predictable by those at T2. CONCLUSIONS: A ≥30% reduction in headache frequency at T2 cut-off is not adequate in predicting a late response to treatment: more than a quarter of excluded patients would miss a clinical improvement with an ongoing treatment, while in a similar percentage of Responders the treatment would lose efficacy. Results from our real-life study suggest that we possibly have to postpone the definition of Responder/Non-Responder to OBT-A at least after 1 year of treatment (4 cycles).

CGRP and PTX3 as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine: An Observational Study.

OBJECTIVE: The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA). BACKGROUND: OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome. METHODS: We measured serum levels of biomarkers of inflammation (IL-6, IL-10, TNF-α, and hs-CRP), endothelial dysfunction (PTX3 and sTWEAK), blood-brain barrier disruption (cFN), brain damage (S100b, NSE), and trigemino-vascular activation (CGRP) by ELISA in a group of CM patients treated with OnabotA and healthy controls. After 24 weeks, patients were classified in two groups according to their outcome considering variations in headache frequency: nonresponders (nonimprovement or improvement <50%) and responders (improvement >50%). We compared baseline levels of biomarkers between these groups. RESULTS: Sixty-two patients diagnosed with CM (IHS 2013 criteria) who fulfilled criteria for treatment with OnabotA and 24 healthy controls were included. Fifteen patients did not respond to treatment (24.2%) and 47 were responders (75.8%). Pentraxin 3 (PTX3) serum levels (1455.4 ± 487.5 pg/mL versus 720.3 ± 334.1 pg/mL, P < .0001) and calcitonin gene-related peptide (CGRP) serum levels (133.1 ± 86.6 ng/mL versus 58.2 ± 91.7 ng/mL, P = .004) were significantly higher in responders than nonresponders. Serum basal levels of PTX3 >1000 pg/mL (AUC 0.908; 95% CI: 0.827-0.990) and CGRP >50 ng/mL (AUC 0.800; 95% CI: 0.652-0.947) were associated with good response to OnabotA treatment. CONCLUSIONS: These results show that molecular markers of trigeminovascular activation (CGRP) and endothelial dysfunction (PTX3) are associated with response to OnabotA and may act as new biomarkers for the selection of treatment in chronic migraineurs.

Complications of Botox and their Management.

PURPOSE OF REVIEW: Adherence to anticholinergic medications is known to be a problem in patients with overactive bladder, with only 13.2% of patients continuing anticholinergic therapy beyond 1 year D'Souza et al. (J Manag Care Pharm. 14:291-301, 2008). RECENT FINDINGS: Prior to the advent of third line therapies such as onabotulinumtoxin A, refractory overactive bladder (OAB) was managed with augmentation cystoplasty, a lengthy surgery with associated side effects including lifetime need for self-catheterization, ileus, and metabolic disturbances. The advent of onabotulinumtoxin A has drastically reduced the rates of augmentation cystoplasties being performed for refractory OAB. However, all procedures are associated with side effects which should be relayed to the patient prior to beginning therapy, as well as their management. In the current review, we summarize the common complications following onabotulinumtoxin A injection as well as their management.

OnabotulinumtoxinA in the treatment of refractory chronic cluster headache.

BACKGROUND: Cluster headache (CH) is a clinically well-defined primary headache disorder, approximately 20% of cluster headache sufferers experience recurrent attacks without periods of significant remission. For the treatment of chronic cluster headache (CCH) only limited therapeutic options are available. METHODS: A potential refractory CCH patient group was identified according to the clinical definition of rCCH based on the consensus statement of the European Headache Federation (EHF). Treatment with OnabotulinumtoxinA (BoNT-A; Botox®, 150 Allergan IU) was done according to the PREEMPT study protocol. A standardized headache diary was used for recording frequency, duration of attacks and pain intensity. To assess personal burden the HIT-6 and the Hospital Anxiety and Depression scale was used. Primary outcome measure was a > 50% reduction in headache minutes. RESULTS: Seventeen male patients suffering from rCCH, aged 32 ± 11 (mean ± SD) years, presenting a mean disease duration of 6.6 years completed the study of 28 weeks. The cut-off point of > 50% reduction in headache minutes as positive result was reached in 58.8%, 29.4% experienced an improvement of 30-50%. Mean frequency of headache days dropped from 28.2 to 11.8 days at week 24 (p = 0.0001; 95% CI -21.33 to - 11.61;). Intensity of remaining attacks was also reduced significantly. Headache disability scores showed a trend to improvement after BoNT-A. CONCLUSIONS: Encouraging results for the treatment with BoNT-A in rCCH patients were observed in our study population.

Real-life clinical practice of onabotulinum toxin A intravesical injections for overactive bladder wet: an Italian consensus statement.

PURPOSE: We developed a consensus on best practice in the real-life management of patients with overactive bladder (OAB) with onabotulinumtoxin A (Onabot/A). METHODS: In March 2015, an interdisciplinary conference was convened. Eleven panelists were invited to review the literature, to present their personal experience and to respond to a number of questions from: "when do we propose Onabot/A treatment" to "when do you decide to re-inject a patient?" A summary of findings of the meeting was provided to all panelists for review and approval. RESULTS: The following statements were agreed. Refractory OAB can be defined based on lack of adherence to first- and second-line treatments for OAB regardless of the underlying cause. Onabot/A treatment can be proposed to refractory OAB patients provided they are willing to perform intermittent catheterization if needed. Before treatment, uroflowmetry with post-void residual evaluation is needed to rule out voiding dysfunction, while urodynamics should be done in cases of complicated OAB wet. Urinary tract infection should be ruled out or treated before the injection. The injection can be performed in the endoscopy room, in an out-patient basis, with local anesthesia. Antibiotic prophylaxis should be initiated with oral drugs. A first follow-up visit should be planned 10-15 days after treatment and residual urine checked. Retreatment can be decided on patients' request, when symptoms worsen. CONCLUSIONS: This consensus document provides a guide for the management of refractory OAB patients with Onabot/A in real life. A number of questions about the effectiveness of Onabot/A in real life remain open.

Onabotulinumtoxin A for chronic migraine with medication overuse: clinical results of a long-term treatment.

The use of Onabotulinumtoxin A as treatment for different neurological conditions is more common in the last decades; its application has been consolidated on the basis of significant clinical results. The clinical experiences with Onabotulinumtoxin A for chronic migraine are on the increase in Italy: at the moment, clinical results are encouraging and enforce the application of the toxin for chronic migraine, according to the results of the PREEMPT studies. The possibility for the patients to be treated with a second cycle of therapy after the first year of treatment is under discussion, in particular for patients who obtained significant clinical benefit from the first period of treatment. In this report, a group of patients treated with Onabotulinumtoxin A for 1 year, according to the PREEMPT protocol, has been retreated for one more year in order to confirm the clinical benefit obtained after the first year of treatment.

Onabotulinumtoxin A for the management of chronic migraine in current clinical practice: results of a survey of sixty-three Italian headache centers.

BACKGROUND: Chronic migraine is a complex clinical condition often undertreated. Onabotulinumtoxin A (OBT-A) was approved in Italy in 2013 for symptom relief in patients with chronic migraine who have failed, or do not tolerate, oral prophylactic treatments. However, the impact of OBT-A in clinical practice remains to be defined. METHODS: To investigate the current management of chronic migraine with OBT-A in clinical practice, a web-based survey was conducted among clinicians working in third-level headache centers across Italy. A 26-item questionnaire was designed and developed by a group of 10 Italian headache specialists to address the following issues: treatment paradigm and OBT-A injection intervals, frequency of treatment and retreatment, definition of responders/non-responders, satisfaction with treatment potential impact of early treatment with OBT-A. Ninety-six headache centers were selected and contacted via e-mail. The online survey was anonymous and carried out using a secure website. RESULTS: Overall, 64 of the 96 centers (66.7%) completed the questionnaire. Most centers (98.4%) had been using OBT-A for >1 year. OBT-A was administered according to the PREEMPT paradigm in most centers (88.9%). While during the first year of prophylaxis with OBT-A most clinicians (93.6%) repeated OBT-A treatment every 3 months, as recommended, in the following years interval duration was variable. Response to OBT-A was defined as a ≥ 50% reduction in the headache days by 58.7% of the clinicians, and as a ≥ 30% reduction by 25.4% of them. Almost 60% of the clinicians considered OBT-A as a long-lasting therapy, while for one-third of them treatment could be discontinued in patients showing a benefit for ≥6 months. According to 80% of the clinicians, early administration of OBT-A after the onset of chronic migraine was associated with better outcomes, and 47.6% felt that OBT-A should be recommended as a first-line option. CONCLUSIONS: This survey indicates that in third-level headache centers in Italy OBT-A is used in good compliance with current recommendations. There is agreement about the definition of response as a reduction in headache days by 30% to 50%. Additional effort is required to define response to OBT-A and to establish optimal treatment duration.

Influence of Onabotulinumtoxin A on testes of the growing rat.

Onabotulinumtoxin A (onabotA) is gaining wide medical use in children. The present study was planned to investigate the influence of its injection on the maturing testicular structures in rats. Immature rats were injected in the bilateral cremaster muscles by onabotA with three doses of (10, 20, and 40 U/kg) three times in a 2-week interval. The effect of these injections on fertility indices was examined. Levels of antisperm antibodies and several apoptosis parameters were also investigated. DNA content in form of ploidy and histopathological alterations were assessed. OnabotA-injected groups showed decreased sperm count and semen quality, while sperm vitality, morphology, and testosterone levels were not significantly affected. Furthermore, DNA flow cytometric analysis confirmed delayed sperm maturation. Apoptosis markers were significantly increased by the injections. In conclusion, onabotA injection in growing rats adversely affected sperm count and maturation. OnabotA testicular effects are mediated, at least partly, by apoptosis.

Onabotulinumtoxin-A treatment in Greek patients with chronic migraine.

BACKGROUND: Chronic migraine is a disabling condition, with limited treatment options. We conducted an open label, single arm, prospective clinical trial, to assess the efficacy and safety of onabotulinumtoxin-A in Greek patients with chronic migraine. Since recent evidence suggests that a meaningful clinical response may be delayed until after a third onabotulinumtoxin-A administration, we aimed at assessing outcomes at this time point. METHODS: A total of 119 patients with CM, scheduled to be treated with Onabotulinumtoxin-A (Botox ®) every 3 months, according to the approved indication and standard clinical practice, were prospectively enrolled. Data documenting changes from baseline (T0-trimester before Onabotulinumtoxin-A first administration) to the period after its third administration (T3) in (i) mean number of monthly headache days (ii) migraine severity as expressed by the mean number of days with peak headache intensity of >4/10 in a 0-10 numerical scale, and (iii) mean number of days with use of any acute headache medication, were collected from patients' headache diaries at each visit. RESULTS: Of the 119 patients, a total of 81 received 3 courses of onabotulinumtoxin-A and were included in the efficacy population. In those 81 patients, there was a significant decrease in mean headache days/month between T0 and T3 (21.3 ± 5.4 vs 7.7 ± 4.8; P < 0.001); a significant decrease in days with peak headache intensity of >4/10 (11.9 ± 5.5 vs 3.7 ± 3.3; P < 0.001) and finally, the change in days using acute headache medications per month between was also significant (16.2 ± 7.8 vs 5.2 ± 4.3; P < 0.001). Adverse events were few and of non- serious nature. CONCLUSION: Our results strongly support the use of onabotulinumtoxin-A for the prophylaxis of CM, as this intervention proved effective, safe and well tolerated in our cohort of Greek patients.