A series of three sequential, randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine prophylaxis.

We examined the effects of multiple treatments with low doses of botulinum toxin type A (BoNTA; BOTOX(R), Allergan Inc., Irvine, CA) versus placebo for prophylaxis of episodic migraine. This was a series of 3 sequential, randomized, controlled studies of 418 patients with a history of 4 to 8 moderate to severe migraines per month. In study I, patients were randomized to treatment with placebo or BoNTA (7.5 U, 25 U, or 50 U) in predetermined fixed injection sites on the front and sides of the head only. In study II, patients continued to receive, or were randomized to, 2 consecutive treatments with 25 U or 50 U. In study III, patients were randomized to placebo or continuation of 25 U or 50 U. Injection cycles were each 4 months long. BoNTA and placebo produced comparable decreases from baseline in the frequency of migraines at each time point examined (P >or= .201). No consistent, statistically significant differences were observed for any efficacy variable. Adverse events were similar among the groups within each study. In these exploratory studies of episodic migraine patients, repeated injections of low doses of BoNTA into fixed frontal, temporal, and glabellar sites were not more effective than placebo. BoNTA was safe and well tolerated. PERSPECTIVE: Beneficial effects of BoNTA in the treatment of migraine have been reported, but positive results are not universal, possibly because the optimal patient population and regimen are not yet definitively established. This study explores the effects of multiple injections of low BoNTA doses into fixed sites for episodic migraine.     

Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: a multicentre, double-blind, randomized, placebo-controlled, parallel-group study

We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin type A (BoNTA; BOTOX); Allergan, Inc., Irvine, CA, USA) for the prophylaxis of chronic tension-type headache (CTTH). Three hundred patients (62.3% female; mean age 42.6 years) enrolled. For the primary endpoint, the mean change from baseline in the number of TTH-free days per month, there was no statistically significant difference between placebo and four BoNTA groups, but a significant difference favouring placebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headache-free days/month; P = 0.007). All treatment groups improved at day 60. Although efficacy was not demonstrated for the primary endpoint, at day 90, more patients in three BoNTA groups had >or=50% decrease in tension headache days than did placebo (P 相似文献   

Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine

OBJECTIVE: To compare the efficacy and safety of botulinum toxin type A (BoNTA; BOTOX: Allergan, Inc.) and divalproex sodium (DVPX; DEPAKOTE: Abbott Laboratories) as prophylaxis in reducing disability and impact associated with migraine. BACKGROUND: There is a need for effective, well-tolerated prophylactic treatment of migraine. DESIGN/METHODS: This was a randomized, double-blind, single-center prospective study. Fifty-nine patients received either BoNTA 100 U/placebo-DVPX bid or placebo-BoNTA/DVPX 250 mg bid. BoNTA/placebo injections were given at Day 0 and at Month 3. Patients were evaluated at Months 1, 3, 6, and 9. RESULTS: Both treatments showed significant improvements in migraine disability scores and reductions in headache days and headache index. A trend to decreased headache severity was observed with BoNTA. A greater percentage of DVPX patients reported adverse events possibly related to treatment (DVPX 75.8% vs BoNTA 50%, P = .04) and discontinued because of adverse events (DVPX 27.6% vs BoNTA 3.3%, P = .012). CONCLUSIONS: Both BoNTA and DVPX significantly reduced disability associated with migraine; BoNTA had a favorable tolerability profile compared with DVPX.     

Influence of botulinum toxin type A treatment of elbow flexor spasticity on hemiparetic gait

OBJECTIVE: To assess whether walking velocity could be improved in patients with disorders related to upper-motor neuron syndrome (UMNS) by treating elbow flexor spasticity with botulinum toxin type A (BoNTA). DESIGN: This was a prospective, open-label, multicenter, interventional evaluation. The study group of 15 patients (mean age, 51.3 yrs; ten men, five women) were independent ambulators with residual hemiparesis attributable to stroke or traumatic brain injury of at least 18-mo duration. Patients were injected with 120-200 units of BoNTA (BOTOX, Allergan, Inc., Irvine, CA) to the affected biceps, brachialis, and/or brachioradialis. Modified Ashworth scores and gait velocity were assessed before and after BoNTA treatment. An untreated control group was employed to assess the potential impact of time on test-retest reliability of the selected temporal spatial gait parameters. RESULTS: The BoNTA group demonstrated a statistically significant increase in walking velocity from 0.56 m/sec before treatment to 0.63 m/sec after treatment (P = 0.037). The mean modified Ashworth score was significantly reduced from 2.6 before BoNTA treatment to 1.4 after treatment (P = 0.00003). CONCLUSIONS: Treatment of upper-limb spasticity may be an important adjuvant treatment for patients with gait disturbance related to the UMNS.     

A multicentre, double-blind, randomized, placebo-controlled, parallel group study of multiple treatments of botulinum toxin type A (BoNTA) for the prophylaxis of episodic migraine headaches

Our aim was to evaluate the safety and efficacy of botulinum toxin type A (BoNTA; BOTOX) for prophylaxis of episodic migraine. In this double-blind, placebo-controlled study, patients were randomized to 225, 150 or 75 U of BoNTA or placebo after a 30-day placebo run-in for three 90-day treatment cycles. The primary efficacy end-point was the mean reduction from baseline in the frequency of migraine episodes at day 180 in the placebo non-responder stratum. All groups (N = 495) improved, with no significant differences. At day 180, the frequency of migraine episodes was reduced from baseline means of 4.3, 4.7, 4.7 and 4.4 by 1.6, 1.7, 1.5 and 1.4 for BoNTA 225 U, 150 U and 75 U and placebo, respectively. The primary end-point was not met. Treatment-related adverse events were transient and mild to moderate. BoNTA treatment was safe and well tolerated but did not result in significantly greater improvement than placebo in this study. Several factors may have confounded the results.     

Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study

OBJECTIVE: This exploratory trial evaluated the safety and efficacy of multiple treatments of botulinum toxin type A (BoNTA; BOTOX, Allergan, Inc., Irvine, CA, USA) as prophylactic treatment of episodic migraine headaches. DESIGN AND METHODS: This was an 11-month randomized, double-blind, placebo-controlled, exploratory study. Patients were screened during a 30-day baseline period, and eligible patients with 4 or more migraine episodes and < or =15 headache days entered a single-blind 30-day placebo run-in period. Patients were classified as placebo nonresponders (PNR) if they had at least 4 moderate-to-severe migraine episodes and did not experience at least a 50% decrease from baseline in the frequency of migraine episodes following their placebo treatment. All other subjects were classified as placebo responders (PR). Patients were randomized within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA per treatment cycle) or placebo at 90-day intervals using a modified follow-the-pain treatment paradigm. The primary efficacy outcome measure was the mean change from baseline in the frequency of migraine episodes for the 30 days prior to day 180 in the PNR group. Secondary efficacy measures included the proportion of patients with a decrease from baseline of 50% or more migraine episodes per 30-day period. Patients were allowed to take concomitant acute and prophylactic headache medications. Adverse events were reported. RESULTS: A total of 809 patients were screened and 369 patients (89.2% female; mean age, 45 years; range, 20 to 65 years) entered the placebo run-in period and were subsequently randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U) (range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met. Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were observed (P > .999). From day 180 through the end of the study (day 270) at least 50% of all patients in each treatment group had a decrease from baseline of 50% or more migraine episodes per 30-day period. However, in the group of patients with > or =12 headache days at baseline (and < or =15 headache days), BoNTA patients experienced a mean change from baseline of -4.0 headache episodes at day 180 compared with -1.9 headache episodes in the placebo group (P= .048). The majority of treatment-related adverse events were transient and mild to moderate in severity. Only 7 patients (1.9%) discontinued the study due to adverse events (6 BoNTA, 1 placebo). CONCLUSION: There were no statistically significant between-group differences in the mean change from baseline in the frequency of migraine episodes per 30-day period. There were substantial, sustained improvements during the course of the study in all groups. Multiple treatments with BoNTA were shown to be safe and well tolerated over an active treatment period lasting 9 months.     

Botulinum toxin type A for the treatment of nummular headache: four case studies

OBJECTIVE: We assessed the efficacy and safety of botulinum toxin type A (BoNTA; BOTOX): Allergan, Inc., Irvine, CA, USA) in patients with nummular headache who did not respond to other treatments including nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics, and/or gabapentin. BACKGROUND: Nummular headache is characterized by circumscribed round or elliptical areas of fluctuating mild-to-moderate head pain in a chronic or remitting pattern. It is a relatively rare primary headache disorder that responds poorly to adequate treatment trials with local anesthetic, migraine, or neuropathic pain agents or NSAIDs. METHODS: Four patients aged 35-58 years with intractable nummular headaches were given 25 units of BoNTA divided among 10 injection sites in and around the circumscribed affected areas of pain, paresthesia, and allodynia. All patients had 2 sets of injections approximately 14 weeks apart. RESULTS: All patients met the International Headache Society criteria for nummular headache (International Classification of Headache Disorders, A13.7.1). Patients were female; mean age of onset was 42 years. Average disease duration prior to BoNTA treatment was 3.75 years. One patient reported concurrent episodic migraine and another reported concurrent tension-type headache. Patients reported round-shaped (n = 2; 6 and 3 cm in diameter), oval (n = 1; 4 x 2 cm), and elliptical (n = 1; 6 cm in length) areas of pain. Painful symptoms were reported in the right parietal convexity (n = 2) and the posterior frontal, unilaterally (n = 2). All patients experienced spontaneous or stimuli-triggered exacerbations and variable combinations of sensory disturbances, including allodynia, tenderness, and paresthesia. The temporal pattern was continuous in 3 patients and intermittent in one. Both the size and shape of the pain remained unchanged in all patients since the onset of nummular headache symptoms. Six to 10 days following BoNTA treatment, all patients experienced a reduction in nummular headache symptoms, which lasted approximately 14 weeks on average. Repeat injections gave the same degree of improvement. No treatment-related adverse events were reported. CONCLUSIONS: BoNTA appears to be a well-tolerated effective treatment for intractable, persistent nummular headache in patients with an inadequate response to other treatments including NSAIDs, gabapentin, or local anesthetics.     

Comparison of botulinum neurotoxin preparations for the treatment of cervical dystonia

BACKGROUND: Comparative studies of botulinum neurotoxin preparations to date have generally examined 2 preparations at prespecified dose ratios in relatively homogeneous groups of patients under controlled study conditions. It is unclear whether the differences in adverse-event rates that have been noted under these controlled conditions can be generalized to the broader population of cervical dystonia patients, who are treated with a wider range of doses in a variety of settings. OBJECTIVE: We conducted a systematic review and analysis of the published literature to compare rates of dysphagia and dry mouth in studies of botulinum neurotoxin products. METHODS: We searched the MEDLINE, EMBASE, Biosis, SciSearch, JICST (Japan Science and Technology Center), and Pascal databases from 1985 through 2006 using the terms cervical dystonia, spasmodic torticollis, and botulinum toxin for original English-language studies of Botox, Dysport, or Myobloc in the treatment of cervical dystonia (or spasmodic torticollis) that documented adverse events by treatment or patient. Studies that involved patients with various types of dystonias or movement disorders were included as long as adverse events were reported separately for those with cervical dystonia. Rates of dysphagia with the original preparation of Botox were considered separately from those with the current preparation of Botox. RESULTS: Seventy published articles were included in the analysis (30 Botox, 24 Dysport, 3 Botox + Dysport, 11 Myobloc, 2 Botox + Myobloc). Mean total doses per treatment ranged from 60 to 374 U for Botox, 125 to 1200 U for Dysport, and 579 to 19,853 U for Myobloc. Botox was associated with a significantly lower rate of dysphagia than Dysport, with mean dysphagia rates of 10.5% for original Botox, 8.9% for current Botox, and 26.8% for Dysport (both, P < 0.05). Myobloc was associated with dry mouth (3.2%-90.0%) in 9 of 13 studies, but this adverse event was not reported in a sufficient number of studies of botulinum toxin type A preparations (Botox, n = 2; Dysport, n = 6) to permit statistical comparison. In the weighted analysis, the duration of effect differed between botulinum neurotoxin products (current Botox > Myobloc > original Botox > Dysport; all, P < 0.001), but only 43 (61.4%) of the 70 studies reported duration, and the definitions varied. CONCLUSION: The results of this analysis indicate differences in adverse-event rates between botulinum neurotoxin preparations, suggesting that use of these products should be based on their individual dosing, efficacy, and safety profiles.     

Botulinum toxin in urology: a review of clinical potential in the treatment of urologic and sexual conditions

Introduction: In recent years, there has been an increased interest in the use of botulinum neurotoxin (BoNT) to treat medical conditions refractory to conventional treatment. The following article provides an overview of the clinical use and efficacy of BoNT in the treatment of various urologic and sexual conditions.

Areas covered: BoNT has been accepted and/or explored as novel treatment for various lower urinary tract and sexual dysfunctions such as overactive bladder/detrusor overactivity (DO), detrusor-sphincter dyssynergia (DSD), benign prostatic hyperplasia, interstitial cystitis/painful bladder syndrome, chronic pelvic pain and more recently premature ejaculation. The following terms ‘botulinum toxin’, ‘BoNT’, ‘botulinum toxin A’, ‘Botox’, ‘Dysport’, ‘Xeomin’, ‘botulinum toxin B’, ‘Myobloc’, ‘OnabotulinumA’, ‘RimabotulinumA’, ‘IncobotulinumA’ and ‘AbobotulinumA’ were used to search several databases including MEDLINE, Pubmed, EMBASE, CINAHL and clinicaltrials.gov for inclusion in this review article. Only English language articles were considered and all studies were limited to BoNT therapy in urological conditions in the adult population.

Expert opinion: BoNT-A has received regulatory approval for use in neurogenic DO and overactive bladder, but its use remains unlicensed in other lower urinary tract conditions such as non-neurogenic lower urinary tract symptoms in men with benign prostatic hyperplasia, bladder pain syndrome and DSD. Published literature shows that BoNT can be effective in carefully selected patient groups, has minimal adverse event profile and is generally well tolerated by many patients. However, many questions remain unanswered and larger scale multi-institutional studies are required to determine the key factors in BoNT treatment success.     

BOTOX: a review.

BOTOX cosmetic is proving to be an affordable alternative for thousands of people looking to enhance their appearance without the cost, risks and downtime associated with surgical procedures. Botulinum toxin is a neuromuscular blocking agent produced by Clostridium Botulinum, an anaerobic bacterium. When first discovered BOTOX was pinpointed as the cause of severe paralysis acquired through the ingestion of contaminated food. Paralysis related to BOTOX is caused by chemodenervation, which is a result of blockage of the presynaptic release of acetylcholine at the neuromuscular junction. The corrugator (medial eyebrows), crow's feet, forehead, platysmal neckbands, and the jowl are frequently targeted areas for BOTOX injections. There are no current guidelines for physical limitations following the administration of BOTOX. Side effects associated with BOTOX infections appear to be either local, due to the paralysis of adjacent muscles, or mild flu-like symptoms lasting a few days in a small number of patients.     

Predictors of response to botulinum toxin type A (BoNTA) in chronic daily headache

OBJECTIVE: To evaluate predictors of response to botulinum toxin type A (BoNTA; BOTOX, Allergan Inc., Irvine, CA, USA) in patients with chronic daily headache (CDH). BACKGROUND: Chronic migraine (CM) and chronic tension-type headache (CTTH) form the majority of CDH disorders. Controlled trials indicate that BoNTAis effective in reducing the frequency of headache and number of headache days in patients with CDH disorders. A recent migraine study found that patients with imploding or ocular types of headaches were responders to BoNTA, whereas those with exploding headaches were not. To date, there are no data on factors that might predict response to BoNTA in patients with CDH. METHODS: A total of 71 patients with CM and 11 patients with CTTH were treated with 100 units BoNTA. Every patient received at least 2 sets of injections at intervals of 12-15 weeks; fixed sites, fixed dose, and "follow-the-pain" approaches were used for the injections. A detailed medical history was taken for each patient in addition to recording Migraine Disability Assessment Scale (MIDAS) scores at baseline and every 3 months after each set of injections. Headache frequency was assessed throughout the study from baseline to weeks 24-27. Patients recorded the frequency, severity, and duration of headaches in Headache Diaries. Patients were divided into responders (> or = 50% reduction in both headache frequency and MIDAS scores compared with baseline) and nonresponders (< 50% reduction in either of the above variables). Variables analyzed for predictors of response include headache that is predominantly unilateral or bilateral in location, presence of cutaneous allodynia (scalp allodynia), and presence of pericranial muscle tenderness (also referred to as muscle allodynia). Chi-square analysis was used for parallel-group comparisons (proportion of CM responders vs proportion of CM nonresponders and proportion of CTTH responders vs proportion of CTTH nonresponders). RESULTS: In the CM group, 76.1% (54 /71) of patients were responders to BoNTA, of which 68.5% (37/54) had headache that was predominantly unilateral in location and the remaining 31.5% (17/54) had headache that was predominantly bilateral in location (both P < .01 vs CM nonresponders). Of the 23.9% (17/71) CM nonresponders, 76.5% (13/17) reported predominantly bilateral headache and in the remaining 23.5% (4/17) the headache was unilateral. In the CM responders group, 81.5% (44/54) had clinically detectable scalp allodynia, while pericranial muscle tenderness was present in 61.1% (33/54) (both P < .01 vs CM nonresponders). The presence of scalp allodynia and pericranial muscle tenderness in the CM nonresponders was 11.8% (2/17) and 17.6% (3/17), respectively. In the CTTH group where all patients (100%, 11/11) had bilateral headache, 36.4% (4/11) of patients were responders to BoNTA. All of those CTTH responders (100%, 4/4) had pericranial muscle tenderness (P < .05 vs CTTH nonresponders). None of the CTTH nonresponders had pericranial muscle tenderness. No clinically significant serious adverse events (AEs) were reported. Mild AEs, eg, injection-site pain that persisted for 1-9 days, were reported in 11 patients. One patient had transient brow ptosis. CONCLUSIONS: A greater percentage of patients with CM responded to BoNTA than patients with CTTH. Headaches that were predominantly unilateral in location, presence of scalp allodynia, and pericranial muscle tenderness appear to be predictors of response to BoNTA in CM, whereas in CTTH, pericranial muscle tenderness may be a predictor of response.     

Formation of neutralizing antibodies in patients receiving botulinum toxin type A for treatment of poststroke spasticity: a pooled-data analysis of three clinical trials

OBJECTIVE: The purpose of this study was to investigate the incidence of neutralizing antibody (NAb) formation in patients with poststroke spasticity treated with a specific formulation of botulinum toxin type A (BoNTA). METHODS: Data from 3 previous clinical trials of BoNTA in patients with upper and/or lower limb spasticity were pooled and evaluated. Study 1 was a randomized, double-blind, placebo-controlled, multicenter trial of BoNTA in patients aged >/=21 years who had experienced a stroke >6 months before the initiation of the study. Study 2 was an open-label extension of study 1. Study 3 was a randomized, double-blind, multicenter trial of a specific BoNTA formulation in patients aged >/= 21 years who had experienced a stroke >/=6 weeks before study entry. Patients with a fixed contracture of the studied limb were excluded from participation in studies 1 and 2. Serum samples were obtained from each patient before each BoNTA treatment and at the end of each study. The mouse protection assay (MPA) was used for detection of NAbs to BoNTA in serum. RESULTS: A total of 235 individual patients with post-stroke spasticity were enrolled in the 3 trials, including 126, 111 (all of whom participated in study 1), and 109 in studies 1, 2, and 3, respectively. Study 1 had an equal (50.0%) distribution of male and female patients (63/63). The distribution of male and female patients was 56 (50.5%) and 55 (49.5%), respectively, in study 2, and 55 (50.5%) and 54 (49.5), respectively, in study 3. The mean (SD) ages of patients in studies 1, 2, and 3 were 61.4 (13.8), 61.5 (14.1), and 58.5 (13.9) years, respectively. The MPA was used for detection of NAbs to BoNTA in the serum samples of 191 patients, including 64 from study 1, 111 from study 2 (55 of these patients were placebo recipients and 56 received their first BoNTA injection in study 1), and 72 (a sample was not obtained for 1 patient who had not received an injection) from study 3. The median number of BoNTA treatments received by these patients was 2 (range, 1-4 treatments) over a period lasting from 12 to 42 weeks. The mean dose of BoNTA was 241 U (range, 100-400 U), with a maximum dose of 960 U in any 1 patient. NAbs to BoNTA were detected in the serum sample of 1/191 (0.5%) patient who had participated in studies 1 and 2. Based on muscle-tone scores (3 and 4 for wrist and fingers, respectively) on a 5-point Ashworth Scale (0 = none to 4 = severe), the patient did not appear to exhibit a clinical response to BoNTA at any time during the studies. CONCLUSION: Formation of NAbs was rare (1/191) in this group of adults with poststroke spasticity from three 12- to 42-week clinical trials who received >/=1 treatment with a specific BoNTA formulation at doses ranging from 100 to 400 U.     

Headache Prophylaxis With BoNTA: Patient Characteristics

( Headache 2010;50:63-70)
Objective.— To assess the characteristics of patients receiving botulinum toxin type A (BoNTA; BOTOX^®) in the treatment of headache (HA) disorders.
Methods.— The following observational epidemiologic data and baseline patient characteristics were prospectively collected from eligible patients treated with BoNTA at 10 US HA specialty centers: demographics; HA diagnoses and characteristics (frequency, severity, and disability); prior and current HA treatments and response; clinical response to BoNTA; Migraine Disability Assessment (MIDAS) questionnaire; and adverse events. Patients maintained a daily HA diary and were evaluated at each follow-up visit.
Results.— Of 703 patients enrolled (mean age 43.1 years, 78.5% females, 95.4% white), nearly 66% had a diagnosis of chronic migraine (CM), with or without medication overuse. Approximately 75% had severe disability (MIDAS grade IV), and the mean pain rating was 6.5 (where 0 = no pain, 10 = pain as bad as it can be). More than 90% of patients had ≥1 prophylactic HA treatment failure; median number of failures was 4. Significant association was observed between HA frequency and MIDAS grade ( P  < .001). Approximately 80% of patients with CM had severe (grade IV) disability. The median number of monthly medication days was higher in the group with MIDAS grade IV ( P  < .001). HA frequency and severity, failed prophylactic therapies, and greater number of coexisting medical conditions were all negatively associated with measures of health-related quality of life.
Conclusions.— Majority of patients treated with BoNTA in a specialty HA center presented with a CM diagnosis. HA disability was correlated with measures of frequency and treatment utilization.     

体外冲击波联合肉毒毒素治疗对痉挛型脑瘫运动功能和身体活动的影响

目的：探讨体外冲击波（ESW）联合肉毒毒素（BoNT A）治疗对痉挛型脑瘫下肢运动功能和身体活动的影响。方法：将60例2~10岁痉挛型脑瘫儿童随机分为对照组和治疗组各30例，2组均接受患侧小腿三头肌BoNT A注射及常规康复治疗，治疗组在BoNT A注射24h后给予低能量ESW治疗。治疗前后对2组患儿的改良Asworth分级(MAS)、粗大运动功能评分(GMFM)D区和E区、身体活动水平进行评估。结果：治疗后，2组患儿MAS评分降低、GMFM D区和E区评分均较治疗前明显增加（P<0.05），治疗组MAS降低和D区评分增加较对照组显著（P<0.05）。治疗后，2组患儿的静坐时间百分比减少、轻强度身体活动时间百分比增加（P<0.05），且治疗组改善幅度较对照组显著（P<0.05）。结论：ESW联合BoNT A治疗是改善痉挛型脑瘫肌痉挛、站立功能及身体活动的有效方法，比单独BoNT A治疗效果更佳。     

Botulinum toxin type A for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial

OBJECTIVES: To identify a treatment-responsive population for botulinum toxin type A (BoNTA) and to evaluate the safety and efficacy of 3 different doses of BoNTA as prophylactic treatment of chronic daily headache (CDH). PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled study of BoNTA in patients with CDH was conducted from July 6, 2001, through November 7, 2003, at 28 North American study centers. Eligible patients were injected with BoNTA at 225 U, 150 U, 75 U, or placebo and returned for additional masked treatments at day 90 and day 180. Patients were assessed every 30 days for 9 months. The primary efficacy end point was the mean change from baseline in the frequency of headache-free days at day 180 for the placebo nonresponder group. RESULTS: For this study, 702 patients were enrolled and randomized. The primary efficacy end point was not met. Mean improvements from baseline at day 180 of 6.0, 7.9, 7.9, and 8.0 headache-free days per month were observed in the placebo nonresponder group treated with BoNTA at 225 U, 150 U, 75 U, or placebo, respectively (P=.44). An a priori-defined analysis of headache frequency revealed that BoNTA at 225 U or 150 U had significantly greater least squares mean changes from baseline than placebo at day 240 (-8.4, -8.6, and -6.4, respectively; P=.03 analysis of covariance). Only 27 of 702 patients (3.8%) withdrew from the study because of adverse events, which generally were transient and mild to moderate. CONCLUSIONS: Although the primary efficacy end point was not met, all groups responded to treatment. The 225 U and 150 U groups experienced a greater decrease in headache frequency than the placebo group at day 240. The placebo response was higher than expected. BoNTA was safe and well tolerated. Further study of BoNTA prophylactic treatment of CDH appears warranted.     

Prophylactic botulinum type A toxin complex (Dysport®) for migraine without aura

(Headache 2011;51:52‐63) Objective.— To evaluate the efficacy, safety, and optimum dose of a highly purified Clostridium botulinum type A toxin‐hemagglutinin complex (Dysport) for migraine prophylaxis. Background.— Botulinum toxin type‐A has demonstrated good efficacy in several open‐label studies of patients with migraine, involving either individualized or standardized protocols, although data from placebo‐controlled trials have been conflicting. Methods.— A 12‐week, double‐blind, randomized trial of Dysport (120 or 240 units) vs placebo was conducted in 6 centers in Thailand to evaluate the efficacy, safety, and optimum dose of botulinum toxin type‐A (Dysport) for migraine prophylaxis. A total of 128 patients with migraine without aura were enrolled. The primary end point was the change in the mean number of migraine attacks per 4‐week period from the pre‐treatment period to 8‐12 weeks post injection. Secondary efficacy measures included the change in the mean total intensity score from the pre‐treatment period to 8‐12 weeks, the investigator and patient global assessments of change at each visit compared with pre‐treatment, and Migraine Disability Assessment and Short Form‐36 scores. Results.— Change in number of migraine attacks from pre‐treatment to weeks 8‐12 was not significantly different. There was a greater improvement in total intensity score at weeks 8‐12 with Dysport‐240 (not significant), and interim visit data showed that this was significant at weeks 0‐4 (P = .03 Dysport‐240 vs placebo). The mean duration of headache during weeks 0‐4 was lower with Dysport‐240 (P = .04 vs placebo). Improvements in patient and investigator global assessments of change between weeks 0‐4 and 8‐12 were significant for the Dysport‐240 group (both P < .05 vs placebo). Conclusions.— Limitations in study design and assessment tools employed may have contributed to the inconclusive nature of the primary end point data. Dysport‐240 showed significant benefit over placebo at some end points and further trials with more appropriate outcome measures are required to evaluate effectively this treatment.     

体验式教学在ICU缩减约束行动中的应用研究

目的将体验式教学应用于ICU护士身体约束培训,探讨其在缩减约束行动中的效果。方法采取便利抽样法,选取2017年1月—2018年10月在石家庄市某三级甲等医院ICU的903例住院患者为研究对象。将2017年1—10月的491例患者设为对照组,2018年1—10月的412例患者设为试验组。对照组采用常规约束护理,试验组采取缩减约束护理,比较两组身体约束率、身体约束合格率、身体约束护理文件书写质量及患者满意度得分。结果试验组患者约束率为62.14%(256/256),低于对照组的71.69%(352/491),试验组约束合格率89.06%(228/256),高于对照组的80.68%(284/352),两组比较差异均有统计学意义(P<0.05)。试验组身体约束护理文件书写质量得分(98.32±2.22)分,患者家属满意度得分(98.11±2.53)分,均高于对照组,两组得分比较差异均有统计学意义(P<0.05)。结论基于体验式教学的缩减约束护理降低了ICU患者身体约束率,提高了身体约束质量和患者满意度,值得临床推广。     

Botulinum toxin type A as migraine preventive treatment in patients previously failing oral prophylactic treatment due to compliance issues

Objective.— To examine the efficacy and safety of and satisfaction with botulinum toxin type A (BoNTA; BOTOX^®: Allergan, Inc., Irvine, CA) for prophylactic treatment of migraine headache in patients previously failing prophylaxis because of issues pertaining to compliance. Background.— Numerous factors (eg, adverse effects, tolerability, cost, frequency of dosage, hesitancy to take daily medication, failure to complete treatment) negatively influence compliance with the preventive pharmacology for migraine prophylaxis. BoNTA may offer benefit in improving compliance because of its long duration of action, injectable route of administration, and its tolerability (adverse event [AE]) profile. Methods.— This was a randomized, double‐blind, single‐center, placebo‐controlled study (months 1 to 3) of BoNTA with a cross‐over to open‐label BoNTA treatment (months 4 to 6). Criteria for enrollment included patients with disabling headache (International Headache Society, International Classification of Headache Disorders [ICHD‐I] diagnosis 1.1, 1.2, 1.7, or 2.2, and Headache Impact Test [HIT]‐6 scores ≥56) previously failing prophylaxis because of compliance, tolerability, or adherence issues. After baseline evaluation, subjects were randomized 2 : 1 to a single set of BoNTA (139 units [U] total; 17 sites/6 muscle groups) or placebo injections. After month 3, only placebo‐treated subjects were eligible to receive BoNTA in the open‐label continuation study. Treatment outcomes were evaluated by headache episodes and days and maximum headache severity. Headache impact was assessed by the HIT‐6, Migraine Disability Assessment (MIDAS) score, and Quality of Life (QoL) questionnaires. Treatment satisfaction was assessed with the Migraine Impact Questionnaire (MIQ), which included MIDAS and QoL. Results.— Of the 73 subjects screened, 61 (40 BoNTA; 21 placebo) with migraine headache diagnosis 1.1 and 1.2 who met all study criteria were enrolled in the 3‐month, blinded study, with 54 completing the study; 19 of 21 placebo‐treated subjects participated in the open‐label period (months 4 to 6), with 18 completing the study. Between‐group comparisons, demonstrated through analysis of the subjects' headache diaries, did not reach statistical significance at months 1 to 3 for the number of headache episodes or days (primary endpoint). At month 2, a decrease from baseline in the number of headache episodes (?0.99 ± 2.38; P = .0147 vs 0.42 ± 3.23; P = not significant [NS]) and headache days (?1.52 ± 3.84; P = .0194 vs 0.23 ± 4.67; P = NS) was noted in the BoNTA‐treated subjects but not in the placebo‐treated subjects, respectively. During the open‐label study, BoNTA‐treated subjects had a decrease in the number of headache episodes at months 5 and 6 (?1.58 ± 2.88 and ?1.58 ± 2.85, respectively; P < .05 vs baseline for both) and headache days at months 5 and 6 (?2.84 ± 4.47 and ?2.73 ± 4.86, respectively; P < .05 vs baseline for both). BoNTA did not affect maximum headache severity compared with baseline or placebo during the first 3 months of the study. A decrease in HIT‐6 scores was significantly greater for BoNTA‐treated subjects than for placebo‐treated subjects at month 3 (?7.77 vs ?3.58, P = .0466). Within‐group decreases in HIT‐6 scores were significant in BoNTA‐treated subjects during each month of the blinded trial (?5.10 ± 8.85, ?6.63 ± 7.49, ?7.77 ± 8.78 for months 1 to 3, respectively; P < .0001 for all vs baseline) and throughout the open‐label portion of the study (?7.89 ± 6.48, ?10.39 ± 10.81, ?9.00 ± 11.12 for months 4 to 6, respectively; P < .01 for all vs baseline). The within‐group decrease in placebo‐treated subjects was significant at months 1 and 3 (?3.35 ± 6.07 and ?3.58 ± 5.40, respectively; P < .05 for both). At 3 months, BoNTA was significantly better than placebo (P = .001) in the reduction of MIDAS total score. The change from baseline in the MIDAS total scores was significant in BoNTA‐treated subjects (?21.62 ± 38.70; P < .0001) but not in placebo recipients (4.76 ± 18.85; P = NS). BoNTA‐treated subjects showed improvement in 11 of 13 and 7 of 13 assessments of treatment satisfaction in MIQ at months 3 and 6, respectively, while the placebo group showed no improvement at any measured time interval in the study. At month 3 (blinded period), there were no treatment‐related AEs reported in both groups. However, there were 18 possible/probable occurrences of treatment‐related AEs in the BoNTA group. At month 6 (open‐label period), 4 treatment‐related AEs were reported, along with 2 possible occurrences. The majority of treatment‐related AEs were transient and mild to moderate in severity, with no subjects discontinuing the study because of AEs. Conclusions.— BoNTA‐treated subjects showed improvements from baseline in measures of headache frequency, and improvements from baseline and in comparison with placebo treatment in headache impact and treatment satisfaction at multiple time points in this study. However, BoNTA‐treated subjects did not differ from placebo‐treated subjects in measures of headache frequency and severity. BoNTA may be a useful treatment option for headache patients demonstrating poor compliance, adherence, or AE profile with oral prophylactic regimens.     

Analgesic Effect of Botulinum Toxin A in Myofascial Pain Syndrome Patients Previously Treated with Local Infiltration of Anesthetic and Steroids

The purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P <.0001. As regards the side effects, 19 (23.2%) patients reported transient soreness at the injection site for 2 to 3 days with BoNTA. The MPS patients previously treated with a local infiltration of anesthetic and steroids who then received a single injection of BoNTA experienced significantly reduced pain for a relatively long time.     

Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study

Botulinum type A toxin (BoNT-A) has antinociceptive and muscle-relaxant properties and may help relieve the symptoms of myofascial pain syndrome. In this study we evaluated the efficacy and tolerability of BoNT-A (Dysport) in patients with myofascial pain syndrome of the upper back. We conducted a prospective, randomized, double-blind, placebo-controlled, 12-week, multicentre study. Patients with moderate-to-severe myofascial pain syndrome affecting cervical and/or shoulder muscles (10 trigger points, disease duration 6-24 months) were randomized to Dysport or saline. Injections were made into the 10 most tender trigger points (40 units per site). The primary outcome was the proportion of patients with mild or no pain at week 5. Secondary outcomes included changes in pain intensity and the number of pain-free days per week. Tolerability and safety were also assessed. At week 5, significantly more patients in the Dysport group reported mild or no pain (51%), compared with the patients in the placebo group (26%; p=0.002). Compared with placebo, Dysport resulted in a significantly greater change from baseline in pain intensity during weeks 5-8 (p<0.05), and significantly fewer days per week without pain between weeks 5 and 12 (p=0.036). Treatment was well tolerated, with most side effects resolving within 8 weeks. In conclusion, in patients with upper back myofascial pain syndrome, injections of 400 Ipsen units of Dysport at 10 individualised trigger points significantly improved pain levels 4-6 weeks after treatment. Injections were well tolerated.