Cumulative effects of long-term treatment with abobotulinumtoxinA in cervical dystonia: Findings from a prospective, observational study.

OBJECTIVE: Patients with cervical dystonia (CD) require regular injections of botulinum neurotoxin type A (BoNT-A) to maintain treatment effectiveness. In this secondary analysis of a large routine-practice study, we assessed the response to abobotulinumtoxinA over repeated cycles and compared the responses of patients previously naïve to BoNT treatment to those already treated with BoNT-A. METHODS: INTEREST IN CD2 was a prospective, 3-year, observational study following CD patients treated with BoNT-A. Patients were assessed at each injection visit using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scale; patient satisfaction with symptom control (previous cycle) was recorded. RESULTS: This analysis included 466 patients treated with abobotulinumtoxinA over 3 years. TWSTRS-Total scores continually decreased; the mean ± SD reduction from baseline to 36 months was -7.4 ± 11.9. BoNT-naïve patients tended to show greater reductions in TWSTRS scores than already treated patients, particularly in the first 6 months. Incremental improvements were also seen in Tsui-tremor scores. Overall levels of patient satisfaction at peak effect (84.1-91.2%) were consistently higher than at the end of cycle (47.2-53.2%). The most frequently reported adverse events were dysphagia (6.8%) and muscular weakness (3.7%). CONCLUSIONS: These data support the long-term effectiveness and safety of abobotulinumtoxinA in a real-world setting.

Impact of abobotulinumtoxinA on the clinical features of cervical dystonia in routine practice.

INTRODUCTION: The efficacy and safety of abobotulinumtoxinA in the management of cervical dystonia has been established in randomized, controlled trials that use a selected trial population. In this meta-analysis of observational data, we evaluated the real-life effectiveness of abobotulinumtoxinA as delivered in routine clinical practice. METHODS: Meta-analysis of patient-level data for adult patients with cervical dystonia treated with abobotulinumtoxinA from three prospective, multicenter, observational studies (NCT01314365, NCT00833196 and NCT01753349). RESULTS: We report data for patients treated with abobotulinumtoxinA over one injection cycle at 181 neurology centers in 35 countries. CD clinical features as assessed by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total scores (N = 920) significantly reduced by a mean [95%CI] of -12.9 [-13.9, -11.8] points at Week 4 (N = 449) and -3.2 [-3.8, -2.7] points at the end of the injection cycle (N = 890). All three TWSTRS domains (symptom severity, disability and pain) contributed to the overall improvement. Patients were generally content with symptom control at peak effect of the treatment cycle, with 86% reporting overall satisfaction. CONCLUSION: Findings from this meta-analysis of observational studies confirm the effectiveness of abobotulinumtoxinA in routine practice. Despite inclusion of a broader population sample, the magnitude of improvements observed is consistent with that seen in the pivotal, randomized controlled trials.

Correction to: How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective, long-term observational study.

The article How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment?

How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective, long-term observational study.

BACKGROUND: Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice. METHODS: This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle. RESULTS: Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of - 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years. CONCLUSIONS: Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction.

Spectrum of practice in the routine management of cervical dystonia with abobotulinumtoxinA: findings from three prospective open-label observational studies.

BACKGROUND: Cervical dystonia is a heterogeneous disorder with several possible presentations, for which first-line therapy is often botulinum toxin (BoNT). In routine clinical practice the success of each BoNT injection is dependent on several variables, including individual presentation and injection technique. Large multicenter, observational studies provide important information on individualized administration strategies that cannot be otherwise ascertained from controlled clinical trials. In this meta-analysis of patient level data, we aimed to evaluate the clinical characteristics of patients with cervical dystonia undergoing routine treatment with botulinum toxin, specifically abobotulinumtoxinA. We also aimed to characterize current abobotulinumtoxinA injection techniques and parameters and to explore international differences in patient presentation and treatment. METHODS: This was a meta-analysis of baseline data from three prospective, international, multicenter, observational studies (NCT01314365, NCT00833196 and NCT01753349) of botulinum toxin treatment for the routine management of adult cervical dystonia. RESULTS: Data presented illustrate the significant heterogeneity of CD presentation in routine practice. Most subjects presented with a complex pattern of dystonic movements and the majority had additional components of shoulder elevation, tremor and/or jerk. Dosing was generally in accordance with that recommended in the abobotulinumtoxinA prescribing information, although the range of dosing also indicates that injections are tailored to individual presentation. Sub-group analyses at the country level revealed distinct differences in injection practice. CONCLUSIONS: This meta-analysis is based on the largest dataset of subjects with cervical dystonia studied to date. The heterogeneity revealed in our baseline findings support the need to develop consistent, practical and comprehensive best practice guidelines.

INTEREST IN CD2, a global patient-centred study of long-term cervical dystonia treatment with botulinum toxin.

BACKGROUND: Longitudinal cohort studies provide important information about the clinical effectiveness of an intervention in the routine clinical setting, and are an opportunity to understand how a population presents for treatment and is managed. METHODS: INTEREST IN CD2 (NCT01753349) is a prospective, international, 3-year, longitudinal, observational study following the course of adult idiopathic cervical dystonia (CD) treated with botulinum neurotoxin type A (BoNT-A). The primary objective is to document long-term patient satisfaction with BoNT-A treatment. Here we report baseline data. RESULTS: This analysis includes 1036 subjects (67.4% of subjects were female; mean age was 54.7 years old; mean TWSTRS Total score was 31.7). BoNT-A injections were usually given in line with BoNT-A prescribing information. The most commonly injected muscles were splenius capitis (87.3%), sternocleidomastoid (82.6%), trapezius (64.3%), levator scapulae (40.9%) and semispinalis capitis (26.9%); 35.5% of subjects were injected using a guidance technique. Most subjects (87.8%) had been previously treated with BoNT-A (median interval between last pre-study injection and study baseline was 4 months); of these 84.8% reported satisfaction with BoNT-A treatment at peak effect during their previous treatment cycle and 51.5% remained satisfied at the end of the treatment. Analyses by geographical region revealed heterogeneity in the clinical characteristics and BoNT-A injection practice of CD subjects presenting for routine treatment. CONCLUSIONS: These baseline analyses provide sizeable data regarding the epidemiology and clinical presentation of CD, and demonstrate an international heterogeneity of clinical practice. Future longitudinal analyses of the full 3-year study will explore how these factors impact treatment satisfaction.

Histologic analysis of a covered stent implanted for pseudoaneurysm in a coronary artery.

Covered stents are the standard of care when coronary perforations complicate percutaneous coronary interventions and have also been utilized in the treatment of coronary aneurysms. We present the clinical and histologic features of a patient who developed a coronary perforation and pseudoaneurysm 4 years following deployment of intracoronary stents. Although the covered stent successfully sealed the perforation, subsequent thrombosis led to a fatal acute myocardial infarction.

Transcatheter closure of left ventricular pseudoaneurysm.

Left ventricular pseudoaneurysm is a rare complication of myocardial infarction, cardiovascular surgery, trauma, or infection. Untreated left ventricular pseudoaneurysm can have significant morbidity and mortality. Surgical treatment has generally been the standard of care. However, with a sicker and older population, surgical risks can sometimes be significant. We report a case of successful percutaneous closure of left ventricular pseudoaneurysm using coils and a vascular plug. We emphasize the role and importance of multimodality imaging for accurate diagnosis and therapy, and briefly review the literature on the various approaches used for percutaneous closure of left ventricular pseudoaneurysms.

Factors influencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study.

OBJECTIVES: Real-life data on response to Botulinum toxin A (BoNT-A) in cervical dystonia (CD) are sparse. An expert group of neurologists was convened with the overall aim of developing a definition of treatment response, which could be applied in a non-interventional study of BoNT-A-treated subjects with CD. DESIGN: International, multicentre, prospective, observational study of a single injection cycle of BoNT-A as part of normal clinical practice. SETTING: 38 centres across Australia, Belgium, Czech Republic, France, Germany, The Netherlands, Portugal, Russia and the UK. PARTICIPANTS: 404 adult subjects with idiopathic CD. Most subjects were women, aged 41-60 years and had previously received BoNT-A. OUTCOME MEASURES: Patients were classified as responders if they met all the following four criteria: magnitude of effect (≥25% improvement Toronto Western Spasmodic Torticollis Rating Scale), duration of effect (≥12-week interval between the BoNT-A injection day and subject-reported waning of treatment effect), tolerability (absence of severe related adverse event) and subject's positive Clinical Global Improvement (CGI). RESULTS: High rates of response were observed for magnitude of effect (73.6%), tolerability (97.5%) and subject's clinical global improvement (69.8%). The subjective duration of effect criterion was achieved by 49.3% of subjects; 28.6% of subjects achieved the responder definition. Factors most strongly associated with response were age (<40 years; OR 3.9, p<0.05) and absence of baseline head tremor (OR 1.5; not significant). CONCLUSIONS: Three of four criteria were met by most patients. The proposed multidimensional definition of response appears to be practical for routine practice. Unrealistically high patient expectation and subjectivity may influence the perception of a quick waning of effect, but highlights that this aspect may be a hurdle to response in some patients. CLINICAL REGISTRATION NUMBER: (NCT00833196; ClinicalTrials.gov).

Oral antiplatelet therapy in diabetes mellitus and the role of prasugrel: an overview.

Diabetics have a prothrombotic state that includes increased platelet reactivity. This contributes to the less favorable clinical outcomes observed in diabetics experiencing acute coronary syndromes as well as stable coronary artery disease. Many diabetics are relatively resistant to or have insufficient response to several antithrombotic agents. In the setting of percutaneous coronary intervention, hyporesponsiveness to clopidogrel is particularly common among diabetics. Several strategies have been examined to further enhance the benefits of oral antiplatelet therapy in diabetics. These include increasing the dose of clopidogrel, triple antiplatelet therapy with cilostazol, and new agents such as prasugrel. The large TRITON TIMI 38 randomized trial compared clopidogrel to prasugrel in the setting of percutaneous coronary intervention for acute coronary syndromes. The diabetic subgroup (n = 3146) experienced considerable incremental benefit with a 4.8% reduction in cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke at 15-month follow-up with prasugrel treatment. Among diabetics on insulin this combined endpoint was reduced by 7.9% at 15 months. Major bleeding was not increased in the diabetic subgroup. This confirms the general hypothesis that more potent oral antiplatelet therapy can partially overcome the prothrombotic milieu and safely improve important clinical outcomes in diabetics.

Coronary artery spasm during angiography in a pediatric heart transplant recipient: subsequent prevention by intracoronary nitroglycerin administration.

Coronary artery spasm can occur during coronary angiography in pediatric heart transplant recipients. The angiographic appearance can suggest allograft vasculopathy. We report coronary artery spasm in a pediatric heart transplant recipient in whom intracoronary nitroglycerin administration prevented a repetition of spasm upon subsequent diagnostic coronary angiography. Additional studies of dose response, particularly in cardiac transplant recipients, may help determine whether lower doses of intracoronary nitrates, such as that administered to our patient, can be effective in preventing coronary artery vasospasm in pediatric heart transplant recipients.

Liver transplantation after radioembolization in a patient with unresectable HCC.

BACKGROUND: A 58-year-old white man who was being followed by his hepatologist for nonalcoholic steatohepatitis-related liver cirrhosis and portal hypertension and who had been found to have a biopsy-proven hepatocellular carcinoma (HCC) on routine screening, self-referred to our center for a second opinion on the management of his HCC. INVESTIGATIONS: Laboratory investigations, CT scan of the abdomen and chest, bone scan and technetium macroaggregated albumin scan. DIAGNOSIS: The patient had unresectable HCC. MANAGEMENT: The patient underwent two treatments with Yttrium-90 glass microspheres, which were performed as outpatient procedures 1 month and 3 months after diagnosis. He underwent orthotopic liver transplantation (OLT) 1 year after the initial diagnosis of HCC. The post-OLT immunoregimen included OKT3 plus rituximab and high-dose steroids. On discharge from hospital he was on immunosuppressive treatment with tacrolimus. He had de novo autoimmune hepatitis 6 months post-OLT, which was treated with a short course of low-dose steroids and addition of mycophenolate mofetil.

Pretreatment with nitroprusside for microcirculatory protection in saphenous vein graft interventions.

OBJECTIVES: We hypothesized that the prophylactic administration of sodium nitroprusside (NTP) during saphenous vein graft (SVG) PCI would ameliorate the detrimental effects of distal embolization and reduce the frequency and magnitude of post-procedural myonecrosis. METHODS: Sixty-four consecutive patients with normal preprocedural cardiac enzymes underwent SVG PCI without embolic protection devices and received prophylactic intragraft NTP before initial device activation. For each case, 2 control patients were selected in reverse chronologic order and were matched for stent use, thromboatherectomy device use, clinical presentation, presence of thrombus and pre-PCI thrombolysis in myocardial infarction (TIMI) flow. RESULTS: Mean patient age was 66 +/- 10 years, 78% of whom were males. Stent and thromboatherectomy use was 95.3% and 3.1%, respectively in both groups (p = ns). Prior to intervention, TIMI < 3 flow was present in 26.6% of cases and in 24.2% of control patients (p = ns). Thrombus was present in 20.3% of cases and in 19.5% of controls (p = ns). Post-PCI creatinine kinase (CK)-MB elevation > 3 x the upper limit of normal (ULN) occurred in 6.3% of cases vs. 16.4% of controls (p = 0.049) and > 5 x ULN in 1.6% of cases vs.10.9% of controls (p = 0.022). In a multivariate regression model that included stent use, in-stent restenosis, thrombus presence, preprocedural TIMI 3 flow, MI as procedural indication, NTP and glycoprotein IIb/IIIa use, NTP was the only independent and significant predictor of reduced post-procedural CK-MB elevation > 5 x ULN. CONCLUSION: Prophylactic administration of intragraft NTP during SVG PCIs results in a lower frequency and magnitude of post-procedural cardiac enzyme elevation.

Nonalcoholic fatty liver disease and cardiovascular risk.

Nonalcoholic fatty liver disease (NAFLD) is a very common cause of chronic liver disease in the United States. A large proportion of patients with NAFLD have coexisting metabolic syndrome, a major risk factor for cardiovascular disease. A strong association between NAFLD and cardiovascular disease has been long suspected, and recent studies have confirmed that cardiovascular disease is the single most important cause of mortality in this patient population. NAFLD may pose cardiovascular risk beyond the risk conferred by traditional factors such as dyslipidemia, diabetes, and smoking. Health care providers managing patients with NAFLD should recognize this increased cardiovascular risk and should undertake early, aggressive risk factor modification.

Rheolytic thrombectomy for dural venous sinus thrombosis.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis is a rare condition. Its diagnosis and management can be difficult. Treatment options include systemically delivered anticoagulation or thrombolysis. Intrasinus thrombolysis is an increasingly used intervention but it increases the risk of hemorrhage, especially in patients who have a rapidly deteriorating neurological condition. Mechanical thrombectomy that provides rapid canalization without increased risk of hemorrhage is an attractive alternative treatment. METHODS: We describe the use of AngioJet rheolytic thrombectomy in 4 patients with extensive cerebral venous sinus thrombosis, preexisting intracranial hemorrhage, and severe progressive neurological deficit despite heparin therapy. RESULTS: Partial or complete sinus patency was restored in all 4 patients and complete neurological recovery was achieved in 3 patients. CONCLUSION: Intracranial hemorrhage or a rapidly deteriorating neurological condition may preclude the use of thrombolytic agents in the treatment of patients with cerebral venous sinus thrombosis. In such patients, mechanical thrombectomy offers a useful alternative.