Topiramate Treatment of Chronic Migraine: A Randomized, Placebo-Controlled Trial of Quality of Life and Other Efficacy Measures

Objective.— To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double‐blind, placebo‐controlled, multicenter clinical trial. Background.— We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated. Methods.— Variables analyzed included between‐treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache‐free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine‐Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change. Results.— The intent‐to‐treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate‐ vs placebo‐treated subjects were as follows: for ≥25% reduction: 68.6% vs 51.6% (P = .005); ≥50%: 37.3% vs 28.8% (P = .093); and ≥75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache‐free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine‐Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine‐Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062). Conclusions.— In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events.     

Allodynia‐Associated Symptoms,Pain Intensity and Time to Treatment: Predicting Treatment Response in Acute Migraine Intervention

Objective.— To evaluate the relationship between treatment outcomes and allodynia‐associated symptoms (AAS) at the time of treatment with almotriptan. Methods.— Analyses were performed with data collected prospectively from patients in 2 recently completed early intervention trials, AXERT^® Early miGraine Intervention Study (AEGIS) and AXERT^® 12.5 mg time vs Intensity Migraine Study (AIMS): 2‐hour pain free, 2‐hour pain relief (AEGIS only), sustained pain free (SPF), use of rescue medication, and median headache duration (AIMS only), in the presence and absence of pretreatment AAS, which was determined by responses to a questionnaire. Analyses were conducted to evaluate possible prognostic variables. Results.— The presence of pretreatment AAS did not have a significant effect on 2‐hour pain‐free, 2‐hour pain‐relief or SPF rates, use of rescue medication, or headache duration. Significant factors for most favorable outcomes (greater 2‐hour pain‐free, 2‐hour pain‐relief and SPF rates, less use of rescue medication, and shorter headache duration) included treatment with almotriptan 12.5 mg, treatment of mild or moderate headache pain, and treatment within 1 hour of headache onset. Conclusion.— Almotriptan 12.5 mg was efficacious in providing 2‐hour pain free, 2‐hour pain relief, SPF, and reducing rescue medication use irrespective of the presence of AAS at the time of treatment. The most optimal efficacy outcomes occurred when patients treated migraine attacks early and before the onset of severe pain. The presence of AAS, which may indicate an early phase of allodynia, did not influence the efficacy of almotriptan therapy.     

Prophylaxis of migraine,transformed migraine,and cluster headache with topiramate

OBJECTIVE: To assess the efficacy and tolerability of topiramate for prophylaxis of migraine and cluster headache via a retrospective chart analysis. BACKGROUND: Topiramate has multiple mechanisms of action that could potentially contribute to migraine prophylaxis. We conducted a retrospective chart review to assess the efficacy of topiramate as add-on therapy in patients with transformed migraine or cluster headache, and as first-line therapy in patients with episodic migraine. METHODS: Patients diagnosed with transformed migraine, episodic migraine, or cluster headache, who received topiramate either as add-on therapy or monotherapy were selected via retrospective chart review. Patients had begun topiramate therapy at 25 mg/day for the first week and increased their dosage by 25 mg/week to a maximum of 200 mg/day. Topiramate was used as add-on therapy for patients with transformed migraine and cluster headache, and as a first-line monotherapy in patients with episodic migraine who had no previous prophylactic therapy. The outcome parameters examined included a mean 28-day migraine frequency, migraine severity, number of headache days/month, number of abortive medication tablets/month, patient global evaluation, and the MIDAS scale. RESULTS: One hundred seventy-eight patients (transformed migraine: n = 96; episodic migraine: n = 70; and cluster headache: n = 12) were included in the retrospective analysis. The mean dose of topiramate for all patients was 87.5 mg/day. For patients with transformed migraine, mean migraine frequency decreased from 6.3/28 days to 3.7 (P = 0.005). Mean severity decreased from 7.1 to 3.8 on a 10-point scale, with 10 representing the most severe pain (P = 0.003). The mean number of headache days/month decreased from 22.1 to 9.6 (P = 0.001), and the mean number of abortive medication tablets decreased from 28.7/month to 10.6 (P = 0.001). Patient global evaluation indicated substantial or moderate improvement in 53% of patients with transformed migraine who used topiramate as add-on therapy. Mean MIDAS scale values decreased from 90.2 to 24.9 (P< 0.0001). The 70 episodic migraine patients who were administered topiramate as first-line therapy exhibited a decrease in mean migraine frequency (5.8/28 days to 1.9, P = 0.001), while mean migraine severity decreased from 8.1 to 2.0 (P = 0.003). Sixty-one percent of patients reported marked improvement. Nine of the 12 cluster headache patients exhibited substantial or moderate improvement in symptoms, whereas three had no improvement. The most common adverse effects were paresthesias (12%), cognitive effects (11%), and dizziness (6%). Eight patients discontinued topiramate due to adverse effects; cognitive effects were the most common reason. No patient discontinued topiramate treatment due to lack of efficacy. Twelve percent of patients lost more than 5 lbs during treatment (a range of 5-120 lbs). CONCLUSION: For both patients with transformed migraine (add-on therapy) and patients with episodic migraine (first-line monotherapy), topiramate yielded significant reductions in migraine frequency, migraine severity, number of headache days/month, and use of abortive medications. Topiramate also appears to be well tolerated and useful in the adjunctive treatment of cluster headache. Prospective double-blind, placebo-controlled trials will be required to confirm our results.     

Synoptic reporting in tumor pathology: advantages of a web-based system

The American College of Surgeons Commission on Cancer (ACS-CoC) mandates that pathology reports at ACS-CoC-approved cancer programs include all scientifically validated data elements for each site and tumor specimen. The College of American Pathologists (CAP) has produced cancer checklists in static text formats to assist reporting. To be inclusive, the CAP checklists are pages long, requiring extensive text editing and multiple intermediate steps. We created a set of dynamic tumor-reporting templates, using Microsoft Active Server Page (ASP.NET), with drop-down list and data-compile features, and added a reminder function to indicate missing information. Users can access this system on the Internet, prepare the tumor report by selecting relevant data from drop-down lists with an embedded tumor staging scheme, and directly transfer the final report into a laboratory information system by using the copy-and-paste function. By minimizing extensive text editing and eliminating intermediate steps, this system can reduce reporting errors, improve work efficiency, and increase compliance.     

Adhesive strength and curing rate of marine mussel protein extracts on porcine small intestinal submucosa

An adhesive protein extracted from marine mussels (Mytilus edulis) was used to bond strips of connective tissue for the purpose of evaluating the use of curing agents to improve adhesive curing. Specifically, mussel adhesive protein solution (MAPS, 0.5mM dihydroxyphenylalanine) was applied, with or without the curing agents, to the ends of two overlapping strips of porcine small intestinal submucosa (SIS).The bond strength of this lap joint was determined after curing for 1h at room temperature (25 degrees C). The strength of joints formed using only MAPS or with only the ethyl, butyl or octyl cyanoacrylate adhesives were determined. Although joints bonded using ethyl cyanoacrylate were strongest, those using MAPS were stronger than those using butyl and octyl cyanoacrylates. The addition of 25mM solutions of the transition metal ions V5+, Fe3+ and Cr6+, which are all oxidants, increased the bond strength of the MAPS joints. The V5+ gave the strongest bonds and the Fe3+ the second strongest. In subsequent tests with V5+ and Fe3+ solutions, the bond strength increased with V5+ concentration, but it did not increase with Fe3+ concentration. Addition of 250mM V5+ gave a very strong bond.     

A long-term open-label study of oral almotriptan 12.5 mg for the treatment of acute migraine

OBJECTIVE: Evaluate the long-term tolerability of almotriptan 12.5 mg for the treatment of acute migraine attacks occurring over a 6-month period. BACKGROUND: Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular selectivity for meningeal arteries and has demonstrated efficacy for the treatment of acute migraine in short-term controlled trials. METHODS: This was a 6-month open-label study. Adults (18 years of age or older) were required to have a diagnosis of acute migraine with or without aura (according to the diagnostic criteria of the International Headache Society), a history of at least 1 year of moderate-to-severe migraine pain with at least two and a maximum of six migraines per month, and at least 24 hours of freedom from head pain between attacks. Patients were instructed to take a single 12.5-mg dose of almotriptan at the onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape medication could be taken; if relapse occurred in less than 24 hours, a second 12.5-mg dose could be taken. Tolerability was assessed from the nature and incidence of all adverse events, and efficacy was assessed according to the end point of pain relief 2 hours following almotriptan administration. RESULTS: Of 585 patients treated, 582 were included in the intent-to-treat population. The most frequent drug-related adverse events were nausea (3.1%) and dizziness (2.4%). No serious drug-related adverse events were reported, and no deaths occurred. Adverse events led to discontinuation of treatment in 36 patients (6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six percent of patients achieved pain relief at 2 hours for all attacks treated, and 49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and pain-free rates were higher among those with moderate baseline pain. CONCLUSIONS: When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and effective for the long-term treatment of acute migraine.     

Quality initiatives: Establishing an interventional radiology patient radiation safety program

The Interventional Radiology Patient Radiation Safety Program was created to better educate patients who are scheduled to undergo high-dose interventional radiologic procedures about the risks of radiation, better monitor the delivered doses, and reduce the risk for deterministic effects. The program combines preprocedure evaluation and counseling, intraprocedure monitoring, and postprocedure documentation and counseling with the guidelines of the National Cancer Institute and the Society of Interventional Radiology. Between July 2009, when the program was implemented, and September 2010, over 3500 interventional radiologic procedures were monitored and documented, and 63 procedures with an adjusted cumulative dose of more than 3 Gy were identified and further analyzed; four procedures were found to be outside the control limits. Additional review of these four procedures resulted in practice modifications. Anecdotal feedback from physician assistants and attending physicians indicated that the program had another positive effect: Patients who required postprocedure counseling about the potential for radiation-induced skin injuries were no longer surprised by this information. Implementation of this program is straightforward, requires little infrastructure and few resources, and may be applied in most interventional radiology practices. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.321115002/-/DC1.     

Migration of immature mouse DC across resting endothelium is mediated by ICAM-2 but independent of beta2-integrins and murine DC-SIGN homologues

Immature dendritic cells (DC) reside in tissues where they initiate immune responses by taking up foreign antigens. Since DC have a limited tissue half-life, the DC pool in tissues has to be replenished constantly. This implies that precursor/immature DC must be able to cross non-activated endothelium using as yet unknown mechanisms. Here we show that immature, but not mature bone marrow-derived murine DC migrate across resting endothelial monolayers in vitro. We find that endothelial intercellular adhesion molecule-2 (ICAM-2) is a major player in transendothelial migration (TEM) of immature DC, accounting for at least 41% of TEM. Surprisingly, the ICAM-2-mediated TEM was independent of beta2-integrins, the known ICAM-2 ligands, since neither blocking of beta2-integrins with antibodies nor the use of CD18-deficient DC affected the ICAM-2-specific TEM. In humans, the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) was shown to interact with ICAM-2, suggesting a similar role in mice. However, we find that none of the murine DC-SIGN homologues mDC-SIGN, murine DC-SIGN-related molecule-1 (mSIGN-R1) and mSIGN-R3 is expressed on the surface of bone marrow-derived mouse DC. Taken together, this study shows that ICAM-2 strongly supports transmigration of immature DC across resting endothelium by interacting with ligands that are distinct from beta2-integrins and DC-SIGN homologues.