Hyperbaric oxygen (HBO) has also been studied as a treatment for acute CH attacks.21,22 Weiss et al treated a CH patient with hyperbaric (2 atmospheres) 100% oxygen, after she had been refractory to conventional oxygen therapy.21 Two attacks were treated with HBO, with prompt and complete pain relief. Di Sabato et al treated 7 ECH patients with HBO in a placebo controlled study.22 Six patients responded well to treatment, with interruption of their attack. Moreover, in 3 of the responders the CH period ended after HBO treatment. Placebo treatment had no effect selleck chemical on pain. In summary, normobaric oxygen is an effective treatment of acute CH

attacks in the majority of patients. It is well tolerated and has virtually no AEs. buy ABT-199 As opposed to triptans, there is no limitation to the number of times per

day it can be used. A proper technique of use is crucial for good results with oxygen therapy. The patient should be instructed to use the oxygen via a non-rebreathable mask, at a rate of 7-10 L/min, in a sitting position, for at least 15-20 minutes. Patients may increase the flow rate up to 15 L/min if needed. The optimal flow rate should be determined individually for each patient. The major disadvantage of oxygen therapy is its inconvenience of use, particularly when the patient is out of home. Portable oxygen tanks are available for patients who wish to use it in these circumstances. Oxygen therapy for CH should be used with caution, or even avoided, in patients with chronic obstructive pulmonary disease, because of the risk of respiratory depression. HBO may be considered for refractory CH patients. However, because this is not a readily available therapy, and there is no evidence for a sustained effect of it on CH,23 the majority of patients are not likely to benefit from it. Ergot derivatives were among the first agents to be used in CH treatment.

Reports on the efficacy of ergotamine for this indication date Dipeptidyl peptidase back to the 1940s and 1950s.1 These data, however, were based on small, open-label studies and on case reports. The drug has not been evaluated in controlled studies for this indication. Kudrow compared the efficacy of sublingual ergotamine with that of oxygen in 50 patients with CH.17 The response rate to ergotamine was 70%, as compared with 82% for oxygen (with no significant between-group difference). Oxygen was better tolerated than ergotamine; however, the latter was more convenient to use. Because of limited availability and potentially serious AEs, most notably those related to the drug’s vasoconstrictive effect, ergotamine is currently rarely used for acute CH. Dihydroergotamine (DHE) is available in injectable (intravenous, intramuscular, or subcutaneous) and intranasal formulations. Although no data from controlled trials are available, clinical experience suggests efficacy of intravenous DHE for acute CH.

Thus, derangement of central modulation of the trigeminal system as a result of chronic medication use may increase sensitivity to pain perception and foster or reinforce medication overuse headache. Overuse of symptomatic medications is a common problem observed in patients with primary headaches, especially migraine and tension-type headache. In addition to other adverse effects, prolonged use of these abortive compounds can produce the paradoxical effect of deteriorating the underlying headache pathophysiology. This learn more results in a clinical syndrome known as “medication overuse headache” (MOH). According to the International Classification of Headache Disorders (2nd edition), MOH refers to the frequent

headache condition (15 days per month or more) that occurs in patients with primary headaches who regularly use 1 or more acute and/or symptomatic drugs for more than 3 months.[1] This clinical syndrome is common. Population-based studies report the 1-year prevalence rate

of MOH to be from 1% to 2%.[2] The relative frequency is much higher in secondary and tertiary care centers.[3] This disorder strongly affects the quality of life of patients and causes substantial LY2835219 ic50 economic burden. There is no clear explanation of how chronic abortive drug exposure can increase headache frequency and result in MOH. Some possible mechanisms have been summarized in recent reviews.4-6 In this article, we review the recent studies, both clinical and preclinical,

investigating the pathogenesis of this condition. Possible mechanisms underlying the process of medication-induced headache transformation are also proposed. Some clinical features SPTLC1 of MOH provide clues about its pathogenesis. First, MOH occurs mostly in patients with primary headaches. Chronic analgesic consumption rarely induces MOH in nonheadache patients.[7] This condition also occurs in headache-prone patients who regularly take analgesics for other indications. For instance, Wilkinson et al showed that migraine patients who regularly took opiates to control bowel motility developed chronic headache, while those without a history of migraine did not.[8] These observations suggest 2 things. Analgesic overuse is the cause of chronic headache, not the consequence; and MOH results from an interaction between an excessive use of abortive medication and a susceptible patient. Second, MOH usually occurs in patients with migraine or tension-type headache. Although the pathogenesis of these 2 primary headaches has not yet been completely understood, it is widely accepted that both conditions are the result of an increase in excitability of neurons in the central nervous system. By contrast, MOH rarely occurs in patients with cranial neuralgias, a condition in which abnormalities in neuronal excitability of the peripheral nervous system play a major role.

11 Comparable antimicrobial activity

was seen between rifaximin and other antimicrobials for E. coli. In addition, activity against Clostridium difficile was comparable to metronidazole and vancomycin (MIC90 = 0.005 through 2 μg/mL).10, 12 Of importance, in studies on traveler’s diarrhea, aerobic gut species return to baseline after the end of rifaximin therapy.10 Therapy with rifaximin can be associated with adverse effects that are relatively minor and rarely require reduction or discontinuation of therapy. Patients who are allergic to not only rifaximin, but also rifabutin (Mycobutin), rifampin (Rifadin, Rifamate, Rifater, Rimactane), and rifapentine (Priftin) should avoid use of rifaximin. The main gastrointestinal adverse events are flatulence, nausea, vomiting, abdominal pain, and weight loss which have been reported in ranges from 5%-17%, no different from placebo. Clostridium difficile in cirrhosis has selleck chemical a poor prognosis therefore the notion of long-term antibiotic therapy in this population does raise some concerns.13 In the Bass et al. trial, there were two cases of C. difficile in the rifaximin group but none in the placebo group. This is interesting

because rifaximin is active against C. difficile.6, 12 It is a relevant concern, specifically because of depressed immunity, frequent hospitalization and other antibiotic use in these patients.13 Additionally, if patients Selleck HDAC inhibitor are on lactulose concomitantly, C. difficile diarrhea may be mistakenly attributed to lactulose, further delaying the diagnosis. Clinicians should be vigilant against C. difficile in patients

with cirrhosis triclocarban and specifically those receiving long-term therapy such as rifaximin. Development of drug resistance is discussed in the next section. Although rifaximin has been approved for therapy in several European countries and the experience in those countries has not raised any significant concerns, the U.S. experience remains limited. The specific areas of uncertainty involve the evolving role of rifaximin as a possible first or second-line therapy, emergence of resistant strains and the possibility of clinical drug interactions. Rifaximin is currently a second-line therapy for HE in part due to the extreme cost difference between rifaximin and lactulose and also because lactulose therapy alone can prevent recurrent HE in selected patients. Also, there are only short-term studies that use rifaximin as an initial therapy for HE.10 With U.S. Food and Drug Administration (FDA) approval for this in the United States for prevention of recurrence, the current role appears to be a second-line. The role of rifaximin is evolving and it is feasible that with longer-term and head-to-head studies and with reduction in cost, it may become first-line therapy for HE.

Here we present a series of studies conducted by our group (Fig 1) and review the literature. Methods: We first determine whether certain serum miRNAs tested by qRT-PCR could represent potential diagnostic and prognostic

biomarkers for PDAC on 2010. Then the value of such miRNAs compared with serum CA19-9 was evaluated. We used serum samples to screen the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled Kinase Inhibitor Library solubility dmso serum samples followed by validation of a large number of samples arranged in multiple stages. Finally, the role of PDAC-specific miRNA was also studied by using transfection and animal model. Results: Of the serum miRNAs detected, miR-21, miR-155 and miR-196a were identified as differentially expressed in PDAC and control groups (chronic pancreatitis or normal). selleck chemicals Furthermore, serum miR-196a expression level was found to have a potential value in predicting median survival time of PDAC

patients. The combination of miR-16, miR-196a and CA19-9 was more effective for discriminating PDAC from normal (sensitivity 92.0%; specificity 95.6%) compared with CA19-9 alone. Most significantly, the combination was effective at identification of tumors in Stage 1 (85.2%). A 7 miRNA – based biomarker can serve as a novel noninvasive approach for PDAC diagnosis and prognosis. Mir-196a was found to modulate PDAC progression via its target gene of inhibitor of growth 5 (ING5). Conclusion: Circulating miRNAs show promising value in diagnosis of PDAC. The origin and their roles on PDAC formation and invasion warrant further studies. Key Word(s): 1. pancreatic cancer; 2. miRNA; Presenting Author: RAJESH GUPTA Additional Authors: SUNIL SHENVI, YELLAKANTIRAGHAVENDRA Megestrol Acetate BABU, PRASANNA C, SURINDER RANA, DEEPAK BHASIN, MANDEEP KANG, RAKESH KAPOOR Corresponding Author: RAJESH GUPTA Affiliations: PGIMER Objective: Despite advances in surgery and perioperative care that have resulted in markedly reduced postoperative mortality after pancreaticoduodenectomy(PD), the median survival for pancreatic cancer patients has changed minimally over the past two decades. Apart from SMA margin and Neoadjuvant

chemotherapy which have effect on long term survival of patients; reducing early mortalityfurthur following PD can also lead to improved results. Present study analysis the reasons and outcome for early mortality following PD. Methods: We retrospectively reviewed details of patients undergoing pancreatico-duodenectomy between January 2002 and Dec 2011 at Division of Surgical Gastroenterology, PGIMER, Chandigarh. A total of 101 patients underwent pancreaticoduodenectomy. Indications being Carcinoma head of pancreas/Periampullary carcinoma in 81, PNET in 11, chronic pancreatits in 6, duodenal GIST in 1, adenoma with high grade dysplasia in 2 patients. Results: There were 60 male patients. Mean age was 52±12.9 SEM (Range 25-78 years).Mean post op stay was 13.8days±6.5 SEM.

4%, and HCV-related deaths by 76.1%. However, treatment with LDV/SOF at F2 rather than F3-F4 is projected to have even greater

efficacy, decreasing the average number of cases of DCC by 63.3%, cases of HCC by 89.0%, liver transplants by 83.3%, and HCV-related deaths by 84.5%. LDV/SOF is projected to lead to an average decrease in the number of cases of DCC by 49.5%, cases Erlotinib price of HCC by 39.6%, liver transplants by 42.4%, and HCV-related deaths by 41.6 %across all fibrotic states in comparison with SOF+PR. Conclusions: This analysis projects delaying treatment initiation for HCV TN GT1 patients could lead to substantially more cases of advanced liver disease complications. While early treatment strategies greatly reduce future liver disease, treatment with more effective interferon- and ribavirin-free therapies like LDV/SOF could curb future liver disease and the downstream costs associated with advancing disease. Disclosures: Aijaz Ahmed – Consulting: BMS, Gilead, Vertex, Genentech, Onyxx Stuart C. Gordon – Advisory Committees or Review Panels: Tibotec; Consulting: Merck, CVS Caremark, Gilead Sciences, BMS, Abbvie; Grant/Research Support: Roche/Genentech, Merck, Vertex Pharmaceuticals,

Gilead Sciences, BMS, Abbott, Intercept Pharmaceuticals, Exalenz Sciences, Inc. Sammy Saab – Advisory Committees or Review Panels: BMS, Gilead, Merck, Genentech; Grant/Research Selleckchem Ponatinib Support: Merck, Gilead; Speaking and Teaching: BMS, Gilead, Merck, Genentech, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Salix, Johnson and Johnson, BMS, Gilead The following people have nothing to disclose: Zobair Younossi Background: HCV direct-acting antivirals (DAAs) will improve cure rates but are costly. European guidelines recommend prioritizing DAAs for severe liver disease for individual benefit, but earlier treatment of those at risk of transmission such as people who inject drugs (PWID) may be more cost-effective. We determine the most cost-effective HCV treatment prioritization strategy by disease stage and risk status. Methods: A dynamic HCV transmission and Buspirone HCl disease progression cost-effectiveness model is used

to compare prioritization of HCV treatment (using pegylated interferon+ribavirin or interferon-free DAAs) by disease stage (mild, moderate, compensated cirrhosis) and risk status (PWID, non/ex PWID) in three HCV chronic prevalence settings among PWID (20%, 40%, and 60%). We perform a probabilistic cost-utility analysis estimating long-term costs (in UK £) and outcomes (quality-adjusted life-years gained, QALYs). We compare strategies by plotting cost-effectiveness efficiency frontiers on the cost-effectiveness plane; interventions which lie off the frontier are dominated (more expensive and gaining fewer QALYs). Results: In settings with very high (60%) chronic HCV prevalence among PWID, it is most cost-effective to prioritize treatment to individuals with compensated cirrhosis, regardless of treatment regime.

[1, 4-6, 10-12] FOXO transcriptional activity is regulated by a complex array of posttranslational modifications (PTMs). In many circumstances, the primary regulatory event is protein kinase

B (Akt)-mediated phosphorylation of three conserved amino acids, two serines, and one threonine, that see more results in binding to 14-3-3 and nuclear export of the protein. A conceptual theme that has emerged from the study of multiple FOXOs is that they are a major part of the mechanism that allows cells to transition between a fed/unstressed state where cell proliferation is favored and a fasting/stressed state which initially favors cell cycle arrest, DNA repair, and antioxidant enzyme induction, but can proceed toward apoptosis and cell death Selleck LDE225 (see Fig. 1). The action of the FOXO factors varies depending of the nature of the cell type and circumstances. A combination of different FOXO proteins, each with specific PTM combinations, is able to tailor the response to the situation. FOXO1 plays a major role in regulating the insulin

response, and the liver is one of its critical sites of action. The liver adapts to feeding through several insulin mediated events including increasing glucose uptake into hepatocytes, suppressing gluconeogenesis and glycogenolysis, and upregulating glycogen synthesis. In fasting, the withdrawal of insulin stimulation results in gluconeogensis through an upregulation of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G-6-Pase), and induction of autophagy. This response is largely dependent on the interplay between Akt and FOXO1. The role of FOXO1 in the adaptation to fasting has been largely documented by animal studies of overexpression and heterozygous null expression leading to increased or decreased FOXO1 expression. When FOXO1 is

constitutively expressed in the liver, fasting blood glucose rises.[13] Conversely, liver specific FOXO1 knock-out mice develop fasting hypoglycemia.[14] The mechanism behind these phenomena appears to be relatively straightforward. FOXO1 is active in the fasted state where it is dephosphorylated 4-Aminobutyrate aminotransferase at the Akt sites and localized in the nucleus. This results in the transcriptional induction of two gluconeogenic enzymes, glucose-6-phosphatase catalytic subunit (G6Pc), and PEPCK[15] and increased hepatic glucose production. In the fed state, insulin signaling activates phosphatidylinositol 3-kinase (PI3)-kinase and the subsequent production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) activates Akt. Akt phosphorylates FoxO1 at Thr24, Ser253, and Ser316 leading to its nuclear exportation and inactivation[16] with subsequent suppression of gluconeogenesis. The importance of FOXO1 as a counter of Akt in the glycogen synthesis-gluconeogensis balance has been recently demonstrated using liver specific knock-out mice for both Akt and FOXO1.

The specific activity of purified F8V by a chromogenic assay was similar to FVIII-BDD and PEGylation had minimal impact on the specific activity of F8V in this assay. Analysis by Biacore indicated that both F8V and PEG-F8V display greatly

reduced vWF binding in vitro. Pharmacokinetic studies in FVIII knockout (HaemA) mice showed that the terminal half-life (T1/2) of F8V was dramatically reduced relative to FVIII-BDD (0.6 h vs. 6.03 h). PEGylation of F8V promoted a significant increase in T1/2, although PEGylation did not fully compensate for the loss in vWF binding. PEG-F8V showed a shorter T1/2 than PEG-FVIII-BDD both in HaemA mice (7.7 h vs. 14.3 h) and in Sprague-Dawley male rats (2.0 ± 0.3 h vs. 6.0 ± 0.5 h). These data demonstrated that vWF contributes to the longer T1/2 of PEG-FVIII-BDD. Furthermore, this suggests that the clearance of the FVIII:vWF complex, through vWF receptors, is not the sole factor which places an upper limit on GPCR Compound Library clinical trial the duration of PEG-FVIII circulation in plasma. “
“The history of concentrated factor VIII (FVIII) begins in the early 1940s, when Edwin J. Cohn [1]

pioneered fractionation of plasma with various proportions of ethanol. His ‘fraction I’ contained fibrinogen and also FVIII (but methods of assay had not yet been developed) and von Willebrand factor (which had not Epigenetics inhibitor yet been defined). The utility of fraction I in haemophilia was demonstrated early [2] and modest amounts were used in developed countries throughout the 1950s and 1960s, but its sterile production required a large laboratory. A commercial version became available in the United Ureohydrolase States as a concentrate of fibrinogen, rich in FVIII; in one measurement [3], the ratio of FVIII to total protein was sevenfold that of native plasma. In 1965, it cost about 17.5 cents (U.S. $ 0.175) per FVIII unit [4]. Meanwhile, community blood banks were separating and freezing plasma from whole blood for local use. Blood banks in the United

States generally set the price of plasma low, as a by-product of whole blood collection, so it was widely used. The hemostatic efficacy of whole plasma was sub-optimal because only a limited volume could be infused at one time. In the early 1960s, Cutter Laboratories in Berkeley, California, and its scientists were trying to make an improved concentrate of FVIII, with help from northern California ‘clotters’, including Paul M. Aggeler of the University of California at San Francisco and Judith Graham Pool of Stanford University. I had the felicity of being a haematology Fellow in Dr. Aggeler’s laboratory from 1962 to 1965, which were heady years in the history of haemophilia treatment. The first FVIII concentrate I ever saw, in 1963, was an experimental, lyophilized product from Cutter Laboratories. We were planning to extract all remaining, very rotten teeth from a malnourished man with severe haemophilia A, to prepare him for dentures.

Overall, these and past studies dealing with the examination of H. pylori-derived effects on DCs suggest that local and monocyte-derived DC populations in the gastric mucosa may differ functionally and support conditions for a diverse population of T cells. It will require further studies, but by exploiting the murine model these intricate

relations may be dissectible. Th17 and Treg CD4+ cell subsets have been the focus of many recent immunologic studies on the course of Helicobacter infection. Regulatory T cells are thought to expand and eventually dominate in chronic infection hindering the function of protective T cells. Recent work is substantiating this scenario; for instance, Kindlund et al. [45] showed that eradication of H. pylori reduced Treg numbers, and Jang AZD2014 research buy et al. [46] reported increased numbers of Tregs in the stomachs of H. pylori-positive gastric cancer patients. Treg differentiation depends on TGF-β but, in the presence of IL-6, TGF-β rather promotes Th17. Th17 cells have become a new focus in this field because of their role in neutrophil recruitment and activation. Th17 thrive in particular when IL-1 and IL-23 are also present [47]. Shi et al. [48] confirmed the latter scenario after H. pylori infection of mice and found that Th17 and Th1 cells contribute to the overall pro-inflammatory T-cell response. Similar to other infection and autoimmune

disease models, Th17 and Th1 cells modulate each other. However, in the study by Shi et al., Th17 cells promoted an inflammatory component and Th1 response that correlated with higher H. pylori colonization when wild-type mice were compared with Selleck PLX4032 IL-17-deficient or normal mice treated with an anti-IL-17 antibody

just before infection. Similarly, IL-17, when delivered by recombinant Rolziracetam adenovirus just before H. pylori infection, increased inflammation and bacterial load 4 weeks later. These findings are at odds with work by Otani et al. [49], who observed an increase in gastritis and Th1 cytokines in mice treated with anti-IL-17 antibodies 6 months after infection. It also contradicts work by Kao et al. [44] who showed a negative correlation of IL-17 production and H. pylori burden. Complicating the issue further, Algood et al. [50] reported that mice deficient in the IL-17A receptor developed increased inflammation over a 6 -month time scale but also suffered tenfold increased bacterial burdens. Consistent with the model that IL-17 amplifies recruitment of neutrophils, the inflammatory infiltrate contained more lymphocytes, in particular B cells at the expense of granulocytes. In humans, serum levels of IL-17 seem to correlate with severity of disease; for instance, Jafarzadeh et al. [51] found increased levels of IL-17 in duodenal ulcer patients when compared to asymptomatic H. pylori-positive patients. Moreover, genetic typing for IL-17A alleles in over 800 individuals, 300 of which were gastric cancer patients, by Shibata et al.

Over the course of healing, the wounds also have abnormal histological features, including (i) reduced neutrophil influx and delayed macrophage influx; (ii) subcutaneous haematoma formation; (iii) an unexpected increase in wound site angiogenesis and (iv) persistent deposition of iron in

the wound bed and adjacent tissues. We found that temporarily restoring thrombin generation with a single dose of FIX replacement or high dose FVIIa restored neutrophil and macrophage influx. However, it did not correct delayed epithelial closure, excess angiogenesis or late rebleeding [23]. Thus, although formation of an adequate fibrin clot at the time of injury plays a role in tissue repair, the ability to generate thrombin and/or other activated coagulation factors remains important during the later phases of wound healing. Proper haemostatic function later in the healing process prevents bleeding at

the wound R788 in vivo site and at adjacent sites of angiogenesis. This prevents deposition of additional iron in the wound area, which can promote inflammation that impedes healing [37]. Our data suggest that sites of angiogenesis are at high risk of rebleeding during wound healing [14]. Inhibition of angiogenesis does not further impair wound healing in haemophilia. Celecoxib, a non-steroidal anti-inflammatory agent, reduced angiogenesis in healing wounds in the haemophilia B mouse model, but did not further delay healing [4]. Inflammation alone does not seem to provoke selleck screening library bleeding in haemophilic mice [38]. However, certain inflammatory mediators can drive angiogenesis and may possibly provoke bleeding at sites where inflammation is secondarily associated with angiogenesis. Although our studies have been conducted using skin wounds, we feel that they reveal general principles that likely apply to bleeding and healing in other tissues, such as joints. We believe that modulators of angiogenesis and inflammation hold promise as adjunctive therapies to reduce joint and soft tissue bleeding in haemophilia. Cartilage is composed of chondrocytes embedded in an extracellular

matrix. Chondrocytes are responsible for maintenance of the matrix. The cartilage matrix consists of two major components: collagen, which provides shape and tensile strength, and proteoglycans, which are responsible for the negative Liothyronine Sodium charge. This causes high osmotic pressure, thereby attracting water and with that resisting compressive forces in a joint. Previous in vitro research showed that a single blood-exposure of cartilage leads to persistent damage [39]. It was demonstrated that monocytes/macrophages and red blood cells, as present in blood, are responsible for the irreversible inhibition of cartilage matrix synthesis [40]. This is caused by induction of chondrocyte apoptosis due to formation of hydroxyl radicals in the vicinity of chondrocytes [41]. Small amounts of interleukin (IL)-1β, produced by activated monocytes/macrophages, increase production of hydrogen peroxide by chondrocytes.

There were no significant differences in headache severity or duration between amitriptyline and placebo groups at RG7204 anytime during the study. Within the study sample, there were 36 amitriptyline and 22 placebo subjects who had headaches ≥17 days/month that fit the current definition of CDH by the Silberstein-Lipton criteria. These were analyzed separately as a

subgroup for comparison of amitriptyline vs placebo using a metric of (1) no change or worsening; (2) up to a 50% improvement; and (3) ≥50% improvement in headache frequency. Amitriptyline was superior to placebo in number with improvement in frequency of ≥50% at 8 weeks (25% vs 5% [P = .031]) and at 16 weeks (46% vs 9% [P = .043]). There was a trend for amitriptyline to be superior to placebo at 12 and 20 weeks but this did not

reach significance. Conclusions.— In this study, using headache frequency as the primary metric, for the entire group, amitriptyline was superior to placebo in migraine prophylaxis at 8 weeks but, because of a robust placebo response, not at subsequent time points. For the subgroup with CDH, amitriptyline was statistically significantly superior to placebo at 8 weeks and 16 weeks with a similar but nonsignificant trend at 12 and 20 weeks. Compared with placebo amitriptyline is effective in CDH. Amitriptyline was also significantly effective in IM compared intragroup to its own baseline; however, placebo was equally effective in the same analysis. The reason for the robust placebo response in the IM group is not clear, but has been occasionally reported. “
“Objective.— To assess efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Background.— There are limited data from prospective controlled trials demonstrating the benefit of triptans in patients who experience migraine attacks while taking prophylactic medication. Methods.— This was a worldwide, randomized, placebo-controlled, double-blind, multiple-attack study in adults with a >1-year history of migraine taking a stable dose of topiramate for migraine prophylaxis and experiencing

≥2 moderate/severe attacks per month. Participants treated 3 moderate/severe D-malate dehydrogenase attacks in crossover fashion (2 with rizatriptan 10-mg ODT, 1 with placebo) following random assignment to 1 of 3 treatment sequences. The primary end point was 2-hour pain relief. Results.— Two-hour pain relief was significantly greater with rizatriptan compared with placebo (55.0% vs 17.4%, P < .001). Response rates also favored rizatriptan for sustained pain relief from 2-24 hours (32.6% vs 11.1%, P < .001), 2-hour pain freedom (36.0% vs 6.5%, P < .001), normal functional ability at 2 hours (42.2% vs 12.7%, P < .001), and overall treatment satisfaction at 24 hours (60.8% vs 33.6%, P < .001). Few participants reported adverse experiences (16 [15.