[1, 2] The approval of the first HCV NS3/4A protease inhibitors (

[1, 2] The approval of the first HCV NS3/4A protease inhibitors (PIs), boceprevir and telaprevir, has established a new era of direct-acting antiviral (DAA) therapy for CHC.[3] Most importantly, the combination of a PI and Peg-IFN/RBV increases SVR rates in both treatment-naïve and previously treated patients with HCV genotype (G) 1 infection.[4] Furthermore, response-guided therapy (RGT) is possible with both of these PIs, which decreases treatment duration for many patients. These benefits have established PI-based triple therapy as the new standard of care for HCV G1 patients.[3, 9] Although boceprevir PLX4032 molecular weight and telaprevir

have efficacy advantages over Peg-IFNα-2a/RBV therapy, new issues include cost, an increased side-effect burden, potential for rapid emergence of resistance, potential for numerous drug-drug interactions and the inconvenience of thrice-daily dosing.[3] High rates of anemia were observed

in clinical trials of both telaprevir and boceprevir, and rash was prevalent in studies of telaprevir.[4] These adverse effects were associated with treatment discontinuation in clinical trials and have negative implications for patient acceptability and treatment compliance in practice.[4] Mericitabine is an investigational nucleoside analog polymerase inhibitor that terminates viral RNA chain elongation by inhibition of the HCV NS5B RNA GSK126 chemical structure Ibrutinib datasheet polymerase.[10] The active site of the NS5B polymerase is highly conserved across all HCV genotypes, offering the potential of broad cross-genotype activity.[11] This phase IIb clinical trial (PROPEL) was conducted to evaluate the efficacy and safety of mericitabine, together with standard doses of Peg-IFNα-2a (40 kD)/RBV for 8 or 12 weeks, followed by Peg-IFNα-2a/RBV for up to 40 weeks, in treatment-naïve patients infected with HCV G1 or G4. PROPEL, a phase IIb randomized, double-blind, active-controlled, parallel-group study, took place at 65 sites in North America, Europe, and Australia (http://www.clinicaltrials.gov. NCT00869661; funded

by F. Hoffmann-La Roche Ltd). The study was conducted in accord with the Declaration of Helsinki, the protocol was approved by all institutional review boards at participating sites, and each patient provided informed consent. Eligible participants were treatment-naïve males and females 18-65 years of age with HCV G1 or G4 infection of at least 6 months’ duration, serum HCV RNA level of at least 50,000 IU/mL, liver biopsy consistent with CHC within 24 calendar months of first dose (36 months for patients with cirrhosis or incomplete/transition to cirrhosis, fibrosis stage 3-4), and no concomitant infection with hepatitis A or B viruses or human immunodeficiency virus. (Further details on eligibility and exclusion criteria provided in the Supporting Information.

6 [1 4-9 3], Pc = 0 0242), but this correlation was abolished whe

6 [1.4-9.3], Pc = 0.0242), but this correlation was abolished when hepatocellular type of injury was included (n = 42). There were no differences in the distribution of demographic characteristics, clinical findings, laboratory findings, and outcome among DILI patients classified MAPK inhibitor by the presence of a mutant allele of SOD2 or GPX1 and the wild-type

genotype. However, among the cholestatic/mixed cases, the mean age (61 years [range, 18-83 years]) was significantly higher in cases homozygous for the SOD2 Ala allele (P = 0.037). The total number of risk alleles (SOD2 C and GPX1 T alleles) was determined for each DILI patient and compared with those of the controls (Table 5). The presence of two or more risk alleles (n = 100) was significantly more frequent in DILI patients than in controls (OR = 2.1 [1.4-3.0], EPZ-6438 Pc = 0.0006), suggesting that these alleles constitute a cumulative effect on DILI susceptibility. The presence of a single risk allele (n = 52) was more frequently found in the controls (OR = 0.5 [0.4-0.8], Pc = 0.0097). Extending the risk allele analysis to also include the GSTM1 and GSTT1 null alleles determined in an earlier study17 showed a significant

risk of DILI development in the presence of four or more risk alleles (OR = 3.1 [1.7-5.6], Pc = 0.0004, n = 146). To further examine the role of risk alleles in DILI development, risk allele distribution was determined in DILI patients classified by time (days) to DILI onset. When divided into three distinct “time to onset” groups (≤30 days, 31-60 days, and >60 days), a clear trend was noted whereby DILI patients with higher number of risk alleles displayed a significantly shorter time to onset (P = 0.019) (Fig. 1). Among the patients with a time to onset of 30 or fewer days, 62% contained two or more

risk alleles, and 38% contained one or no risk allele. As the time to onset increased to 31 to 60 days or more than 60 days, the frequency of patients with two or more risk alleles decreased to 47% and 39%, respectively. The role of oxidative stress in DILI development is still relatively undefined. In this study, we have looked at functional polymorphisms in SOD2 and GPX1 that both lead to enhanced H2O2 generation, to seek potential associations between enhanced ROS net levels and risk of DILI development. Sclareol We found that carriers of the SOD2 Ala/Ala (CC) genotype or the GPX1 Leu/Leu (TT) genotype were both at higher risk of developing cholestatic and mixed type of DILI, but not hepatocellular type of injury. This result is not in agreement with Huang and coworkers,5 who found that the SOD2 Ala/Ala and Ala/Val genotypes increased the risk of developing hepatocellular DILI. However, most (55%) of the Taiwanese cohort were anti-tuberculosis drug–induced DILI cases, whereas only 3% of our DILI cohort corresponded to this category.

Thus, it is instructive

to contrast the pathophysiologica

Thus, it is instructive

to contrast the pathophysiological features of biliary atresia with the normal programmed loss of entire biliary apparatus in sea lamprey larvae. Biliary atresia in human infants is characterized by the complete obstruction of bile flow as a result of the destruction or absence of all or a portion of the extrahepatic bile ducts.2–4 As HDAC phosphorylation part of the underlying disease process or as a result of biliary obstruction, concomitant injury and fibrosis of the intrahepatic bile ducts also occurs to a variable extent. The disorder occurs in 1 in 10,000 to 15,000 live births in the United States, and accounts for approximately one-third of cases of neonatal cholestatic jaundice. It is the most frequent cause of death from liver disease and accounts for about 50% of all liver transplants in children. There is some evidence for two forms of biliary atresia, a fetal or embryonic form

and a peri- or postnatal form. In infants with the less common fetal variant (∼10%-25% of cases) cholestasis with acholic stools is present from birth with no jaundice-free interval after resolution of normal physiological hyperbilirubinemia. At the time of exploratory laparotomy, little or none of Tamoxifen mouse the extrahepatic biliary structures can be found in the hepatic hilum, and there are often associated malformations such as the polysplenia syndrome and abdominal situs inversus. In contrast, in Acesulfame Potassium the postnatal form there is progressive inflammatory destruction of the extrahepatic biliary tract in a baby appearing healthy in the first weeks of life. Clinical features support the concept that in most cases injury to the biliary tract occurs after biliary morphogenesis usually after birth. In practice, differentiation of

these clinical forms on the basis of the onset of liver dysfunction and occurrence of congenital malformations is inexact. Indeed, a recent study showed that over half of patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth.5 The cause of biliary atresia is unknown. Several mechanisms have been proposed to account for the progressive obliteration of the extrahepatic biliary tree. There is no evidence that biliary atresia results from a failure in morphogenesis in the majority of affected infants or from an ischemic or toxic injury to the bile ducts. There is emerging, convincing evidence for initiation of the process probably in response to a common viral infection or unknown environmental factor in a genetically susceptible host. A dysregulated cellular, humoral, and innate immune response all seem to be involved based on studies in humans and a mouse model of the disease.

Average 1,467 people visited per monthly and the 48 people visite

Average 1,467 people visited per monthly and the 48 people visited per day. Between

number of visitiors and the cumulative number of registered post was showed a positive correlation. The site as most access path of visitors is blog.iseverance.com (41.6%), followed by naver (31.6%) and google. It is different from domestic leading search site. The buy JQ1 most search term in blog was found intestinal metaplasia (11.9%), followed by dizziness (7.8%), diverticulitis (6.4%). Conclusion: Personal blog can functionalize as a communication with digestive disease patients. The blog analysis provides information that title of ‘intestinal metaplasia’ on the health lecture in the future be helpful to patients. In range non-infringement of the personal information, long-term studies and larger data should be necessary in the future. Key Word(s): 1. Big data; 2. digestive blog Presenting Author: OSAMA ELGEMAABI Additional Authors: OMAYMA M SABIR, AHMED B ALI Corresponding Author: OSAMA ELGEMAABI Affiliations: Al Neelain University, Al Neelain University Objective: Portal Hypertension is a major problem in our Sudanese children, it is the second cause of Heamatemsis in our children after Gastritis,GERD,and Deudenitis, and it is mainly due to Extra Hepatic Portal find more Vein Obstruction and Chronic Liver

Disease due mainly to infections and hereditary diseases (1). Portal Hypertensive Gastropathy (PHG) is a macroscopic lesion well recognized in adults, although controversy still exists with regard to its incidence and the factors influencing its development (2). Gastritis has been associated with chronic liver disease,

mainly cirrhosis (3,4). Very few data are available in the pediatric age group for either PHG or gastritis (5). The objectives of this study were to determine the frequency of PHG and gastritis in Sudanese children with Portal hypertension and the factors associated with both conditions in these children. Methods: All patients younger than 15 years who referred to the pediatric endoscopy unit of Gafaar Ibn Oaf Specialized Children Hospital, Khartoum, Sudan and the endoscopy Hydroxychloroquine chemical structure unit of the Military Hospital, Omderman, Sudan, during the last 5 years who under went an upper GI endoscopy for various reasons, of those children with known or suspected Portal hypertension or who were found to have evidences of Portal hypertension during the procedure, during this period, were included in the study. Verbal informed consent was taken from the parents and the older children. Patients who had abnormal coagulation factors (Prothrombin time <50%, platelet count <50,000/mm3), and those for whom verbal informed consent was not obtained were excluded from the study. Upper gastrointestinal endoscopy was performed by the same Pediatric endoscopist and the adult Surgeon endoscopist,during the study period.

Objective — To evaluate the prevalence of migraine and its associ

Objective.— To evaluate the prevalence of migraine and its association with stress and unipolar psychiatric comorbidities among a cohort of African adults. Methods.— This was a cross-sectional epidemiologic study evaluating 2151 employed adults in sub-Saharan Africa.

A standardized VX-770 in vivo questionnaire was used to identify sociodemographic, headache, and lifestyle characteristics of participants. Migraine classification was based on the International Classification of Headache Disorders-2 diagnostic criteria. Depressive, anxiety, and stress symptoms were ascertained with the Patient Health Questionnaire and the Depression Anxiety Stress Scale, respectively. Multivariable logistic regression models were used to estimate adjusted odds ratio (OR) and

95% confidence intervals (CIs). Results.— A total of 9.8% (n = 212) of study participants fulfilled criteria for migraine (9.8%, 95% CI 8.6-11.1) with a higher frequency among women (14.3%, 95% CI 11.9-16.6) than men (6.9%, 95% CI 5.5-8.3). Similar to predominantly Caucasian migraine cohorts, sub-Saharan African migraineurs were more likely to be younger, have a lower education, and more likely to report a poor health status than non-migraineurs. However, in contrast with historical reports in predominantly Caucasian migraine cohorts, sub-Saharan African migraineurs were less likely to report smoking than non-migraineurs. Participants with selleck kinase inhibitor moderately severe depressive symptoms had over a 3-fold increased odds old of migraine (OR = 3.36, 95% CI 1.30-8.70) compared with those classified as having minimal or no depressive symptoms, and the odds of migraine increased with increasing severity of depressive symptoms (P trend < 0.001).

Similarly, those with mild, moderate, and severe anxiety symptoms had increased odds of migraine (OR = 2.28, 95% CI 1.24-4.21; OR = 1.77, 95% CI 0.93-3.35; and OR = 5.39, 95% CI 2.19-13.24, respectively). Finally, those with severe stress had a 3.57-fold increased odds of migraine (OR = 3.57, 95% CI 1.35-9.46). Conclusion.— Although historically it has been reported that migraine prevalence is greater in Caucasians than African Americans, our study demonstrates a high migraine prevalence among urban-dwelling Ethiopian adults (9.9%) that is comparable with what is typically reported in predominantly Caucasian cohorts. Further, among employed sub-Saharan African adults and similar to predominantly Caucasian populations, migraine is strongly associated with stress and unipolar psychiatric symptoms. The high burden of migraine and its association with stress and unipolar psychiatric symptoms in our study of well-educated and urban-dwelling African adults has important clinical and public health implications pending confirmation in other African populations. “
“(Headache 2011;51:262-271) Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society.

Results are presented as means ± standard error of the mean (SEM)

Results are presented as means ± standard error of the mean (SEM). Statistical comparisons were performed using one-way analysis of variance (ANOVA), or ANOVA on ranks with Tukey’s or Dunn’s posttest. P

< 0.05 was considered significant. First we confirmed that ARC protein is expressed endogenously in heart, but not liver-derived tissue e.g., murine and human liver by immunoblot7 (Fig. 1A). The therapeutic time window during lethal liver failure is limited; hence, we aimed to apply a protein-based therapy approach using the transduction domain of HIV-1 TAT.15 Earlier results demonstrated that intraperitoneally injection of the 120-kDa βgal protein, fused to the protein transduction domain derived from the HIV TAT domain, results in rapid delivery of biologically active fusion protein into mouse organs including the liver.16 Strong and rapid expression of TAT-ARC and TAT-βgal fusion proteins were detected in mouse liver lysates for 24 hours after single intraperitoneal injection (Fig. 1B) and subcellular fractions of cytoplasm and mitochondrial heavy membrane (data not shown). Of note, no adverse or toxic

effects related to TAT fusion protein transduction were evident as indicated by normal serum transaminase levels following TAT protein transduction (Fig. 2B). Hepatocytes are Apoptosis inhibitor highly susceptible to Fas-induced apoptosis.2 A prominent role of the Fas-FasL system has been reported in hepatic injury

from diverse insults, including viruses, autoimmunity, and transplant rejection.17, 18 To determine whether ARC protects from Fas-mediated ALF in vivo, mice were injected intravenously with Jo2 2 hours after pretreatment with TAT-ARC, TAT-βgal, or PBS intraperitoneally, respectively. Jo2 stimulation resulted in death of TAT-βgal or PBS-pretreated mice within 12 hours (Fig. 2A). This was associated with extensive hepatocellular damage, as indicated by a massive increase of serum HA 1077 transaminases (Fig. 2B). In contrast to the PBS or TAT-βgal cotreated group, all TAT-ARC-pretreated mice survived a lethal dose of Jo2 challenge without signs of liver injury showing normal serum transaminase levels (Fig. 2A-C). Notably, all mice survived Fas-mediated ALF even when TAT-ARC fusion protein was given 1 hour after Jo2 stimulation (Fig. 2A). The protective effect of ARC was already detectable macroscopically on liver appearance, with strong hemorrhagic changes in livers derived from Jo2−, and Jo2+ TAT βgal-treated mice, but normal liver structure in Jo2+ TAT-ARC treated and untreated control mice (Fig. 2C). Staining of liver sections by H&E and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay confirmed extensive hepatocyte apoptosis in mice treated with Jo2 and TAT-βgal or PBS, whereas TAT-ARC pretreated mice appeared unaffected (Fig. 2C).

An excess of subviral particles over infectious virions in plasma

An excess of subviral particles over infectious virions in plasma is common during viral infections. For instance, HBV surface antigen (HBsAg) circulates in the blood as nucleocapsid-free, envelope-containing subviral particles that

also outnumber HBV DNA–positive Dane particles by 1 × 103 to 1 × 105.36 Subviral, nucleocapsid-free particles, bearing the envelope glycoprotein, are also frequently found during dengue virus or tick-borne encephalitis virus Flavivirus infections.37, 38 Subviral particles appear to exert biologically relevant properties. For example, HBsAg inhibits TLR9-mediated activation and interferon-α production in plasmacytoid dendritic cells (DCs).39 Similarly, HCV LVPs interfere with Toll-like receptor 4–triggered maturation of DCs, inducing a shift in DC function that stimulates T helper 2 cells LY2157299 chemical structure instead of T helper 1 cells.40, 41 Recombinant

LVPs also fuse with liposomes in a fusion process leading to the coalescence of internal contents of TRL particles and liposomes.32 The presence of such high proportions of modified lipoproteins during hepatitis C may modify the physiologic functions of lipoprotein, particularly if they have membrane fusion property, and participate to some HCV-induced metabolic dysfunctions. We Alvelestat in vivo also observed the presence of low-density viral particles that did not contain detectable apoB. Because we could not quantify the envelope glycoproteins, and because the number of glycoproteins per particles is not known, the proportion of nucleocapsid-positive and -negative particles could not be estimated. Thus, it remains to be determined whether subviral, nucleocapsid-negative, and apoB-negative low-density particles, either resembling HCVcc or the recombinant glycoprotein subviral particles produced by Huh7 cells, are also produced in vivo. For four patients, such particles were the only low-density viral particles and they may also be present in unknown proportion in all patients. These particles could contribute to the high molar ratios of neutral lipid over apoB, assuming that they could be coimmunoprecipitated with apoB-positive LVPs; their presence would further increase the overall proportion of subviral particles.

It should click here be stressed, however, that for some patients, all HCV RNA are immunoprecipitated by anti-apoB antibody.8 In conclusion, the HCV circulating viral particle populations are complex and include several forms, such as apoB-positive and -negative as well as nucleocapsid-positive and -negative LVPs that may contribute in different extent to the pathophysiology of chronic hepatitis C. We acknowledge the contribution of the AniRA – Laboratoire L3/UMS platform of SFR Biosciences Gerland-Lyon Sud (UMS344/US8) for their help. We thank Patricia Barbot, Virobiotec, Center for Biological Resources, Hospices Civils de Lyon, and Claude Vieux for patient and sample management. We thank Vincenzo Vinzi (ESSEC, Cergy-Pontoise, F95000) for his help with statistical testing.

Exclusion reason was no IC at RY anastomosis in 10 patients, unre

Exclusion reason was no IC at RY anastomosis in 10 patients, unrecognizing RY in 4 patients, inaccessibility RY in 2 patients, absence of judge in 3 patients. Accuracy rate in total was 77.3% (58/75). Accuracy rate in TG group and in non TG group was 78.3%(9/12), 77.8%(49/63) respectively (P = 0.833). Insertion time was 39.7 min in correct group, 56.6 min in incorrect group (P = 0.023). Conclusion: In conclusion, accuracy rate of IC method in identifying

the afferent limb was 77%. Accuracy rate was no significance between in TG group and non learn more TG group. Insertion time in correct group was 17 min shorter than in incorrect group. Key Word(s): 1. double-balloon ERCP; 2. indigo carmine; 3. insertion time Presenting Author: WEN HSIN HUANG Additional Authors: CHUN FU TING, CHENG JU YU, CHI YING

YANG, CHENG YUAN PENG Corresponding Author: WEN-HSIN HUANG Affiliations: China Medical University Hospital, China Medical University Hospital, China Medical University Hospital, China Medical University Hospital Objective: Adenomas of the major duodenal papilla are not common. Surgical resection is usually performed as a definitive treatment. Endoscopic snare papillectomy (ESP) provides an endoscopic option. The aims of this study was to assess the technical feasibility, clinical outcome, and adverse events of ESP in comparison to surgical treatment of patients with adenomas of the major duodenal papilla. Methods: Between November 2004 and buy Tanespimycin June 2014, forty-five patients (24 men and 21 women; median age 65.66 ± 12.84 years, range 38–92 years) with adenomas of the major duodenal papilla at ERCP were retrospectively reviewed. Fifteen patients undergoing ESP (Group I) and fifteen patients undergoing surgical

resection (13 Whipple resection and 2 transduodenal local resection) (Group II) were enrolled in the study. Results: Except for tumor size (19.14 ± 6.88 mm in Group I and 32.47 ± 8.97 mm in Group II), there were no significant difference between two groups in clinical characteristics. ESP was technically feasible in 14 (93%) patients. Eleven of 15 (73%) patients were successfully treated with one tumor removal procedure. In Group selleckchem I, four uremic patients (27%) suffering from GI bleeding and bacteremia after tumor resection required blood transfusion and intravenous antibiotics therapy. One of 4 patients expired because of severe bacterial sepsis. In Group II, 7 patients (47%) had wound leakage, intra-abdominal abscess, and sepsis requiring drainage and antibiotics treatment. Two of 7 patients had septic shock and acute respiratory failure requiring endotracheal intubation. The duration time of hospitalization was 7.64 ± 4.41 days in Group I and 33.53 ± 20.03 days in Group II (P < 0.0001). In the duration of follow-up (46.7 ± 36.04 months), two (13%) residual adenoma were detected in the ESP group. Conclusion: Compared with surgery, ESP group had shorter hospital stay and fewer complications.

Health care providers should also pay attention to the possible a

Health care providers should also pay attention to the possible adverse effects of CAM or interactions between CAM and conventional medical treatments among headache and migraine patients.


“(Headache 2011;51:201-207) Background.— An association between the 677C>T polymorphism (rs1801133) in the methylenetetrahydrofolate reductase gene (MTHFR) and cluster headache is plausible, but has not been investigated. Objective.— To investigate this association among Caucasians. Methods.— Case–control study among 147 cluster headache patients and 599 population-based age- and gender-matched controls. Cluster headache was diagnosed ACP-196 purchase according to the criteria of the International Headache Society. Genotypes of the MTHFR 677C>T polymorphism were detected by restriction fragment length polymorphism analysis. We used logistic regression analysis to investigate the association between cluster headache and genotypes with additive, dominant, and recessive models. We considered a Bonferroni-corrected

P value <.004 as significant. Results.— Mean age at study entry among patients was 44.9 years (SD 11.4), of whom 76.2% were men. The genotype distribution among controls and patients was in Hardy–Weinberg equilibrium. The genotype and allele distribution did not differ between patients with any cluster headache and this website controls. We also did not find an association when assuming additive, dominant or recessive genetic models. When we looked at subgroups, the effect estimates suggested an increased risk for chronic cluster headache (dominant model: odds ratio = 2.82; 99.6% confidence interval = 0.72-11.07; P = .03). Conclusions.— Data from our case–control study do not indicate an association

between genotypes of the MTHFR 677C>T polymorphism and cluster headache overall. Subgroup analyses suggested that carriers of the MTHFR 677T allele may have an increased risk for chronic cluster headache. This may be regarded as hypothesis-generating and should be further investigated selleck chemicals llc in independent studies. “
“(Headache 2011;51:581-589) Background.— Migraine is associated with significant negative impact, including reduced quality of life, impaired functioning, and comorbid psychiatric disorders. However, the impact of migraine on university students is understudied, despite their high prevalence of migraine and psychiatric disorders and their frequent use in research studies. Objectives.— The aim of this cross-sectional study was to evaluate the impact of migraine among college students on quality of life, functional impairment, and comorbid psychiatric symptoms. Methods.— Three hundred and ninety-one students (76.73% female, mean age = 19.43 ± 2.

39, P < 0001), and moderate agreement between patient self-assig

39, P < .0001), and moderate agreement between patient self-assignment via selection of representative pictures and patient self-assignment via answering the written question (Kappa coefficient 0.43, P < .0001). For exploding headaches, there was weak agreement between physician diagnosis according to scripted questionnaire and patient

self-assignment via selection of representative pictures (Kappa coefficient 0.33, P < .0001), weak agreement between physician diagnosis according to scripted questionnaire and patient self-assignment via answering the written question (Kappa coefficient 0.35, P < .0001), and weak agreement between patient self-assignment U0126 ic50 via selection of representative pictures and patient self-assignment via answering the written question (Kappa coefficient 0.39, P < .0001). For ocular headaches, there was moderate agreement http://www.selleckchem.com/products/torin-1.html between physician diagnosis according to scripted questionnaire and patient self-assignment via selection of representative pictures (Kappa coefficient 0.42, P < .0001), weak agreement between physician diagnosis according to scripted questionnaire and patient self-assignment via answering the written question (Kappa coefficient 0.37, P < .0001), and moderate agreement between patient self-assignment via selection of representative

pictures and patient self-assignment via answering the written question (Kappa coefficient 0.57, P < .0001). Responses to migraine therapies vary substantially among patients. For example, when measuring response to prophylactic therapy as at least a 50% reduction in headache frequency, less than one-half of patients treating with a first-line therapy are responders.[4] Identification of clinical factors that predict a patient's likelihood of responding to a specific migraine therapy would transition the treatment of migraine from a process of trial-and-error to a this website process of individualized medicine, maximize patient outcomes, and

minimize patient exposure to the potential adverse events from medications to which they are unlikely to respond. Published reports have suggested that migraine pain directionality is predictive of a response to onabotulinumtoxin A therapy. Studies have found an association between headache pain directionality and response to onabotulinumtoxin A[3, 5, 8] and more recently to botulinum toxin B.[7] Headache pain directionality has been described as imploding (a vice-like pain and pressure squeezing in), exploding (pain and pressure pushing outward), or ocular (pain focused on the eye).[3, 7] However, methods for determination of headache pain directionality have not been standardized. A number of different methods for determining headache pain directionality have been described.