Antimigraine efficacy of telcagepant based on patient's historical triptan response

(Headache 2011;51:64‐72) Objective.— To evaluate whether the same or different patients respond to triptans and telcagepant. Background.— Telcagepant is an oral calcitonin gene‐related peptide receptor antagonist with acute antimigraine efficacy comparable to oral triptans. It is currently unknown whether migraine patients who cannot be adequately helped with triptans might benefit from treatment with telcagepant. Methods.— Post‐hoc analysis of data from a randomized, controlled trial of telcagepant (150 mg, 300 mg) zolmitriptan 5 mg, or placebo for a moderate/severe migraine. Responder rates were analyzed according to patients' self‐reported historical triptan response (HTR): (1) good HTR (N = 660): response in 75‐100% of attacks; (2) intermediate HTR (N = 248): response in 25‐74% of attacks; (3) poor HTR/no use (N = 407): response in <25% of attacks, or patient did not take triptans. A limitation of the analysis is that the last subgroup comprised mainly (91%) patients who reported that they did not take triptans, but it was not known whether these patients were triptan‐naïve or had previously used triptans and stopped taking them. Results.— For zolmitriptan, 2‐hour pain relief rates were higher in the good HTR subgroup (116/162, 72%) than in the intermediate (29/62, 47%) and poor/no use (44/111, 40%) HTR subgroups. The 2‐hour pain relief rates were similar across HTR subgroups for telcagepant 150 mg (48‐58%), 300 mg (52‐58%), and placebo (26‐31%). In the poor/no use HTR subgroup, more patients receiving telcagepant 300 mg (56/98, 57.1%) had 2‐hour pain relief than those receiving zolmitriptan (44/111, 39.6%; odds ratio = 2.11 [95% CI: 1.20,3.71], P = .009); the percentage for telcagepant 150 mg (57/119, 47.9%) was not significantly different from zolmitriptan (odds ratio = 1.41 [95% CI: 0.82, 2.40], P = .211). Conclusions.— This suggests that different patients may respond to triptans or telcagepant 300 mg. Caution should be exercised in interpreting the results because of the post‐hoc nature of the analysis (clinical trial registry: NCT00442936).     

Randomized, controlled study of telcagepant in patients with migraine and coronary artery disease

Objective.— To evaluate the efficacy of telcagepant in patients with migraine and coronary artery disease. Background.— Calcitonin gene‐related peptide receptor antagonists, such as telcagepant, may be useful for acute migraine treatment in patients with cardiovascular disease, a population for whom triptans are contraindicated. Methods.— Randomized, double‐blind, two‐period (6 weeks per period) crossover study in patients with stable coronary artery disease and migraine. Patients were randomized 1:1 to either: (1) Period 1: telcagepant (280‐mg tablet/300‐mg capsule), Period 2: acetaminophen (1000‐mg); or (2) Period 1: placebo for attack 1 then acetaminophen for subsequent attacks, Period 2: telcagepant. Patients could treat up to 12 migraine attacks per period to assess the tolerability of telcagepant. The primary efficacy analysis evaluated telcagepant vs placebo on 2‐hour pain freedom during the first attack of Period 1. Results.— One hundred and sixty‐five of the planned 400 patients were enrolled, and 114 took at least one dose of treatment. Telcagepant was not statistically different from placebo for 2‐hour pain freedom (25.0% vs 18.9%, odds ratio = 1.62 [95% confidence interval: 0.62, 4.25]). The median number of attacks treated per period was 3. No cardiovascular thrombotic adverse events occurred within 14 days of dosing. Conclusion.— The study was underpowered due to enrollment difficulties and did not demonstrate a significant efficacy difference between telcagepant and placebo for the treatment of a migraine attack in patients with stable coronary artery disease. Telcagepant was generally well tolerated for acute intermittent migraine treatment in these patients.     

Association of Musculoskeletal Pain With Sedentary Behavior in Public School Teachers: The Role of Habitual Physical Activity

BackgroundSedentary behavior has been associated with musculoskeletal pain in school teachers. However, our hypothesis is that physical activity practice could mitigate this association.AimThe aim of this study was to investigate the relationship of musculoskeletal pain with high screen-based sedentary behavior among public school teachers and whether physical activity could mitigate this relationship.MethodA sample of 246 teachers from 13 public schools were assessed (45.0 ± 10.4 years, 76.0% of women). Musculoskeletal pain was assessed using the Nordic Musculoskeletal Questionnaire, screen-based sedentary behavior was measured considering the sum of screen time in television, computer, and smartphone/tablet, and physical activity using the Baecke habitual physical activity questionnaire. Binary logistic regression was used to verify the associations between high screen-based sedentary behavior and musculoskeletal pain in school teachers (Model 1-unadjusted; Model 2-adjusted by age, sex, and socioeconomic status; Model 3-variables of Model 2 + adjusted by physical activity).ResultsHigh screen-based sedentary behavior was associated with pain in neck (odds ratio = 2.09; 95%confidence interval = 1.08-4.04), upper back (odds ratio = 2.21; 95%confidence interval = 1.07-4.56), and low back (odds ratio = 1.91; 95%confidence interval = 1.00-3.65). However, after inserting the variables, including physical activity, these associations were mitigated.ConclusionsHigh screen-based sedentary behavior was associated with musculoskeletal pain in public school teachers. However, this relationship was mitigated after the inclusion of confounding variables, including physical activity.     

Use of Endoscopic Ultrasound to Evaluate Large Gastric Folds: Features Predictive of Malignancy

The aim of this study was to investigate with endoscopic ultrasound (EUS) the features of the gastric wall that can be used to predict malignant disease in patients with large gastric folds. We retrospectively reviewed the EUS findings of 65 patients (26 with benign and 39 with malignant disease) with large gastric folds on endoscopy and EUS and analyzed the predictors of malignant disease (e.g., gastric wall thickness, preservation of five-layered structure, thickened layers). Gastric wall thickness (≥9.8 mm), thickened deep layer, thickened muscularis propria and non-preserved wall layer structures were significantly more prevalent in patients with malignant disease on EUS. Among them, gastric wall thickness (≥9.8 mm) (odds ratio = 6.72, 95% confidence interval = 1.23–36.73, p = 0.028) and thickened muscularis propria (odds ratio = 37.14, 95% confidence interval = 7.02–196.49, p < 0.001) were significantly associated with malignant disease. Our data indicate that EUS is a useful tool for assessing large gastric folds and that gastric wall thickness (≥9.8 mm) and thickened muscularis propria are significant features predictive of malignant disease on EUS.     

Effects of Parity and Breastfeeding Duration on Bone Density in Postmenopausal Women

PurposeThis study aimed to identify the effect of parity and breastfeeding duration and the occurrence of lumbar vertebral and femoral neck osteoporosis in Korean postmenopausal women.MethodsThis study analyzed the data of 1,770 women based on the 2010–2011 results of the Korea National Health and Nutrition Examination Survey. Extracted data concerning bone density included variables known to be associated with osteoporosis. Complex sample multivariate logistic regression analysis was conducted to determine whether parity and breastfeeding duration were associated with osteoporosis in postmenopausal women.ResultsParity was not associated with postmenopausal osteoporosis in the femoral neck or lumbar vertebrae; however, the risk of femoral neck osteopenia was significantly higher in women with a history of 12–24 months of breastfeeding than in women who breastfed for less than 12 months (odds ratio = 2.12, 95% confidence interval = 1.07–4.21). In women who breastfed for 24 months or longer, the risk of lumbar vertebral osteoporosis was significantly higher than in those who breastfed for less than 12 months (odds ratio = 2.73, 95% confidence interval = 1.18–6.32).ConclusionBreastfeeding duration may affect the occurrence of lumbar vertebral or femoral neck osteopenia or osteoporosis. Therefore, women who breastfeed for one year or more require education on the risk of bone loss and the need for preventive measures such as adequate calcium intake and physical exercise.     

Effect of telcagepant on spontaneous ischemia in cardiovascular patients in a randomized study

(Headache 2011;51:954‐960) Objective.— The primary purpose of the study was to explore the safety and tolerability of telcagepant in patients with stable coronary artery disease. Background.— Triptans are effective acute anti‐migraine drugs whose vasoconstrictive effects limit their use in patients at risk for adverse cardiovascular events. Telcagepant, a calcitonin gene‐related peptide receptor antagonist, is being developed for the acute treatment of migraine. Antagonism of calcitonin gene‐related peptide, which does not appear to cause vasoconstriction, may allow for treatment of migraine in patients with coronary artery disease. Methods.— In this randomized, double‐blind, placebo‐controlled, crossover study, patients with documented stable coronary artery disease were assigned to 1 of 2 treatment sequences: telcagepant then placebo, or placebo then telcagepant. In each treatment period, patients received 2 doses of telcagepant 300 mg or placebo 2 hours apart. They remained in the research center for 24 hours after receiving the first dose of each period, during which time continuous 12‐lead ambulatory electrocardiographic (Holter) monitoring was performed. Results.— Twenty‐eight patients were enrolled; all patients completed the study and were included in all analyses. Telcagepant was generally well tolerated. No laboratory or serious adverse experiences were reported, and no patient discontinued due to an adverse experience. There were no consistent treatment‐related changes in laboratory, vital signs or electrocardiogram safety parameters. Three patients (2 after receiving placebo and 1 after receiving telcagepant) experienced ST segment depression during the study; none of these patients reported chest pain. Conclusions.— Two doses of 300‐mg telcagepant, administered 2 hours apart, did not appear to exacerbate spontaneous ischemia and were generally well tolerated in a small cohort of patients with stable coronary artery disease. Results of this study support further evaluation of telcagepant in patients with stable coronary artery disease.     

Excellent tolerability but relatively low initial clinical efficacy of telcagepant in migraine

In 3 randomized clinical trials (n = 1585) the calcitonin gene-related peptide antagonist telcagepant 300 mg orally had an incidence of adverse events similar to placebo when used in the acute treatment of migraine. Telcagepant, thus, has excellent tolerability in migraine. Only a quarter (26%) (334/1307) of patients were, however, pain free after 2 hours, while 56% (729/1297) of patients had pain relief at 2 hours. Telcagepant 300 mg in one randomized clinical trial was equipotent to zolmitriptan 5 mg. Based on results from a meta-analysis, rizatriptan 10 mg (41%) and almotriptan (35%) seem superior to telcagepant (26%) for pain free at 2 hours whereas rizatriptan 10 mg (25%) showed no difference from telcagepant 300 mg (19 %) for sustained pain free (2-24 hours). The introduction of calcitonin gene-related peptide receptor antagonism in the acute treatment of migraine is a major step forward but so far mostly because of its specific mode of action and excellent tolerability.     

Meta‐Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

(Headache 2010;50:808‐818) Objective.— To assess the efficacy and safety of naproxen sodium in the treatment of acute migraine attacks. Background.— Non‐steroidal anti‐inflammatory drugs including naproxen sodium have been used in treating migraine attack. A number of clinical trials of naproxen sodium in migraine have been reported. However, it remains to be established whether naproxen sodium unequivocally offers clinical benefits taken into account the desired outcomes in acute migraine therapy as recommended by the International Headache Society. Methods.— Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to June 2009 and historical searches of relevant articles. Studies were included in the meta‐analysis if they were (1) double‐blind, randomized, placebo‐controlled trials that evaluated naproxen sodium tablet in moderate or severe migraine attacks in adult patients, and (2) reporting the efficacy in terms of headache relief, pain‐free, relief of migraine‐associated symptoms, sustained headache relief, sustained pain‐free, or headache recurrence. Data extraction and study quality assessment were performed independently by 2 investigators. Disagreements were resolved by a third investigator. Treatment effects and adverse effects were expressed as risk ratio. A random effects model was used when significant heterogeneity existed, otherwise the fixed effects model was performed. Results.— We identified 16 published randomized controlled trials of naproxen in the treatment of migraine. Four trials met the inclusion criteria and were included in the meta‐analysis. Naproxen sodium was more effective than placebo in reducing pain intensity and providing pain‐free within 2 hours in adults with moderate or severe migraine attacks. The pooled risk ratios were 1.58 (95% confidence interval [CI] 1.41‐1.77, P < .00001), and 2.22 (95% CI 1.46‐3.37, P = .0002), respectively, for headache relief at 2 hours and pain‐free at 2 hours. It was also effective in achieving headache relief at 4 hours, relief of migraine‐associated symptoms, sustained headache relief, and sustained pain‐free responses. There was no significant difference in headache recurrence rate between naproxen sodium and placebo. The risk of any adverse event was greater with naproxen sodium than with placebo (pooled risk ratio 1.29, 95% CI 1.04‐1.60, P = .02). The adverse events commonly associated with naproxen sodium were nausea, dizziness, dyspepsia, and abdominal pain. Conclusions.— The available evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain‐free at 2 hours and improving migraine‐associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head‐to‐head clinical trials.     

The effectiveness of early prophylactic hypothermia in adult patients with traumatic brain injury: A systematic review and meta-analysis

ObjectivesPreviously published systematic reviews have explored the effects of therapeutic hypothermia on adult patients with traumatic brain injury (TBI). However, none explored the effect of early prophylactic hypothermia (within 6 h from injury to hypothermia induction). Animal studies indicated that early prophylactic hypothermia may reduce secondary injury and improve neurological outcomes. This systematic review aimed to investigate the effects of early prophylactic hypothermia on adult TBI regarding mortality, favourable outcomes, and complications.Data sourceWe searched electronic databases including Cochrane CENTRAL, PubMed, MEDLINE, CINAHL, EMBASE, Web of Science, OpenGrey, and ClinicalTrials.gov from inception to June 12, 2019. Manual search was conducted for additional information.Review methodsOnly randomised controlled trials were included. The Cochrane Collaboration Risk of Bias Tool was used to assess the quality of included studies. We extracted general demographic characteristics, the initiation timing, methods of cooling, duration, target temperature, rewarming rate, mortality, neurological outcomes, and complications.ResultsSix studies with a total of 1207 participants were included. Meta-analyses showed no significant difference in mortality and favourable outcomes (risk ratio = 1.11, 95% confidence interval = 0.90–1.37, P = 0.32; risk ratio = 1.03, 95% confidence interval = 0.91–1.16, P = 0.65, respectively). Similar results were found regarding different durations of hypothermia and different rewarming rates. Various complications were reported in the included studies. No statistical difference was found in three studies, while complications were reported to be significantly higher in the hypothermia group in the other three studies.ConclusionsThis review does not support the use of early prophylactic hypothermia (within 6 h after injury) as a neurological protection strategy in adult patients with TBI, irrespective of the short term or long term. No significant benefits were found regarding hypothermia with different rewarming rates. Owing to the limited number of studies, more randomised controlled trials with higher quality are required to establish true effects of early hypothermia in adult TBI.     

Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial

(Headache 2011;51:73‐84) Objective.— To evaluate the long‐term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.— Telcagepant is a calcitonin gene‐related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine. Methods.— Migraine patients were randomized 2:1 to double‐blind treatment with telcagepant 280/300 mg or rizatriptan 10 mg for an acute mild, moderate, or severe migraine. Patients could administer a second dose within 2‐24 hours for nonresponse or migraine recurrence. Patients could treat up to 8 attacks per month for up to 18 months. Safety assessments included spontaneous reports of adverse events and collection of vital signs, electrocardiograms, and laboratory assessments. The primary endpoint was the percentage of patients with ≥1 triptan‐related adverse events in the 14‐day period post dose. Results.— Of 1068 patients randomized, 641 (90%) patients treated ≥1 attack with telcagepant and 313 (88%) treated ≥1 attack with rizatriptan. A total of 19,820 attacks were treated with telcagepant (mean per patient = 31) and 10,981 with rizatriptan (mean per patient = 35). Fewer triptan‐related adverse events (difference: ?6.2%; 95% CI ?10.4, ?2.6; P < .001) and drug‐related adverse events (difference: ?15.6%; 95% CI ?22.2, ?9.0) were reported for telcagepant vs rizatriptan. The most common adverse events appeared to have generally similar incidence proportions between the treatment groups. Those with an incidence >5% in the telcagepant group were dry mouth (9.7%, rizatriptan = 13.7%), somnolence (9.2%, rizatriptan = 16.6%), dizziness (8.9%, rizatriptan = 10.2%), and nausea (9.0%, rizatriptan = 6.4%). Conclusions.— Telcagepant was generally well tolerated when administered for the acute intermittent treatment of migraine for up to 18 months. The incidences of triptan‐related and drug‐related adverse events favored telcagepant over rizatriptan.     

Rizatriptan for treatment of acute migraine in patients taking topiramate for migraine prophylaxis

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 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 [15.8%] with rizatriptan, 3 [3.2%] with placebo); none were serious. Conclusion.— Rizatriptan 10‐mg ODT was superior to placebo at all pain end points for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Rizatriptan was generally well tolerated in this population. These results are comparable with those from clinical trials in patients not using prophylaxis, suggesting that the use of topiramate does not affect the efficacy or tolerability of rizatriptan for acute migraine treatment.     

MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine

(Headache 2011;51:507‐517) Objective.— To evaluate the efficacy and tolerability of MAP0004 compared with placebo for a single migraine in adult migraineurs: The FREEDOM‐301 Study. Background.— Acute treatment of migraine remains a clinical challenge despite the availability of triptans and other agents. Injectable dihydroergotamine, although effective, is considered invasive and inconvenient, and intranasal dihydroergotamine is associated with inconsistent systemic dosage delivery. MAP0004 is an orally inhaled formulation of dihydroergotamine delivered to the systemic circulation. In a phase 2 study, MAP0004 provided significant early onset of pain relief (10 minutes, P < .05) and sustained pain relief for up to 48 hours with a favorable adverse event profile. Methods.— A phase 3, randomized, double‐blind, placebo‐controlled, parallel‐group, single‐attack, outpatient study of MAP0004, an inhaled dihydroergotamine was conducted at 102 sites in 903 adults with a history of episodic migraine. Patients were randomized (1:1) to receive MAP0004 (0.63 mg emitted dose; 1.0 mg nominal dose) or placebo, administered after onset of a migraine headache with moderate to severe pain. The co‐primary endpoints were patient‐assessed pain relief and absence of photophobia, phonophobia, and nausea at 2 hours after treatment. Results.— A total of 903 patients (450 active, 453 placebo) were randomized, and 792 (395 active, 397 placebo) experienced a qualifying migraine. MAP0004 was superior to placebo in all 4 co‐primary endpoints: pain relief (58.7% vs 34.5%, P < .0001), phonophobia free (52.9% vs 33.8%, P < .0001), photophobia free (46.6% vs 27.2%, P < .0001), and nausea free (67.1% vs 58.7%, P = .0210). Additionally, significantly more patients were pain‐free at 2 hours following treatment with MAP0004 than with placebo (28.4% vs 10.1%, P < .0001). MAP0004 was well tolerated; no drug‐related serious adverse events occurred. Conclusions.— In this study, MAP0004 was effective and well tolerated for the acute treatment of migraine with or without aura, providing statistically significant pain relief and freedom from photophobia, phonophobia, and nausea in adults with migraine compared with placebo.     

The Impact of COVID-19 Surge on Clinical Palliative Care: A Descriptive Study From a New York Hospital System

ContextIn spring 2020, New York experienced a surge of patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) disease, as part of a global pandemic. There are limited data on populations of COVID-19–infected patients seen by palliative care services.ObjectiveTo describe a palliative care population at one New York hospital system during the initial pandemic surge.MethodsThis repeated cross-sectional, observational study collected data on palliative care patients in a large health system seen during the COVID-19 outbreak and compared it with pre-COVID data.ResultsPalliative service volume surged from 678 (4% of total admissions) before COVID-19 to 1071 (10% of total admissions) during the COVID-19 outbreak. During the outbreak, 695 (64.9%) of the total palliative patients tested positive for the virus. Compared with a preoutbreak group, this COVID-19–positive group had higher rates of male (60.7% vs. 48.6%, P < 0.01) and Latino (21.3% vs. 13.3%; P < 0.01) patients and less white patients (21.3% vs. 13.3%; P < 0.01). Our patients with COVID-19 also had greater prevalence of obesity and diabetes and lower rates of end-stage organ disease and cancers. The COVID-19–positive group had a higher rate of intensive care unit admissions (58.9% vs. 33.9%; P < 0.01) and in-hospital mortality rate (57.4% vs. 13.1%; P < 0.01) than the preoutbreak group. There was increased odds of mortality in palliative care patients who were COVID-19 positive (odds ratio = 3.21; 95% confidence interval = 2.43–4.24) and those admitted to the intensive care unit (odds ratio = 1.45; 95% confidence interval = 1.11–1.9).ConclusionDuring the initial surge of the COVID-19 pandemic in New York, palliative care services experienced a large surge of patients who tended to be healthier at baseline and more acutely ill at the time of admission than pre–COVID-19 palliative patients.     

Randomized controlled study of telcagepant plus Ibuprofen or acetaminophen in migraine

(Headache 2011;51:533‐543) Objective.— To evaluate the efficacy and tolerability of telcagepant when co‐administered with ibuprofen or acetaminophen for the acute treatment of migraine. Background.— Telcagepant is an oral calcitonin gene‐related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy. Methods.— Randomized, double‐blind, placebo‐controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N = 170), or placebo (N = 171). The primary efficacy endpoint was 2‐hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests. Results.— The percentages of patients with 2‐hour pain freedom were greater in each active treatment group compared to placebo (P < .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor. Conclusions.— The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).     

The Effect of the Pain Symptom Cluster on Performance in Women Diagnosed with Advanced Breast Cancer: The Mediating Role of the Psychoneurological Symptom Cluster

Background: Pain, depression, anxiety, sleep disturbances, and constipation were reported in different symptom clusters at different stages of breast cancer. Managing symptom clusters rather than individual symptoms can improve performance status. Aim: The study examined the effect of pain symptom cluster (pain and constipation) on performance when mediated by the psychoneurological symptom cluster (depression, anxiety, and sleep disturbances) using age as a moderator. Design: A secondary analysis. Settings: Palliative care center at a tertiary medical center in northeast Ohio. Participants: Eighty-six women diagnosed with advanced breast cancer. Method: A quantitative cross-sectional approach. Results: Ordinal logistic regression showed that pain symptom cluster did not have a significant mediation effect on performance. Odds ratio indicated that subjects with pain symptom cluster were 63% more likely to be bedridden (odds ratio = 1.63, confidence interval = .69-3.84). Women who reported pain symptom cluster were 5% more likely to have psychoneurological symptom cluster (odds ratio = 1.05, confidence interval = .400-2.774). Stratified analysis of age showed no differences in performance. Post-hoc analysis showed that the components of pain symptom cluster had a significant effect on psychoneurological symptom cluster (odds ratio: 3 [1.18-7.62]). Conclusions: Pain, constipation, depression, anxiety, and sleep disturbances were highly prevalent in women with advanced breast cancer. However, they tended to cluster in different symptom clusters. Although some findings were not significant, they all supported the direction of the tested hypotheses. Variations in symptom clusters research, including methodology, instruments, statistical tests, and chosen symptom cluster correlation coefficient, should be addressed.     

Migraine,inflammatory bowel disease and celiac disease: A Mendelian randomization study

Objective

To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.

Background

Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.

Methods

Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.

Results

Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction.

Conclusions

We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.     

Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium

Objective.— To review and analyze published reports on the acute treatment of migraine headache with triptans, dihydroergotamine (DHE), and magnesium in emergency department, urgent care, and headache clinic settings. Methods.— MEDLINE was searched using the terms “migraine” and “emergency,” and “therapy” or “treatment.” Reports from emergency department and urgent care settings that involved all routes of medication delivery were included. Reports from headache clinic settings were included only if medications were delivered by a parenteral route. Results.— Acute rescue treatment studies involving the triptans were available for injectable and nasal sumatriptan, as well as rizatriptan. Effectiveness varied widely, even when the pain‐free and pain‐relief statistics were evaluated separately. As these medications are known to work best early in the migraine, part of this variability may be attributed to the timing of triptan administration. Multiple studies compared triptans with anti‐emetics, dopamine antagonists, and non‐steroidal anti‐inflammatory drugs. The overall percentage of patients with pain relief after taking sumatriptan was roughly equivalent to that recorded with droperidol and prochlorperazine. Sumatriptan was equivalent to DHE when only paired comparisons were performed. While the data extracted suggest that magnesium may be effective in treating all symptoms in patients experiencing migraine with aura across all migraine patients, its effectiveness seems to be limited to treating only photophobia and phonophobia. Conclusions.— Although there are relatively few studies involving health‐care provider‐administered triptans or DHE for acute rescue, they appear to be equivalent to the dopamine antagonists for migraine pain relief. The relatively rare inclusion of a placebo arm and the frequent use of combination medications in active treatment arms complicate the comparison of single agents with each other.     

Optimizing Lung Ultrasound: The Effect of Depth,Gain and Focal Position on Sonographic B-Lines

Ultrasonographic B-lines are artifacts present in alveolar-interstitial syndromes. We prospectively investigated optimal depth, gain, focal position and transducer type for B-line visualization and image quality. B-Lines were assessed at a single rib interspace with curvilinear and linear transducers. Video clips were acquired by changing parameters: depth (6, 12, 18 and 24 cm for curvilinear transducer, 4 and 8 cm for linear transducer), gain (10%, 50% and 90%) and focal position (at the pleural line or half the scanning depth). Clips were scored for B-lines and image quality. Five hundred sixteen clips were obtained and analyzed. The curvilinear transducer improved B-line visualization (63% vs. 37%, p < 0.0001), with higher image quality (3.52 ± 0.71 vs. 3.31 ± 0.86, p = 0.0047) compared with the linear transducer. B-Lines were better visualized at higher gains (curvilinear: gain of 50% vs. 10%, odds ratio = 7.04, 95% confidence interval: 4.03–12.3; gain of 90% vs. 10%, odds ratio = 9.48, 95% confidence interval: 5.28–17.0) and with the focal point at the pleural line (odds ratio = 1.64, 95% confidence interval: 1.02–2.63). Image quality was highest at 50% gain (p = 0.02) but decreased at 90% gain (p < 0.0001) and with the focal point at the pleural line (p < 0.0001). Image quality was highest at depths of 12–18 cm. B-Lines are best visualized using a curvilinear transducer with at least 50% gain and focal position at the pleural line. Gain less than 90% and image depth between 12 and 18 cm improve image quality.     

Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment

Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81–92% headache relief after 2 h. The intrinsic activity of a parenteral triptan, a 5HT_1B/1D receptor agonist, is thus higher than the maximum effect of the parenteral CGRP receptor antagonist olcegepant. For the orally bioavailable CGRP antagonist telcagepant 300 mg, the headache relief was only 55% in one phase III study. These results indicate that CGRP receptor antagonism results in success in the acute treatment of migraine in only a certain fraction of the patients.