Postprandial facial rash in an infant.

ABSTRACT: This article describes an infant who developed a facial rash within minutes of eating certain foods. The rash resolved within 30 minutes. The patient was diagnosed with auriculotemporal syndrome or Frey syndrome, which is characterized by sweating or flushing in the preauricular area when the patient consumes certain foods, especially those that are acidic, sour, or spicy. Because most patients outgrow the syndrome, no treatment is needed.

The Efficacy, Safety, and Pharmacology of a Ghrelin O-Acyltransferase Inhibitor for the Treatment of Prader-Willi Syndrome.

CONTEXT: Acylated ghrelin (AG) stimulates appetite and is elevated compared to its unacylated (UAG) counterpart in Prader-Willi syndrome (PWS). GLWL-01 is a selective, reversible inhibitor of ghrelin O-acyltransferase (GOAT), the enzyme that converts UAG into AG. OBJECTIVE: This work aimed to assess the efficacy, pharmacokinetics, pharmacodynamics, and safety of GLWL-01 in the treatment of PWS patients. METHODS: A double-blind, placebo-controlled, phase 2 crossover study was conducted with 2 active treatment periods of 28 days in 19 patients (aged 16-65 years; body mass index (BMI) ≥ 28) with genetically confirmed PWS. The study took place in 7 hospital-based study centers in the United States and Canada. Patients received placebo or GLWL-01 (450 mg twice daily) orally after lead-in placebo and washout periods. The Hyperphagia Questionnaire for Clinical Trials and Caregiver Global Impression of Change were used to measure reductions in hyperphagia. Plasma concentrations of AG and UAG were evaluated as correlates. RESULTS: Treatment resulted in statistically significant differences compared to placebo in plasma AG (P = .0002), UAG (P = .0488), and AG/UAG (P = .0003). GLWL-01 did not statistically significantly reduce hyperphagia-related behavior or bring about changes in global clinical end points, as assessed by caregivers. Anthropometric and clinical parameters correlated with obesity did not statistically significantly change in response to treatment. Less than half of patients reported a treatment-emergent adverse event (TEAE). No deaths, serious adverse events, or severe TEAEs were reported. CONCLUSION: GLWL-01 is safe and well tolerated. Pharmacological parameters confirmed the inhibition of GOAT following administration of GLWL-01. Patients' eating behaviors, BMI, blood glucose, and total cholesterol, among other similar measures, were not modified.

Migrating a research data warehouse to a public cloud: challenges and opportunities.

OBJECTIVE: Clinical research data warehouses (RDWs) linked to genomic pipelines and open data archives are being created to support innovative, complex data-driven discoveries. The computing and storage needs of these research environments may quickly exceed the capacity of on-premises systems. New RDWs are migrating to cloud platforms for the scalability and flexibility needed to meet these challenges. We describe our experience in migrating a multi-institutional RDW to a public cloud. MATERIALS AND METHODS: This study is descriptive. Primary materials included internal and public presentations before and after the transition, analysis documents, and actual billing records. Findings were aggregated into topical categories. RESULTS: Eight categories of migration issues were identified. Unanticipated challenges included legacy system limitations; network, computing, and storage architectures that realize performance and cost benefits in the face of hyper-innovation, complex security reviews and approvals, and limited cloud consulting expertise. DISCUSSION: Cloud architectures enable previously unavailable capabilities, but numerous pitfalls can impede realizing the full benefits of a cloud environment. Rapid changes in cloud capabilities can quickly obsolete existing architectures and associated institutional policies. Touchpoints with on-premise networks and systems can add unforeseen complexity. Governance, resource management, and cost oversight are critical to allow rapid innovation while minimizing wasted resources and unnecessary costs. CONCLUSIONS: Migrating our RDW to the cloud has enabled capabilities and innovations that would not have been possible with an on-premises environment. Notwithstanding the challenges of managing cloud resources, the resulting RDW capabilities have been highly positive to our institution, research community, and partners.

The Emergency Medicine Specimen Bank: An Innovative Approach To Biobanking In Acute Care.

The Emergency Medicine Specimen Bank (EMSB) was developed to facilitate precision medicine in acute care. The EMSB is a biorepository of clinical health data and biospecimens collected from all adult English- or Spanish-speaking individuals who are able and willing to provide consent and are treated at the UCHealth-University of Colorado Hospital Emergency Department. The EMSB is the first acute care biobank that seeks to enroll all patients, with all conditions who present to the ED. Acute care biobanking presents many challenges that are unique to acute care settings such as providing informed consent in a uniquely stressful and fast-paced environment and collecting, processing, and storing samples for tens of thousands of patients per year. Here, we describe the process by which the EMSB overcame these challenges and was integrated into clinical workflow allowing for operation 24 hours a day, 7 days a week at a reasonable cost. Other institutions can implement this template, further increasing the power of biobanking research to inform treatment strategies and interventions for common and uncommon phenotypes in acute care settings.

Federated Aggregate Cohort Estimator (FACE): an easy to deploy, vendor neutral, multi-institutional cohort query architecture.

Cross-institutional data sharing for cohort discovery is critical to enabling future research. While particularly useful in rare diseases, the ability to target enrollment and to determine if an institution has a sufficient number of patients is valuable in all research, particularly in the initiation of projects and collaborations. An optimal technology solution would work with any source database with minimal resource investment for deployment and would meet all necessary security and confidentiality requirements of participating organizations. We describe a platform-neutral reference implementation to meet these requirements: the Federated Aggregate Cohort Estimator (FACE). FACE was developed and implemented through a collaboration of The University of Alabama at Birmingham (UAB), The Ohio State University (OSU), the University of Massachusetts Medical School (UMMS), and the Denver Health and Hospital Authority (DHHA) a clinical affiliate of the Colorado Clinical and Translational Sciences Institute. The reference implementation of FACE federated diverse SQL data sources and an i2b2 instance to estimate combined research subject availability from three institutions. It used easily-deployed virtual machines and addressed privacy and security concerns for data sharing.

A pre-marketing ALT signal predicts post-marketing liver safety.

Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT ≥ 3 times upper limits normal [× ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 ≥ 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT ≥ 3× ULN in treated versus placebo) was examined. An ALT signal of ≥ 1.2% was significantly associated with a post-marketing liver safety signal (p ≤ 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT ≥ 3× ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety.

Polychlorinated dibenzo(p)dioxin and furan (PCDD/F) congener profiles in cement kiln emissions and impacts.

Cement kilns are known to emit polychlorinated dibenzo(p)dioxins and furans (PCDD/Fs; "dioxins"), but estimates of the amounts and patterns of these emissions vary widely. These variations may stem from a combination of factors, including the design and operating conditions of the kiln, and the fuels and raw materials fed into the kiln. The goal of this study was to examine the patterns of dioxin emissions in a large set of stack-tests at two Portland cement kilns in Portugal that use a variety of fuels. A total of 152 stack-tests provided data on PCDD/F congener concentrations during which the kilns combusted a varied mix of fuels, including petroleum coke, coal, various "special" supplemental fuels, and refinery distillation ends, which are classified as hazardous wastes. The use of coal to fuel the kilns was found to generate significantly different emission-profiles relative to the use of petroleum coke, but the addition of hazardous wastes as a supplemental fuel did not significantly alter profiles. All of the kiln emission profiles were found to differ markedly from profiles in ambient air. However, the small absolute dioxin emission rates from the kilns suggested that kiln impacts would not be detectable via ambient air monitoring, even in rural settings.

Emissions of metals and polychlorinated dibenzo(p)dioxins and furans (PCDD/Fs) from Portland cement manufacturing plants: inter-kiln variability and dependence on fuel-types.

Emissions from Portland cement manufacturing facilities may increase health risks in nearby populations and are thus subject to stringent regulations. Direct testing of pollutant concentrations in exhaust gases provides the best basis for assessing the extent of these risks. However, these tests (i) are often conducted under stressed, rather than typical, operating conditions, (ii) may be limited in number and duration, and (iii) may be influenced by specific fuel-types and attributes of individual kilns. We report here on the results of more than 150 emissions-tests conducted of two kilns at a Portland cement manufacturing plant in Portugal. The tests measured various regulated metals and polychlorinated dibenzo(p)dioxins and furans (PCDD/Fs). Stack-gas concentrations of pollutants were found to be highly variable, with standard deviations on the order of mean values. Emission rates of many pollutants were higher when coal was used as the main kiln fuel (instead of petroleum coke). Use of various supplemental fuels, however, had little effect on stack emissions, and few statistically significant differences were observed when hazardous waste was included in the fuel mix. Significant differences in emissions for some pollutants were observed between the two kilns despite their similar designs and uses of similar fuels. All measured values were found to be within applicable regulatory limits.

Prevalence of deep vein thrombosis (DVT) in non-surgical patients at hospital admission.

Venous thromboembolism (VTE) is known as a common complication in surgical and non-surgical patients. We hypothesized that according to the underlying risk factors and the acute illness, the prevalence ofVTE in non-surgical patients admitted to hospital is widely underestimated. For three months each patient admitted to the department of internal medicine with an acute illness, but without known deep venous thrombosis (DVT) was investigated by ultrasound compression sonography. Patients' history, risk factors and extent of immobilisation were documented. In patients with newly detected DVT D-dimer and fibrinogen were measured as well as computer tomography scans performed. Follow-up investigations of the DVT population were performed at four weeks and three months. Six hundred seventeen patients (49.3% men) were included. In 16 patients (men = 7) a previously unknown thrombosis (2.6%) was detected, mainly in patients with acute cardio-pulmonary disease (56%) and the elderly (mean age 75.6 years). Eight patients had femoro-popliteal (50.0%), four a femoral (25.0%), and four a popliteal vein thrombosis (25.0%). Five had pulmonary embolism (31.3%). In patients with DVT D-dimer was 875 +/- 1,228 mg/l, fibrinogen 568 +/- 215 mg/dl and C-reactive-protein 58.54 +/- 73.65 mg/dl. One patient died from sepsis during hospitalisation, one died from sudden cardiac death at home. None of the other 14 surviving patients relapsed. The study shows a 2.6% risk for DVT in outpatients with acute illness admitted to the department of internal medicine. These data demonstrate the high risk of DVT is in non-surgical patients. Early prophylaxis has to be considered in internal medicine patients especially in the elderly.

Two double-blind, multicenter, randomized, placebo-controlled, single-dose studies of sumatriptan/naproxen sodium in the acute treatment of migraine: function, productivity, and satisfaction outcomes.

OBJECTIVE: To describe return to normal function, productivity, and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium, sumatriptan alone, naproxen sodium alone, or placebo. PATIENTS, DESIGN, AND SETTING: Patients in 2 identical, US, phase 3, randomized, double-blind, parallel-group, placebo-controlled, single-dose, multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium (85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation), sumatriptan, naproxen sodium, or placebo. MAIN OUTCOME MEASURES: Ability to function (not impaired, mildly impaired, severely impaired, or required bed rest) was collected in diary cards completed immediately prior to treatment, every 30 minutes for the first 2 hours, and hourly from 2 to 24 hours while awake. Patients completed the Productivity Assessment Questionnaire (PAQ) 24 hours after study drug administration. The Patient Perception of Migraine Questionnaire (PPMQ) was administered at screening and 24 hours post treatment to capture patient satisfaction. RESULTS: Compared with the other groups, the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing. They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies, and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications. CONCLUSIONS: Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly, and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups. Overall productivity loss was significantly reduced following use of sumatriptan/naproxen sodium.

Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies.

BACKGROUND: In a pilot study, naratriptan was significantly more effective than placebo in preventing menstrually related migraine (MRM) when given as 1 mg twice daily for 5 days beginning 2 days before the predicted onset of MRM for up to 4 menstrual cycles. OBJECTIVE: To evaluate the efficacy and tolerability of naratriptan for short-term prevention of MRM in 2 large, identically designed, randomized, double-blind, placebo-controlled, parallel-group studies. METHODS: MRM was defined as any migraine beginning during the perimenstrual period (PMP). By definition, the PMP consisted of Days -2, -1, 1, 2, 3, and 4, with Day 1 being the first day of menstrual flow. Adult women were eligible if they reported a history of MRM, had regular menstrual cycles, and could predict within 2 days both the onset of menstrual flow and MRM. The studies comprised a baseline phase and a treatment phase. During the baseline phase, patients prophylactically treated their first PMP after the screening visit with single-blind placebo. Patients who documented an MRM while receiving placebo were eligible for the treatment phase. During the treatment phase, patients were randomized to receive either naratriptan 1 mg twice daily or placebo beginning 3 days before the predicted onset of MRM for a total of 6 days for 4 PMPs or 6 months, whichever occurred sooner. The primary efficacy endpoint was the mean percentage of treated PMPs without MRM per patient. Secondary efficacy endpoints included the percentage of patients who were free of MRM during all treated PMPs, the median number of days with MRM over 4 PMPs, and patient satisfaction. Safety and tolerability measures included adverse events, standard clinical laboratory tests, and vital signs. RESULTS: The intent-to-treat population was 287 in Study 1 (149 in the naratriptan group and 138 in the placebo group) and 346 in Study 2 (173 in each treatment group). Approximately 20% of randomized patients in each treatment group in Study 1 and 10% in each treatment group in Study 2 withdrew prematurely from the studies over the 4-month treatment period. The mean percentage of PMPs without MRM per patient was 38% and 34% among naratriptan-treated patients treating at least 1 PMP compared with 29% and 24% among placebo-treated patients in each respective study (P < .05 naratriptan vs placebo for both studies). Efficacy of naratriptan did not vary as a function of age, use of oral contraceptives, or use of migraine prophylaxis. More patients who had received naratriptan reported attacks posttreatment compared to patients who had received placebo. Among patients treating at least 1 PMP, the percentage of patients with no MRM in any treated PMP was significantly (P < .05) higher in the naratriptan group (11%; 19/173) than the placebo group (3%; 6 of 173) in Study 2. There were no differences in the percentages of patients with no MRM in any treated PMP in Study 1. The number of MRM days per patient across 4 PMPs was significantly lower in the naratriptan group than in the placebo group in both studies (median 5.0 days vs 6.5 days in Study 1 [P= .005] and 5.3 days vs 6.0 days in Study 2 [P= .018]). Significantly more patients receiving naratriptan were satisfied with the ability of naratriptan to control MRM either by preventing their occurrence or reducing their severity or duration compared with patients receiving placebo. No single drug-related adverse event was reported by more than 2% of patients in a treatment group in either study, and no serious drug-related adverse events were reported. CONCLUSIONS: Naratriptan 1 mg twice daily for 6 days per month is effective and well tolerated when used for short-term prevention of MRM. More patients receiving naratriptan than placebo were satisfied with treatment. The observed increase in posttreatment attacks needs further study.

Open-label, long-term tolerability of naratriptan for short-term prevention of menstrually related migraine.

BACKGROUND: Although naratriptan is not approved for prophylactic use in migraine, naratriptan has been shown to be significantly more effective than placebo for short-term prevention of menstrually related migraine (MRM). The tolerability of naratriptan administered intermittently for prophylaxis for MRM over the long term has not been assessed. OBJECTIVE: To assess the tolerability of naratriptan 1 mg given twice daily for 6 days per month, administered for up to 1 year for short-term prevention of MRM in an open-label study. METHODS: Patients were eligible for the study if they were between 18 and 65 years of age and had at least a 1-year history of migraine, with or without aura, as defined by 1988 International Headache Society criteria; reported a history of MRM; and had at least 1 MRM attack during their last menstrual cycle. MRM was defined as any migraine beginning during the perimenstrual period (PMP). By definition, the PMP consisted of Days -2, -1, 1, 2, 3, and 4, with Day 1 being the first day of menstrual flow. During each menstrual cycle occurring over a 1-year period, patients began short-term treatment with naratriptan 1 mg twice daily (BID) 3 days before the expected onset of MRM and treated for a total of 6 days. Naratriptan 2.5 mg could be taken for breakthrough MRM attacks. Tolerability and safety measures included adverse events, standard clinical laboratory tests, electrocardiograms (ECGs), and vital signs. The secondary endpoints were the percentage of PMPs without MRM; headache disability as measured by the Headache Impact Test (HIT), and psychological health as measured by the Beck Depression Inventory version 2 (BDI-II). RESULTS: The number of patients who took at least 1 dose of study medication (safety population) was 457, and the numbers of patients completing 6 months and 12 months of treatment were 318 and 131, respectively. Note that 171 (37%) patients were asked to leave the study once target enrollment numbers were met. The only adverse event occurring at an incidence of more than 2% during the 6-day treatment periods when naratriptan 1 mg BID was taken with or without an additional 2.5-mg dose for breakthrough attacks was ear, nose, throat infection (3%). No specific adverse event considered at least possibly to be related to study medication occurred in more than 2% of patients. No serious drug-related adverse events were reported. Furthermore, no patient experienced clinically relevant drug-related changes in 12-lead ECGs, vital signs, or clinical laboratory tests. Patients in both the 6- and 12-month populations did not experience an MRM in approximately 50% of treated PMPs. Health outcomes results suggested that naratriptan reduced headache impact when used for up to 12 months for the short-term prevention of MRM. CONCLUSION: Naratriptan 1 mg BID, with the optional use of an additional 2.5-mg dose for breakthrough attacks, was well tolerated when used for 6 continuous days per month for up to 1 year for short-term prevention of MRM.

Sumatriptan/Naproxen sodium for migraine: efficacy, health related quality of life, and satisfaction outcomes.

OBJECTIVE: To describe the pain relief, satisfaction, and health-related quality of life results of moderate or severe migraines treated with a sumatriptan/naproxen sodium combination tablet. METHODS: Sumatriptan and naproxen sodium as a single-dose formulation tablet was used to treat moderate to severe migraines over a 12-month period in a phase 3, open-label, multicenter study (n = 565) in patients with at least 6 months' history of migraine headaches. RESULTS: Seventy percent of all attacks were treated with 1 dose of sumatriptan/naproxen sodium. Overall subjects treated 24,485 attacks; of these, 81% attacks achieved pain relief and 60% pain-free by 2 hours. At 3 months, the percentage of patients satisfied or very satisfied increased from baseline on all 8 Patient Perception of Migraine Questionnaire (PPMQ) items and remained high throughout the study. Mean Migraine-Specific Quality of Life Questionnaire (MSQ) domain scores also increased by 13-15 points from baseline during this time and remained high. CONCLUSIONS: Sumatriptan/naproxen sodium provides consistent relief of migraine attacks over 12 months, resulting in improved patient satisfaction and migraine specific quality of life.

Treatment of vertebral osteomyelitis by radical debridement and stabilization using titanium mesh cages.

STUDY DESIGN: A retrospective clinical and radiologic evaluation of patients with vertebral osteomyelitis treated via radical debridement and stabilization using titanium mesh cages. OBJECTIVE: To assess the efficacy of titanium mesh cages in the treatment of active vertebral osteomyelitis. SUMMARY OF BACKGROUND DATA: Although titanium mesh cages have proven to be superior in trauma and tumor reconstructions, there are few reports regarding the use of titanium mesh cages in the presence of active pyogenic or tuberculotic vertebral osteomyelitis. METHODS: A total of 88 cases with vertebral osteomyelitis were operated on between January 2000 and December 2002. There were 2 craniocervical, 13 cervical, 19 thoracic, 11 thoracolumbar, and 43 lumbar infections. The titanium mesh cages replaced 1 disc in 34 cases, 1 vertebral body in 28 cases, 2 vertebral bodies in 23 cases, and 3 vertebral bodies in 3 cases. RESULTS: All patients showed a solid bony fusion without any recurrence of infection at latest follow-up. Changes in pain score, Frankel's classification, and blood parameters demonstrated a significant clinical improvement in all patients. The sagittal profile was restored. CONCLUSIONS: The use of titanium mesh cages in the treatment of vertebral osteomyelitis effectively reconstructs the anterior column, while adding stability and restoring the sagittal profile. There is no increase in the rate of recurrence or persistence of infection related to the implantation of titanium mesh cages.

Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as "sinus' headache, while ignoring the possible diagnosis of migraine. OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients with migraine presenting with "sinus" headache. METHODS: A randomized, double-blind, placebo-controlled, multicenter study was conducted in adult (aged 18-65 years) migraine patients presenting with self-described or physician-diagnosed "sinus" headache. From November 2001 to March 2002, patients meeting International Headache Society criteria for migraine (with > or =2 of the following: unilateral location, pulsating quality, moderate or severe intensity, aggravation by moderate physical activity; and > or =1 of: phonophobia and phonophobia, nausea and/or vomiting) and with no evidence of bacterial rhinosinusitis were enrolled and randomized in a 1:1 ratio via computer-generated randomization schedule to receive either 1 sumatriptan 50-mg tablet or matching placebo tablet. The primary efficacy end point was headache response (moderate or severe headache pain reduced to mild or no headache pain) at 2 hours after administration. The presence or absence of migraine-associated symptoms and sinus and nasal symptoms was also measured. Tolerability was assessed through patient-reported adverse events (AEs). RESULTS: Two hundred sixteen patients with self-described or physician-diagnosed "sinus" headache received a migraine diagnosis and treated 1 migraine attack with sumatriptan 50 mg. The efficacy (intent-to-treat) analysis included 215 patients treated with sumatriptan 50 mg (n = 108; mean [SD] age, 39.6 [12.3] years; mean [SD] weight, 77.7 [17.7] kg; sex, 71% female; race, 69% white) or placebo (n = 107; mean [SD] age, 41.0 [11.3] years; mean [SD] weight 80.7 [20.9] kg; sex, 69% female; race, 64% white). Significantly more patients treated with sumatriptan 50 mg achieved a positive headache response at 2 and 4 hours after administration compared with those treated with placebo (69% vs 43% at 2 hours and 76% vs 49% at 4 hours, respectively; both, P < 0.001). Significantly more sumatriptan-treated patients were free from sinus pain compared with placebo recipients at 2 hours (63% vs 49% placebo, P = 0.049) and 4 hours (77% vs 55%, P = 0.001). All treatments were generally well tolerated. The most common drug-related AEs reported in the sumatriptan and placebo groups, respectively, were dizziness (5% vs < 1%), nausea (3% vs 2%), other pressure/tightness (defined as sense of heaviness; heaviness of upper body, upper extremities; jaw tension; neck tension) (4% vs 0%), and temperature sensations (defined as warm feeling of back of neck, or flushing) (2% vs 0%). No patients experienced any serious AEs. CONCLUSIONS: Sumatriptan 50-mg tablets were effective and generally well tolerated in the treatment of these patients presenting with migraine headaches that were self-described or physician-diagnosed as sinus headaches.

Efficacy and tolerability of sumatriptan injection for the treatment of morning migraine: two multicenter, prospective, randomized, double-blind, controlled studies in adults.

OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of sumatriptan injection in the treatment of morning migraine. METHODS: In 2 multicenter (20 sites for study 1 and 25 sites for study 2), randomized, double-blind, controlled, parallel-group studies, male and female patients aged 18 to 65 years with migraine meeting International Headache Society criteria received SC sumatriptan succinate injection 6 mg or inactive vehicle (control) for the outpatient treatment of a single morning migraine, defined as migraine with moderate or severe pain on awakening. The primary end point was the percentage of patients who achieved pain-free relief (moderate or severe pain reduced to no pain) at 2 hours after treatment. Tolerability was assessed using spontaneous reporting or noted by a clinician during the studies, assessed at the return visit. RESULTS: The efficacy analysis included, in the succinate group, 145 patients in study 1, 148 in study 2; control, 152 in study 1, 139 in study 2. The mean (SD) ages in the sumatriptan group were 40.2 (9.7) and 38.8 (10.1) years in studies 1 and 2, respectively; control, 41.4 (10.4) and 39.3 (9.7) years. The majority of patients in the 2 studies were female (sumatriptan, 84% and 93% in studies 1 and 2, respectively; control, 82% and 81%) and white (sumatriptan, 83% and 81%; control, 78% and 89%). Two hours after treatment, 48% and 57% of patients treated with sumatriptan injection compared with 18% and 19% of control patients reported pain-free relief in studies 1 and 2, respectively (both, P < 0.001). Two hours after treatment, 72% and 77% of patients treated with sumatriptan injection reported headache relief (moderate or severe pain reduced to mild or no pain) compared with 32% and 41% of control patients (both, P < 0.001). Onset of efficacy versus control (the first time point with statistical significance of pain relief) was observed beginning 10 minutes postdose (P < 0.05 sumatriptan injection vs placebo across pooled studies). Mean time to efficacy in the sumatriptan group was 10 minutes (P < 0.05 vs controls). The most commonly reported adverse events were nausea (sumatriptan, 6% and 4%; control, 2% and 2%) and injection-site reaction (ie, burning or stinging at the injection site) (sumatriptan, 5 % and 5%; control, 2% and 1%). Injection-site reaction was also the only adverse event considered treatment related and reported in > or =5 % of all patients. CONCLUSION: The results of these 2 randomized, double-blind, controlled studies suggest that sumatriptan injection was effective and well tolerated in the acute treatment of morning migraine in these adults.

A modified calculation of ankle-brachial pressure index is far more sensitive in the detection of peripheral arterial disease.

BACKGROUND: Ankle-brachial pressure index (ABI) is a simple, inexpensive, and useful tool in the detection of peripheral arterial occlusive disease (PAD). The current guidelines published by the American Heart Association define ABI as the quotient of the higher of the systolic blood pressures (SBPs) of the two ankle arteries of that limb (either the anterior tibial artery or the posterior tibial artery) and the higher of the two brachial SBPs of the upper limbs. We hypothesized that considering the lower of the two ankle arterial SBPs of a side as the numerator and the higher of the brachial SBPs as the denominator would increase its diagnostic yield. METHODS: The former method of eliciting ABI was termed as high ankle pressure (HAP) and the latter low ankle pressure (LAP). ABI was assessed in 216 subjects and calculated according to the HAP and the LAP method. ABI findings were confirmed by arterial duplex ultrasonography. A significant arterial stenosis was assumed if ABI was <0.9. RESULTS: LAP had a sensitivity of 0.89 and a specificity of 0.93. The HAP method had a sensitivity of 0.68 and a specificity of 0.99. McNemar's test to compare the results of both methods demonstrated a two-tailed P < .0001, indicating a highly significant difference between both measurement methods. CONCLUSIONS: LAP is the superior method of calculating ABI to identify PAD. This result is of great interest for epidemiologic studies applying ABI measurements to detect PAD and assessing patients' cardiovascular risk.

Prevalence of migraine and response to sumatriptan in patients self-reporting tension/stress headache.

OBJECTIVE: This study was conducted to evaluate the prevalence of migraine and its responsiveness to migraine-specific therapy in patients with self-reported tension-type headache. METHODS: Patients were adults (n = 423) consulting one of 54 North American study sites including primary care clinics, neurology clinics, and headache clinics. The study comprised an initial diagnosis phase to determine the headache diagnosis of patients entering the study with self-reported tension/stress headache, including that previously diagnosed by a health care provider. Patients reporting tension/stress headache were evaluated and diagnosed as having migraine with or without aura, probable migraine, tension-type headache, or another headache type. Exclusion criteria included prior diagnosis of migraine or probable migraine and the presence of headache for at least 15 days monthly during either of the 2 months before screening. The initial phase was followed by a randomized, double-blind treatment phase to evaluate the efficacy of sumatriptan 100 mg tablets for the treatment of a single migraine attack in those meeting International Headache Society (IHS) criteria for migraine during the diagnosis phase. RESULTS: Of 423 patients reporting tension/stress headache at study entry, 84% (n = 357) were diagnosed at the clinic visit as fulfilling IHS criteria for migraine without aura or migraine with aura, and 65% (n = 276) were diagnosed with migraine only (i.e., with no other concurrent headache diagnosis). Three hundred thirty-two (332) patients entered the double-blind treatment phase. Headache relief rates 2h post-dose, the primary efficacy endpoint, did not significantly differ between sumatriptan and placebo (p = 0.099). However, improvements were significantly (p < 0.05) greater with sumatriptan than placebo on several other headache-related efficacy measures. CONCLUSIONS: Migraine headache may go unrecognized in patients with self-reported tension headache. Among patients having self-reported tension headache and diagnosed with migraine during the study, response to acute treatment with sumatriptan was inconclusive. Improvement with sumatriptan versus placebo was observed for some measures and not for others. The results should be interpreted in the context of study limitations including use of patient self-reports to assess headache diagnosis and possible lack of representativeness arising from the predominantly white sample.

Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind, placebo-controlled, acute study.

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. BACKGROUND: Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P = .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. METHODS: This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with > or = 6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. RESULTS: Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P = .046) and 2 hours (68% vs. 58%; P = .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P = .087) or for sustained headache relief from 1 to 24 hours (P = .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). CONCLUSIONS: This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population.