Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial.

STUDY OBJECTIVE: More than 1 million patients present to US emergency departments (EDs) annually seeking care for acute migraine. Parenteral antihistamines have long been used in combination with antidopaminergics such as metoclopramide to treat acute migraine in the ED. High-quality data supporting this practice do not exist. We determine whether administration of diphenhydramine 50 mg intravenously+metoclopramide 10 mg intravenously results in greater rates of sustained headache relief than placebo+metoclopramide 10 mg intravenously. METHODS: This was a randomized, double-blind, clinical trial comparing 2 active treatments for acute migraine in an ED. Eligible patients were adults younger than 65 years presenting with an acute moderate or severe headache meeting International Classification of Headache Disorders-2 migraine criteria. Patients were stratified according to presence or absence of allergic symptoms. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining this level of relief without use of any additional headache medication for 48 hours. Secondary efficacy outcomes included mean improvement on a 0 to 10 verbal scale between baseline and 1 hour, the frequency with which subjects indicated they would want the same medication the next time they present to the ED with migraine, and the ED throughput time. Sample size calculation using a 2-sided α of .05, a ß of .20, and a 15% difference between study arms determined the need for 374 patients. An interim analysis was conducted when data were available for 200 subjects. RESULTS: Four hundred twenty patients were approached for participation. Two hundred eight eligible patients consented to participate and were randomized. At the planned interim analysis, the data and safety monitoring board recommended that the study be halted for futility. Baseline characteristics were comparable between the groups. Fourteen percent (29/208) of the sample reported allergic symptoms. Of patients randomized to diphenhydramine, 40% (40/100) reported sustained relief at 48 hours, as did 37% (38/103) of patients randomized to placebo (95% confidence interval [CI] for difference of 3%: -10% to 16%). One hour after medication administration, patients randomized to diphenhydramine improved by a mean of 5.1 on the 0 to 10 scale versus 4.8 for those randomized to placebo (95% CI for difference of 0.3: -0.6 to 1.1). Eighty-five percent (84/99) of the patients in the diphenhydramine arm reported they would want the same medication combination during a subsequent ED visit, as did 76% (77/102) of those who received placebo (95% CI for difference of 9%: -2% to 20%). Median ED length of stay was 122 minutes (interquartile range 84 to 180 minutes) in the diphenhydramine group and 139 minutes (interquartile range 90 to 235 minutes) in the placebo arm. Rates of adverse effects, including akathisia, were comparable between the groups. CONCLUSION: Intravenous diphenhydramine, when administered as adjuvant therapy with metoclopramide, does not improve migraine outcomes.

Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas.

Treatment of Epstein-Barr virus (EBV)-related lymphomas with lytic-inducing agents is an attractive targeted approach for eliminating virus-infected tumor cells. Zidovudine (AZT) is an excellent substrate for EBV-thymidine kinase: it can induce EBV lytic gene expression and apoptosis in primary EBV+ lymphoma cell lines. We hypothesized that the combination of AZT with lytic-inducing chemotherapy agents would be effective in treating EBV+ lymphomas. We report a retrospective analysis of 19 patients with aggressive EBV+ non-Hodgkin lymphoma, including nine cases of acquired immune deficiency syndrome-associated primary central nervous system lymphoma (AIDS-PCNSL) treated with AZT-based chemotherapy. Our results demonstrate that high-dose AZT-methotrexate is efficacious in treating highly aggressive systemic EBV+ lymphomas in the upfront setting. In primary EBV+ lymphoma cell lines, the combination of AZT with hydroxyurea resulted in synergistic EBV lytic induction and cell death. Further, AZT-hydroxyurea treatment resulted in dramatic responses in patients with AIDS-PCNSL. The combination of AZT with chemotherapy, especially lytic-inducing agents, should be explored further in clinical trials for the treatment of EBV-related lymphomas.

Disparities in access to over-the-counter nicotine replacement products in New York City pharmacies.

OBJECTIVES: We surveyed the availability of tobacco products and nonprescription nicotine replacement therapy (NRT) in pharmacies in New York City, stratified by the race, ethnicity, and socioeconomic status (SES) of the surrounding neighborhoods to determine whether disparities in availability existed. METHODS: Surveyors visited a random sample of retail pharmacies to record the availability of tobacco products and nonprescription NRT. We used census data and geographic information systems analysis to determine the SES of each neighborhood. We used logistic modeling to explore relations between SES and the availability of NRT and tobacco products. RESULTS: Of 646 pharmacies sampled, 90.8% sold NRT and 46.9% sold cigarettes. NRT and cigarettes were slightly more available in pharmacies in neighborhoods with a higher SES. NRT was more expensive in poorer neighborhoods. CONCLUSIONS: Small disparities existed in access to nonprescription NRT and cigarettes. The model did not adequately account for cigarette access, because of availability from other retail outlets. These results may explain some of the excess prevalence of cigarette use in low-SES areas.

Efficacy of a brief intervention to improve emergency physicians' smoking cessation counseling skills, knowledge, and attitudes.

The objective of this study was to test whether a brief educational/administrative intervention could increase tobacco counseling by emergency physicians (EPs). Pre-/post-study at eight emergency departments (EDs) with residency programs were carried out. EPs received a 1-hour lecture on the health effects of smoking and strategies to counsel patients. After the lecture, cards promoting a national smokers' quitline were placed in EDs, to be distributed by providers. Providers completed pre-/ post-intervention questionnaires. Patients were interviewed pre-/post-intervention to assess provider behavior. Two hundred eighty-seven EPs were enrolled. Post-intervention, providers were more likely to consider tobacco counseling part of their role, and felt more confident in counseling. Data from 1168 patient interviews and chart reviews showed that, post-intervention, providers were more likely to ask patients about smoking, make a referral, and document smoking counseling. Post-intervention, 30% of smokers were given a Quitline referral card. An educational intervention improved ED-based tobacco interventions. Controlled trials are needed to establish these results' durability.

Race and ethnicity do not affect baseline self-report of pain severity in patients with suspected long-bone fractures.

OBJECTIVE: To determine whether race or ethnicity affect baseline description of pain by patients with suspected long-bone fracture. DESIGN: Secondary analysis of data from an observational study of patients age 18-55 in two urban emergency departments. OUTCOME MEASURES: Patients rated their pain using an 11-point scale, where 0 represents no pain, and 10 represents the worst possible pain. RESULTS: Of 838 patients, 49% were Hispanic, 29% African American, and 22% White. Mean baseline pain scores were, respectively, 8.2, 8.1, and 7.7. In multivariate analysis, pair-wise comparisons showed no significant differences in pain self-report. CONCLUSIONS: Ethnoracial oligoanalgesia cannot be explained by differences in baseline pain severity.

Nicotine dependence, motivation to quit, and diagnosis among adult emergency department patients who smoke: a national survey.

Patients in hospital emergency departments smoke more than the general population. Smoking profiles of these patients have largely been characterized in small, single-institution cohorts. Our objective was to survey adult smokers visiting a sample of U.S. emergency departments, as part of a study examining the efficacy of an educational intervention on physicians' knowledge, attitudes, and behavior regarding tobacco control. A convenience sample of patients in eight academic emergency departments was surveyed from May to July 2006. Eligible patients were aged 18 years or older, were every- or some-day smokers, spoke English or Spanish, were able to provide written informed consent, and were not actively psychotic. Descriptive statistics are reported using parametric and nonparametric measures. A total of 1,168 patients were interviewed (mean age = 40.7 years); 46.5% were female, 54.4% were uninsured or had Medicaid, and 29.9% had no usual source of care. Patients smoked a median of 10 cigarettes daily, with a median score on the Fagerstrom Test for Nicotine Dependence of 4, and a median score of 5 on the nine-point contemplation ladder, indicating a desire to quit within 6 months. Smokers with a diagnosis of cardiovascular, respiratory, or malignant disease were more interested in quitting than others (median ladder score = 4 vs. 6, p<.001), were more likely to believe they had a smoking-related illness, and were more likely to believe their emergency department visit was related to smoking. Smokers with a presenting complaint of chest pain or dyspnea were more interested in quitting than others (median ladder score = 4 vs. 6, p = .002). Emergency department patients smoked at moderate amounts, with moderate levels of addiction and interest in quitting. Smokers with tobacco-related diagnoses, or who believed their emergency department visit was related to smoking, were more interested in quitting. These findings suggest that the emergency department visit may provide a teachable moment to reach smokers who have tobacco-related problems.

Azidothymidine inhibits NF-kappaB and induces Epstein-Barr virus gene expression in Burkitt lymphoma.

The antiviral compound azidothymidine (AZT), alone or in combination with other agents, induces apoptosis in early-passage, Epstein-Barr virus-positive Burkitt lymphoma (EBV+ BL) lines and has clinical activity in EBV+ BL. We report here a mechanism of AZT's antitumor activity. The nuclei of these cells contain activated nuclear factor-kappaB (NF-kappaB) subunits p50, c-Rel, RelB, and p52, but not p65. Treatment of primary EBV+ BL lines with AZT inhibited NF-kappaB within 1 to 2 hours. This was followed by up-regulation of EBV gene expression including viral thymidine kinase (vTK) and apoptosis. Subclones of EBV+ BL cells that demonstrated activated p65 were resistant to AZT. In EBV+ BLs, AZT but not ganciclovir (GCV) was highly phosphorylated to its monophosphate form (AZT-MP). Phosphorylation, as well as apoptosis, was markedly enhanced in the presence of hydroxyurea. AZT inhibits NF-kappaB and up-regulates EBV gene expression in primary EBV+ BLs. AZT with hydroxyurea may represent an inexpensive, targeted regimen for endemic BL.

Potentiation of TRAIL-induced apoptosis in primary effusion lymphoma through azidothymidine-mediated inhibition of NF-kappa B.

The survival of viral mediated lymphomas depends upon constitutive nuclear factor kappa B (NF-kappaB) activity. AIDS-related human herpesvirus type 8-associated primary effusion lymphoma (PEL) responds poorly to chemotherapy and is almost invariably fatal. We have previously demonstrated that the antiviral combination of interferon alpha (IFN-alpha) and azidothymidine (AZT) induces apoptosis in PEL cell lines. We therefore used these agents as therapy for an AIDS patient with PEL. The patient had a dramatic response, with complete resolution of his malignant effusion in 5 days. In PEL cells, the death receptor ligand known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is markedly up-regulated by IFN-alpha; however, signals transduced by death receptors may also activate an antiapoptotic response mediated by NF-kappaB. In both the primary tumor cells from our patient and PEL cell lines, AZT selectively blocked nuclear entry of the NF-kappaB heterodimer p50 and p65, an effect not seen with other nonthymidine antiviral nucleosides. AZT monophosphate, the principal intracellular metabolite, inhibited phosphorylation and degradation of IkappaB by the IkappaB kinase complex. AZT- and IFN-alpha-mediated apoptosis was blocked by expression and nuclear localization of an IkappaB-resistant form of NF-kappaB (the p50 subunit linked to the transactivation domain of herpes simplex virus VP16). The proapoptotic effect of AZT and IFN-alpha in PEL occurs through the concomitant activation of TRAIL and blockade of NF-kappaB and represents a novel antiviral therapy for a virally mediated tumor.