Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis.

There is a lack of large, randomized, double-blind studies that address antihistamine updosing for chronic spontaneous urticaria (CSU). The objective of this systematic review is to explore and analyse available data to provide clinical evidence for the efficacy of antihistamine updosing. We searched the literature in Medline, Scopus, Google Scholar, Embase, Web of Science and Cochrane databases using the keywords 'chronic, urticaria, antihistamines' to identify studies published between January 1990 and November 2014. We assessed quality using the Jadad score that evaluates quality of randomization, double-blinding and losses to follow-up. We identified 1042 articles and 15 articles were included in the final evaluation. We performed two meta-analyses, one that included studies that analysed treatment response among groups receiving different antihistamine dosages vs. placebo, and another that analysed antihistamine updosing in those patients who did not respond to standard dosages. Only five articles obtained a high quality level score. We did not find significant differences in response rates or number of weals in those patients who received a standard dosage vs. a high dosage. We found a significant improvement only in the pruritus variable of the Urticaria Activity Score scale. The estimated relative risk for improvement by increasing the antihistamine dosage was 2·27 [95% confidence interval (CI) 1·68-3·06]; however, there was significant heterogeneity. The proportion of nonrespondent patients with CSU who responded to antihistamine updosing was 63·2% (95% CI 57-69·6). We found that updosing antihistamines significantly improved control of pruritus but not weal number. However, the relative weakness of the studies and the significant heterogeneity among them made it difficult to reach a final conclusion.

The defeat of Philip Morris' 'California Uniform Tobacco Control Act'.

OBJECTIVES: This paper describes the strategies used by Philip Morris and other tobacco companies to promote a California initiative (Proposition 188) preempting local control of tobacco and those used by public health groups to defeat the initiative. METHODS: Interviews with key informants were conducted, and the written record was reviewed. RESULTS: Tobacco companies nearly succeeded in passing Proposition 188 by presenting it as a pro-health measure that would prevent children from obtaining cigarettes and provide protection against secondhand smoke. Public health groups defeated it by highlighting tobacco industry backing. A private charitable foundation also played an innovative role by financing a non-partisan public education campaign. CONCLUSIONS: Public health forces must be alert to sophisticated efforts by the tobacco industry to enact preemptive state legislation by making it look like tobacco control legislation. The coalition structure that emerged in the "No on 188" campaign represents an effective model for future tobacco control activities. The new role of charitable foundations defined in the Proposition 188 campaign can be used in other public health issues.

Inhibitory effect of cromakalim in human detrusor muscle is mediated by glibenclamide-sensitive potassium channels.

The effects of cromakalim, a potassium channel activating drug, and glibenclamide, a relatively selective antagonist of ATP-sensitive potassium channels, have been investigated on isolated detrusor muscle from human bladder. Specimens of human bladder were cut into strips and suspended in an organ bath filled with modified Tyrode solution for measurement of isometric contractile force. Concentration-response curves to acetylcholine were constructed before and after pretreatment with cromakalim and cromakalim plus glibenclamide. The concentration-response curves to acetylcholine were displaced to the right, and the maximal response to acetylcholine was significantly inhibited by cromakalim in a concentration-dependent manner. The inhibitory effect of cromakalim on acetylcholine-induced contraction was significantly reduced by glibenclamide. Following sustained contraction induced by 20 mM. KCl, the cumulative addition of cromakalim to the organ bath produced a concentration-dependent relaxation. However, in strips precontracted with 60 mM. KCl, the addition of cromakalim in concentrations as high as 10(-5) M. did not induce relaxation. The relaxation induced by cromakalim in strips precontracted with 20 mM. KCl was significantly inhibited by glibenclamide. These results suggest that the inhibitory effect of cromakalim in human bladder involves activation of glibenclamide-sensitive potassium channels.