Clinical trial : Randomized-controlled clinical study comparing the efficacy and safety of a low-volume vs. a high-volume mesalazine foam in active distal ulcerative colitis

Members of the International Salofalk Foam Study Group are listed in the Appendix of this article. Members from Latvia are: J.Derova, J.Trofimovica, J.Pokrotnieks, A.Danilans, A.Pukitis, I.Tolmanis, M.Leja, I.Poikane, A.Sudraba.Background: Rectally administered mesalazine (mesalamine; 5-aminosalicylic acid) is the first-line therapy for treatment of distal ulcerative colitis. Recently, a high-volume 5-aminosalicylic acid foam has been shown to be as effective and safe as standard 5-aminosalicylic acid enema. Aim: To study the efficacy and safety of a low-volume vs. a high-volume 5-aminosalicylic acid foam. Methods: In this investigator-blinded study, patients with active distal ulcerative colitis [Clinical Activity Index (CAI) > 4, Endoscopic Index ≥ 4] were randomized to receive 2 × 1 g/30 mL low-volume (n = 163) or 2 × 1 g/60 mL high-volume 5-aminosalicylic acid foam (n = 167) for 42 days. Primary end point was clinical remission (CAI ≤ 4) at the final/withdrawal visit (per-protocol). Results: 330 patients were evaluable for efficacy and safety by intention-to-treat, 290 for per-protocol analysis. Clinical remission rates at week 6 (per-protocol) were 77% on low-volume foam vs. 77% on high-volume foam (P = 0.00002 for non-inferiority). The low-volume foam was associated with a lower frequency of severe discomfort, pain and retention problems. Conclusions: Low-volume 5-aminosalicylic acid foam is as effective and safe as a high-volume 5-aminosalicylic acid foam in the treatment of active distal ulcerative colitis, but offers compliance advantages compared to the high-volume preparation.publishersversionPeer reviewe

Generic pregabalin : current situation and implications for health authorities, generics and biosimilars manufacturers in the future

The manufacturer of pregabalin has a second use patent covering prescribing for neuropathic pain: its principal indication. The manufacturer has threatened legal action in the UK if generic pregabalin rather than Lyrica is prescribed for this indication. No problems exist for practitioners who prescribe pregabalin for epilepsy or generalized anxiety disorder. This has serious implications for health authorities. In Germany, however, generics could be legally prescribed for any approved indication once one indication loses its patent. We aim to establish the current situation with pregabalin among principally European countries. Personnel from 33 regional and national health authorities mainly from Europe, and nine from universities across Europe working as advisers to health authorities or with insight into their activities, were surveyed regarding four specific questions via email to shed light on the current situation with Lyrica and pregabalin in their country. The information collated from each country was subsequently checked for accuracy with each co-author by email and face-to-face contact and collated into five tables. The scenarios ranged from extending the patent life of Lyrica (e.g. France), endorsing the prescribing of Lyrica for neuropathic pain (e.g. Catalonia and South Korea), and current prescribing of pregabablin for all indications (e.g. Serbia and Germany). Little activity has taken place in European countries in which generic pregabalin is not yet reimbursed. The availability of generic pregabalin has prompted a number of different activities to be undertaken among the 33 countries and regions surveyed. The situation in Serbia and the historic situation in Germany provide examples of ways to maximize savings once a product loses its patent for at least one indication

Corrigendum to "Utilisation trend of long-acting insulin analogues including biosimilars across Europe: findings and implications"

In the article titled "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications" [1], the captions of Figures 3 and 4 were incorrect. The corrected captions for Figures 3 and 4 appear below

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Can subnational autonomy strengthen democracy in Bolivia?

Bolivia is one of the most radical and sincere of decentralization reformers. It recently implemented new reforms granting autonomy to departmental, regional, municipal, and indigenous and rural governments. What effects might these have on public investment patterns, government responsiveness, intergovernmental fiscal relations, the sustainability of public finances, and political accountability? I examine autonomies in light of both fiscal federalism theory and evidence on the effects of Bolivia's 1994 decentralization. By submitting new reforms to the dual rigors of theory and evidence, we can arrive at contingent projections of their likely effects. I identify adjustments to improve efficiency and sustainability in intergovernmental relations, and reduce horizontal imbalances. In sum, the reform has the potential to improve citizen participation, make government more accountable, and deepen Bolivian democracy