Tolerability of topical NSAIDs in the elderly - Do they really convey a safety advantage?

Non-steroidal anti-inflammatory drugs (NSAIDs) are very widely prescribed but they have a poor safety profile, with a range of potential adverse effects. NSAIDs that are used in topical formulation have been developed in the last fifteen years and their use is increasing. The purpose is to achieve a high local concentration of the active ingredient at the affected site, with as low a plasma concentration as possible to minimise possible systemic side-effects. This paper reviews the evidence available regarding the safety of topical NSAIDs, with particular reference to gastrointestinal and renal toxicity which have recently been highlighted in the medical press. The effects on the elderly are also discussed. The authors conclude that more formal epidemiological evaluation of the safety of topical NSAIDs is required in the post-marketing situation

Doping and band-gap engineering of an intrazeolite tungsten(VI) oxide supralattice

New results are presented concerning the topotactic self-assembly, n-type doping and band-gap engineering of an intrazeolite tungsten(VI) oxide supralattice n(W03)-Na56Y, where 0 < η < 32, built-up of single size and shape (W03)2 dimers. In particular it has been found that the oxygen content of these dimers can be quantitatively adjusted by means of a thermal vacuum induced reversible reductive-elimination oxidative-addition of dioxygen. This provides access to new n(W03.x)-Na56Y materials (0 < χ ^ 1.0) in which the oxygen content, structural properties and electronic architecture of the dimers are changed. In this way one can precisely control the oxidation state, degree of η-doping and band-filling of a tungsten(VI) oxide supralattice through an approach which can be considered akin to, but distinct in detail to, that found in the Magneli crystallographic shear phases of non-stoichiometric bulk W03.x . Another discovery concerns the ability to alter local electrostatic fields experienced by the tungsten(VI) oxide moieties housed in the 13Ä supercages of 16(W03)-M36Y, by varying the ionic potential of the constituent supercage M + cations across the alkali metal series. This method provides the first opportunity to fine-tune the band-gap of a tungsten(VI) oxide supralattice. Α miniband electronic description is advanced as a qualitative first attempt to understand the origin of the above effects. The implications of these discoveries are that cluster size, composition and intrinsic electrostatic field effects can be used to "chemically manipulate" (engineer) the doping and band architecture of intrazeolite supralattices of possible interest in quantum electronics and nonlinear optics

Direct oral anticoagulants‐Remove versus Taipan snake venom time for detection of a lupus anticoagulant in patients taking oral direct factor Xa inhibitors

Background: The optimal method of detecting a lupus anticoagulant (LA) for patients taking direct factor Xa inhibitor (DFXaI) direct oral anticoagulants (DOACs) remains controversial. Methods include charcoal adsorption of the DOACs to allow testing with the activated partial thromboplastin time (APTT) and dilute Russell viper venom time (dRVVT), or use of the DFXaI‐insensitive Taipan snake venom time (TSVT) and Ecarin time (ET) assays on neat plasma. Objectives: The objective was to compare the utility of APTT and dRVVT analysis following DOAC Remove against TSVT/ET on untreated plasma for LA detection in spiked plasmas and routine clinical samples for patients on DFXaIs. Patients/methods: Various LA‐negative and LA‐positive samples were assayed by APTT, dRVVT, and TSVT/ET, and then separately spiked with rivaroxaban, apixaban, and edoxaban calibrators to a concentration of ~190 ng/ml and the assays repeated on spiked plasma before and after DOAC Remove treatment. Testing of 284 consecutive samples from DFXaI‐anticoagulated patients by APTT/dRVVT and TSVT/ET before and after DOAC Remove treatment was undertaken. Results: In the spiking model, we found that both TSVT/ET and DOAC Remove strategies generally distinguished LA‐negative and LA‐positive samples, but some false‐positive LA results occurred. In the investigation of 284 consecutive patient samples on DFXaIs, the percentage agreement for LA detection in neat samples tested by TSVT/ET versus APTT and dRVVT after DOAC Remove treatment was 90% (Cohen kappa 0.12). Conclusion: Our data highlight uncertainty and disagreement for testing LA in patients on DFXaI. Further studies are required

Nitric oxide and cardiovascular effects: new insights in the role of nitric oxide for the management of osteoarthritis

Nitric oxide (NO) is an important mediator in both health and disease. In addition to its effects on vascular tone and platelet function, it plays roles in inflammation and pain perception that may be of relevance in osteoarthritis. Many patients with osteoarthritis take nonsteroidal anti-inflammatory drugs (NSAIDs) long term for pain control. Over recent years concern has been raised about the possible cardiovascular side effects of NSAIDs. The reasons for this possible increased cardiovascular risk with NSAIDs are not yet entirely clear, although changes in blood pressure, renal salt handling and platelet function may contribute. Recently, drugs that chemically link a NSAID with a NO donating moiety (cyclo-oxygenase-inhibiting NO-donating drugs [CINODs]) were developed. NO is an important mediator of endothelial function, acting as a vasodilator and an inhibitor of platelet aggregation, and having anti-inflammatory properties. The potential benefits of CINODs include the combination of effective analgesic and anti-inflammatory actions with NO release, which might counterbalance any adverse cardiovascular effects of NSAIDs. Effects of CINODs in animal studies include inhibition of vasopressor responses, blood pressure reduction in hypertensive rats and inhibition of platelet aggregation. CINODs may also reduce ischemic damage to compromised myocardial tissue. In addition, endothelial dysfunction is a recognized feature of inflammatory arthritides, and therefore a drug that might provide slow release of NO to the vasculature while treating pain is an attractive prospect in these conditions. Further studies of the effects of CINODs in humans are required, but these agents represent a potential exciting advance in the management of osteoarthritis

Introduction to the Special Issue: Terrorist Online Propaganda and Radicalization

This is the introduction to issue 1 of volume 40 of Studies in Conflict & Terrorism, which was a special issue focused on terrorist online propaganda and radicalisation

Diagonalization of an Integrable Discretization of the Repulsive Delta Bose Gas on the Circle

We introduce an integrable lattice discretization of the quantum system of n bosonic particles on a ring interacting pairwise via repulsive delta potentials. The corresponding (finite-dimensional) spectral problem of the integrable lattice model is solved by means of the Bethe Ansatz method. The resulting eigenfunctions turn out to be given by specializations of the Hall-Littlewood polynomials. In the continuum limit the solution of the repulsive delta Bose gas due to Lieb and Liniger is recovered, including the orthogonality of the Bethe wave functions first proved by Dorlas (extending previous work of C.N. Yang and C.P. Yang).Comment: 25 pages, LaTe

Non-market Valuation Biases Due to Aboriginal Cultural Characteristics in Northern Saskatchewan: The Values Structures Component

Current non-market valuation techniques have been developed based on assumptions about values held within the Eurocentred culture. Contentions between cultures over natural resources are hypothesized to occur because of differences in held values resulting in different values being assigned to the resources in question. This study measured the held values of an Aboriginal band in Northern Saskatchewan as the first dimension of a non-market valuation study of natural resources. These held value structures are presented noting differences by age and gender and in comparison with the local Non-Aboriginal community and another Aboriginal group in northern Alberta.Resource /Energy Economics and Policy,