Effectiveness and Cost Effectiveness of Expanding Harm Reduction and Antiretroviral Therapy in a Mixed HIV Epidemic: A Modeling Analysis for Ukraine

A cost-effectiveness study by Sabina Alistar and colleagues evaluates the effectiveness and cost effectiveness of different levels of investment in methadone, ART, or both, in the mixed HIV epidemic in Ukraine

Recommendations for increasing the use of HIV/AIDS resource allocation models

The article of record as published may be found at: http://dx.doi.org/10.1186/1471-2458-9-S1-S8Background: Resource allocation models have not had a substantial impact on HIV/AIDS resource allocation decisions in spite of the important, additional insights they may provide. In this paper, we highlight six difficulties often encountered in attempts to implement such models in policy settings; these are: model complexity, data requirements, multiple stakeholders, funding issues, and political and ethical considerations. We then make recommendations as to how each of these difficulties may be overcome. Results: To ensure that models can inform the actual decision, modellers should understand the environment in which decision-makers operate, including full knowledge of the stakeholders' key issues and requirements. HIV/AIDS resource allocation model formulations should be contextualized and sensitive to societal concerns and decision-makers' realities. Modellers should provide the required education and training materials in order for decision-makers to be reasonably well versed in understanding the capabilities, power and limitations of the model. Conclusion: This paper addresses the issue of knowledge translation from the established resource allocation modelling expertise in the academic realm to that of policymaking

Environment influences on the aromatic character of nucleobases and amino acids

Geometric (HOMA) and magnetic (NICS) indices of aromaticity were estimated for aromatic rings of amino acids and nucleobases. Cartesian coordinates were taken directly either from PDB files deposited in public databases at the finest resolution available (≤1.5 Å), or from structures resulting from full gradient geometry optimization in a hybrid QM/MM approach. Significant environmental effects imposing alterations of HOMA values were noted for all aromatic rings analysed. Furthermore, even extra fine resolution (≤1.0 Å) is not sufficient for direct estimation of HOMA values based on Cartesian coordinates provided by PDB files. The values of mean bond errors seem to be much higher than the 0.05 Å often reported for PDB files. The use of quantum chemistry geometry optimization is strongly advised; even a simple QM/MM model comprising only the aromatic substructure within the QM region and the rest of biomolecule treated classically within the MM framework proved to be a promising means of describing aromaticity inside native environments. According to the results presented, three consequences of the interaction with the environment can be observed that induce changes in structural and magnetic indices of aromaticity. First, broad ranges of HOMA or NICS values are usually obtained for different conformations of nearest neighborhood. Next, these values and their means can differ significantly from those characterising isolated monomers. The most significant increase in aromaticities is expected for the six-membered rings of guanine, thymine and cytosine. The same trend was also noticed for all amino acids inside proteins but this effect was much smaller, reaching the highest value for the five-membered ring of tryptophan. Explicit water solutions impose similar changes on HOMA and NICS distributions. Thus, environment effects of protein, DNA and even explicit water molecules are non-negligible sources of aromaticity changes appearing in the rings of nucleobases and aromatic amino acids residues

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Liposome bupivacaine in peripheral nerve blocks and epidural injections to manage postoperative pain

IntroductionThe duration of postsurgical pain greatly outlasts the duration of analgesia (typically < 12 h) following single administration of traditional formulations of local anesthetics. Bupivacaine , one of the most widely studied and extensively used local anesthetics, is now available in a liposomal formulation that has shown promise of providing postsurgical analgesia for a duration of up to 72 h when administered as part of a peripheral (e.g., femoral) or neuraxial (e.g., epidural) nerve block. However, it is currently approved for administration in the surgical site.Areas coveredThis publication provides an overview of liposome bupivacaine and its potential utility in peripheral nerve blocks and epidural administration.Expert opinionThe potential to provide postoperative analgesia lasting 3 days with a single administration at the time of surgery holds considerable promise. This modality could have distinct advantages over currently available techniques, such as continuous perineural local anesthetic infusion, as it would preclude the need for a catheter and pump. However, potential risks and benefits of liposome bupivacaine in peripheral and neuraxial nerve blocks must be further elucidated in surgical populations, and US Food and Drug Administration (FDA) approval must be granted for these indications. Until FDA approval is provided, the use of liposome bupivacaine in peripheral and neuraxial nerve blocks must be considered investigational

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention

Intermolecular interactions between chelate rings and phenyl rings in square-planar copper(II) complexes

Analysis of the geometrical parameters in crystal structures of square-planar copper(II) complexes from the CSD shows that the short noncovalent copper (II)-phenyl carbon distances are a consequence of the interaction between the phenyl ring and the chelate ring with delocalized pi-bonds. The data show a correlation between the distances between the centers of the chelate and phenyl rings and the copper(II)-carbon distances, as well as a mutual slipped-parallel orientation of the phenyl and chelate rings. ((C) Wiley-VCH Verlag GmbH and Co. KGaA, 69451 Weinheim, Germany, 2004)

Crystal structure of bis[acetone-1-naphthoylhydrazinato(-1)]copper(II) and investigations of intermolecular interactions

In the crystal structure of the bis (acetone-1-naphthoylhydrazinato)copper(II) complex there are interactions of neighbouring molecules via naphthyl groups; the naphthyl group of one molecule interacts with the copper centre and CH3 group of another molecule. The geometry of the crystal structure and dispositions of charges in the naphthyl and chelate rings indicate that there are stacking interactions between the aromatic ring and, not only the copper atom, but also the whole chelate ring. ((C) Wiley-VCH Verlag GmbH and Co. KGaA, 69451 Weinheim, Germany, 2003)