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New Analysis (new + analysis)
Selected AbstractsThe impairments caused by social phobia in the general population: implications for intervention,ACTA PSYCHIATRICA SCANDINAVICA, Issue 2003R. C. KesslerArticle first published online: 29 AUG 200 Objective: Although social phobia is common, treatment remains low. In order to gauge public health implications of this low treatment, information is needed on the impairments caused by social phobia. Method: A computer literature review searched for the terms ,social anxiety disorder' and ,social phobia' in the MEDLINE and PsycLIT databases. New analyses were carried out in the US National Comorbidity Survey. Results: The literature shows that social phobia has serious effects on role functioning and quality of life. These effects are least severe for pure non-generalized social phobia and most severe for comorbid generalized social phobia with avoidant personality disorder. The most direct impairments involve social interactions and information processing errors in these interactions. Indirect effects are even more important. Three indirect effects are highlighted: effects on secondary mental (e.g. depression), substance (e.g. alcoholism) and physical (e.g. cardiovascular disease) disorders; effects on normative role transitions (e.g. educational attainment); and effects on help-seeking. Conclusion: Given the early age of onset and impacts on secondary disorders and early adult life course transitions, the greatest public health impact of increasing treatment of social phobia is likely to be achieved by developing programs targeted at early identification and treatment through schools. [source] Influences of species, latitudes and methodologies on estimates of phenological response to global warmingGLOBAL CHANGE BIOLOGY, Issue 9 2007CAMILLE PARMESANArticle first published online: 14 AUG 200 Abstract New analyses are presented addressing the global impacts of recent climate change on phenology of plant and animal species. A meta-analysis spanning 203 species was conducted on published datasets from the northern hemisphere. Phenological response was examined with respect to two factors: distribution of species across latitudes and taxonomic affiliation or functional grouping of target species. Amphibians had a significantly stronger shift toward earlier breeding than all other taxonomic/functional groups, advancing more than twice as fast as trees, birds and butterflies. In turn, butterfly emergence or migratory arrival showed three times stronger advancement than the first flowering of herbs, perhaps portending increasing asynchrony in insect,plant interactions. Response was significantly stronger at higher latitudes where warming has been stronger, but latitude explained < 4% of the variation. Despite expectation, latitude was not yet an important predictor of climate change impacts on phenology. The only two previously published estimates of the magnitude of global response are quite different: 2.3 and 5.1 days decade,1 advancement. The scientific community has assumed this difference to be real and has attempted to explain it in terms of biologically relevant phenomena: specifically, differences in distribution of data across latitudes, taxa or time periods. Here, these and other possibilities are explored. All analyses indicate that the difference in estimated response is primarily due to differences between the studies in criteria for incorporating data. It is a clear and automatic consequence of the exclusion by one study of data on ,stable' (nonresponsive) species. Once this is accounted for, the two studies support each other, generating similar conclusions despite analyzing substantially nonoverlapping datasets. Analyses here on a new expanded dataset estimate an overall spring advancement across the northern hemisphere of 2.8 days decade,1. This is the first quantitative analysis showing that data-sampling methodologies significantly impact global (synthetic) estimates of magnitude of global warming response. [source] Testing hypotheses of speciation in the Plethodon jordani species complex with allozymes and mitochondrial DNA sequencesBIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 1 2006DAVID W. WEISROCK Salamander populations of the Plethodon jordani species complex form a challenging system for applying the general lineage concept of species to diagnose population-level lineages. The present study reports and analyses mitochondrial-DNA haplotypes (,1200 nucleotide bases from the genes encoding ND2, tRNATrp, and tRNAAla from 438 salamanders) from 100 populations representing six species of the P. jordani complex (Plethodon amplus, Plethodon cheoah, Plethodon jordani, Plethodon meridianus, Plethodon metcalfi, and Plethodon montanus) with comparative analyses of previously published allozymic data to reconstruct the evolutionary history of this group and to diagnose species lineages. Analyses of mitochondrial haplotypic data include nested-cladistic analysis of phylogeography, analysis of molecular variance, hierarchical analysis of nucleotide-diversity measures, and likelihood-based estimates of recent temporal changes in population size. New analyses of allozymic data include multidimensional scaling and principal component analyses, and both data sets are analysed and compared for congruent genetic structure using Mantel correlation tests. These analyses in combination identify the six named species as distinct evolutionary lineages despite sporadic genetic exchanges among them and some discordance between mitochondrial DNA and allozymic markers. Sexual isolation is not complete for any pair of these six species, but they replace each other geographically and appear to block the geographical spreading of their neighbours. The P. jordani complex is a strong study system for investigating the genetic and ecological processes responsible for vicariant speciation. © 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 89, 25,51. [source] PROCESSION AND SYMBOLISM AT TARA: ANALYSIS OF TECH MIDCHÚARTA (THE ,BANQUETING HALL') IN THE CONTEXT OF THE SACRAL CAMPUSOXFORD JOURNAL OF ARCHAEOLOGY, Issue 4 2007CONOR NEWMAN Summary. New analysis explores Tech Midchúarta (the ,Banqueting Hall') from the point of view of a sacral, processional approach to the summit of the Hill of Tara, the pre-eminent cult and inauguration site of prehistoric and early medieval Ireland. It is suggested that aspects of its architectural form symbolize the liminal boundary between the human world and the Otherworld of Tara, and that in so far as Tech Midchúarta is also designed to control and manipulate how the ceremonial complex is disclosed to the observer, it assembles the existing monuments into one, integrated ceremonial campus. It is argued that Tech Midchúarta is one of the later monuments on the Hill of Tara and that it may date from the early medieval period. Using the evidence of documentary sources and extant monuments, a possible processional route from Tech Midchúarta to Ráith na Ríg is described. Immráidem fós Long na Láech frisanabar Barc Ban mbáeth. Tech na Fían, nirbo long lec, co cethri doirsib deac. Let us consider too the Hall of the Heroes which is called the Palace of Vain Women; the House of Warriors, it was no mean hall, with fourteen doors. (Gwynn 1903,35, Metrical Dindshenchas III, 18) [source] Use of response functions in selecting lodgepole pine populations for future climatesGLOBAL CHANGE BIOLOGY, Issue 12 2006T. WANG Abstract Although growth response functions have previously been developed for lodgepole pine (Pinus contorta Dougl. ex Loud.) populations in British Columbia, new analyses were conducted: (1) to demonstrate the merit of a new local climate model in genecological analysis; (2) to highlight new methods for deriving response functions; and (3) to evaluate the impacts of management options for existing geographically defined seed planning units (SPUs) for reforestation. Results of this study suggest that new methods for anchoring population response functions, and a multivariate approach for incorporating climate variables into a single model, considerably improve the reliability of these functions. These functions identified a small number of populations in central areas of the species distribution with greater growth potential over a wide range of mean annual temperature (MAT). Average productivity of lodgepole pine is predicted to increase (up to 7%) if moderate warming (,2°C MAT) occurs in the next few decades as predicted, although productivity would substantially decline in some SPUs in southern BC. Severe global warming (>3°C MAT) would result in either a drastic decline in productivity or local populations being extirpated in southern SPUs. New deployment strategies using the best seed sources for future reforestation may not only be able to mitigate the negative impact of global warming, but may even be able to increase productivity in some areas. [source] The Black,White Paradox in Health: Flourishing in the Face of Social Inequality and DiscriminationJOURNAL OF PERSONALITY, Issue 6 2009Corey L. M. Keyes ABSTRACT This paper reviews published research and presents new analyses from the 1995 nationally representative sample from the Midlife in the United States (MIDUS) study to investigate whether there is support for the paradox of race and health in the United States. Findings reveal that Blacks have lower rates of several common mental disorders, but Blacks also have higher rates of flourishing than Whites. Blacks are mentally resilient in the face of greater social inequality and exposure to discrimination as well as high rates of physical morbidity,all of which are distinctive risk factors for mental distress and mental illness in the general population. Findings also show that controlling for perceived discrimination increases the Black advantage in 12 of the 13 signs of flourishing, suggesting that Blacks would have even better mental health were it not for discrimination. This paper concludes by considering what mechanisms,both adaptive and maladaptive,might explain this particular example of resilience in the Black population. [source] Analyses of Digman's Child-Personality Data: Derivation of Big-Five Factor Scores From Each of Six SamplesJOURNAL OF PERSONALITY, Issue 5 2001Lewis R. Goldberg One of the world's richest collections of teacher descriptions of elementary-school children was obtained by John M. Digman from 1959 to 1967 in schools on two Hawaiian islands. In six phases of data collection, 88 teachers described 2,572 of their students, using one of five different sets of personality variables. The present report provides findings from new analyses of these important data, which have never before been analyzed in a comprehensive manner. When factors developed from carefully selected markers of the Big-Five factor structure were compared to those based on the total set of variables in each sample, the congruence between both types of factors was quite high. Attempts to extend the structure to 6 and 7 factors revealed no other broad factors beyond the Big Five in any of the 6 samples. These robust findings provide significant new evidence for the structure of teacher-based assessments of child personality attributes. [source] Proposals for 2001 samples of anonymized records: An assessment of disclosure riskJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 3 2001Angela Dale In 1991 Marsh and co-workers made the case for a sample of anonymized records (SAR) from the 1991 census of population. The case was accepted by the Office for National Statistics (then the Office of Population Censuses and Surveys) and a request was made by the Economic and Social Research Council to purchase the SARs. Two files were released for Great Britain,a 2% sample of individuals and a 1% sample of households. Subsequently similar samples were released for Northern Ireland. Since their release, the files have been heavily used for research and there has been no known breach of confidentiality. There is a considerable demand for similar files from the 2001 census, with specific requests for a larger sample size and lower population threshold for the individual SAR. This paper reassesses the analysis of Marsh and co-workers of the risk of identification of an individual or household in a sample of microdata from the 1991 census and also uses alternative ways of assessing risks with the 1991 SARs. The results of both the reassessment and the new analyses are reassuring and allow us to take the 1991 SARs as a base-line against which to assess proposals for changes to the size and structure of samples from the 2001 census. [source] Heterogeneous agglutinitic glass and the fusion of the finest fraction (F3) modelMETEORITICS & PLANETARY SCIENCE, Issue 12 2002Abhijit Basu They include (1) theoretical expectations that shock pulses should engulf and melt smaller grains more efficiently than larger grains, (2) experimental results of impact shock, albeit at lower than presumed hypervelocity impacts of micrometeorites on the lunar regolith, and (3) new analyses confirming previous results that average compositions of agglutinitic glass are biased towards that of the finest fraction of lunar soils from which they had formed. We add another reason in support of the F3 model. Finer grains of lunar soils are also much more abundant. Hence, electrostatic forces associated with the rotating terminator region bring the finest grains that are obviously much lighter than courser grains to the surface of the Moon. This further contributes to the preferential melting of the finest fraction upon micrometeoritic impacts. New backscattered electron imaging shows that agglutinitic glass is inhomogeneous at submicron scale. Composition ranges of agglutinitic glass are extreme and deviate from that of the finest fraction, even by more than an order of magnitude for some components. Additionally, we show how an ilmenite grain upon impact would produce TiO2 -rich agglutinitic glass in complete disregard to the requirements of fusion of the finest fraction. We propose an addition to the F3 model to accommodate these observations (i.e., that micrometeorite impacts indiscriminately melt the immediate target regardless of grain size or grain composition). We, therefore, suggest that (1) agglutinitic glass is the sum of (a) the melt produced by the fusion of the finest fraction of lunar soils and (b) the microvolume of the indiscriminate target, which melts at high-shock pressures from micrometeoritic impacts, and that (2) because of the small volume of the melt and incorporating cold soil grains, the melt quenched so rapidly that it did not mix and homogenize to represent any preferential composition, for example, that of the finest fraction. [source] Perspectives on the Recent Decline in Disability at Older AgesTHE MILBANK QUARTERLY, Issue 3 2005DOUGLAS A. WOLF A decline has been found in the prevalence of disability among the older U.S. population during the 1980s and 1990s. One source of evidence for this decline is data from the National Long-Term Care Survey (NLTCS). This article investigates possible ambiguities in measuring disability using large-scale household surveys, illustrating the consequences of such problems with new analyses of NLTCS data. The reanalysis suggests a more gradual decline in disability than that found in prior research. The article also discusses three societal trends in areas other than health or functioning that might contribute to declines in disability levels: a reduced supply of informal care, changes in the technology of self-care, and changes in the definition and perception of both "ability" and "disability." [source] The International Adult Literacy Survey in Britain: Impact on policy and practiceDYSLEXIA, Issue 2 2003Angela J. Fawcett Abstract There is increasing concern for the skills of the workforce in the UK and elsewhere, but despite this concern until recently there has been little information available which objectively measures basic skills in adults. In this paper, evidence derived from the prose scale of the International Adult Literacy Survey (IALS, 1996) is outlined, with emphasis on the performance of adults at the lowest levels, 1 and 2 in the United Kingdom. A new analysis based on the 183 adults who self-reported learning disabilities demonstrates that over 50% of this group perform at level 1 on the prose scale. Over 60% report that these disabilities persist into adult life, although this number falls to 50% in the youngest age group, reflecting changes in recognition of learning disabilities within the education system. The paper concludes with a case study of the redefinition of basic skill levels in Britain based on the IALS levels. The impact of the IALS findings on policy and practice, and in particular through the recommendations of the Moser report, are discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] Assessing the effect of elevated carbon dioxide on soil carbon: a comparison of four meta-analysesGLOBAL CHANGE BIOLOGY, Issue 8 2009BRUCE A. HUNGATE Abstract Soil is the largest reservoir of organic carbon (C) in the terrestrial biosphere and soil C has a relatively long mean residence time. Rising atmospheric carbon dioxide (CO2) concentrations generally increase plant growth and C input to soil, suggesting that soil might help mitigate atmospheric CO2 rise and global warming. But to what extent mitigation will occur is unclear. The large size of the soil C pool not only makes it a potential buffer against rising atmospheric CO2, but also makes it difficult to measure changes amid the existing background. Meta-analysis is one tool that can overcome the limited power of single studies. Four recent meta-analyses addressed this issue but reached somewhat different conclusions about the effect of elevated CO2 on soil C accumulation, especially regarding the role of nitrogen (N) inputs. Here, we assess the extent of differences between these conclusions and propose a new analysis of the data. The four meta-analyses included different studies, derived different effect size estimates from common studies, used different weighting functions and metrics of effect size, and used different approaches to address nonindependence of effect sizes. Although all factors influenced the mean effect size estimates and subsequent inferences, the approach to independence had the largest influence. We recommend that meta-analysts critically assess and report choices about effect size metrics and weighting functions, and criteria for study selection and independence. Such decisions need to be justified carefully because they affect the basis for inference. Our new analysis, with a combined data set, confirms that the effect of elevated CO2 on net soil C accumulation increases with the addition of N fertilizers. Although the effect at low N inputs was not significant, statistical power to detect biogeochemically important effect sizes at low N is limited, even with meta-analysis, suggesting the continued need for long-term experiments. [source] Optimum shapes of tire-treads for avoiding lateral slippage between tires and roadsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 6 2005S. Reaz Ahmed Abstract Optimum design of tire-tread sections is an important practical issue. However, useful study of the problem that can suggest a reliable guideline for determining the optimum tread sections had hardly been made in the past. The present paper describes a new analysis of the state of stresses in tire-tread sections in contact with the road surface, taking special care of the boundary conditions. Based on the analysis, a method is proposed to determine the optimum tread shapes for avoiding lateral slippage between tires and roads. The displacement potential function formulation, an ideal mathematical model for the practical stress problems, has been used in conjunction with finite-difference method of solution. For the present analysis, lateral slipping in absence of frictional resistance as well as the no-slip conditions of the tire-tread contact surface have been considered along with a large number of tread aspect ratios. The present computational approach proves to be a powerful tool for determining the optimum tread shapes for avoiding the lateral slippage of tire-treads. Copyright © 2005 John Wiley & Sons, Ltd. [source] Dependence between extreme sea surge, river flow and precipitation in eastern BritainINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 10 2002Cecilia Svensson Abstract Flooding in estuaries may be caused by both high river flows and by high sea levels. In order to investigate whether these tend to occur simultaneously in eastern Britain, the dependence between high sea surge (observed sea level minus predicted astronomical tide), river flow and precipitation was studied using a measure of dependence specially developed for extremal dependence. Extreme events were interpreted using meteorological maps. This new analysis found that the strongest flow,surge dependence occurs between river flow on the north shore of the Firth of Forth and sea surge at Aberdeen, Wick and Lerwick. In contrast to most other catchments in eastern Britain, the area to the north of the Firth of Forth is not sheltered from south-westerly winds by any major topographical barrier. Therefore, precipitation from this direction may be orographically enhanced as it encounters the hills on the northern side of the firth, and high river flows may ensue. Events resulting in both high river flow and surge in the northern part of the study area were found to be caused by cyclones travelling north-eastward to the north of Scotland. High surge events, only, were associated with similar storm tracks, but without much precipitation from the fronts. High river flows, only, were associated with rain-bearing east,west-directed fronts over northern Britain, with slow-moving depressions located over or to the west of the British Isles where they are unable to generate a strong surge in the North Sea. The dependence between river flow and surge was found to be stronger during winter than summer, and a lagged analysis revealed that the dependence is strongest when flow and surge occur on the same day, but was also strong for lags of plus and minus 1 day. For precipitation, the dependence with both flow and surge is strongest when precipitation precedes them by 1 day. Copyright © 2002 Royal Meteorological Society. [source] Opportunists, Predators and Rogues: The Role of Local State Relations in Shaping Chinese Rural DevelopmentJOURNAL OF AGRARIAN CHANGE, Issue 2 2005MICHELLE S. MOOD Chinese rural enterprises have developed in various ways in different parts of the country, giving rise to competing explanations of the variation in terms of the role of structure, historical legacies, norms, bureaucratic controls and agency. A new analysis seeks to resolve these contradictions by placing development in the context of township and village cadres' relationships. Townships can either enforce village compliance with county policy or not, and can promote economic development or not, resulting in bureaucratic controls working where compliance is enforced, and norms and agency guiding development where they are not. Perverse incentives allow compliance without achieving larger goals of economic development, and can trap villages in opportunistic or predatory townships. While structure and historical legacies do constrain development in general, inter-level relationships are key to understanding micro-variations. Village wealth and village elections further empower the village level and give agency greater salience. [source] Anticipating catastrophes through extreme value modellingJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 4 2003Stuart Coles Summary. When catastrophes strike it is easy to be wise after the event. It is also often argued that such catastrophic events are unforeseeable, or at least so implausible as to be negligible for planning purposes. We consider these issues in the context of daily rainfall measurements recorded in Venezuela. Before 1999 simple extreme value techniques were used to assess likely future levels of extreme rainfall, and these gave no particular cause for concern. In December 1999 a daily precipitation event of more than 410 mm, almost three times the magnitude of the previously recorded maximum, caused devastation and an estimated 30000 deaths. We look carefully at the previous history of the process and offer an extreme value analysis of the data,with some methodological novelty,that suggests that the 1999 event was much more plausible than the previous analyses had claimed. Deriving design parameters from the results of such an analysis may have had some mitigating effects on the consequences of the subsequent disaster. The themes of the new analysis are simple: the full exploitation of available data, proper accounting of uncertainty, careful interpretation of asymptotic limit laws and allowance for non-stationarity. The effect on the Venezuelan data analysis is dramatic. The broader implications are equally dramatic; that a naïve use of extreme value techniques is likely to lead to a false sense of security that might have devastating consequences in practice. [source] Density gradients in Galactic planetary nebulaeMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2007J. P. Phillips ABSTRACT Certain hydrodynamic models of planetary nebulae (PNe) suggest that their shells possess appreciable radial density gradients. However, the observational evidence for such gradients is far from clear. On the one hand, Taylor et al. claim to find evidence for radio spectral indices 0.6 < , < 1.8, a trend which is taken to imply a variation ne,r,2 in most of their sample of PNe. On the other hand, Siódmiak & Tylenda find no evidence for any such variations in density; shell inhomogeneities, where they occur, are primarily attributable to ,blobs or condensations'. It will be suggested that both of these analyses are unreliable, and should be treated with a considerable degree of caution. A new analysis within the log(F(5 GHz)/F(1.4 GHz)),log(TB(5 GHz)) plane will be used to show that at least 10,20 per cent of PNe are associated with strong density gradients. We shall also show that the ratio F(5 GHz)/F(1.4 GHz) varies with nebular radius; an evolution that can be interpreted in terms of varying shell masses, and declining electron densities. [source] A pre-event configuration for biological threats: Preparedness and the constitution of biosecurity eventsAMERICAN ETHNOLOGIST, Issue 3 2009LIMOR SAMIMIAN-DARASH ABSTRACT Drawing on an inquiry into Israel's preparedness for biological threats, in this article I suggest a new analysis of biosecurity events. A complex and dynamic assemblage emerges to prepare for biological threats, one that I call a "pre-event configuration." The assemblage is composed of three core elements,the scientific element, the security element, and the public health element,each of which diagnoses threats and suggests appropriate solutions. This configuration also determines what will be perceived as an event for which preparation is needed and what will remain a nonevent. I maintain that the constitution of an event takes place beyond the actual time of its occurrence and is determined by the pre-event configuration in the "time of event." Therefore, a comprehensive analysis of events should combine an examination of actual events and their aftermath with an inquiry into their potentialities as determined by the pre-event configuration. [biosecurity, preparedness, events, disasters] [source] What Moore's Paradox Is AboutPHILOSOPHY AND PHENOMENOLOGICAL RESEARCH, Issue 1 2001CLAUDIO DE ALMEIDA On the basis of arguments showing that none of the most influential analyses of Moore's paradox yields a successful resolution of the problem, a new analysis of it is offered. It is argued that, in attempting to render verdicts of either inconsistency or self-contradiction or self-refutation, those analyses have all failed to satisfactorily explain why a Moore-paradoxical proposition is such that it cannot be rationally believed. According to the proposed solution put forward here, a Moore-paradoxical proposition is one for which the believer can have no non-overridden evidence. the arguments for this claim make use of some of Peter Klein's views on epistemic defeasibility. It is further suggested that this proposal may have important meta-epistemological implications. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2008Article first published online: 2 DEC 200 Osteoporosis guideline A new guideline on the management of osteoporosis in men over 50 and post-menopausal women has been published by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG), a group of organisations representing health professionals and patients, with funding from several pharmaceutical companies. The guideline recommends using the FRAX tool (www.shef.ac.uk/FRAX) to assess the 10-year fracture risk in individuals with risk factors to facilitate targeting DXA scans to measure bone mineral density. Patients who have already sustained a fragility fracture should be treated without risk assessment. Treatment recommendations are similar to those published in draft NICE guidance on primary and secondary prevention, selecting alendronate as the drug of first choice for most patients. Efalizumab efficacy A multicentred postapproval trial has demonstrated long-term efficacy and a favourable safety profile for efalizumab (Raptiva) in moderate to severe chronic plaque psoriasis. The CONTROL II study, presented in September at the 17th EADV congress in Paris, was conducted at 170 sites in 18 European countries and involved 1255 patients who had failed to respond to traditional systemic therapies. In this non-blinded study, 68 per cent of participants achieved the primary efficacy end-point and showed improvement within the first 12 weeks; control was maintained in responding patients who continued treatment. Adverse effects were graded as mild or moderate and similar to those reported in earlier studies. There was no evidence of an increase in malignancies or infections. New oral anticoagulant Rivaroxaban (Xarelto), an oral factor Xa inhibitor, has been introduced for the prevention of venous thrombo-embolism in patients undergoing elective hip or knee replacement surgery. Compared with the low molecular weight heparin enoxaparin (Clexane), rivaroxaban has been shown to reduce the risk of venous thrombosis by 70 per cent after hip replacement and by 49 per cent after knee replacement; the risk of bleeding was similar. At the recommended dose of 10mg once daily, prophylaxis after hip surgery lasts five weeks and costs £157; prophylaxis after knee surgery lasts two weeks and costs £63. New products UCB Pharma has introduced lacosamide (Vimpat) as adjunctive treatment of partial-onset epilepsy with or without secondary generalisation in patients aged 16 and over. A month's treatment at the recommended maintenance dose of 100-200mg twice daily costs approximately £73-£140. A new non-nucleoside reverse transcriptase inhibitor (NNRI) is available for the treatment of HIV-1 infection in combination with a boosted protease inhibitor (PI) and other antiretrovirals in treatment-experienced adults. Etravirine (Intelence) costs approximately £320 for one month's treatment at the recommended dose of 200mg twice daily. Voltarol Pain-Eze (diclofenac) 12.5mg tablets are now available without prescription; a pack of 18 tablets costs £5.99. Atypicals and EPS risk Atypical antipsychotics are not associated with a significantly lower risk of extra-pyramidal symptoms than first-generation agents such as perphenazine (Fentazin), a new analysis of the CATIE study has shown (Br J Psychiatry 2008;193:279,88). CATIE was a large trial comparing the efficacy and safety of antipsychotics in the treatment of schizophrenia in which perphenazine was a representative first-generation agent (Am J Psychiatry 2006;163:611,22). This analysis found no differences in the risk of parkinsonism, dystonia, akathisia or tardive dyskinesia between perphenazine and the newer antipsychotics; use of antiparkinsonian medication was higher with risperidone and lower with quetiapine (Seroquel). Mental health website A new website offering information about mental illnesses and drug treatment has been launched by the United Kingdom Psychiatric Pharmacy Group (UKPPG), the College of Mental Health Pharmacists (CMHP), the Pharmaceutical Schizo-phrenia Initiative (PSI) and the National Institute for Mental Health in England (NIMHE). www.choiceandmedication.org.uk includes information about 17 mental illnesses and a large number of drug treatments. It offers links to other sites offering information and downloadable leaflets, help to identify the local mental health trust and downloadable charts comparing treatments for each indication. [source] Latest news and product developmentsPRESCRIBER, Issue 18 2008Article first published online: 3 OCT 200 Inhaled steroids for all children with asthma? Some children with mild well-controlled asthma may not need a daily inhaled steroid, a Scandinavian study suggests (Arch Dis Child 2008;93:654-9). A total of 176 children aged 5-10 years were randomised to treatment with cromoglicate (Intal) or budesonide. Initially high doses of budesonide (400,g twice daily) were reduced after one month to 200,g twice daily for four months; subsequent treatment for a further year was 100,g twice daily as required for exacerbations or 100,g twice daily regularly. Budesonide was associated with greater improvement in lung function and fewer exacerbations compared with cromoglicate, but after 18 months lung function improvements did not differ. Regular budesonide was associated with fewer exacerbations than as-required administration (0.97 vs 1.69 per patient in months 7-18) but no difference in asthma-free days or use of rescue medication. Growth suppression was slightly greater with continuous budesonide. Interventions to reduce atypicals weight gain A systematic review has found that techniques such as cognitive behaviour therapy and nutritional counselling can reduce weight gain associated with atypical antipsychotics (Br J Psychiatry 2008;193:101-7). Analysis of 10 randomised trials lasting eight weeks to six months found that nonpharmacological intervention increased mean weight loss by about 2.5kg compared with usual care. Check flu vaccine delivery Production of flu vaccine is proceeding according to plan, the Director of Immunisation has told GPs. Practices should now contact their suppliers to confirm a delivery schedule so that clinics can be arranged. New BNF for Children The fourth BNF for Children has been published, containing new sections on HPV vaccination, contraception, treatment of pelvic inflammatory disease and the use of continuous iv infusions in neonates. BNFC 2008 is available online at bnfc.org/bnfc. MMR catch-up ,urgent' The DoH has called for urgent action to reduce the risk of a measles epidemic. Following years of relatively low uptake of MMR vaccine, the pool of unprotected children is now large enough to raise the prospect of 30 000-100 000 measles cases in England. A catch-up campaign will now target children and young people who have never been vaccinated, followed by those who have not completed their course of immunisation. Resource materials are available at www.immunisation.nhs.uk. , A new brand of MMR vaccine is now available. Sanofi Pasteur MSD has replaced MMRII with a new formulation and presentation, MMRvaxPro. The new vaccine is equivalent to its predecessor and interchangeable with Priorix. Early primary prevention with low-dose aspirin? GPs should consider prescribing low-dose aspirin for primary prevention for men aged 48 and women aged 57, say UK researchers (Heart 2008; published online 15 August 2008. doi:10.1136/hrt.2008.150698). Using data from the THIN network of electronic patient records, they modelled the age at which 10-year coronary risk changed from <10 per cent to >10 per cent in men and women without diabetes, not taking lipid-lowering therapy and with no history of cardiovascular disease. Does COPD therapy slow progression? Treatment with an inhaled steroid and long-acting beta-agonist may slow progression of COPD, according to a new analysis of the TORCH study (Am J Respir Crit Care Med 2008;178:332-8). TORCH was designed to determine the effects of COPD treatment on mortality; the primary analysis found no significant difference between fluticasone/salmeterol (Seretide) and placebo (N Engl J Med 2007;356:775-89). This analysis found that the rate of decline in FEV1 (a marker of disease progression) was significantly greater with placebo (55ml per year) than with salmeterol or fluticasone monotherapy (both 42ml per year) or their combination (39ml per year). Faster decline in FEV1 was associated with current smoking, lower BMI and more frequent exacerbations. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 7 2008Article first published online: 28 APR 200 Referrals from Boots The majority of people requesting Boots' erectile dysfunction or weight management programmes are referred to their GP(Pharm J 2008;280:297). The programmes are run under patient group directions and exclude people with elevated blood pressure, blood glucose or cholesterol. Over 80 per cent of customers screened for the erectile dysfunction programme in Manchester and two-thirds of those screened for the national obesity programme were referred. Vildagliptin: new DPP-4 inhibitor for diabetes Novartis has introduced the DPP-4 inhibitor vildagliptin for the treatment of type 2 diabetes. Two formulations are available: Galvus (vildagliptin 50mg) is licensed for use with metformin, a sulphonylurea or a thiazolidinedione when these agents do not achieve glycaemic control alone, and Eucreas (vildagliptin 50mg plus metformin 850 or 1000mg) is licensed for patients requiring combined therapy with vildagliptin and metformin. Inhibition of DPP-4 blocks the breakdown of the incretin hormones GIP and GLP-1, reducing fasting plasma glucose and postprandial hyperglycaemia. Vildagliptin is the second DPP-4 inhibitor to be introduced; the first was sitagliptin (Januvia), which has similar licensed indications. The third available drug acting on the incretin system is the incretinmimetic exenatide (Byetta); administered by injection, this is licensed for use with metformin and/or a sulphonylurea and is the only agent in this class to be approved for triple therapy. No comparative trials of these agents have been published. A month's treatment with twice-daily vildagliptin 50mg or either strength of vildagliptin plus metformin costs £31.76. Sitagliptin 100mg once daily costs £33.26. Sinusitis symptoms don't guide treatment The severity and duration of symptoms do not help to identify which patients with sinusitis will be helped by antibiotics, a new meta-analysis suggests (Lancet 2008;371: 908-14). The analysis of patient-level data from nine trials involving a total of 2547 adults showed that the number needed to treat (NNT) to cure one patient with rhinosinusitis was 15. Cure took longer to achieve in older patients and in those reporting symptoms for longer or with more severe symptoms. The authors comment that treatment is not justified given the risk of resistance and adverse effects and cost of antibiotics. Draft guidance from the National Institute for Health and Clinical Excellence (NICE) on the management of respiratory infections states that no antibiotic therapy or a delayed antibiotic prescribing strategy should be negotiated for patients with acute sinusitis. Taking cod liver oil leads to fewer NSAIDs Cod liver oil could help some patients with rheumatoid arthritis to reduce their NSAID consumption, according to a study from Dundee (Rheumatology online: 24 March 2008; doi: 10.1093/rheumatology/ ken024). A total of 97 patients were randomised to nine months' treatment with cod liver oil 10g per day or placebo. After 12 weeks, patients attempted to reduce or stop their use of NSAIDs. Significantly more of those taking cod liver oil achieved at least a 30 per cent reduction in NSAID use compared with placebo (39 vs 10 per cent). There were no differences in adverse effects or disease activity. Welsh prescriptions up The reduction in the prescription charge in Wales in 2004 was followed by an increase in prescribing of nonsedating antihistamines in wealthier areas, a study suggests (Health Policy online: 5 March 2008; doi:10.1016/j. healthpol.2008.01.006). In the two years preceding the cut, prescriptions for nonsedating antihistamines increased by about 7 per cent; in the two years after the cut, the increase was nearly 14 per cent. By contrast, there was no change in the rate of increase in the south-east of England (4,5 per cent in both periods). The increased growth in prescribing was statistically significant in the five least deprived but not in the five most deprived health boards in Wales. Aspirin linked with reduced asthma risk Low-dose aspirin is associated with a reduced risk of developing asthma, a new analysis of the Women's Health Study has shown (Thorax online: 13 March 2008; doi:10.1136/ thx.2007.091447). The analysis included 37 270 women with no asthma at baseline who were randomised to take placebo or aspirin 100mg every other day. After 10 years, 872 cases of asthma occurred in women taking aspirin and 963 with placebo, a 10 per cent reduction in risk. However, risk was not reduced in obese women. The mechanism by which aspirin may affect the risk of asthma is unknown. The latest evidence is consistent with findings published by the same investigators after analysis of two other large observational studies, the Physicians' Health Study and the Nurses Health Study. Anastrozole bone loss Long-term follow-up of the ATAC (Anastrozole, Tamoxifen, Alone or in Combination) trial has confirmed that adjuvant therapy with anastrozole (Arimidex) is associated with greater loss of bone mineral density (BMD) than tamoxifen in postmenopausal women with invasive primary breast cancer (J Clin Oncol 2008;26: 1051,7). After five years, median BMD was reduced by 6 and 7 per cent in the lumbar spine and hip with anastrozole compared with approximately 3 and 1 per cent respectively for tamoxifen, though no patients developed osteoporosis. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 3 2008Article first published online: 26 FEB 200 Higher risk of CV events in aspirin resistance More than one in four patients may have aspirin resistance, a new metaanalysis shows, and they face a four-to sixfold increased risk of a major cardiovascular event or death compared with aspirin-sensitive patients taking low-dose aspirin (BMJ online: 17 Jan 2008; doi:10. 1136/bmj.39430.529549.BE). The analysis included 20 studies involving a total of 2930 patients with cardiovascular disease. Of these, 28 per cent were defined as having aspirin resistance (according to the various definitions in each study). Compared with aspirin-sensitive patients, the odds ratio of any cardiovascular event or acute coronary syndrome was about 4 and the odds ratio of death was 6. Aspirin-resistant patients did not benefit from other antiplatelet treatment. ADOPT: rosiglitazone fracture risk in women A new analysis of the ADOPT trial (N Engl J Med 2006;355: 2427-43) has found that the risk of fractures during treatment with rosiglitazone (Avandia) is approximately twice as high as with metformin or glibenclamide, but mainly in women (Diabetes Care online: 25 Jan 2008; doi: 10.2337/dc07-2270). The study found a significant difference in risk between the drugs only for women, with a cumulative incidence of 15.1 per cent with rosiglitazone, 7.3 per cent with metformin and 7.7 per cent with glibenclamide after five years. No risk factors were identified although the incidence of fractures was higher among postmenopausal than premenopausal women. New from NICE Infliximab for the treatment of adults with psoriasis. Technology Appraisal Guidance No. 134, Jan 2008 Infliximab (Remicade), a monoclonal antibody against TNF-alpha, should be an option for treating very severe plaque psoriasis in adults, NICE recommends. Using its fast-track single technology appraisal procedure, NICE concluded that infliximab should be considered when standard therapies,methotrexate or ciclosporin (Neoral), or PUVA , have failed or are unsuitable. The criteria for disease severity are defined by the Psoriasis Area Severity Index (PASI) score (,20) and the Dermatology Life Quality Index (DLQI) score (>18). Treatment response is also defined by these measures and infliximab should be continued for longer than 10 weeks only when predefined thresholds are met. Infliximab costs an average of £11 750 annually. In 2006, NICE recommended etanercept (Enbrel) and efalizumab (Raptiva) for patients with severe psoriasis (PASI ,10 and DLQI >10). Commons committee wants tougher targets Most GPs get full QOF points for medicines management even though there is inexplicably large variation in good prescribing practice between PCTs, the Public Accounts Select Committee points out in its latest report, Prescribing Costs in Primary Care. The Committee wants to see tougher QOF targets among several initiatives to reduce prescribing costs. Although most publicity centred on its endorsement of the National Audit Office claim that GPs could save £200 million by prescribing lower-cost drugs, the report contains some more far-reaching proposals. GPs should prescribe generic alternatives within a therapeutic category, so when a brand is not available generically, eg Lipitor, a different drug that is, eg simvastatin, should be used when clinically appropriate. Further, this form of substitution should be rewarded via QOF targets. There should be greater uniformity in the appearance, labelling and packaging of generic and branded equivalents. The Department of Health should consider raising awareness of the value of medicines by printing the cost on packaging, and to reduce the £100 million wasted annually in dumped medicines, it should investigate which drugs aren't used and why patients won't take them. Strategic health authorities should work with the National Prescribing Centre to develop more prescribing indicators with which to measure PCT performance and support PCTs to promulgate best practice. They should also collaborate on promoting joint primary-secondary care formularies and increase the consistency of prescribing, not only between hospital specialists and GPs but also between PCTs. To monitor the influence of the pharmaceutical industry, PCTs should keep a record of gifts and hospitality and publish a register. Questions to ask about mental health treatment The Department of Health has published a booklet designed to raise awareness of medicines management issues affecting people using mental health services and their carers, and professionals in the health and social services. Although one aim of Medicines Management: Everybody's Business is to empower people with mental health problems to ask about their medication, its formal style is better suited to staff who need to improve their person-centred approach to care. It covers what information people should expect and what questions to ask when drug treatment is being considered, what to expect at review and issues to consider when contemplating stopping treatment. Copies can be downloaded at www.dh.gov.uk. Consider statins for all patients with diabetes Treatment with a statin should be considered for all patients with diabetes unless their risk is low, say the authors of a new study (Lancet 2008;371:117-25). Their meta-analysis of 14 randomised trials involving 18 686 people with diabetes and an average follow-up of 4.3 years found that statins reduced vascular events and vascular mortality as much as in nondiabetic populations. The overall benefit was 42 fewer major events per 1000 people treated for five years. This was independent of a history of vascular disease or other baseline characteristics. No evidence for OTC cough medicines There is no evidence that over-the-counter cough medicines for adults and children are effective in relieving acute cough, a new Cochrane review has concluded (Cochrane Database of Systematic Reviews 2008, Issue 1). The review of 17 randomised trials involving 2876 adults and eight involving 616 children reported conflicting findings of uncertain clinical relevance. The trials were heterogeneous and of low quality. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 2 2008Article first published online: 11 FEB 200 NICE should evaluate all new medicines NICE should determine the cost effectiveness of all new medicines, the Health Select Committee has concluded in its second review of the Institute. The review, prompted by criticisms from patients, health professionals and the pharmaceutical industry, found that NICE is doing ,a vital job in difficult circumstances'. The Committee called for the costs to carers and society to be included in cost effectiveness estimates (this is currently prohibited) and for cost per QALY thresholds to be aligned with NHS affordability. NICE should publish brief appraisals at the time of a product launch , these could be used to negotiate prices. GPs responsible for unlicensed co-proxamol GPs who prescribe co-proxamol are now responsible for the consequences, the MHRA warns. The Agency agrees that the drug may be needed by ,a small group of patients who are likely to find it very difficult to change from co-proxamol or where alternatives appear not to be effective or suitable'. Following the withdrawal of product licences, stock that is currently in the supply chain may be dispensed but no new stock should be released by suppliers. The Drug Tariff price of co-proxamol has now increased from £2.79 to £20.36 per 100 tablets. Vitamin D deficiency on the increase Pregnant and breastfeeding women may need vitamin D supplements, the Department of Health has warned, and GPs are seeing increasing numbers of patients with vitamin D deficiency. Endogenous synthesis may be low in some ethnic groups and dark-skinned people, and north of Birmingham there is no light of the appropriate wavelength for the synthesis of vitamin D during the winter. The Department says free vitamin supplements are available for eligible patients through its Healthy Start Scheme (www.healthystart.nhs.uk) and may also be supplied at low cost by some PCTs. Innovation and good practice recognised Innovative practice and better outcomes for patients have been recognised through awards from the NHS Alliance and Improvement Foundation presented by the Secretary of State for Health, Rt Hon Alan Johnson, at the annual NHS Alliance conference held in Manchester. The Mountwood Surgery in Northwood, Middlesex, won the CHD QOF GP Practice Award sponsored by Schering Plough for their outstanding multidisciplinary approach to tackling CHD. In addition to having a highly organised in-house cardiology team, they have produced an interactive, patient-empowering booklet for CHD. Mountwood Surgery achieved blood pressure targets of 96.79 per cent in their CHD patients. North Tees PCT wins the CHD QOF PCO Award, also sponsored by Schering Plough, for their support and encouragement to GP practices to ,own' CHD care. They provide timely feedback of performance data using funnel plots and regular communication by the CHD LIT and Cardiac Network. Even though North Tees PCT has a high CHD prevalence, 4.2 per cent vs 3.6 per cent nationally, across the 27 practices 85 per cent of patients achieved cholesterol targets and 91 per cent reached the QOF blood pressure target. The St Benedict's Hospice Day Centre Project (for the Sunderland Teaching Primary Care Trust) won the Guy Rotherham Award for its excellent multidisciplinary team improvement of the palliative care provided. This team demonstrated a thorough understanding of the use of quality improvement methods to improve patient care, and carefully measured the individual improvements they made. Through the use of a referral ,decision tree', nonattenders were reduced by 300 per cent and average waiting times halved. The Extended Primary Care (EPC) Gynaecology Service (for the Practice Based Commissioning Consortium South Manchester Hub) was highly commended for its development of an effective and innovative service offering gynaecological treatment managed within a primary care setting, allowing patients improved access closer to home. The Salford Perinatal Mental Health Project was also highly commended for effectively challenging the high levels of maternal suicides. The awards were also supported by Prescriber, the British Cardiac Patients Association and the British Cardiac Society. Anastrozole superior to tamoxifen in long term A new analysis of the ATAC trial (Lancet Oncology 2008;9:45-53) shows that the advantages of the aromatase inhibitor anastrozole (Arimidex) over tamoxifen as adjuvant therapy for breast cancer persist for at least four years after the end of treatment. After primary treatment with surgery, chemotherapy or radiotherapy, postmenopausal women with localised invasive breast cancer were randomised to five years' treatment with anastrozole or tamoxifen. Among 5216 women who were hormone-receptor positive, anastrozole increased disease-free survival by 15 per cent after 100 months. Time to recurrence and distant recurrence were also increased, though overall survival was similar; the absolute difference in time to recurrence was greater at nine years (4.8 per cent) than at five years (2.8 per cent). Joint symptoms and fractures were more frequent with anastrozole during treatment but not thereafter. Use a steroid with a LABA , MHRA reminder The MHRA has reminded clinicians that patients treated with an inhaled long-acting beta-agonist (LABA) should also use an inhaled steroid. In the latest edition of Drug Safety Update (2008;1:No.6), the Agency reviews the implications of the SMART study (Chest 2006;129:15-26), which reported an increased risk of respiratory- and asthma-related deaths among patients using salmeterol (Serevent). This is contradicted by epidemiological data suggesting that asthma-related admissions have declined since LABAs were introduced. Randomised trials also do not support such a risk, probably because inhaled steroids are used more consistently in trial settings. The latest Update notes that product licences for carisoprodol (Carisoma) have been suspended due to concerns about the risk of abuse and psychomotor effects. It also includes a comprehensive summary of drug interactions with statins, a warning that methylene blue should not be prescribed for a patient taking a drug with serotonergic activity, and a reminder that only oral formulations of desmopressin are now licensed for primary nocturnal enuresis. This issue of Update is available at www.mhra.gov.uk. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 23-24 2007Article first published online: 8 JAN 200 Cervical cancer risk falls after COC use ends Combined oral contraceptives (COCs) are associated with a slight increase in the risk of cervical cancer but this diminishes with time after use ends, an international study has shown (Lancet 2007;370:1609,21). Analysis of data for 16 573 women with and 35 509 women without cervical cancer confirmed that using a COC for 10 years between the ages of 20 and 30 increases the incidence of invasive cervical cancer from 3.8 to 4.5 per 1000 by age 50. However, the excess risk disappears 10 years after cessation of use. , A new analysis of the US Nurses' Health Study suggests that protection against ovarian cancer does not persist beyond 20 years after cessation of COC use. This study also showed that tubal ligation is associated with reduced risk of ovarian cancer (Am J Epidemiol 2007; 166;894,901). Pharmaceutical services fund moves to PCTs The ,global sum' that provides central funding for NHS pharmaceutical services is being shifted to PCTs. The Government has included legislation for the change in the recent Health and Social Care Bill. The fund pays the fees and allowances for pharmacy contractors and appliance contractors. The Government says this is a ,natural progression and in keeping with moves to devolve NHS funds to the frontline' that will enable PCTs to manage pharmacy services better by ,encouraging best prescribing practice'. Fewer fluoroquinolones in the community Restricting prescribing of fluoroquinolone antibacterials does not increase hospital admissions for infection among older people, say Canadian researchers (Am J Med 2007;120:893,900). Their analysis of an Ontario medical database shows that, in a community where fluoroquinolones were the most widely prescribed antibacterials, a one-third reduction in prescribing was not followed by an increase in hospital admissions for infectious episodes in the over,65s. On the contrary, there was a 32 per cent reduction in admissions for gastrointestinal conditions. FDA reports increased TB risk with infliximab The US Food and Drug Administration has published an analysis of cases of TB associated with infliximab (Remicade) detected via its spontaneous adverse event reporting scheme (Ann Intern Med 2007;147: 699,702). In 2001 the FDA placed a warning about the risk of TB on product labelling for infliximab and advised testing for TB before initiating treatment. This analysis of 130 cases of TB since reported in patients treated with infliximab found that 45 per cent had developed extra-pulmonary disease; risk factors included use of immunosuppressants (including methotrexate), a history of TB and time spent in an endemic area. Of 67 cases in which treatment was initiated after the warning was issued, 34 with a negative tuberculin skin test developed TB after receiving infliximab. MHRA announces anticounterfeit strategy The UK is a transit point, distribution hub and end-user of counterfeit medicines, says the MHRA in its first anti-counterfeiting strategy (www.mhra.gov.uk). Counterfeits have been detected in the legitimate supply chain with increasing frequency since 2004, resulting in nine batch recalls and a further five incidents detected at wholesale level. The MHRA's proposed approach includes: communication to raise awareness of the risk and facilitate reporting, collaboration with the WHO, the industry and law enforcement agencies, and targeted surveillance, prosecution and regulation. Evidence lacking for choosing DMARD There is insufficient evidence to choose one DMARD or biological agent over another in patients with RA, US investigators say (www.annals.org/cgi/content/abstract/0000605,20080115000192v1). Their systematic review of meta-analyses and intervention and observational trials found no evidence of differences among DMARDs or anti-TNF agents. Mono-therapy with an anti-TNF agent was associated with superior radiographic but not clinical outcomes; methotrexate plus an anti-TNF agent was superior in clinical and functional terms to either drug given alone. Be alert to psychiatric ADRs with rimonabant Clinicians should remain alert for the development of anxiety, depression and an increased risk of suicide with rimonabant (Acomplia), say Danish investigators (Lancet 2007;370:1706,13). Their meta-analysis of four randomised trials involving a total of 4105 patients showed that rimonabant was associated with an increased risk of serious adverse events (odds ratio 1.4; number needed to harm, NNH, 59), including a 2.5,fold increased risk of depression (NNH 49) and a threefold increased risk of anxiety (NNH 166). Following a warning from the FDA of an increased risk of suicide with rimonabant, the authors say their findings indicate a need for ,increased alertness by physicians to these potentially severe psychiatric adverse reactions'. New strategy for NHS medicines information The UK Medicines Information Service (www.ukmi.nhs.uk) has published its new management strategy setting out how it will respond to recent developments in the NHS. Developments include greater access to information for patients, support for nontraditional prescribers and new commissioning arrangements. New antiretroviral Maraviroc (Celsentri) is the first CCR5 antagonist to be introduced for the treatment of HIV infection. CCR5 is one of two co-receptors to which the HIV virus must attach to achieve cell entry. Maraviroc is licensed for use by treatment-experienced patients in whom only CCR5-tropic HIV-1 is detectable. The recommended dose ranges from 150 to 600mg twice daily depending on interactions with concurrent medication. Dimeticone superior Dimeticone 4 per cent lotion (Hedrin) is superior to malathion 0.5 per cent in the eradication of head lice, a UK study in 58 children and 15 adults has shown (PLoS ONE 2007;2: e1127. doi:10.1371/journal.pone. 0001127). Two applications of dimeticone lotion one week apart cleared active infestation in 70 per cent of participants compared with 33 per cent in those who used a single application of malathion. Copyright © 2007 Wiley Interface Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 14 2007Article first published online: 19 OCT 200 Studies suggest risk of bone loss with SSRIs Two cross-sectional studies have suggested the SSRI antidepressants may be associated with an increased risk of bone loss (Arch Intern Med 2007;167:1240,5 &1246,51). In 2722 older women (mean age 79) living in the community who were participating in the Study of Osteoporotic Fractures cohort study, use of SSRIs was associated with a significant increase in the rate of loss of hip bone density compared with nonusers(0.82 vs 0.47 per cent per year). The rate of loss among women taking a tricyclic antidepressant was also 0.47 per cent per year. Excluding women with more severe depression did not alter the findings. In 5995 men aged 65 or older taking an SSRI in another study, mean bone density was 3.9 per cent lower at the hip and 5.9 per cent lower in the lumbar spine compared with no use of antidepressants. Use of a tricyclic antidepressant or trazodone was not associated with increased bone loss. The authors comment that the degree of bone loss is comparable with that associated with corticosteroids. Serotonin transporters have been identified in osteoblasts and osteocytes. Risk of rare birth defects with SSRIs Two US case-control studies have found qualified evidence that use of SSRIs during the first trimester may be associated with a small increase in the risk of rare neonatal defects (N Engl J Med 2007;356:2675,83 & 2684,92). The Slone Epidemiology Center Birth Defects Study identified 9849 infants with birth defects and 5860 without and found no significant association between SSRI use overall and defects previously attributed to SSRIs (craniosynostosis, omphalocele or heart defects). There was some evidence that sertraline and paroxetine may cause specific defects, but this was based on few cases and the absolute risk remained low. The National Birth Defects Prevention Study identified 9622 infants with major birth defects and 4092 controls. There was no significant association with heart defects but the odds of anencephaly, craniosynostosis and omphalocele were each significantly increased by a factor of 2,3. The authors say the absolute risk remains small and their findings require confirmation. UK data do not support MI link with rosiglitazone An interim analysis of a UK clinical trial of rosiglitazone (Avandia) has found no evidence that it is associated with an increased risk of myocardial infarction (N Eng J Med 2007;357:28,38). A US meta-analysis (N Engl J Med 2007;356:2457,71) recently suggested that the odds of an MI or cardiovascular (CV) death in patients taking rosiglitazone were increased by 40,60 per cent compared with controls. The UK analysis of an ongoing nonblinded trial comparing rosiglitazone plus a sulphonylurea or metformin with sulphonylurea/metformin found no significant differences in the risk of MI or CV death. The risk of heart failure was doubled in patients taking rosiglitazone. The authors comment that, with a mean follow-up of 3.75 years, they had too few data to reach a conclusive finding. Switch piroxicam users to another NSAID The European Medicines Agency has advised prescribers to switch patients who are taking oral piroxicam to another NSAID. The advice follows a reappraisal of the safety of piroxicam when the 2006 review of all nonselective NSAIDs suggested it may be associated with increased risks of GI adverse effects and serious skin reactions. The advice does not apply to topical formulations. Piroxicam should not be prescribed for acute conditions and should not be first-choice for osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The maximum dose should be 20mg per day and treatment should be reviewed after 14 days. The MHRA states there is no need for urgent action; long-term treatment should be reviewed at the next routine appointment. OTC azithromycin? The MHRA is consulting on a request by a pharmaceutical company to reschedule azithromycin to pharmacy-only status for the treatment of known or suspected Chlamydia trachomatis infection in individuals aged 16 years or older. The applicant envisages supplies being made only when a nucleic acid amplification test (NAAT) is positive. Responses should be submitted to the MHRA (www.mhra.gov.uk) by 2 August. Computers can reduce prescribing errors Computerised prescribing reduces by two-thirds the rate of medication errors associated with handwritten prescriptions, a new review has found (Health Services Research 2007; online doi:10.1111/j.1475,6773. 2007.00751.x). There was some evidence that the risk of all errors, dose errors and adverse effects were reduced by computerisation. The greatest impact was seen in settings with very high error rates (>12 per cent) associated with handwritten prescriptions. However, the studies included produced heterogeneous results and the reduction in errors in prescribing for children was not statistically significant. Furthermore, computerisation did not reduce the rate of prescribing the wrong drug. Echinacea works for colds, new study finds The herbal remedy Echinacea does reduce the risk of catching a cold, according to a new metaanalysis (Lancet Infect Dis 2007;7:473,80). In 2006, a Cochrane review found insufficient evidence to support the benefits claimed for Echinacea. The new study, which additionally included experimentally-induced infections among the 14 trials analysed, found that Echinacea reduced the odds of catching a cold by about half and reduced the average duration of a cold by 1.4 days. Though inconclusive, the possibility of publication bias and heterogeneity between the trials could not be excluded. HRT may reduce cardiovascular risk after all A subgroup analysis of the Women's Health Initiative (WHI) suggests that HRT may reduce the risk of coronary heart disease if started soon after the menopause (N Engl J Med 2007;356:2591,602). The main analysis of WHI showed no cardiovascular benefit for HRT, a finding attributed to the relatively old mean age of participants (59). In the new analysis of 1064 women aged 50,59, HRT use was associated with a significant reduction in coronary artery calcification compared with nonuse, with greater effect associated with greater adherence. Reducing BP key to avoiding heart failure An angiotensin,II receptor blocker (ARB) is no better than other antihypertensives at avoiding the development of heart failure in individuals with hypertension, say US investigators (Lancet 2007;369:2079,87). Drugs that affect the renin-angiotensin system can reduce ventricular hypertrophy and may therefore prevent the development of heart failure in patients with hypertension. This study found similar improvements in diastolic function in 384 patients with hypertension and left ventricular dysfunction randomised to valsartan (Diovan) or placebo in addition to standard antihypertensive treatment for 38 weeks. The authors conclude that blood pressure reduction, not choice of drug, is the most important factor. Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 9 2007Article first published online: 3 SEP 200 Clinical trials flatter anti-TNFs in RA The efficacy of anti-TNF agents in clinical trials is not matched by experience in daily practice in patients with rheumatoid arthritis, say Dutch investigators (Ann Rheum Dis online: 10 April 2007; doi:10.1136/ard.2007.072447). They compared outcomes from a systematic review of trials of etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) and a national postmarketing surveillance scheme (DREAM). In 5 of 11 comparisons, the response rate in DREAM was significantly lower than that in RCTs. Responses among DREAM patients who met the inclusion criteria for clinical trials were significantly greater than among noneligible patients and comparable with those of patients participating in the trials. The authors conclude that patients in trials have more severe disease and therefore a response to treatment that is not matched in daily practice. Methadone prescriptions double in 10 years Methadone treatment for opiate addicts has more than doubled in the past 10 years, according to an audit of opiate substitution in England by the National Treatment Agency for Substance Misuse (www.nta.nhs.uk). The total number of methadone prescriptions increased from 970 900 in 1995 to over 1.8 million in 2004. The introduction of buprenorphine (Subutex) has not reduced methadone prescribing , 96 per cent of responding centres prescribed methadone and 88 per cent prescribed buprenorphine. Seventy-two per cent of centres prescribe benzodiazepines to opiate addicts, causing the NTA some concern. GPs were involved in prescribing management in about 60 per cent of centres. Next NICE guidelines The Department of Health has referred eight topics to NICE for the development of clinical guidelines: preventing venous thromboembolism, acute coronary syndromes, chest pain, social complications during pregnancy (eg drug misuse), benign prostatic hyperplasia, constipation in children, neonatal jaundice and metastatic disease of unknown primary origin. Errors with children , Every step of drug treatment for children, from prescribing to writing notes, is associated with a substantial level of error, say US investigators (Quality and Safety in Health Care 2007;16:116-26). Their systematic review of 31 studies reporting medication errors in paediatrics found that 3-37 per cent were associated with prescribing errors, 5-58 per cent with dispensing errors, 72-75 per cent with errors of administration, and 17-21 per cent with documentation errors. Suggestions for remedial strategies were not evidence based, the authors found. , and transplant patients Errors in medication are common among outpatients who have received liver, kidney or pancreas transplants, a second US study has found (Arch Surg 2007;142:278-83). Twelve months' follow-up of 93 patients revealed a total of 149 errors of drug treatment, with a frequency of 15 in 219 visits over a four-week period. One-third of errors were associated with adverse events including hospital admission and graft rejection. Patients were taking an average of 11 medicines; analysis showed that over half of errors originated with the patients and 13 per cent were associated with prescribing. Paracetamol pack benefit challenged A new study has challenged accepted wisdom that reducing the OTC pack size of paracetamol cut the suicide rate (PLoS Medicine 2007;4:e105). In 1998, pack sizes of paracetamol were limited to 16 in general sale outlets and 32 in pharmacies. Suicide rates subsequently decreased but, though widely assumed, a causal link has not been established. Researchers from London and the Office of National Statistics have now examined mortality trends from suicide associated with antidepressants, aspirin, compound paracetamol preparations and nondrug poisoning. They found that all fatal suicides declined at similar rates after the pack size reductions. While not excluding the possibility that restricting easy access to paracetamol may have helped, these data suggest that other factors were also important. CV risk with ibuprofen among aspirin users Ibuprofen, but not naproxen, is associated with a higher risk of cardiovascular events and heart failure than lumiracoxib (Prexige) in high-risk patients, according to a new analysis of the TARGET trial (Ann Rheum Dis online: 5 April 2007; doi:10.1136/ard.2006.066001). TARGET comprised two studies comparing naproxen or ibuprofen with lumiracoxib in a total of 18 325 patients with OA. This post-hoc analysis stratified patients by their cardiovascular risk; the primary end-point was a composite of cardiovascular mortality, nonfatal myocardial infarction and stroke at one year. Among those at high risk who were taking aspirin, ibuprofen was associated with an increased risk of the composite end-point compared with lumiracoxib (2.14 vs 0.25 per cent). The risk was similar for naproxen and lumiracoxib (1.58 vs 1.48 per cent). In high-risk patients not taking aspirin, the risk was similar for ibuprofen and lumiracoxib, but lower for naproxen than lumiracoxib. Congestive heart failure was more common in patients taking ibuprofen than lumiracoxib (1.28 vs 0.14 per cent); the risk was similar with naproxen and lumiracoxib. The authors emphasise that their findings should be considered hypothesis-generating. CVD guidelines criticised The second edition of the guidelines of the Joint British Societies on preventing cardiovascular disease have been harshly criticised for failing to meet international quality standards (Int J Clin Pract online doi: 10.1111/j.1742-1241.2007.01310.x). Kent GP Dr Rubin Minhas evaluated the guidelines against the criteria of the Appraisal of Guidelines and Research (AGREE) Collaboration. He identified areas of weakness including stakeholder involvement, rigour of development, applicability (by not considering cost) and editorial independence from the pharmaceutical industry. The guidelines should not be recommended for clinical practice, he concludes. OTC naproxen? The MHRA is consulting on switching naproxen 250mg to pharmacy-only status for the treatment of period pain in women aged 15-50. The change would offer an alternative to ibuprofen, currently the only other OTC medicine with this indication. Responses should be submitted by 23 May. The Agency is currently considering responses to its consultation on switching tranexamic acid to OTC status for heavy menstrual bleeding. Diabetes costs The total cost of prescribing for diabetes in England has doubled in only five years, official statistics show. The NHS Information Centre (www.ic.nhs.uk) report shows that spending in primary and secondary care in 2006 was £561 million, up 14 per cent on 2005. Growth was due to increased prescribing of oral hypoglycaemic agents (notably the glitazones , up by one-third over 2005) and the higher costs of insulins. Pharmacists may give flu jabs PCTs may consider using pharmacists to administer flu vaccines to some at-risk groups in the 2007/08 season, according to Department of Health plans. Flu vaccination payment for patients with diabetes, coronary heart disease, and stroke and TIA is provided under the Quality Outcomes Framework. The Department suggests that PCTs consider contracting a local enhanced service from pharmacists to reach other patients at increased risk, such as those with chronic liver disease, multiple sclerosis and related conditions, hereditary and degenerative disease of the CNS and carers. Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 2 2007Article first published online: 1 MAR 200 Venlafaxine: same suicide risk Venlafaxine (Efexor) is probably not associated with a higher risk of suicide than citalopram, fluoxetine or dosulepin, even when prescribed for patients at higher risk, according to an analysis of the UK General Practice Research Database (BMJ, doi:10.1136/bmj.39041.445104.BE. Published 12 December 2006). The retrospective cohort study found that venlafaxine was associated with a significantly higher risk of completed and attempted suicide in adults than the other antidepressants but, after adjusting for risk factors, the authors concluded that much, if not all, of the difference could be explained by confounding. Raised glucose with thiazides not clinically significant? A new analysis of the ALLHAT trial suggests that the small increase in blood glucose levels associated with long-term thiazide therapy is not associated with an increased risk of cardiovascular events (Arch Intern Med 2006;166:2191-201). The ALLHAT trial compared cardiovascular outcomes in over 18 000 patients with hypertension who were treated with chlortali- done (Hygroton), amlodipine and lisinopril. After two years, fasting blood glucose had increased in all groups (by 0.47, 0.31 and 0.19mmol per litre respectively); compared with chlortalidone, the odds of developing diabetes were 45 per cent lower with lisinopril and 27 per cent lower with amlodipine. However, there was no significant link between fasting blood glucose levels and cardiovascular events, end-stage renal disease or death; developing diabetes was associated with an increased risk of CHD overall but this was not statistically significant for chlortalidone in particular. Withdrawing alendronate after five years' treatment Discontinuing treatment of osteoporosis with alendronate after five years does not significantly increase fracture risk for many women, a US study has shown (J Am Med Assoc 2006;296:2927-38). In this five-year extension to the Fracture Intervention Trial, 1099 women who had taken alendronate for five years were randomised to continue treatment or switch to placebo for a further five years. In those taking placebo, bone mineral density decreased by 2.4 per cent at the hip and 3.7 per cent in the spine but remained above pre- treatment levels. Continuing with alendronate was associated with a lower risk of clinical vertebral fractures (2.4 vs 5.3 per cent) but no significant reduction in morphometric vertebral fractures (9.8 vs 11.3 per cent respectively). The cumulative risk of nonvertebral fractures was 19 per cent in each group. The authors conclude that women at very high risk of clinical vertebral fractures may benefit from continuing alendronate, but for many discontinuation does not appear to increase fracture risk. Instructions on labels Patients with low levels of literacy are at high risk of not understanding medicines labelling (Ann Intern Med 2006;145:887-94). In 395 English-speaking adults, 71 per cent correctly repeated simple label instructions, but only 35 per cent could demonstrate the correct number of tablets involved. Low literacy levels were associated with a twofold increased risk of misunderstanding labelling. Statins campaign The National Prescribing Centre (NPC) has launched a campaign to increase prescribing of low-cost statins. Resources available from its website at www.npc.co.uk/statins.htm are divided into four categories: policy and guidance, therapeutics, implementation resources and monitoring tools. Formats include documents and case studies, Powerpoint presentations and E-learning workshops. patients feeling rested on waking and daytime functioning. The Z-drugs were also believed to cause fewer adverse effects. GPs believe in ,Z' drugs A survey of GPs in Lincolnshire has revealed that their beliefs about nonbenzodiazepine hypnotics are inconsistent with NICE guidance and published evidence (Br J Gen Pract 2006; 56:964-7). Responders believed that zaleplon (Sonata), zopiclone and zolpidem were superior to benzodiazepines in increasing sleep time, patients feeling rested on waking and daytime functioning. The Z-drugs were also believed to cause fewer adverse effects. The authors note that, while benzodiazepine prescribing is declining, that of the Z-drugs is increasing, and they suggest this may be explained by misplaced beliefs about their relative effectiveness and safety. Pharmacy EHC guidance Pharmacists can supply emergency hormonal contraception (EHC) in advance but should consider when it is clinically appropriate to do so, according to revised guidance from the Royal Pharmaceutical Society. The move follows support for advance supply from the British Pregnancy Advisory Service and Marie Stopes International. Pharmacists are advised to decline repeated requests and recommend contraception instead, and to counsel users on using EHC safely and appropriately. More support from NICE NICE has developed two databases to support implementation of its recommendations. The shared learning database (www.nice.org.uk/ sharedlearning) includes experiences of implementing NICE guidance. The second, known as ERNIE (Evaluation and Review of NICE Implementation Evidence), includes data provided by NICE on uptake of its advice and external information (www.nice.org.uk/ernie). Mental health briefings The DoH (www.dh.gov.uk) has published several briefing documents to explain the main changes to mental health legislation, covering professional roles, criteria for detention and supervised community treatment (SCT). SCT applies to patients with a stable chronic mental disorder who have been discharged from hospital and who, but for their treatment, may pose a risk to themselves or others. Patients remain the responsibility of the mental health team. Copyright © 2007 Wiley Interface Ltd [source] New Phylogenetic Analysis of the Family Elephantidae Based on Cranial-Dental Morphology,THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2010Nancy E. Todd Abstract In 1973, Vincent Maglio published a seminal monograph on the evolution of the Elephantidae, in which he revised and condensed the 100+ species named by Henry Fairfield Osborn in 1931. Michel Beden further revised the African Elephantidae in 1979, but little systematic work has been done on the family since this publication. With addition of new specimens and species and revisions of chronology, a new analysis of the phylogeny and systematics of this family is warranted. A new, descriptive character dataset was generated from studies of modern elephants for use with fossil species. Parallel evolution in cranial and dental characters in all three lineages of elephants creates homoplastic noise in cladistic analysis, but new inferences about evolutionary relationships are possible. In this analysis, early Loxodonta and early African Mammuthus are virtually indistinguishable in dental morphology. The Elephas lineage is not monophyletic, and results from this analysis suggest multiple migration events out of Africa into Eurasia, and possibly back into Africa. New insight into the origin of the three lineages is also proposed, with Stegotetrabelodon leading to the Mammuthus lineage, and Primelephas as the ancestor of Loxodonta and Elephas. These new results suggest a much more complex picture of elephantid origins, evolution, and paleogeography. Anat Rec, 2010. © 2009 Wiley-Liss, Inc. [source] Bond lengths in organic and metal-organic compounds revisited: X,H bond lengths from neutron diffraction dataACTA CRYSTALLOGRAPHICA SECTION B, Issue 3 2010Frank H. Allen The number of structures in the Cambridge Structural Database (CSD) has increased by an order of magnitude since the preparation of two major compilations of standard bond lengths in mid-1985. It is now of interest to examine whether this huge increase in data availability has implications for the mean bond-length values published in the late 1980s. Those compilations reported mean X,H bond lengths derived from rather sparse information and for rather few chemical environments. During the intervening years, the number of neutron studies has also increased, although only by a factor of around 2.25, permitting a new analysis of X,H bond-length distributions for (a) organic X = C, N, O, B, and (b) a variety of terminal and homometallic bridging transition metal hydrides. New mean values are reported here and are compared with earlier results. These new overall means are also complemented by an analysis of X,H distances at lower temperatures (T, 140,K), which indicates the general level of librational effects in X,H systems. The study also extends the range of chemical environments for which statistically acceptable mean X,H bond lengths can be obtained, although values from individual structures are also collated to further extend the chemical range of this compilation. Updated default `neutron-normalization' distances for use in hydrogen-bond and deformation-density studies are also proposed for C,H, N,H and O,H, and the low-temperature analysis provides specific values for certain chemical environments and hybridization states of X. [source] | |||||||||||||||||||||||||||||||