Identifying enablers and barriers to individually tailored prescribing: a survey of healthcare professionals in the UK.

BACKGROUND: Many people now take multiple medications on a long-term basis to manage health conditions. Optimising the benefit of such polypharmacy requires tailoring of medicines use to the needs and circumstances of individuals. However, professionals report barriers to achieving this in practice. In this study, we examined health professionals' perceptions of enablers and barriers to delivering individually tailored prescribing. METHODS: Normalisation Process Theory (NPT) informed an on-line survey of health professionals' views of enablers and barriers to implementation of Individually Tailored Prescribing (ITP) of medicines. Links to the survey were sent out through known professional networks using a convenience/snowball sampling approach. Survey questions sought to identify perceptions of supports/barriers for ITP within the four domains of work described by NPT: sense making, engagement, action and monitoring. Analysis followed the framework approach developed in our previous work. RESULTS: Four hundred and nineteen responses were included in the final analysis (67.3% female, 32.7% male; 52.7% nurse prescribers, 19.8% pharmacists and 21.8% GPs). Almost half (44.9%) were experienced practitioners (16+ years in practice); around one third reported already routinely offering ITP to their patients. GPs were the group least likely to recognise this as consistent usual practice. Findings revealed general support for the principles of ITP but significant variation and inconsistency in understanding and implementation in practice. Our findings reveal four key implications for practice: the need to raise understanding of ITP as a legitimate part of professional practice; to prioritise the work of ITP within the range of individual professional activity; to improve the consistency of training and support for interpretive practice; and to review the impact of formal and informal monitoring processes on practice. CONCLUSION: The findings will inform the ongoing development of our new complex intervention (PRIME Prescribing) to support the individual tailoring of medicines needed to address problematic polypharmacy

Spectral quantification of nonlinear behaviour of the nearshore seabed and correlations with potential forcings at Duck, N.C., U.S.A

Local bathymetric quasi-periodic patterns of oscillation are identified from monthly profile surveys taken at two shore-perpendicular transects at the USACE field research facility in Duck, North Carolina, USA, spanning 24.5 years and covering the swash and surf zones. The chosen transects are the two furthest (north and south) from the pier located at the study site. Research at Duck has traditionally focused on one or more of these transects as the effects of the pier are least at these locations. The patterns are identified using singular spectrum analysis (SSA). Possible correlations with potential forcing mechanisms are discussed by 1) doing an SSA with same parameter settings to independently identify the quasi-periodic cycles embedded within three potentially linked sequences: monthly wave heights (MWH), monthly mean water levels (MWL) and the large scale atmospheric index known as the North Atlantic Oscillation (NAO) and 2) comparing the patterns within MWH, MWL and NAO to the local bathymetric patterns. The results agree well with previous patterns identified using wavelets and confirm the highly nonstationary behaviour of beach levels at Duck; the discussion of potential correlations with hydrodynamic and atmospheric phenomena is a new contribution. The study is then extended to all measured bathymetric profiles, covering an area of 1100m (alongshore) by 440m (cross-shore), to 1) analyse linear correlations between the bathymetry and the potential forcings using multivariate empirical orthogonal functions (MEOF) and linear correlation analysis and 2) identify which collective quasi-periodic bathymetric patterns are correlated with those within MWH, MWL or NAO, based on a (nonlinear) multichannel singular spectrum analysis (MSSA). (...continued in submitted paper)Comment: 50 pages, 3 tables, 8 figure

Anaerobe-enriched gut microbiota predicts pro-inflammatory responses in pulmonary tuberculosis

BACKGROUND: The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood. METHODS: To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB. FINDINGS: Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched "death receptor" and "EIF2 signalling" pathways whereas Anaerostipes positively correlated with enriched "interferon signalling", "Nur77 signalling" and "inflammasome" pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways. INTERPRETATION: TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases' stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiota's role in TB. FUNDING: European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases

Getting into hot water:sick guppies frequent warmer thermal conditions

Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate

Motivated learning with digital learning tasks: what about autonomy and structure?

Article about Motivated learning with digital learning tasks: what about autonomy and structure

Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease

The fitness of African malaria vectors in the presence and limitation of host behaviour

<p>Background Host responses are important sources of selection upon the host species range of ectoparasites and phytophagous insects. However little is known about the role of host responses in defining the host species range of malaria vectors. This study aimed to estimate the relative importance of host behaviour to the feeding success and fitness of African malaria vectors, and assess its ability to predict their known host species preferences in nature.</p> <p>Methods Paired evaluations of the feeding success and fitness of African vectors Anopheles arabiensis and Anopheles gambiae s.s in the presence and limitation of host behaviour were conducted in a semi-field system (SFS) at Ifakara Health Institute, Tanzania. In one set of trials, mosquitoes were released within the SFS and allowed to forage overnight on a host that was free to exhibit natural behaviour in response to insect biting. In the other, mosquitoes were allowed to feed directly on from the skin surface of immobile hosts. The feeding success and subsequent fitness of vectors under these conditions were investigated on 6 host types (humans, calves, chickens, cows, dogs and goats) to assess whether physical movements of preferred host species (cattle for An. arabiensis, humans for An. gambiae s.s.) were less effective at preventing mosquito bites than those of common alternatives.</p> <p>Results Anopheles arabiensis generally had greater feeding success when applied directly to host skin than when foraging on unrestricted hosts (in five of six host species). However, An. gambiae s.s obtained blood meals from free and restrained hosts with similar success from most host types (four out of six). Overall, the blood meal size, oviposition rate, fecundity and post-feeding survival of mosquito vectors were significantly higher after feeding on hosts free to exhibit behaviour, than those who were immobilized during feeding trials.</p> <p>Conclusions Allowing hosts to move freely during exposure to mosquitoes was associated with moderate reductions in mosquito feeding success, but no detrimental impact to the subsequent fitness of mosquitoes that were able to feed upon them. This suggests that physical defensive behaviours exhibited by common host species including humans do not impose substantial fitness costs on African malaria vectors.</p&gt

Sexual Selection and the Evolution of Brain Size in Primates

Reproductive competition among males has long been considered a powerful force in the evolution of primates. The evolution of brain size and complexity in the Order Primates has been widely regarded as the hallmark of primate evolutionary history. Despite their importance to our understanding of primate evolution, the relationship between sexual selection and the evolutionary development of brain size is not well studied. The present research examines the evolutionary relationship between brain size and two components of primate sexual selection, sperm competition and male competition for mates. Results indicate that there is not a significant relationship between relative brain size and sperm competition as measured by relative testis size in primates, suggesting sperm competition has not played an important role in the evolution of brain size in the primate order. There is, however, a significant negative evolutionary relationship between relative brain size and the level of male competition for mates. The present study shows that the largest relative brain sizes among primate species are associated with monogamous mating systems, suggesting primate monogamy may require greater social acuity and abilities of deception

Reliability, construct validity and measurement potential of the ICF comprehensive core set for osteoarthritis

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the reliability and construct validity of the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for osteoarthritis (OA) in order to test its possible use as a measuring tool for functioning.</p> <p>Methods</p> <p>100 patients with OA (84 F, 16 M; mean age 63 yr) completed forms including demographic and clinical information besides the Short Form (36) Health Survey (SF-36^®) and the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC). The ICF Comprehensive Core Set for OA was filled by health professionals. The internal construct validities of "Body Functions-Body structures" (BF-BS), "Activity" (A), "Participation" (P) and "Environmental Factors" (EF) domains were tested by Rasch analysis and reliability by internal consistency and person separation index (PSI). External construct validity was evaluated by correlating the Rasch transformed scores with SF-36 and WOMAC.</p> <p>Results</p> <p>In each scale, some items showing disordered thresholds were rescored, testlets were created to overcome the problem of local dependency and items that did not fit to the Rasch model were deleted. The internal construct validity of the four scales (BF-BS 16 items, A 8 items, P 7 items, EF 13 items) were good [mean item fit (SD) 0.138 (0.921), 0.216 (1.237), 0.759 (0.986) and -0.079 (2.200); person item fit (SD) -0.147 (0.652), -0.241 (0.894), -0.310 (1.187) and -0.491 (1.173) respectively], indicating a single underlying construct for each scale. The scales were free of differential item functioning (DIF) for age, gender, years of education and duration of disease. Reliabilities of the BF-BS, A, P, and EF scales were good with Cronbach's alphas of 0.79, 0.86, 0.88, and 0.83 and PSI's of 0.76, 0.86, 0.87, and 0.71, respectively. Rasch scores of BF-BS, A, and P showed moderate correlations with SF-36 and WOMAC scores where the EF had significant but weak correlations only with SF36-Social Functioning and SF36-Mental Health.</p> <p>Conclusion</p> <p>Since the four different scales derived from BF-BS, A, P, and EF components of the ICF core set for OA were shown to be valid and reliable through a combination of Rasch analysis and classical psychometric methods, these might be used as clinical assessment tools.</p