A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations

Insulin analogues have been engineered to enhance desired molecular properties without altering immunogenicity. The majority of insulin pharmacology studies are conducted in healthy volunteers and patients with type 1 diabetes. At present, there are more patients with type 2 than type 1 diabetes receiving insulin treatment. As the responsibility for initiating insulin therapy in these patients continues to shift to primary care, it will be important for general practitioners to understand the different pharmacological properties of insulin preparations in patients with type 2 diabetes, so that treatment can be adapted to meet patients’ physiological and lifestyle requirements. The purpose of this review is to summarize pharmacological studies of insulin analogues in patients with type 2 diabetes. Faster onset of action of rapid acting insulin analogues has improved postprandial glycaemic control. Biphasic insulin analogues are associated with a lower incidence of nocturnal hypoglycaemia compared with human biphasic preparations and allow for intensification from once to twice or thrice daily dosing. More predictable glycaemic-lowering profiles of the insulin analogues have also led to reductions in nocturnal hypoglycaemia, particularly comparing long-acting insulin analogues with protaminated human insulin. Enhancing insulin self-association and reversible binding with albumin has led to further reductions in variability. However, improvements can still be made. Effective once daily clinical dosing of long-acting insulin analogues is not possible in all patients. In addition, the protaminated component of biphasic insulin analogues do not provide the duration of action or profile for physiological basal insulin replacement and neither insulin glargine nor insulin detemir are suitable for mixing with other insulin analogues as this would substantially alter their pharmacokinetic properties. Enhancing the pharmacological predictability and extending the duration of action could simplify insulin titration and further reduce the incidence of hypoglycaemia

Seasonal Training-Load Quantification in Elite English Premier League Soccer Players

Purpose: To quantify the seasonal training load completed by professional soccer players of the English Premier League. Methods: Thirty players were sampled (using GPS, heart rate, and rating of perceived exertion [RPE]) during the daily training sessions of the 2011–12 preseason and in-season period. Preseason data were analyzed across 6 × 1-wk microcycles. In-season data were analyzed across 6 × 6-wk mesocycle blocks and 3 × 1-wk microcycles at start, midpoint, and end-time points. Data were also analyzed with respect to number of days before a match. Results: Typical daily training load (ie, total distance, high-speed distance, percent maximal heart rate [%HRmax], RPE load) did not differ during each week of the preseason phase. However, daily total distance covered was 1304 (95% CI 434–2174) m greater in the 1st mesocycle than in the 6th. %HRmax values were also greater (3.3%, 1.3–5.4%) in the 3rd mesocycle than in the first. Furthermore, training load was lower on the day before match (MD-1) than 2 (MD-2) to 5 (MD-5) d before a match, although no difference was apparent between these latter time points. Conclusions: The authors provide the 1st report of seasonal training load in elite soccer players and observed that periodization of training load was typically confined to MD-1 (regardless of mesocycle), whereas no differences were apparent during MD-2 to MD-5. Future studies should evaluate whether this loading and periodization are facilitative of optimal training adaptations and match-day performance

COUNTERMOVEMENT JUMP PERFORMANCE IS NOT AFFECTED DURING AN IN-SEASON TRAINING MICROCYCLE IN ELITE YOUTH SOCCER PLAYERS

This study examined the change in countermovement jump (CMJ) performance across a microcycle of training in professional soccer players during the in-season period. Nine elite youth soccer players performed a CMJ test pre and post four consecutive soccer training sessions of an in-season weekly microcycle. Training load was quantified using global positioning systems (GPS), heart rate (HR) and rating of perceived exertion (RPE). Absolute change (pre to post training) in CMJ height across each training session was analysed using one-way repeated measures analysis of variance (ANOVA). Magnitude of effects was reported with the effect size (ES) statistic. Correlation analyses assessed the relationships between training load measures and the absolute change in CMJ height. Training load remained similar on all training days apart from a significant decrease in training load (all variables except high speed distance) on the last training session (P 0.05). This study revealed no significant change in CMJ performance across the in-season microcycle. This suggests that soccer players are able to maintain CMJ performance across an in-season training microcycle

Effect of low-compression balls on wheelchair tennis match-play

The purpose of this study was to compare court-movement variables and physiological responses to wheelchair tennis match-play when using low versus standard compression tennis balls. Eleven wheelchair basketball players were monitored during repeated bouts of tennis (20-minutes) using both ball types. Graded and peak exercise tests were completed. For match-play, a data logger was used to record distance and speed. Individual linear heart rate oxygen consumption relationships were used to estimate match-play oxygen uptake. Significant main effects for ball type revealed that total distance (P<0.05), forwards distance (P<0.05), and average speed (P<0.05) were higher for play using a low compression ball. A lower percentage of total time was spent stationary (P<0.001), with significantly more time spent at speeds of 1 to 1.49 (P<0.05), 1.5 to 1.99 (P<0.05) and 2.0 to 2.49 (P<0.05) m∙sec-1 when using the low compression ball. Main effects for physiological variables were not significant. Greater total and forwards distance, and higher average speeds are achieved using a low compression ball. No difference in measured HR and estimated physiological responses indicates that players move further and faster at no additional mean physiological cost. This type of ball will be useful for novice players in the early phases of skill development

A pragmatic cluster randomised trial evaluating three implementation interventions

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

Characterizing Interdisciplinarity of Researchers and Research Topics Using Web Search Engines

Researchers' networks have been subject to active modeling and analysis. Earlier literature mostly focused on citation or co-authorship networks reconstructed from annotated scientific publication databases, which have several limitations. Recently, general-purpose web search engines have also been utilized to collect information about social networks. Here we reconstructed, using web search engines, a network representing the relatedness of researchers to their peers as well as to various research topics. Relatedness between researchers and research topics was characterized by visibility boost-increase of a researcher's visibility by focusing on a particular topic. It was observed that researchers who had high visibility boosts by the same research topic tended to be close to each other in their network. We calculated correlations between visibility boosts by research topics and researchers' interdisciplinarity at individual level (diversity of topics related to the researcher) and at social level (his/her centrality in the researchers' network). We found that visibility boosts by certain research topics were positively correlated with researchers' individual-level interdisciplinarity despite their negative correlations with the general popularity of researchers. It was also found that visibility boosts by network-related topics had positive correlations with researchers' social-level interdisciplinarity. Research topics' correlations with researchers' individual- and social-level interdisciplinarities were found to be nearly independent from each other. These findings suggest that the notion of "interdisciplinarity" of a researcher should be understood as a multi-dimensional concept that should be evaluated using multiple assessment means.Comment: 20 pages, 7 figures. Accepted for publication in PLoS On

Accessibility and implementation in UK services of an effective depression relapse prevention programme - mindfulness-based cognitive therapy (MBCT): ASPIRE study protocol

notes: PMCID: PMC4036706types: Journal Article© 2014 Rycroft-Malone et al.; licensee BioMed Central Ltd.Mindfulness-based cognitive therapy (MBCT) is a cost-effective psychosocial prevention programme that helps people with recurrent depression stay well in the long term. It was singled out in the 2009 National Institute for Health and Clinical Excellence (NICE) Depression Guideline as a key priority for implementation. Despite good evidence and guideline recommendations, its roll-out and accessibility across the UK appears to be limited and inequitably distributed. The study aims to describe the current state of MBCT accessibility and implementation across the UK, develop an explanatory framework of what is hindering and facilitating its progress in different areas, and develop an Implementation Plan and related resources to promote better and more equitable availability and use of MBCT within the UK National Health Service.NIHRHS&D

Single-Species Microarrays and Comparative Transcriptomics

BACKGROUND: Prefabricated expression microarrays are currently available for only a few species but methods have been proposed to extend their application to comparisons between divergent genomes. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that the hybridization intensity of genomic DNA is a poor basis on which to select unbiased probes on Affymetrix expression arrays for studies of comparative transcriptomics, and that doing so produces spurious results. We used the Affymetrix Xenopus laevis microarray to evaluate expression divergence between X. laevis, X. borealis, and their F1 hybrids. When data are analyzed with probes that interrogate only sequences with confirmed identity in both species, we recover results that differ substantially analyses that use genomic DNA hybridizations to select probes. CONCLUSIONS/SIGNIFICANCE: Our findings have implications for the experimental design of comparative expression studies that use single-species microarrays, and for our understanding of divergent expression in hybrid clawed frogs. These findings also highlight important limitations of single-species microarrays for studies of comparative transcriptomics of polyploid species

Young neutron stars with soft gamma ray emission and anomalous X-ray pulsar

The observational properties of Soft Gamma Repeaters and Ano\-malous X-ray Pulsars (SGR/AXP) indicate to necessity of the energy source different from a rotational energy of a neutron star. The model, where the source of the energy is connected with a magnetic field dissipation in a highly magnetized neutron star (magnetar) is analyzed. Some observational inconsistencies are indicated for this interpretation. The alternative energy source, connected with the nuclear energy of superheavy nuclei stored in the nonequilibrium layer of low mass neutron star is discussed.Comment: 29 pages, 13 figures, Springer International Publishing Switzerland 2016 A.W. Alsabti, P. Murdin (eds.), Handbook of Supernova