PINCER trial: a cluster randomised trial comparing the effectiveness and cost-effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors in general practice are an important source of potentially preventable morbidity and mortality. Building on previous descriptive, qualitative and pilot work, we sought to investigate the effectiveness, cost-effectiveness and likely generalisability of a complex pharm acist-led IT-based intervention aiming to improve prescribing safety in general practice. Objectives: We sought to: • Test the hypothesis that a pharmacist-led IT-based complex intervention using educational outreach and practical support is more effective than simple feedback in reducing the proportion of patients at risk from errors in prescribing and medicines management in general practice. • Conduct an economic evaluation of the cost per error avoided, from the perspective of the National Health Service (NHS). • Analyse data recorded by pharmacists, summarising the proportions of patients judged to be at clinical risk, the actions recommended by pharmacists, and actions completed in the practices. • Explore the views and experiences of healthcare professionals and NHS managers concerning the intervention; investigate potential explanations for the observed effects, and inform decisions on the future roll-out of the pharmacist-led intervention • Examine secular trends in the outcome measures of interest allowing for informal comparison between trial practices and practices that did not participate in the trial contributing to the QRESEARCH database. Methods Two-arm cluster randomised controlled trial of 72 English general practices with embedded economic analysis and longitudinal descriptive and qualitative analysis. Informal comparison of the trial findings with a national descriptive study investigating secular trends undertaken using data from practices contributing to the QRESEARCH database. The main outcomes of interest were prescribing errors and medication monitoring errors at six- and 12-months following the intervention. Results: Participants in the pharmacist intervention arm practices were significantly less likely to have been prescribed a non-selective NSAID without a proton pump inhibitor (PPI) if they had a history of peptic ulcer (OR 0.58, 95%CI 0.38, 0.89), to have been prescribed a beta-blocker if they had asthma (OR 0.73, 95% CI 0.58, 0.91) or (in those aged 75 years and older) to have been prescribed an ACE inhibitor or diuretic without a measurement of urea and electrolytes in the last 15 months (OR 0.51, 95% CI 0.34, 0.78). The economic analysis suggests that the PINCER pharmacist intervention has 95% probability of being cost effective if the decision-maker’s ceiling willingness to pay reaches £75 (6 months) or £85 (12 months) per error avoided. The intervention addressed an issue that was important to professionals and their teams and was delivered in a way that was acceptable to practices with minimum disruption of normal work processes. Comparison of the trial findings with changes seen in QRESEARCH practices indicated that any reductions achieved in the simple feedback arm were likely, in the main, to have been related to secular trends rather than the intervention. Conclusions Compared with simple feedback, the pharmacist-led intervention resulted in reductions in proportions of patients at risk of prescribing and monitoring errors for the primary outcome measures and the composite secondary outcome measures at six-months and (with the exception of the NSAID/peptic ulcer outcome measure) 12-months post-intervention. The intervention is acceptable to pharmacists and practices, and is likely to be seen as costeffective by decision makers.

The synthesis, structure, and reactions of some simple unsaturated σ-hydrocarbylplatinum(II) complexes

Trimethyltin compounds Me3SnR(R = CHCH2, CFCF2, or CCPh) are selective reagents for the synthesis of unsaturated hydrocarbyl derivatives such as trans-PtCl(R)(PPhEt2)2, by R/Cl exchange or oxidative addition (e.g., to Pt(PPh3)3); single crystal X-ray analyses of two such compounds (R = CHCH2 or CCPh) show that the trans-influence of R has only a low sensitivity to hybridisation at carbon, with sp3 > sp ⩾ sp2.

A simple column model to explore anticipated problems in variational assimilation of satellite observations

We investigate a simplified form of variational data assimilation in a fully nonlinear framework with the aim of extracting dynamical development information from a sequence of observations over time. Information on the vertical wind profile, w(z ), and profiles of temperature, T (z , t), and total water content, qt (z , t), as functions of height, z , and time, t, are converted to brightness temperatures at a single horizontal location by defining a two-dimensional (vertical and time) variational assimilation testbed. The profiles of T and qt are updated using a vertical advection scheme. A basic cloud scheme is used to obtain the fractional cloud amount and, when combined with the temperature field, this information is converted into a brightness temperature, using a simple radiative transfer scheme. It is shown that our model exhibits realistic behaviour with regard to the prediction of cloud, but the effects of nonlinearity become non-negligible in the variational data assimilation algorithm. A careful analysis of the application of the data assimilation scheme to this nonlinear problem is presented, the salient difficulties are highlighted, and suggestions for further developments are discussed.

A simple device for multiplex ELISA made from melt-extruded plastic microcapillary film

We present a simple device for multiplex quantitative enzyme-linked immunosorbant assays (ELISA) made from a novel melt-extruded microcapillary film (MCF) containing a parallel array of 200µm capillaries along its length. To make ELISA devices different protein antigens or antibodies were immobilised inside individual microcapillaries within long reels of MCF extruded from fluorinated ethylene propylene (FEP). Short pieces of coated film were cut and interfaced with a pipette, allowing sequential uptake of samples and detection solutions into all capillaries from a reagent well. As well as being simple to produce, these FEP MCF devices have excellent light transmittance allowing direct optical interrogation of the capillaries for simple signal quantification. Proof of concept experiments demonstrate both quantitative and multiplex assays in FEP MCF devices using a standard direct ELISA procedure and read using a flatbed scanner. This new multiplex immunoassay platform should find applications ranging from lab detection to point-of-care and field diagnostics.

Simple model of adsorption on external surface of carbon nanotubes: a new analytical approach basing on molecular simulation data

Nitrogen adsorption on carbon nanotubes is wide- ly studied because nitrogen adsorption isotherm measurement is a standard method applied for porosity characterization. A further reason is that carbon nanotubes are potential adsorbents for separation of nitrogen from oxygen in air. The study presented here describes the results of GCMC simulations of nitrogen (three site model) adsorption on single and multi walled closed nanotubes. The results obtained are described by a new adsorption isotherm model proposed in this study. The model can be treated as the tube analogue of the GAB isotherm taking into account the lateral adsorbate-adsorbate interactions. We show that the model describes the simulated data satisfactorily. Next this new approach is applied for a description of experimental data measured on different commercially available (and characterized using HRTEM) carbon nanotubes. We show that generally a quite good fit is observed and therefore it is suggested that the observed mechanism of adsorption in the studied materials is mainly determined by adsorption on tubes separated at large distances, so the tubes behave almost independently.

Simple solution for a complex problem: Proanthocyanidins, galloyl glucoses and ellagitannins fit on a single calibration curve in high performance-gel permeation chromatography

This study was undertaken to explore gel permeation chromatography (GPC) for estimating molecular weights of proanthocyanidin fractions isolated from sainfoin (Onobrychis viciifolia). The results were compared with data obtained by thiolytic degradation of the same fractions. Polystyrene, polyethylene glycol and polymethyl methacrylate standards were not suitable for estimating the molecular weights of underivatized proanthocyanidins. Therefore, a novel HPLC-GPC method was developed based on two serially connected PolarGel-L columns using DMF that contained 5% water, 1% acetic acid and 0.15 M LiBr at 0.7 ml/min and 50 degrees C. This yielded a single calibration curve for galloyl glucoses (trigalloyl glucose, pentagalloyl glucose), ellagitannins (pedunculagin, vescalagin, punicalagin, oenothein B, gemin A), proanthocyanidins (procyanidin B2, cinnamtannin B1), and several other polyphenols (catechin, epicatechin gallate, epicallocatechin gallate, amentoflavone). These GPC predicted molecular weights represented a considerable advance over previously reported HPLC-GPC methods for underivatized proanthocyanidins. (C) 2011 Elsevier B.V. All rights reserved.

WAXS studies of global molecular orientation induced in nematic liquid crystals by simple shear flow

Global molecular orientation function coefficients for the nematic liquid crystal 4-cyano 4'-nn -pentylbiphenyl (5CB) in shear flow are presented, being extracted from 2-dimensional Wide-Angle X-ray Scattering data. A linear increase in orientation parameter P2 is observed with a logarithmic increase in shear rate. It is proposed that this arises from an increased number of LC directors aligning to the shear axis. Upon cessation of shear flow, the anisotropy is seen to relax away completely, over a time scale which is inversely proportional to the previously applied shear rate.

Relaxing the Tropics to an ‘observed’ state: analysis using a simple baroclinic model

The technique of relaxation of the tropical atmosphere towards an analysis in a month-season forecast model has previously been successfully exploited in a number of contexts. Here it is shown that when tropical relaxation is used to investigate the possible origin of the observed anomalies in June–July 2007, a simple dynamical model is able to reproduce the observed component of the pattern of anomalies given by an ensemble of ECMWF forecast runs. Following this result, the simple model is used for a range of experiments on time-scales of relaxation, variables and regions relaxed based on a control model run with equatorial heating in a zonal flow. A theory based on scale analysis for the large-scale tropics is used to interpret the results. Typical relationships between scales are determined from the basic equations, and for a specified diabatic heating a chain of deductions for determining the dependent variables is derived. Different critical time-scales are found for tropical relaxation of different dependent variables to be effective. Vorticity has the longest critical time-scale, typically 1.2 days. For temperature and divergence, the time-scales are 10 hours and 3 hours, respectively. However not all the tropical fields, in particular the vertical motion, are reproduced correctly by the model unless divergence is heavily damped. To obtain the correct extra-tropical fields, it is crucial to have the correct rotational flow in the subtropics to initiate the Rossby wave propagation from there. It is sufficient to relax vorticity or temperature on a time-scale comparable or less than their critical time-scales to obtain this. However if the divergent advection of vorticity is important in the Rossby Wave Source then strong relaxation of divergence is required to accurately represent the tropical forcing of Rossby waves.

A simple analysis of thermodynamic properties for classical plasmas: I. theory

By eliminating the short range negative divergence of the Debye–Hückel pair distribution function, but retaining the exponential charge screening known to operate at large interparticle separation, the thermodynamic properties of one-component plasmas of point ions or charged hard spheres can be well represented even in the strong coupling regime. Predicted electrostatic free energies agree within 5% of simulation data for typical Coulomb interactions up to a factor of 10 times the average kinetic energy. Here, this idea is extended to the general case of a uniform ionic mixture, comprising an arbitrary number of components, embedded in a rigid neutralizing background. The new theory is implemented in two ways: (i) by an unambiguous iterative algorithm that requires numerical methods and breaks the symmetry of cross correlation functions; and (ii) by invoking generalized matrix inverses that maintain symmetry and yield completely analytic solutions, but which are not uniquely determined. The extreme computational simplicity of the theory is attractive when considering applications to complex inhomogeneous fluids of charged particles.

The effect of nonlinearity on the variational assimilation of satellite observations using a simple column model

Cloud imagery is not currently used in numerical weather prediction (NWP) to extract the type of dynamical information that experienced forecasters have extracted subjectively for many years. For example, rapidly developing mid-latitude cyclones have characteristic signatures in the cloud imagery that are most fully appreciated from a sequence of images rather than from a single image. The Met Office is currently developing a technique to extract dynamical development information from satellite imagery using their full incremental 4D-Var (four-dimensional variational data assimilation) system. We investigate a simplified form of this technique in a fully nonlinear framework. We convert information on the vertical wind field, w(z), and profiles of temperature, T(z, t), and total water content, qt (z, t), as functions of height, z, and time, t, to a single brightness temperature by defining a 2D (vertical and time) variational assimilation testbed. The profiles of w, T and qt are updated using a simple vertical advection scheme. We define a basic cloud scheme to obtain the fractional cloud amount and, when combined with the temperature field, we convert this information into a brightness temperature, having developed a simple radiative transfer scheme. With the exception of some matrix inversion routines, all our code is developed from scratch. Throughout the development process we test all aspects of our 2D assimilation system, and then run identical twin experiments to try and recover information on the vertical velocity, from a sequence of observations of brightness temperature. This thesis contains a comprehensive description of our nonlinear models and assimilation system, and the first experimental results.

Bifurcation Analysis of Eigenstructure Assignment Control in a Simple Nonlinear Aircraft Model

Aircraft systems are highly nonlinear and time varying. High-performance aircraft at high angles of incidence experience undesired coupling of the lateral and longitudinal variables, resulting in departure from normal controlled � ight. The construction of a robust closed-loop control that extends the stable and decoupled � ight envelope as far as possible is pursued. For the study of these systems, nonlinear analysis methods are needed. Previously, bifurcation techniques have been used mainly to analyze open-loop nonlinear aircraft models and to investigate control effects on dynamic behavior. Linear feedback control designs constructed by eigenstructure assignment methods at a � xed � ight condition are investigated for a simple nonlinear aircraft model. Bifurcation analysis, in conjunction with linear control design methods, is shown to aid control law design for the nonlinear system.

Closed loop design for a simple nonlinear aircraft model using eigenstructure assignment

Aircraft systems are highly nonlinear and time varying. High-performance aircraft at high angles of incidence experience undesired coupling of the lateral and longitudinal variables, resulting in departure from normal controlled flight. The aim of this work is to construct a robust closed-loop control that optimally extends the stable and decoupled flight envelope. For the study of these systems nonlinear analysis methods are needed. Previously, bifurcation techniques have been used mainly to analyze open-loop nonlinear aircraft models and investigate control effects on dynamic behavior. In this work linear feedback control designs calculated by eigenstructure assignment methods are investigated for a simple aircraft model at a fixed flight condition. Bifurcation analysis in conjunction with linear control design methods is shown to aid control law design for the nonlinear system.

Estimating the volume of tephra deposits: a new simple strategy

Volume determination of tephra deposits is necessary for the assessment of the dynamics and hazards of explosive volcanoes. Several methods have been proposed during the past 40 years that include the analysis of crystal concentration of large pumices, integrations of various thinning relationships, and the inversion of field observations using analytical and computational models. Regardless of their strong dependence on tephra-deposit exposure and distribution of isomass/isopach contours, empirical integrations of deposit thinning trends still represent the most widely adopted strategy due to their practical and fast application. The most recent methods involve the best fitting of thinning data using various exponential seg- ments or a power-law curve on semilog plots of thickness (or mass/area) versus square root of isopach area. The exponential method is mainly sensitive to the number and the choice of straight segments, whereas the power-law method can better reproduce the natural thinning of tephra deposits but is strongly sensitive to the proximal or distal extreme of integration. We analyze a large data set of tephra deposits and propose a new empirical method for the deter- mination of tephra-deposit volumes that is based on the integration of the Weibull function. The new method shows a better agreement with observed data, reconciling the debate on the use of the exponential versus power-law method. In fact, the Weibull best fitting only depends on three free parameters, can well reproduce the gradual thinning of tephra deposits, and does not depend on the choice of arbitrary segments or of arbitrary extremes of integration.