Description and process evaluation of pharmacists’ interventions in a pharmacist-led information technology-enabled multicentre cluster randomised controlled trial for reducing medication errors in general practice (PINCER trial)

Objective To undertake a process evaluation of pharmacists' recommendations arising in the context of a complex IT-enabled pharmacist-delivered randomised controlled trial (PINCER trial) to reduce the risk of hazardous medicines management in general practices. Methods PINCER pharmacists manually recorded patients’ demographics, details of interventions recommended, actions undertaken by practice staff and time taken to manage individual cases of hazardous medicines management. Data were coded and double entered into SPSS v15, and then summarised using percentages for categorical data (with 95% CI) and, as appropriate, means (SD) or medians (IQR) for continuous data. Key findings Pharmacists spent a median of 20 minutes (IQR 10, 30) reviewing medical records, recommending interventions and completing actions in each case of hazardous medicines management. Pharmacists judged 72% (95%CI 70, 74) (1463/2026) of cases of hazardous medicines management to be clinically relevant. Pharmacists recommended 2105 interventions in 74% (95%CI 73, 76) (1516/2038) of cases and 1685 actions were taken in 61% (95%CI 59, 63) (1246/2038) of cases; 66% (95%CI 64, 68) (1383/2105) of interventions recommended by pharmacists were completed and 5% (95%CI 4, 6) (104/2105) of recommendations were accepted by general practitioners (GPs), but not completed at the end of the pharmacists’ placement; the remaining recommendations were rejected or considered not relevant by GPs. Conclusions The outcome measures were used to target pharmacist activity in general practice towards patients at risk from hazardous medicines management. Recommendations from trained PINCER pharmacists were found to be broadly acceptable to GPs and led to ameliorative action in the majority of cases. It seems likely that the approach used by the PINCER pharmacists could be employed by other practice pharmacists following appropriate training.

Overall evaluation of the PETS2009 results

This paper presents the results of the crowd image analysis challenge, as part of the PETS 2009 workshop. The evaluation is carried out using a selection of the metrics available in the Video Analysis and Content Extraction (VACE) program and the CLassification of Events, Activities, and Relationships (CLEAR) consortium. The evaluation highlights the strengths of the authors’ systems in areas such as precision, accuracy and robustness.

Evaluation of the use of radiosonde humidity data to predict the occurrence of persistent contrails

Regular visual observations of persistent contrails over Reading, UK, have been used to evaluate radiosonde measurements of temperature and humidity defining cold ice-supersaturated atmospheric regions which are assumed to be a necessary condition for persistent condensation trails (contrails) to form. Results show a good correlation between observations and predictions using data from Larkhill, 63 km from Reading. A statistical analysis of this result and the forecasts using data from four additional UK radiosonde stations are presented. The horizontal extent of supersaturated layers could be inferred from this to be several hundred kilometres. The necessity of bias corrections to radiosonde humidity measurements is discussed and an analysis of measured ice-supersaturated atmospheric layers in the troposphere is presented. It is found that ice supersaturation is more likely to occur in winter than in summer, with frequencies of 17.3% and 9.4%, respectively, which is mostly due to the layers being thicker in winter than in summer. The most probable height for them to occur is about 10 km.

Evaluation of the Met Office global forecast model using Geostationary Earth Radiation Budget (GERB) data

Simulations of the top-of-atmosphere radiative-energy budget from the Met Office global numerical weather-prediction model are evaluated using new data from the Geostationary Earth Radiation Budget (GERB) instrument on board the Meteosat-8 satellite. Systematic discrepancies between the model simulations and GERB measurements greater than 20 Wm-2 in outgoing long-wave radiation (OLR) and greater than 60 Wm-2 in reflected short-wave radiation (RSR) are identified over the period April-September 2006 using 12 UTC data. Convective cloud over equatorial Africa is spatially less organized and less reflective than in the GERB data. This bias depends strongly on convective-cloud cover, which is highly sensitive to changes in the model convective parametrization. Underestimates in model OLR over the Gulf of Guinea coincide with unrealistic southerly cloud outflow from convective centres to the north. Large overestimates in model RSR over the subtropical ocean, greater than 50 Wm-2 at 12 UTC, are explained by unrealistic radiative properties of low-level cloud relating to overestimation of cloud liquid water compared with independent satellite measurements. The results of this analysis contribute to the development and improvement of parametrizations in the global forecast model.

Synthesis and evaluation of novel boron-containing complexes of potential use for the selective treatment of malignant melanoma

Boron-containing complexes that have the potential to irreversibly accumulate in melanoma cells have been prepared by reaction of amino acids with 9-methoxy-9-borabicyclo[3.3.1]nonane. The ability of each complex to act as a substrate for tyrosinase has been probed by oximetry. Increased uptake of the lead candidate in a tyrosinase-rich cell line, compared with a tyrosinase-absent cell line, is reported, with results correlating well with that for a drug currently approved for BNCT.

Evaluation of ozone and water vapor fields from the ECMWF reanalysis ERA-40 during 1991-1999 in comparison with UARS satellite and MOZAIC aircraft observations

[ 1] The European Centre for Medium-Range Weather Forecasts (ECMWF) 40-year Reanalysis (ERA-40) ozone and water vapor reanalysis fields during the 1990s have been compared with independent satellite data from the Halogen Occultation Experiment (HALOE) and Microwave Limb Sounder (MLS) instruments on board the Upper Atmosphere Research Satellite (UARS). In addition, ERA-40 has been compared with aircraft data from the Measurements of Ozone and Water Vapour by Airbus In-Service Aircraft (MOZAIC) program. Overall, in comparison with the values derived from the independent observations, the upper stratosphere in ERA-40 has about 5 - 10% more ozone and 15 - 20% less water vapor. This dry bias in the reanalysis appears to be global and extends into the middle stratosphere down to 40 hPa. Most of the discrepancies and seasonal variations between ERA-40 and the independent observations occur within the upper troposphere over the tropics and the lower stratosphere over the high latitudes. ERA-40 reproduces a weaker Antarctic ozone hole, and of less vertical extent, than the independent observations; values in the ozone maximum in the tropical stratosphere are lower for the reanalysis. ERA-40 mixing ratios of water vapor are considerably larger than those for MOZAIC, typically by 20% in the tropical upper troposphere, and they may exceed 60% in the lower stratosphere over high latitudes. The results imply that the Brewer-Dobson circulation in the ECMWF reanalysis system is too fast, as is also evidenced by deficiencies in the way ERA-40 reproduces the water vapor "tape recorder'' signal in the tropical stratosphere. Finally, the paper examines the biases and their temporal variation during the 1990s in the way ERA-40 compares to the independent observations. We also discuss how the evaluation results depend on the instrument used, as well as on the version of the data.

An ex-ante evaluation of the economic impact of Bt cotton adoption by spanish farmers facing the EU cotton sector reform

Cotton production in the European Union (EU) is limited to areas of Greece and Southern Spain (Andalusia). The 2004 reform of the EU cotton policy severely affected the profitability of the crop. In this article we analyze how the introduction of genetically modified (GM), insect-resistant cotton varieties (Bt cotton) might help EU cotton farmers to increase profitability and therefore face the cotton policy reform. We first study farmers’ attitudes toward adoption of Bt cotton varieties through a survey conducted in Andalusia (Southern Spain). The results show a positive attitude of Andalusian cotton farmers toward the Bt cotton varieties. Second, we perform an ex-ante analysis of the effects of introducing Bt cotton in Andalusia. Finally, we integrate the analysis of the effects of Bt cotton with the analysis of the EU cotton reform. Our results show that despite the significant economic benefits of Bt cotton, the current policy reform is likely to jeopardize the profitability of cotton production in the EU.

An evaluation of different growth functions for describing the profile of live weight with time (age) in meat and egg strains of chicken

A total of 86 profiles from meat and egg strains of chickens (male and female) were used in this study. Different flexible growth functions were evaluated with regard to their ability to describe the relationship between live weight and age and were compared with the Gompertz and logistic equations, which have a fixed point of inflection. Six growth functions were used: Gompertz, logistic, Lopez, Richards, France, and von Bertalanffy. A comparative analysis was carried out based on model behavior and statistical performance. The results of this study confirmed the initial concern about the limitation of a fixed point of inflection, such as in the Gompertz equation. Therefore, consideration of flexible growth functions as an alternatives to the simpler equations (with a fixed point of inflection) for describing the relationship between live weight and age are recommended for the following reasons: they are easy to fit, they very often give a closer fit to data points because of their flexibility and therefore a smaller RSS value, than the simpler models, and they encompasses simpler models for the addition of an extra parameter, which is especially important when the behavior of a particular data set is not defined previously.

A comparative evaluation of functions for the analysis of growth in male broilers

Data from six studies with male broilers fed diets covering a wide range of energy and protein were used in the current two analyses. In the first analysis, five models, specifically re-parameterized for analysing energy balance data, were evaluated for their ability to determine metabolizable energy intake at maintenance and efficiency of utilization of metabolizable energy intake for producing gain. In addition to the straight line, two types of functional form were used. They were forms describing (i) diminishing returns behaviour (monomolecular and rectangular hyperbola) and (ii) sigmoidal behaviour with a fixed point of inflection (Gompertz and logistic). These models determined metabolizable energy requirement for maintenance to be in the range 437-573 kJ/kg of body weight/day depending on the model. The values determined for average net energy requirement for body weight gain varied from 7(.)9 to 11(.)2 kJ/g of body weight. These values show good agreement with previous studies. In the second analysis, three types of function were assessed as candidates for describing the relationship between body weight and cumulative metabolizable energy intake. The functions used were: (a) monomolecular (diminishing returns behaviour), (b) Gompertz (smooth sigmoidal behaviour with a fixed point of inflection) and (c) Lopez, France and Richards (diminishing returns and sigmoidal behaviour with a variable point of inflection). The results of this analysis demonstrated that equations capable of mimicking the law of diminishing returns describe accurately the relationship between body weight and cumulative metabolizable energy intake in broilers.

A comparative evaluation of functions for describing the relationship between live-weight gain and metabolizable energy intake in turkeys

The suitability of models specifically re-parameterized for analyzing energy balance data relating metabolizable energy intake to growth rate has recently been investigated in male broilers. In this study, the more adequate of those models was applied to growing turkeys to provide estimates of their energy needs for maintenance and growth. Three functional forms were used. They were: two equations representing diminishing returns behaviour (monomolecular and rectangular hyperbola); and one equation describing smooth sigmoidal behaviour with a fixed point of inflexion (Gompertz). The models estimated the metabolizable energy requirement for maintenance in turkeys to be 359-415 kJ/kg of live-weight/day. The predicted values of average net energy requirement for producing 1 g of gain in live-weight, between 1 and 4 times maintenance, varied from 8.7 to 10.9 kJ. These results and those previously reported for broilers are a basis for accepting the general validity of these models.

An evaluation of a Bayesian method of dose escalation based on bivariate binary responses

Recently, various approaches have been suggested for dose escalation studies based on observations of both undesirable events and evidence of therapeutic benefit. This article concerns a Bayesian approach to dose escalation that requires the user to make numerous design decisions relating to the number of doses to make available, the choice of the prior distribution, the imposition of safety constraints and stopping rules, and the criteria by which the design is to be optimized. Results are presented of a substantial simulation study conducted to investigate the influence of some of these factors on the safety and the accuracy of the procedure with a view toward providing general guidance for investigators conducting such studies. The Bayesian procedures evaluated use logistic regression to model the two responses, which are both assumed to be binary. The simulation study is based on features of a recently completed study of a compound with potential benefit to patients suffering from inflammatory diseases of the lung.

Statistical evaluation of an acute dermal toxicity test using the dermal fixed dose procedure

The conventional method for the assessment of acute dermal toxicity (OECD Test Guideline 402, 1987) uses death of animals as an endpoint to identify the median lethal dose (LD50). A new OECD Testing Guideline called the dermal fixed dose procedure (dermal FDP) is being prepared to provide an alternative to Test Guideline 402. In contrast to Test Guideline 402, the dermal FDP does not provide a point estimate of the LD50, but aims to identify that dose of the substance under investigation that causes clear signs of nonlethal toxicity. This is then used to assign classification according to the new Globally Harmonised System of Classification and Labelling scheme (GHS). The dermal FDP has been validated using statistical modelling rather than by in vivo testing. The statistical modelling approach enables calculation of the probability of each GHS classification and the expected numbers of deaths and animals used in the test for imaginary substances with a range of LD50 values and dose-response curve slopes. This paper describes the dermal FDP and reports the results from the statistical evaluation. It is shown that the procedure will be completed with considerably less death and suffering than guideline 402, and will classify substances either in the same or a more stringent GHS class than that assigned on the basis of the LD50 value.

Statistical evaluation of the fixed concentration procedure for acute inhalation toxicity assessment

The conventional method for the assessment of acute inhalation toxicity (OECD Test Guideline 403, 1981) uses death of animals as an endpoint to identify the median lethal concentration (LC50). A new OECD Testing Guideline called the Fixed Concentration Procedure (FCP) is being prepared to provide an alternative to Test Guideline 403. Unlike Test Guideline 403, the FCP does not provide a point estimate of the LC50, but aims to identify an airborne exposure level that causes clear signs of nonlethal toxicity. This is then used to assign classification according to the new Globally Harmonized System of Classification and Labelling scheme (GHS). The FCP has been validated using statistical simulation rather than byin vivo testing. The statistical simulation approach predicts the GHS classification outcome and the numbers of deaths and animals used in the test for imaginary substances with a range of LC50 values and dose response curve slopes. This paper describes the FCP and reports the results from the statistical simulation study assessing its properties. It is shown that the procedure will be completed with considerably less death and suffering than Test Guideline 403, and will classify substances either in the same or a more stringent GHS class than that assigned on the basis of the LC50 value.

Uptake pathways: the potential of Bayesian belief networks to assist the management, monitoring and evaluation of development-orientated research

The effectiveness of development assistance has come under renewed scrutiny in recent years. In an era of growing economic liberalisation, research organisations are increasingly being asked to account for the use of public funds by demonstrating achievements. However, in the natural resources (NR) research field, conventional economic assessment techniques have focused on quantifying the impact achieved rather understanding the process that delivered it. As a result, they provide limited guidance for planners and researchers charged with selecting and implementing future research. In response, “pathways” or logic models have attracted increased interest in recent years as a remedy to this shortcoming. However, as commonly applied these suffer from two key limitations in their ability to incorporate risk and assess variance from plan. The paper reports the results of a case study that used a Bayesian belief network approach to address these limitations and outlines its potential value as a tool to assist the planning, monitoring and evaluation of development-orientated research.

Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline

The International Citicoline Trial in acUte Stroke is a sequential phase III study of the use of the drug citicoline in the treatment of acute ischaemic stroke, which was initiated in 2006 in 56 treatment centres. The primary objective of the trial is to demonstrate improved recovery of patients randomized to citicoline relative to those randomized to placebo after 12 weeks of follow-up. The primary analysis will take the form of a global test combining the dichotomized results of assessments on three well-established scales: the Barthel Index, the modified Rankin scale and the National Institutes of Health Stroke Scale. This approach was previously used in the analysis of the influential National Institute of Neurological Disorders and Stroke trial of recombinant tissue plasminogen activator in stroke. The purpose of this paper is to describe how this trial was designed, and in particular how the simultaneous objectives of taking into account three assessment scales, performing a series of interim analyses and conducting treatment allocation and adjusting the analyses to account for prognostic factors, including more than 50 treatment centres, were addressed. Copyright (C) 2008 John Wiley & Sons, Ltd.