The development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia - an exploratory study

Aims - To develop a method that prospectively assesses adherence rates in paediatric patients with acute lymphoblastic leukaemia (ALL) who are receiving the oral thiopurine treatment 6-mercaptopurine (6-MP). Methods - A total of 19 paediatric patients with ALL who were receiving 6-MP therapy were enrolled in this study. A new objective tool (hierarchical cluster analysis of drug metabolite concentrations) was explored as a novel approach to assess non-adherence to oral thiopurines, in combination with other objective measures (the pattern of variability in 6-thioguanine nucleotide erythrocyte concentrations and 6-thiouric acid plasma levels) and the subjective measure of self-reported adherence questionnaire. Results - Parents of five ALL patients (26.3%) reported at least one aspect of non-adherence, with the majority (80%) citing “carelessness at times about taking medication” as the primary reason for non-adherence followed by “forgetting to take the medication” (60%). Of these patients, three (15.8%) were considered non-adherent to medication according to the self-reported adherence questionnaire (scored ≥ 2). Four ALL patients (21.1%) had metabolite profiles indicative of non-adherence (persistently low levels of metabolites and/or metabolite levels clustered variably with time). Out of these four patients, two (50%) admitted non-adherence to therapy. Overall, when both methods were combined, five patients (26.3%) were considered non-adherent to medication, with higher age representing a risk factor for non-adherence (P < 0.05). Conclusions - The present study explored various ways to assess adherence rates to thiopurine medication in ALL patients and highlighted the importance of combining both objective and subjective measures as a better way to assess adherence to oral thiopurines.

Market risk reporting by the world's top banks:evidence on the diversity of reporting practice and the implications for international accounting harmonisation

The increasing adoption of international accounting standards and global convergence of accounting regulations is frequently heralded as serving to reduce diversity in financial reporting practice. In a process said to be driven in large part by the interests of international business and global financial markets, one might expect the greatest degree of convergence to be found amongst the world’s largest multinational financial corporations. This paper challenges such claims and presumptions. Its content analysis of longitudinal data for the period 2000-2006 reveals substantial, on going diversity in the market risk disclosure practices, both numerical and narrative, of the world’s top-25 banks. The significance of such findings is reinforced by the sheer scale of the banking sector’s risk exposures that have been subsequently revealed in the current global financial crisis. The variations in disclosure practices documented in the paper apply both across and within national boundaries, leading to a firm conclusion that, at least in terms of market risk reporting, progress towards international harmonisation remains rather more apparent than real.

Evaluation of an open-field autorefractor's ability to measure refraction and hence potential to assess objective accommodation in pseudophakes

Background: To evaluate the accuracy of an open-field autorefractor compared with subjective refraction in pseudophakes and hence its ability to assess objective eye focus with intraocular lenses (IOLs). Methods: Objective refraction was measured at 6 m using the Shin-Nippon NVision-K 5001/Grand Seiko WR-5100K open-field autorefractor (five repeats) and by subjective refraction on 141 eyes implanted with a spherical (Softec1 n=53), aspherical (SoftecHD n=37) or accommodating (1CU n=22; Tetraflex n=29) IOL. Autorefraction was repeated 2 months later. Results: The autorefractor prescription was similar (average difference: 0.09±0.53 D; p=0.19) to that found by subjective refraction, with ~71% within ±0.50 D. The horizontal cylindrical components were similar (difference: 0.00±0.39 D; p=0.96), although the oblique (J45) autorefractor cylindrical vector was slightly more negative (by -0.06±0.25 D; p=0.06) than the subjective refraction. The results were similar for each of the IOL designs except for the spherical IOL, where the mean spherical equivalent difference between autorefraction and subjective was more hypermetropic than the Tetraflex accommodating IOL (F=2.77, p=0.04). The intrasession repeatability was

High speed DSC (hyper-DSC) as a tool to measure the solubility of a drug within a solid or semi-solid matrix

Conventional differential scanning calorimetry (DSC) techniques are commonly used to quantify the solubility of drugs within polymeric-controlled delivery systems. However, the nature of the DSC experiment, and in particular the relatively slow heating rates employed, limit its use to the measurement of drug solubility at the drug's melting temperature. Here, we describe the application of hyper-DSC (HDSC), a variant of DSC involving extremely rapid heating rates, to the calculation of the solubility of a model drug, metronidazole, in silicone elastomer, and demonstrate that the faster heating rates permit the solubility to be calculated under non-equilibrium conditions such that the solubility better approximates that at the temperature of use. At a heating rate of 400°C/min (HDSC), metronidazole solubility was calculated to be 2.16 mg/g compared with 6.16 mg/g at 20°C/min. © 2005 Elsevier B.V. All rights reserved.

Estimating time-varying risk premia in UK long-term government bonds

Simple models of time-varying risk premia are used to measure the risk premia in long-term UK government bonds. The parameters of the models can be estimated using nonlinear seemingly unrelated regression (NL-SUR), which permits efficient use of information across the entire yield curve and facilitates the testing of various cross-sectional restrictions. The estimated time-varying premia are found to be substantially different to those estimated using models that assume constant risk premia. © 2004 Taylor and Francis Ltd.

Capital markets and the market structure of foreign investments

Contrary to the long-received theory of FDI, interest rates or rates of return can motivate foreign direct investment (FDI) in concert with the benefits of direct ownership. Thus, access to investor capital and capital markets is a vital component of the multinational’s competitive market structure. Moreover, multinationals can use their superior financial capacity as a competitive advantage in exploiting FDI opportunities in dynamic markets. They can also mitigate higher levels of foreign business risks under dynamic conditions by shifting more financial risk to creditors in the host economy. Furthermore, the investor’s expectation of foreign business risk necessarily commands a risk premium for exposing their equity to foreign market risk. Multinationals can modify the profit maximization strategy of their foreign subsidiaries to maximize growth or profits to generate this risk premium. In this context, we investigate how foreign subsidiaries manage their capital funding, business risk, and profit strategies with a diverse sample of 8,000 matched parents and foreign subsidiary accounts from multiple industries in 38 countries.We find that interest rates, asset prices, and expectations in capital markets have a significant effect on the capital movements of foreign subsidiaries. We also find that foreign subsidiaries mitigate their exposure to foreign business risk by modifying their capital structure and debt maturity. Further, we show how the operating strategy of foreign subsidiaries affects their preference for growth or profit maximization. We further show that superior shareholder value, which is a vital link for access to capital for funding foreign expansion in open market economies, is achieved through maintaining stability in the rate of growth and good asset utilization.

Statin use in rheumatoid arthritis in relation to actual cardiovascular risk:evidence for substantial undertreatment of lipid-associated cardiovascular risk?

Background Cardiovascular disease (CVD) is partially attributed to traditional cardiovascular risk factors, which can be identified and managed based on risk stratification algorithms (Framingham Risk Score, National Cholesterol Education Program, Systematic Cardiovascular Risk Evaluation and Reynolds Risk Score). We aimed to (a) identify the proportion of at risk patients with rheumatoid arthritis (RA) requiring statin therapy identified by conventional risk calculators, and (b) assess whether patients at risk were receiving statins. Methods Patients at high CVD risk (excluding patients with established CVD or diabetes) were identified from a cohort of 400 well characterised patients with RA, by applying risk calculators with or without a ×1.5 multiplier in specific patient subgroups. Actual statin use versus numbers eligible for statins was also calculated. Results The percentage of patients identified as being at risk ranged significantly depending on the method, from 1.6% (for 20% threshold global CVD risk) to 15.5% (for CVD and cerebrovascular morbidity and mortality) to 21.8% (for 10% global CVD risk) and 25.9% (for 5% CVD mortality), with the majority of them (58.1% to 94.8%) not receiving statins. The application of a 1.5 multiplier identified 17% to 78% more at risk patients. Conclusions Depending on the risk stratification method, 2% to 26% of patients with RA without CVD have sufficiently high risk to require statin therapy, yet most of them remain untreated. To address this issue, we would recommend annual systematic screening using the nationally applicable risk calculator, combined with regular audit of whether treatment targets have been achieved.

An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired

AIM To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. METHODS Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual im pairm ent. RESULTS Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. CONCLUSION The faVIQ allows sensitive assessm ent of quality-of-life in the visually im paired and should support studies which evaluate the effectiveness of low vision rehabilitation services. © Copyright International Journal of Ophthalmology Press.

Systemic circulatory influences on retinal microvascular function in middle-age individuals with low to moderate cardiovascular risk

Purpose: To investigate the relationship between retinal microvascular reactivity, circulatory markers for CVD risk and systemic antioxidative defence capacity in healthy middle-aged individuals with low to moderate risk of CVD. Methods: Retinal vascular reactivity to flickering light was assessed in 102 healthy participants (46-60 years) by means of dynamic retinal vessel analysis (DVA). Other vascular assessments included carotid intima-media thickness (C-IMT) and blood pressure (BP) measurements. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood glutathione levels in its reduced (GSH) and oxidized (GSSG) forms were also determined for each participant, along with Framingham risk scores (FRS). Results: Retinal arterial baseline diameter fluctuation (BDF) was independently, significantly and negatively influenced by LDL-C levels (β = -0.53, p = 0.027). Moreover, the arterial dilation slope (SlopeAD) was independently, significantly and positively associated with redox index (GSH: GSSG ratio, β = 0.28, p = 0.016), while the arterial constriction slope (SlopeAC) was significantly and negatively influenced by blood GSH levels (β = -0.20, p = 0.042), and positively associated with FRS (β = 0.25, p = 0.009). Venous BDF and dilation amplitude (DA) were also negatively influenced by plasma LDL-C levels (β = -0.83, p = 0.013; and β = -0.22, p = 0.028, respectively). Conclusions: In otherwise healthy individuals with low to moderate cardiovascular risk, retinal microvascular dilation and constriction responses to stress levels are influenced by systemic antioxidant capacity, and circulating markers for cardiovascular risk.

The challenges of developing an online tool to measure the quality of the passenger experience in a PanEuropean context

METPEX is a 3 year, FP7 project which aims to develop a PanEuropean tool to measure the quality of the passenger's experience of multimodal transport. Initial work has led to the development of a comprehensive set of variables relating to different passenger groups, forms of transport and journey stages. This paper addresses the main challenges in transforming the variables into usable, accessible computer based tools allowing for the real time collection of information, across multiple journey stages in different EU countries. Non-computer based measurement instruments will be used to gather information from those who may not have or be familiar with mobile technology. Smartphone-based measurement instruments will also be used, hosted in two applications. The mobile applications need to be easy to use, configurable and adaptable according to the context of use. They should also be inherently interesting and rewarding for the participant, whilst allowing for the collection of high quality, valid and reliable data from all journey types and stages (from planning, through to entry into and egress from different transport modes, travel on public and personal vehicles and support of active forms of transport (e.g. cycling and walking). During all phases of the data collection and processing, the privacy of the participant is highly regarded and is ensured. © 2014 Springer International Publishing.

Using an Infra-red sensor to measure the dynamic behaviour of N2O gas escaping through different sized holes

An anastomosis is a surgical procedure that consists of the connection of two parts of an organ and is commonly required in cases of colorectal cancer. About 80% of the patients diagnosed with this problem require surgery. The malignant tissue located on the gastrointestinal track must be resected and the most common procedure adopted is the anastomosis. Therefore, an anastomotic leak represents a significant problem and increases the duration of hospital stay, which is associated with remedial treatment and recovery, causing, as a result, a negative financial impact. A number of techniques to treat, prevent and even detect an anastomotic leakage are under investigation. However, studies show that these techniques are not always able to prevent an anastomotic leak from occurring. This paper discusses the monitoring of leakage through differently sized and differently positioned leak holes in phantom colons, using physical experiments and a Computational Fluid Dynamics package called FloWorks. © 2011 Taylor & Francis Group.

The Routledge companion to accounting and risk

To date, there has been little consideration of the many different ways in which accounting and risk intersect, despite organisations being more determined than ever to build resilience against potential risks. This comprehensive volume overcomes this gap by providing an overview of the field, drawing together current knowledge of risk in a wide range of different accounting contexts.