Intensive insulin therapy (IIT) and tight glycaemic control (TGC), particularly in intensive care units (ICU), are the subjects of increasing and con-

BackgroundDerivative based a-priori structural identifiability analyses of mathematical models can offer valuable insight into the identifiability of model parameters. However, these analyses are only capable of a binary confirmation of the mathematical distinction of parameters and a positive outcome can begin to lose relevance when measurement error is introduced. This article presents an integral based method that allows the observation of the identifiability of models with two-parameters in the presence of assay error.MethodsThe method measures the distinction of the integral formulations of the parameter coefficients at the proposed sampling times. It can thus predict the susceptibility of the parameters to the effects of measurement error. The method is tested in-silico with Monte Carlo analyses of a number of insulin sensitivity test applications.ResultsThe method successfully captured the analogous nature of identifiability observed in Monte Carlo analyses of a number of cases including protocol alterations, parameter changes and differences in participant behaviour. However, due to the numerical nature of the analyses, prediction was not perfect in all cases.ConclusionsThus although the current method has valuable and significant capabilities in terms of study or test protocol design, additional developments would further strengthen the predictive capability of the method. Finally, the method captures the experimental reality that sampling error and timing can negate assumed parameter identifiability and that identifiability is a continuous rather than discrete phenomenon.

The objective was to validate the methodology for the dynamic insulin sensitivity and secretion test (DISST) and to demonstrate its potential in clinical and research settings. One hundred twenty-three men and women had routine clinical and biochemical measurements, an oral glucose tolerance test, and a DISST. For the DISST, participants were cannulated for blood sampling and bolus administration. Blood samples were drawn at t = 0, 10, 15, 25, and 35 minutes for measurement of glucose, insulin, and C-peptide. A 10-g bolus of intravenous glucose at t = 5 minutes and 1 U of intravenous insulin immediately after the t = 15 minute sample were given. Fifty participants also had a hyperinsulinemic-euglycemic clamp. Relationships between DISST insulin sensitivity (SI) and the clamp, and both DISST SI and secretion and other metabolic variables were measured. A Bland-Altman plot showed little bias in the comparison of DISST with the clamp, with DISST underestimating the glucose clamp by 0.1·10(-2)·mg·L·kg(-1)·min(-1)·pmol(-1) (90% confidence interval, -0.2 to 0). The correlation between SI as measured by DISST and the clamp was 0.82; the c unit for the receiver operating characteristic curve analysis for the 2 tests was 0.96. Metabolic variables showed significant correlations with DISST SI and the second phase of insulin release. The DISST also appears able to distinguish different insulin secretion patterns in individuals with identical SI values. The DISST is a simple, dynamic test that compares favorably with the clamp in assessing SI and allows simultaneous assessment of insulin secretion. The DISST has the potential to provide even more information about the pathophysiology of diabetes than more complicated tests.

These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS.

BackgroundPreventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).MethodsThe primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.ResultsVarious reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.ConclusionSocio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.