Using clinical guidelines to assess the potential value of laboratory medicine in clinical decision-making

Introduction: It is often quoted that 70% of clinical decisions are based on laboratory results, but the evidence to substantiate this claim is lacking. Since clinical guidelines aim to document best-practice decision making for specific disease conditions, inclusion of any laboratory test means that the best available evidence is recommending clinicians use it. Cardiovascular disease (CVD) is the world’s most common cause of mortality, so this study reviewed all CVD guidelines published by five national/international authorities to determine what proportion of them recommended laboratory testing. Materials and methods: Five leading CVD guidelines were examined, namely the European Society of Cardiology (ESC), the UK National Institute for Health and Clinical Excellence (NICE), the American College of Cardiology (ACC), the Australian Heart Foundation (AHF) and the Cardiac Society of Australia and New Zealand (CSANZ). Results: A total of 101 guidelines were reviewed. Of the 33 individual ESC guidelines relating to CVD, 24/33 made a direct reference to the use of clinical laboratory tests in either diagnosis or follow-up treatment. The same applied to 15/20 of NICE guidelines, 24/32 from the ACC and 15/16 from the AHF/CSANZ. Renal function and blood count testing were the most recommended (39 and 26 times), with lipid, troponin and natriuretic peptide measurement advocated 25, 19 and 19 times respectively. Conclusions: This study has shown that laboratory testing is advocated by between 73% and 94% of individual CVD guideline recommendations from five national/international authorities. This provides an index to assess the potential value of laboratory medicine to healthcare

Minimizing Variability of Cascade Impaction Measurements in Inhalers and Nebulizers

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD)

Table 2 - CO2 accumulation parameters

An analytical solution to the equations describing the flow of a buoyant fluid released into a porous medium below a horizontal impermeable boundary is used to model the growth of CO2 accumulations beneath thin mudstone beds in the Utsira sand reservoir at Sleipner in the North Sea. Here supercritical CO2 has been injected at a rate of ab. 1 MT/yr since 1996 and imaged by time-lapse seismic data in 1999, 2001 and 2002. The CO2 rises as a narrow plume and is partially trapped by a number of thin mudstones before reaching the caprock to the reservoir. The radii of the individual layers of trapped CO2 increase as the square root of time since initiation as predicted by the modelling for constant input flux. However apparent negative initiation times for horizons low in the reservoir suggests that net input fluxes for these layers have decreased with time, most probably as the spreading layers have increased their leakage rates. Accumulation of CO2 in the layers higher in the reservoir was initiated up to 3 yr after injection started. Modelling of the thickness profiles across three of the higher layers suggests that their net input fluxes have increased with time. The observation that the central thicknesses of the deeper layers have remained approximately constant, or have slightly decreased since first imaged in 1999, is consistent with the model predictions that the central thickness is directly proportional to net input flux. However, estimates of the permeability of the reservoir from the rate of increase of the radii of the CO2 accumulations are an order of magnitude less than measured permeabilities on the reservoir sandstone. Permeabilities estimated from the modelling of layer thickness changes scatter in the same range. These discrepancies may arise from, 1) approximations in the model not being valid, 2) the measured permeabilities not being representative of the permeability for two-phase flow on the scale of the reservoir or, considered less likely, 3) that much less CO2 is being stored in the imaged CO2 accumulations than estimated from the seismic reflection profiles. The most probable cause of the discrepancy is that the relative permeability for the CO2 phase is significantly reduced at lower CO2 saturations

People living with moderate-to-severe COPD prefer improvement of daily symptoms over the improvement of exacerbations: a multicountry patient preference study

Introduction This patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan. Methods The inclusion criteria were people living with COPD aged 40 years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles. Preference weights (utilities) were derived from the DCE using hierarchical Bayesian analysis. A preference simulator was developed that enabled different health state scenarios to be evaluated based on the predicted patient preferences. Results 1050 people living with moderate-to-severe COPD completed the survey. All attributes were considered important when patients determined their preferences in the DCE. In a health state preference simulation, two hypothetical health states (comprising attribute levels) with qualitatively equivalent improvements in A) cough and mucus and B) shortness of breath (SOB) resulted in a clear preference for cough and mucus improved profile. When comparing two profiles with C) daily symptoms improved and D) exacerbations improved, there was a clear preference for the daily symptoms improved profile. Conclusions People living with moderate-to-severe COPD prefer to reduce cough and mucus production together over improvement of SOB and would prefer to reduce combined daily symptoms over an improvement in exacerbations