Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples

Costs can hamper the evaluation of the effectiveness of new biomarkers. Analysis of smaller numbers of pooled specimens has been shown to be a useful cost-cutting technique. The Youden index (J), a function of sensitivity (q) and specificity (p), is a commonly used measure of overall diagnostic effectiveness. More importantly, J is the maximum vertical distance or difference between the ROC curve and the diagonal or chance line; it occurs at the cut-point that optimizes the biomarker's differentiating ability when equal weight is given to sensitivity and specificity. Using the additive property of the gamma and normal distributions, we present a method to estimate the Youden index and the optimal cut-point, and extend its applications to pooled samples. We study the effect of pooling when only a fixed number of individuals are available for testing, and pooling is carried out to save on the number of assays. We measure loss of information by the change in root mean squared error of the estimates of the optimal cut-point and the Youden index, and we study the extent of this loss via a simulation study. In conclusion, pooling can result in a substantial cost reduction while preserving the effectiveness of estimators, especially when the pool size is not very large.     

Pay for performance: an excellent idea that simply needs implementation

Pay for performance cannot consist of a one-size-fits-all approach. Variation in quality and cost of care is best measured using a single "value" (quality/cost) score that is decomposed into component cost and quality for every health care encounter type. Economic incentives must be enough to focus the provider's attention on each score part. Tools exist that improve the overall "value" of health care. We need agreement on an overall pay for performance approach together with a toolbox (not an approved list) of scientifically validated tools that payers, providers, and consumers can choose to build the incentives needed for pay for performance.     

What happens to British veterans when they leave the armed forces?

BACKGROUND: Little is known about the factors associated with leaving the armed forces, or what predicts subsequent employment success for veterans. It is likely that there is a complex interaction of adverse social outcomes and mental health status in this group. METHOD: Analysis of existing data from the King's Military Cohort, a large, randomly selected, longitudinal cohort of service personnel, many of whom have now left the armed forces. The sample consisted of 8195 service personnel who served in the armed forces in 1991; a third deployed to the Gulf (1990-91), a third deployed to Bosnia (1992-97) and the final third an 'Era' control group in the Armed Forces in 1991 but not deployed. RESULTS: The majority of service leavers do well after leaving and are in full-time employment. Those with poor mental health during service were more likely to leave and had a greater chance of becoming unemployed after leaving. Mental health problems appear to remain static for veterans after leaving. Veterans of the Gulf War enjoyed more favourable employment outcomes, provided that they came home well. CONCLUSIONS: Only a minority of veterans fare badly after service, even amongst those with active tours of duty behind them. Veterans with mental health problems during service seem to be at higher risk of social exclusion after leaving and therefore these individuals represent an especially vulnerable group of the veteran population.     

Use of dual transarticular screws to fixate simultaneous occipitoatlantal and atlantoaxial dislocations

Occipitoatlantal dislocation and atlantoaxial vertical distraction are caused by similar mechanisms, and few individuals survive these injuries. It is hypothesized that the injurious vertical force manifests as a traumatic lesion at different levels of the same ligamentous complex. The authors report the cases of two patients who presented with this combined lesion, describe surgical alternatives for stabilization, and introduce a new technique that combines the use of transarticular screws in a "dual" construct, without involving the unaffected spine.     

Impedance methods (apparent mass, driving point mechanical impedance and absorbed power) for assessment of the biomechanical response of the seated person to whole-body vibration

Exposure to whole-body vibration is a risk factor for the development of low back pain. In order to develop a fuller understanding of the response of the seated person to vibration, experiments have been conducted in the laboratory investigating the biomechanics of the seated person. Some of these methods are based on the driving force and acceleration at the seat and are reported in the literature as apparent mass, driving point mechanical impedance or absorbed power. This paper introduces the background behind such impedance methods, the theory and application of the methods. It presents example data showing typical responses of the seated human to whole-body vibration in the vertical, fore-and-aft and lateral directions. It also highlights problems that researchers might encounter in performing, analysing and interpreting human impedance data.     

Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress

To evaluate the effects of grape polyphenols on plasma lipids, inflammatory cytokines, and oxidative stress, 24 pre- and 20 postmenopausal women were randomly assigned to consume 36 g of a lyophilized grape powder (LGP) or a placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol, and resveratrol. After a 3-wk washout period, subjects were assigned to the alternate treatment for an additional 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and was similar in appearance and energy content (554 kJ) to LGP. Plasma triglyceride concentrations were reduced by 15 and 6% in pre- and postmenopausal women, respectively (P < 0.01) after LGP supplementation. In addition, plasma LDL cholesterol and apolipoproteins B and E were lower due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein activity was decreased by approximately 15% with intake of LGP (P < 0.05). In contrast to these beneficial effects on plasma lipids, LDL oxidation was not modified by LGP treatment. However, whole-body oxidative stress as measured by urinary F(2)-isoprostanes was significantly reduced after LGP supplementation. LGP also decreased the levels of plasma tumor necrosis factor-alpha, which plays a major role in the inflammation process. Through alterations in lipoprotein metabolism, oxidative stress, and inflammatory markers, LGP intake beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.     

Size determination of bacterial capsular oligosaccharides used to prepare conjugate vaccines against Neisseria meningitidis groups Y and W135

The glycoconjugate vaccines against Neisseria meningitidis groups Y and W135 consist of pools of selected oligosaccharides conjugated to the protein carrier (CRM197). Consistent production of these vaccines requires control and thus determination of the average degree of polymerisation of the oligosaccharides used for conjugation. Acid hydrolysis generates group Y and W135 oligosaccharides with N-acetylneuraminic acid at the reducing end. A method, involving NaBH4 reduction and quantification of this terminal N-acetylneuraminic acid by use of high performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) following acid hydrolysis (2M TFA), was developed. The average degree of polymerisation is calculated from the ratio of reduced N-acetylneuraminic acid to total N-acetylneuraminic acid. The assay was qualified by application to group C, Y and W135 oligosaccharide standards characterised by liquid chromatography, mass and NMR spectroscopy.