Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease-A Meta-Analysis

BACKGROUND: Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source.

METHODS AND FINDINGS: Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94) per correctly treated patient.

CONCLUSIONS: Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.

Hui and Walter's latent-class model extended to estimate diagnostic test properties from surveillance data: a latent model for latent data

Diagnostic test sensitivity and specificity are probabilistic estimates with far reaching implications for disease control, management and genetic studies. In the absence of 'gold standard' tests, traditional Bayesian latent class models may be used to assess diagnostic test accuracies through the comparison of two or more tests performed on the same groups of individuals. The aim of this study was to extend such models to estimate diagnostic test parameters and true cohort-specific prevalence, using disease surveillance data. The traditional Hui-Walter latent class methodology was extended to allow for features seen in such data, including (i) unrecorded data (i.e. data for a second test available only on a subset of the sampled population) and (ii) cohort-specific sensitivities and specificities. The model was applied with and without the modelling of conditional dependence between tests. The utility of the extended model was demonstrated through application to bovine tuberculosis surveillance data from Northern and the Republic of Ireland. Simulation coupled with re-sampling techniques, demonstrated that the extended model has good predictive power to estimate the diagnostic parameters and true herd-level prevalence from surveillance data. Our methodology can aid in the interpretation of disease surveillance data, and the results can potentially refine disease control strategies.

Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics

A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells.

Large scale test of a novel back-pass non-perforated unglazed solar air collector

This paper describes large scale tests conducted on a novel unglazed solar air collector system. The proposed system, referred to as a back-pass solar collector (BPSC), has on-site installation and aesthetic advantages over conventional unglazed transpired solar collectors (UTSC) as it is fully integrated within a standard insulated wall panel. This paper presents the results obtained from monitoring a BPSC wall panel over one year. Measurements of temperature, wind velocity and solar irradiance were taken at multiple air mass flow rates. It is shown that the length of the collector cavities has a direct impact on the efficiency of the system. It is also shown that beyond a height-to-flow ratio of 0.023m/m³/hr/m², no additional heat output is obtained by increasing the collector height for the experimental setup in this study, but these numbers would obviously be different if the experimental setup or test environment (e.g. location and climate) change. An equation for predicting the temperature rise of the BPSC is proposed.

Interpretation of flat FRP coupon test results

The tensile strength obtained from existing testing methods such as ASTM D3039, based on flat coupons, usually has a large scatter for fibre reinforced polymer (FRP) composites. This means that the measured strength may not represent the actual strength of the material, leading to under or over design. This paper develops a new interpretation method which requires fewer tests, saving money and time. Moreover the results are more consistent and more closely represent the actual strength which can lead to a safer and more economical design.

Donor type microchimerism is an infrequent event following liver transplantation and is not associated with graft acceptance

Donor-type microchimerism, the presence of a minority population of donor-derived haematopoietic cells following solid organ transplantation, has been postulated as a mechanism for induction of donor-specific graft tolerance. The stability, frequency, and relevance of microchimerism with respect to long-term outcome, however, remains uncertain. Using a polymerase chain reaction (PCR)-based method of microsatellite analysis of highly polymorphic short tandem repeat sequences (STRs) to detect donor-type cells, DNA from 11 patients was analyzed prospectively at specific time points for 12 months following liver transplantation, and from a further six patients retrospectively 2 years after liver transplantation. Using a panel of STRs, transient peripheral blood donor microchimerism was detected in 2 of 11 patients at a single time-point following transplantation, but persistent evidence of donor-derived cells was not observed during the study period. Analysis of DNA extracted from skin and duodenum in two patients likewise failed to show donor-type cells at these sites. None of the six patients in the retrospective arm showed donor microchimerism, resulting in an overall detection rate of 1.58%. These results suggest that donor microchimerism following liver transplantation is an infrequent event, and that the generation of graft tolerance is independent of microchimerism.