Consensus of Official Position of IOF/ISCD FRAX Initiatives in Asia-Pacific Region.

The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.

Evaluation of two immunoassays for the measurement of human chorionic gonadotropin in urine for anti-doping purposes.

Background: Urinary human chorionic gonadotropin (hCG) concentration is routinely measured in all anti-doping laboratories to exclude the misuse of recombinant or urinary hCG preparations. In this study, extended validation of two commercial immunoassays for hCG measurements in urine was performed. Both tests were initially designed for hCG determination in human serum/plasma. Methods: Access (R) and Elecsys (R) 1010 are two automated immunoanalysers for central laboratories. The limits of detection and quantification, as well as intra-laboratory and inter-technique correlation, precision, and accuracy, were determined. Stability studies of hCG in urine following freezing and thawing cycles (n = 3) as well as storage conditions at room temperature, 4 degrees C and 20 degrees C, were performed. Results: Statistical evaluation of hCG concentrations in male urine samples (n = 2429) measured with the Elecsys (R) 1010 system enabled us to draw a skewed frequency histogram and establish a far outside value equal to 2.3 IU/L. This decision limit corresponds to the concentration at which a sportsman will be considered positive for hCG. Intra-assay precision for the Access (R) analyser was less than 4.0 A, whereas the inter-assay precision was closer to 4.5 % (concentrations of the official external controls contained between 5.5 and 195.0 IU/L). Intra and inter-assay precision for the Elecsys (R) 1010 analyser was slightly better. A good inter-technique correlation was obtained when measuring various urine samples (male and female). No urinary hCG loss was observed after two freeze/thaw cycles. On the other hand, time and inappropriate storage conditions, such as temperatures above 10 degrees C for more than 5 days, can deteriorate urinary hCG. Conclusions: Both analysers showed acceptable performances and are suitable for screening urine for anti-doping analyses. Each laboratory should validate and establish its own reference values because hCG concentrations measured in urine can be different from one immunoassay to another. The time delay between urine collection and analysis should be reduced as much as possible, and urine samples should be transported in optimal conditions to avoid a loss of hCG immunoreactivity.

Official Positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®).

Given the significant impact the use of glucocorticoids can have on fracture risk independent of bone density, their use has been incorporated as one of the clinical risk factors for calculating the 10-year fracture risk in the World Health Organization's Fracture Risk Assessment Tool (FRAX(®)). Like the other clinical risk factors, the use of glucocorticoids is included as a dichotomous variable with use of steroids defined as past or present exposure of 3 months or more of use of a daily dose of 5 mg or more of prednisolone or equivalent. The purpose of this report is to give clinicians guidance on adjustments which should be made to the 10-year risk based on the dose, duration of use and mode of delivery of glucocorticoids preparations. A subcommittee of the International Society for Clinical Densitometry and International Osteoporosis Foundation joint Position Development Conference presented its findings to an expert panel and the following recommendations were selected. 1) There is a dose relationship between glucocorticoid use of greater than 3 months and fracture risk. The average dose exposure captured within FRAX(®) is likely to be a prednisone dose of 2.5-7.5 mg/day or its equivalent. Fracture probability is under-estimated when prednisone dose is greater than 7.5 mg/day and is over-estimated when the prednisone dose is less than 2.5 mg/day. 2) Frequent intermittent use of higher doses of glucocorticoids increases fracture risk. Because of the variability in dose and dosing schedule, quantification of this risk is not possible. 3) High dose inhaled glucocorticoids may be a risk factor for fracture. FRAX(®) may underestimate fracture probability in users of high dose inhaled glucocorticoids. 4) Appropriate glucocorticoid replacement in individuals with adrenal insufficiency has not been found to increase fracture risk. In such patients, use of glucocorticoids should not be included in FRAX(®) calculations.

Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories.

INTRODUCTION: Rivaroxaban (RXA) is licensed for prophylaxis of venous thromboembolism after major orthopaedic surgery of the lower limbs. Currently, no test to quantify RXA in plasma has been validated in an inter-laboratory setting. Our study had three aims: to assess i) the feasibility of RXA quantification with a commercial anti-FXa assay, ii) its accuracy and precision in an inter-laboratory setting, and iii) the influence of 10mg of RXA on routine coagulation tests. METHODS: The same chromogenic anti-FXa assay (Hyphen BioMed) was used in all participating laboratories. RXA calibrators and sets of blinded probes (aim ii.) were prepared in vitro by spiking normal plasma. The precise RXA content was assessed by high-pressure liquid chromatography-tandem mass spectrometry. For ex-vivo studies (aim iii), plasma samples from 20 healthy volunteers taken before and 2 - 3hours after ingestion of 10mg of RXA were analyzed by participating laboratories. RESULTS: RXA can be assayed chromogenically. Among the participating laboratories, the mean accuracy and the mean coefficient of variation for precision of RXA quantification were 7.0% and 8.8%, respectively. Mean RXA concentration was 114±43μg/L .RXA significantly altered prothrombin time, activated partial thromboplastin time, factor analysis for intrinsic and extrinsic factors. Determinations of thrombin time, fibrinogen, FXIII and D-Dimer levels were not affected. CONCLUSIONS: RXA plasma levels can be quantified accurately and precisely by a chromogenic anti-FXa assay on different coagulometers in different laboratories. Ingestion of 10mg RXA results in significant alterations of both PT- and aPTT-based coagulation assays.

The differentiation of fibre- and drug type Cannabis seedlings by gas chromatography/mass spectrometry and chemometric tools

Cannabis cultivation in order to produce drugs is forbidden in Switzerland. Thus, law enforcement authorities regularly ask forensic laboratories to determinate cannabis plant's chemotype from seized material in order to ascertain that the plantation is legal or not. As required by the EU official analysis protocol the THC rate of cannabis is measured from the flowers at maturity. When laboratories are confronted to seedlings, they have to lead the plant to maturity, meaning a time consuming and costly procedure. This study investigated the discrimination of fibre type from drug type Cannabis seedlings by analysing the compounds found in their leaves and using chemometrics tools. 11 legal varieties allowed by the Swiss Federal Office for Agriculture and 13 illegal ones were greenhouse grown and analysed using a gas chromatograph interfaced with a mass spectrometer. Compounds that show high discrimination capabilities in the seedlings have been identified and a support vector machines (SVMs) analysis was used to classify the cannabis samples. The overall set of samples shows a classification rate above 99% with false positive rates less than 2%. This model allows then discrimination between fibre and drug type Cannabis at an early stage of growth. Therefore it is not necessary to wait plants' maturity to quantify their amount of THC in order to determine their chemotype. This procedure could be used for the control of legal (fibre type) and illegal (drug type) Cannabis production.

The future key role of LC-high-resolution-MS analyses in clinical laboratories: a focus on quantification.

For the last decade, high-resolution (HR)-MS has been associated with qualitative analyses while triple quadrupole MS has been associated with routine quantitative analyses. However, a shift of this paradigm is taking place: quantitative and qualitative analyses will be increasingly performed by HR-MS, and it will become the common 'language' for most mass spectrometrists. Most analyses will be performed by full-scan acquisitions recording 'all' ions entering the HR-MS with subsequent construction of narrow-width extracted-ion chromatograms. Ions will be available for absolute quantification, profiling and data mining. In parallel to quantification, metabotyping will be the next step in clinical LC-MS analyses because it should help in personalized medicine. This article is aimed to help analytical chemists who perform targeted quantitative acquisitions with triple quadrupole MS make the transition to quantitative and qualitative analyses using HR-MS. Guidelines for the acceptance criteria of mass accuracy and for the determination of mass extraction windows in quantitative analyses are proposed.

Official Positions for FRAX® clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following: The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper.

Variability in urinary oxalate measurements between six international laboratories.

BACKGROUND: Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement. METHODS: Urine samples from 24-h urine collection covering a broad range of oxalate concentrations were aliquoted and sent, in duplicates, to six blinded international laboratories for oxalate, sodium and creatinine measurement. In a second set of experiments, ten pairs of native urine and urine spiked with 10 mg/L of oxalate were sent for oxalate measurement. Three laboratories used a commercially available oxalate oxidase kit, two laboratories used a high-performance liquid chromatography (HPLC)-based method and one laboratory used both methods. RESULTS: Intra-laboratory reliability for oxalate measurement expressed as intraclass correlation coefficient (ICC) varied between 0.808 [95% confidence interval (CI): 0.427-0.948] and 0.998 (95% CI: 0.994-1.000), with lower values for HPLC-based methods. Acidification of urine samples prior to analysis led to significantly higher oxalate concentrations. ICC for inter-laboratory reliability varied between 0.745 (95% CI: 0.468-0.890) and 0.986 (95% CI: 0.967-0.995). Recovery of the 10 mg/L oxalate-spiked samples varied between 8.7 ± 2.3 and 10.7 ± 0.5 mg/L. Overall, HPLC-based methods showed more variability compared to the oxalate oxidase kit-based methods. CONCLUSIONS: Significant variability was noted in the quantification of urinary oxalate concentration by different laboratories, which may partially explain the differences of hyperoxaluria prevalence reported in the literature. Our data stress the need for a standardization of the method of oxalate measurement.

Mult-class differentiation of cannabis seedlings in a forensic context

This article presents an experimental study about the classification ability of several classifiers for multi-classclassification of cannabis seedlings. As the cultivation of drug type cannabis is forbidden in Switzerland lawenforcement authorities regularly ask forensic laboratories to determinate the chemotype of a seized cannabisplant and then to conclude if the plantation is legal or not. This classification is mainly performed when theplant is mature as required by the EU official protocol and then the classification of cannabis seedlings is a timeconsuming and costly procedure. A previous study made by the authors has investigated this problematic [1]and showed that it is possible to differentiate between drug type (illegal) and fibre type (legal) cannabis at anearly stage of growth using gas chromatography interfaced with mass spectrometry (GC-MS) based on therelative proportions of eight major leaf compounds. The aims of the present work are on one hand to continueformer work and to optimize the methodology for the discrimination of drug- and fibre type cannabisdeveloped in the previous study and on the other hand to investigate the possibility to predict illegal cannabisvarieties. Seven classifiers for differentiating between cannabis seedlings are evaluated in this paper, namelyLinear Discriminant Analysis (LDA), Partial Least Squares Discriminant Analysis (PLS-DA), Nearest NeighbourClassification (NNC), Learning Vector Quantization (LVQ), Radial Basis Function Support Vector Machines(RBF SVMs), Random Forest (RF) and Artificial Neural Networks (ANN). The performance of each method wasassessed using the same analytical dataset that consists of 861 samples split into drug- and fibre type cannabiswith drug type cannabis being made up of 12 varieties (i.e. 12 classes). The results show that linear classifiersare not able to manage the distribution of classes in which some overlap areas exist for both classificationproblems. Unlike linear classifiers, NNC and RBF SVMs best differentiate cannabis samples both for 2-class and12-class classifications with average classification results up to 99% and 98%, respectively. Furthermore, RBFSVMs correctly classified into drug type cannabis the independent validation set, which consists of cannabisplants coming from police seizures. In forensic case work this study shows that the discrimination betweencannabis samples at an early stage of growth is possible with fairly high classification performance fordiscriminating between cannabis chemotypes or between drug type cannabis varieties.

Diagnosis and management of chronic obstructive pulmonary disease: the swiss guidelines: official guidelines of the Swiss Respiratory Society.

The new Swiss Chronic Obstructive Pulmonary Disease (COPD) Guidelines are based on a previous version, which was published 10 years ago. The Swiss Respiratory Society felt the need to update the previous document due to new knowledge and novel therapeutic developments about this prevalent and important disease. The recommendations and statements are based on the available literature, on other national guidelines and, in particular, on the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. Our aim is to advise pulmonary physicians, general practitioners and other health care workers on the early detection and diagnosis, prevention, best symptomatic control, and avoidance of COPD as well as its complications and deterioration.

Evaluation of the susceptibility of pathogenic Candida species to fluconazole. Fluconazole Global Susceptibility Study Group.

A fluconazole 25 microg disk diffusion test was used to test 2230 consecutively isolated Candida strains from 42 different hospital laboratories in 23 countries. Ninety seven percent of 1634 Candida albicans isolates and 83.4% of 596 non-Candida albicans isolates were susceptible to fluconazole, applying the proposed breakpoints (> or = 26 mm for susceptible strains and 18-25 mm for dose-dependent susceptible strains). This is the first hospital laboratory study to evaluate a large number and wide range of sequential Candida isolates from patients with all types of hospital infections. The fluconazole disk diffusion test appears to be a low-cost, reproducible, and accurate means of assessing the in vitro susceptibility of Candida isolates.

Peripheral dual-energy X-ray absorptiometry in the management of osteoporosis: the 2007 ISCD Official Positions.

Peripheral assessment of bone density using photon absorptiometry techniques has been available for over 40 yr. The initial use of radio-isotopes as the photon source has been replaced by the use of X-ray technology. A wide variety of models of single- or dual-energy X-ray measurement tools have been made available for purchase, although not all are still commercially available. The Official Positions of the International Society for Clinical Densitometry (ISCD) have been developed following a systematic review of the literature by an ISCD task force and a subsequent Position Development Conference. These cover the technological diversity among peripheral dual-energy X-ray absorptiometry (pDXA) devices; define whether pDXA can be used for fracture risk assessment and/or to diagnose osteoporosis; examine whether pDXA can be used to initiate treatment and/or monitor treatment; provide recommendations for pDXA reporting; and review quality assurance and quality control necessary for effective use of pDXA.

Official Positions for FRAX® clinical regarding smoking from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The worldwide prevalence of smoking has been estimated at about 50% in men, and 10% in women, with larger variations among different populations studied. Smoking has been shown to affect many organ systems resulting in severe morbidity and increased mortality. In addition, smoking has been identified as a predictor of ten-year fracture risk in men and women, largely independent of an individual's bone mineral density. This finding has eventually lead to incorporation of this risk factor into FRAX®, an algorithm that has been developed to calculate an individual's ten-year fracture risk. However, only little, or conflicting data is available on a possible association between smoking dose, duration, length of time after cessation, type of tobacco and fracture risk, limiting this risk factor's applicability in the context of FRAX®.

Variability between laboratories performing coagulation tests with identical platforms: a nationwide evaluation study.

BACKGROUND: While the assessment of analytical precision within medical laboratories has received much attention in scientific enquiry, the degree of as well as the sources causing variation between them remains incompletely understood. In this study, we quantified the variance components when performing coagulation tests with identical analytical platforms in different laboratories and computed intraclass correlations coefficients (ICC) for each coagulation test. METHODS: Data from eight laboratories measuring fibrinogen twice in twenty healthy subjects with one out of 3 different platforms and single measurements of prothrombin time (PT), and coagulation factors II, V, VII, VIII, IX, X, XI and XIII were analysed. By platform, the variance components of (i) the subjects, (ii) the laboratory and the technician and (iii) the total variance were obtained for fibrinogen as well as (i) and (iii) for the remaining factors using ANOVA. RESULTS: The variability for fibrinogen measurements within a laboratory ranged from 0.02 to 0.04, the variability between laboratories ranged from 0.006 to 0.097. The ICC for fibrinogen ranged from 0.37 to 0.66 and from 0.19 to 0.80 for PT between the platforms. For the remaining factors the ICC's ranged from 0.04 (FII) to 0.93 (FVIII). CONCLUSIONS: Variance components that could be attributed to technicians or laboratory procedures were substantial, led to disappointingly low intraclass correlation coefficients for several factors and were pronounced for some of the platforms. Our findings call for sustained efforts to raise the level of standardization of structures and procedures involved in the quantification of coagulation factors.