Managing inappropriate utilization of laboratory resource

Background The inappropriate use of laboratory resources, due to excessive number of tests not really necessary for patient care or by failure to order the appropriate diagnostic test, may lead to wrong, missed or delayed diagnosis, thus potentially jeopardizing patient safety. It is estimated that 5-95% of tests are currently used inappropriately, depending on the appropriateness criteria, thus significantly contributing to the potential of generating medical errors, the third leading cause of death in the US. Content In this review, we discuss the reasons as well as the medical and financial consequences of inappropriate utilization of laboratory tests. We then provide demand management (DM) tools as a means for overcoming this issue and also discuss their benefits, challenges, limitations and requirements for successful implementation. Summary and outlook When based on current evidence, adapted to local conditions and developed in close collaboration with clinicians, DM is a reasonable strategy for progressing toward better management of over- and underuse of laboratory resources

The VMC survey - XV : The Small Magellanic Cloud-Bridge connection history as traced by their star cluster populations

Date of Acceptance: 19/03/2015We present results based on YJKs photometry of star clusters located in the outermost, eastern region of the Small Magellanic Cloud (SMC). We analysed a total of 51 catalogued clusters whose colour-magnitude diagrams (CMDs), having been cleaned from field-star contamination, were used to assess the clusters' reality and estimate ages of the genuine systems. Based on CMD analysis, 15 catalogued clusters were found to be possible non-genuine aggregates. We investigated the properties of 80 per cent of the catalogued clusters in this part of the SMC by enlarging our sample with previously obtained cluster ages, adopting a homogeneous scale for all. Their spatial distribution suggests that the oldest clusters, log(t/yr) ≥ 9.6, are in general located at greater distances to the galaxy's centre than their younger counterparts - 9.0 ≤ log(t/yr) ≤ 9.4 - while two excesses of clusters are seen at log(t/yr) ~9.2 and log(t yr-1) ˜ 9.7. We found a trail of younger clusters which follow the wing/bridge components. This long spatial sequence does not only harbour very young clusters, log(t yr-1) ~7.3, but it also hosts some of intermediate ages, log(t/yr) ~9.1. The derived cluster and field-star formation frequencies as a function of age are different. The most surprising feature is an observed excess of clusters with ages of log(t/yr) < 9.0, which could have been induced by interactions with the LMC.Peer reviewedFinal Accepted Versio

Prevalence of obesity in preschool Greek children, in relation to parental characteristics and region of residence

<p>Abstract</p> <p>Background</p> <p>The aim of this retrospective cohort study was to record the prevalence of overweight and obesity in relation to parental education level, parental body mass index and region of residence, in preschool children in Greece.</p> <p>Methods</p> <p>A total of 2374 children (1218 males and 1156 females) aged 1–5 years, stratified by parental educational level (Census 1999), were examined from 105 nurseries in five counties, from April 2003 to July 2004, Weight (kg) and height (cm) were obtained and BMI (kg/m²) was calculated. Both the US Centers for Disease Control (CDC) and the International Obesity Task Force (IOTF) methods were used to classify each child as "normal", "at risk of overweight" and "overweight". Parental demographic characteristics, such as age and educational level and parental anthropometrical data, such as stature and body weight, were also recorded with the use of a specifically designed questionnaire.</p> <p>Results</p> <p>The overall estimates of at risk of overweight and overweight using the CDC method was 31.9%, 10.6 percentage points higher than the IOTF estimate of 21.3% and this difference was significant (p < 0.001). Children with one obese parent had 91% greater odds for being overweight compared to those with no obese parent, while the likelihood for being overweight was 2.38 times greater for children with two obese parents in the multivariate model.</p> <p>Conclusion</p> <p>Both methods used to assess prevalence of obesity have demonstarted that a high percentage of the preschool children in our sample were overweight. Parental body mass index was also shown to be an obesity risk factor in very young children.</p

The VMC survey - XXXI: The spatially resolved star formation history of the main body of the Small Magellanic Cloud

We recover the spatially resolved star formation history across the entire main body and Wing of the Small Magellanic Cloud (SMC), using 14 deep tile images from the VISTA survey of the Magellanic Clouds (VMC) in the YJKs filters. The analysis is performed on 168 subregions of size 0.143 deg2 covering a total contiguous area of 23.57 deg2. We apply a colour\u2013magnitude diagram (CMD) reconstruction method that returns the best-fitting star formation rate SFR(t), age\u2013metallicity relation, distance and mean reddening, together with their confidence intervals, for each subregion. With respect to previous analyses, we use a far larger set of the VMC data, updated stellar models, and fit the two available CMDs (Y 12 Ks versus Ks and J 12 Ks versus Ks) independently. The results allow us to derive a more complete and more reliable picture of how the mean distances, extinction values, star formation rate, and metallicities vary across the SMC, and provide a better description of the populations that form its Bar and Wing. We conclude that the SMC has formed a total mass of (5.31 \ub1 0.05) 7 108 M 99 in stars over its lifetime. About two-thirds of this mass is expected to be still locked in stars and stellar remnants. 50 per cent of the mass was formed prior to an age of 6.3 Gyr, and 80 per cent was formed between 8 and 3.5 Gyr ago. We also illustrate the likely distribution of stellar ages and metallicities in different parts of the CMD, to aid the interpretation of data from future astrometric and spectroscopic surveys of the SMC

Efficacy of metamizole versus ibuprofen and a short educational intervention versus standard care in acute and subacute low back pain: a study protocol of a randomised, multicentre, factorial trial (EMISI trial).

INTRODUCTION Low back pain (LBP) is among the top three most common diseases worldwide, resulting in a life with pain-related disability. To date, no study has assessed the efficacy of metamizole (dipyrone), a non-opioid analgesic and antipyretic prodrug compared with the conventional non-steroidal anti-inflammatory drug ibuprofen, in patients with an acute LBP episode. Further, it is unclear, whether a short educational intervention is superior to usual care alone. OBJECTIVES The objective of this study is to assess first, whether metamizole is non-inferior to ibuprofen in a new episode of acute or subacute LBP. Second, we aim to assess whether a short educational intervention including evidence-based patient information on the nature of LBP is superior to usual care alone. METHODS AND ANALYSIS An investigator-initiated multicentre, randomised, double blind trial using a factorial design will be performed. A total of 120 participants with a new episode of LBP will be recruited from GP practices, outpatient clinics and from emergency departments, and randomised into four different treatment groups: ibuprofen alone, ibuprofen and short intervention, metamizole alone, metamizole and short intervention. The primary endpoint for the medical treatment will be change in pain assessed on an 11-point Numeric Rating Scale after 14 days. The primary outcome for the short intervention will be change in the Core Outcome Measures Index assessed after 42 days. ETHICS, DISSEMINATION AND FUNDING This study has been approved by the responsible Ethics Board (Ethikkommission Bern/2018-01986) and the Swiss Agency for Therapeutic Products (Swissmedic/2019DR4002). Results will be published in open access policy peer-reviewed journals. The study is funded by the Swiss National Science Foundation (grant number 32 003B-179346). TRIAL REGISTRATION NUMBER NCT04111315

The basel cocktail for simultaneous phenotyping of human cytochrome P450 isoforms in plasma, saliva and dried blood spots.

BACKGROUND AND OBJECTIVE Phenotyping cocktails use a combination of cytochrome P450 (CYP)-specific probe drugs to simultaneously assess the activity of different CYP isoforms. To improve the clinical applicability of CYP phenotyping, the main objectives of this study were to develop a new cocktail based on probe drugs that are widely used in clinical practice and to test whether alternative sampling methods such as collection of dried blood spots (DBS) or saliva could be used to simplify the sampling process. METHODS In a randomized crossover study, a new combination of commercially available probe drugs (the Basel cocktail) was tested for simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Sixteen subjects received low doses of caffeine, efavirenz, losartan, omeprazole, metoprolol and midazolam in different combinations. All subjects were genotyped, and full pharmacokinetic profiles of the probe drugs and their main metabolites were determined in plasma, dried blood spots and saliva samples. RESULTS The Basel cocktail was well tolerated, and bioequivalence tests showed no evidence of mutual interactions between the probe drugs. In plasma, single timepoint metabolic ratios at 2 h (for CYP2C19 and CYP3A4) or at 8 h (for the other isoforms) after dosing showed high correlations with corresponding area under the concentration-time curve (AUC) ratios (AUC0-24h parent/AUC0-24h metabolite) and are proposed as simple phenotyping metrics. Metabolic ratios in dried blood spots (for CYP1A2 and CYP2C19) or in saliva samples (for CYP1A2) were comparable to plasma ratios and offer the option of minimally invasive or non-invasive phenotyping of these isoforms. CONCLUSIONS This new combination of phenotyping probe drugs can be used without mutual interactions. The proposed sampling timepoints have the potential to facilitate clinical application of phenotyping but require further validation in conditions of altered CYP activity. The use of DBS or saliva samples seems feasible for phenotyping of the selected CYP isoforms

Establishment and Characterization of hTERT Immortalized Hutchinson&ndash;Gilford Progeria Fibroblast Cell Lines

Hutchinson&ndash;Gilford progeria syndrome (HGPS) is a rare premature aging syndrome caused by a dominant mutation in the LMNA gene. Previous research has shown that the ectopic expression of the catalytic subunit of telomerase (hTERT) can elongate the telomeres of the patients&rsquo; fibroblasts. Here, we established five immortalized HGP fibroblast cell lines using retroviral infection with the catalytic subunit of hTERT. Immortalization enhanced the proliferative life span by at least 50 population doublings (PDs). The number of cells with typical senescence signs was reduced by 63 + 17%. Furthermore, the growth increase and phenotype improvement occurred with a lag phase of 50&ndash;100 days and was not dependent on the degree of telomere elongation. The initial telomeric stabilization after hTERT infection and relatively low amounts of hTERT mRNA were sufficient for the phenotype improvement but the retroviral infection procedure was associated with transient cell stress. Our data have implications for therapeutic strategies in HGP and other premature aging syndromes

Minimal modeling of insulin secretion in the perfused rat pancreas: a drug effect case study

The experimental protocol of the perfused rat pancreas is commonly used to evaluate \u3b2-cell function. In this context, mathematical models become useful tools through the determination of indexes that allow the assessment of \u3b2-cell function in different experimental groups and the quantification of the effects of antidiabetic drugs, secretagogues, or treatments. However, a minimal model applicable to the isolated perfused rat pancreas has so far been unavailable. In this work, we adapt the C-peptide minimal model applied previously to the intravenous glucose tolerance test to obtain a specific model for the experimental settings of the perfused pancreas. Using the model, it is possible to estimate indexes describing \u3b2-cell responsivity for first (\u3a6D) and second phase (\u3a6S, T) of insulin secretion. The model was initially applied to untreated pancreata and afterward used for the assessment of pharmacologically relevant agents (the gut hormone GLP-1, the potent GLP-1 receptor agonist lixisenatide, and a GPR40/FFAR1 agonist, SAR1) to quantify and differentiate their effect on insulin secretion. Model fit was satisfactory, and parameters were estimated with good precision for both untreated and treated pancreata. Model application showed that lixisenatide reaches improvement of \u3b2-cell function similarly to GLP-1 (11.7- vs. 13.1-fold increase in \u3a6D and 2.3- vs. 2.8-fold increase in \u3a6S and demonstrated that SAR1 leads to an additional improvement of \u3b2-cell function in the presence of postprandial GLP-1 levels