A model for an uncertainty budget for preanalytical variables in clinical chemistry analyses

BACKGROUND: We sought a practical method to calculate preanalytical uncertainties. In clinical chemistry measurements, the combined preanalytical uncertainty is a function of the magnitude and probability distribution of the different uncertainty sources and the number of such sources. METHODS: Results from an optimal practice for handling of the blood samples (termed the standard method) were compared with alternative methods that deviate from the standard method but are used in current practice. For categorically distributed uncertainty sources (e.g., use of different kinds of blood tubes), alternative treatments were modeled discretely using a known probability distribution for each alternative. For continuously distributed sources (e.g., clotting time), we assumed a rectangular distribution. We calculated the expectation, variance, and SD of differences between results from current practice and the standard method. We tabulated uncertainty budgets for the differences between current practice and the standard method for each uncertainty source. The expected individual biases and variances were summed to obtain the combined expected bias and variance. RESULTS: The combined expected bias (SD) for glucose was -0.15 (0.130) mmol/L, with prolonged clotting time giving the greatest contribution. The combined expected bias (SD) for calcium was -0.011 (0.0182) mmol/L, for magnesium 0.006 (0.026) mmol/L, and for creatinine 0.5 (1.81) micromol/L. CONCLUSION: By comparing a standard method for preanalytical sample handling to alternative methods used in current practice, and considering the distribution of alternative methods, our modeling approach allows the development of an uncertainty budget for preanalytical variables in clinical chemistry analyses.     

Blick in und Wünsche für die Zukunft der Unfallchirurgie

Die Unfallchirurgie -     

Intraoperative fluid balance during cardiopulmonary bypass: effects of different mean arterial pressures

INTRODUCTION: This study investigated whether two levels of mean arterial pressure (MAP) during cardiopulmonary bypass did influence per-operative fluid shifts. METHODS: Sixteen pigs underwent 60 minutes of normothermic cardiopulmonary bypass (CPB) followed by 90 minutes of hypothermic CPB. Eight animals had a MAP of 60-80mmHg by norepinephrine (HP group). Another 8 animals had a MAP of 40-45 mmHg by phentolamine (LP group). Blood chemistry, plasma/interstitial colloid osmotic pressures, plasma volume, fluid balance, fluid extravasation rate and tissue water content were measured or calculated. RESULTS: The plasma volume was significantly lower in the HP group compared with the LP group after 60 minutes of CPB. Net fluid balance was 0.18 (0.05) ml x kg(-1) x min(-1) in the HP group and 0.21 ml x kg(-1) x min(-1) in the LP group (P > 0.05) while fluid extravasation rate was 1.18 (0.5) and 1.13 (0.4) ml x kg(-1) x min(-1) in the HP group and the LP group during CPB (P > 0.05). CONCLUSION: Net fluid balance and fluid extravasation rate were similar in the animals with elevated and with lowered MAP during CPB.     

Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture,Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score > −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Psychotropic medication in geriatric psychiatric patients: use and unreported use in relation to serum concentrations

Purpose

The aim of this observational study was to describe the type, number, and serum concentration levels of psychotropic drugs in elderly patients, on admission to a geriatric psychiatric inpatient unit. We further wanted to investigate the use and unreported use of psychotropic drugs by analyzing for a broad spectrum of drugs in the serum samples.

Methods

A total of 236 patients were included. Drug use, patient characteristics, and diagnoses were recorded, and serum analysis was performed for a total of 56 psychotropic drugs in 233 of the patients.

Results

Nine out of ten patients (88 %) used one or more psychotropic drugs on admission to hospital; the mean use was 2.8 (95 % confidence interval (CI) 2.6–2.9) drugs. In 25 patients (11 %), drugs reported used were not detected in serum. Unreported use of drugs (serum analysis revealing one or more drugs not reported) was found in 100 patients (43 %). This was more common in younger patients. Psychotropic polypharmacy (use of three or more psychotropic drugs) was found in 109 patients (47 %). Patients with a main diagnosis of affective disorder used the most psychotropic drugs.

Conclusions

Psychotropic drugs are commonly used among geriatric psychiatric patients on admission to hospital. Psychotropic polypharmacy is a major concern among these patients. There was considerable unreported use of drugs within this population, and a low threshold for a broader serum analysis for psychotropic drugs appears indicated.