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Electronic exchange of health care data demands code/terminology systems. In the Scandinavian countries, the IFCC-IUPAC's Nomenclature for Properties and Units (NPU) terminology is used for results in biochemistry, pharmacology, and immunology. Implementation, use and administration of NPU has differed between the countries despite similar health care and lab sectors. In Norway and in one Swedish region NPU - with supplementary SNOMED CT codes is also used for reporting results in microbiology. In Denmark and to some extent in Norway and Sweden NPU is also used for ordering tests. In Norway NPU (as part of NLK) has since 2018 been mandatory in requesting governmental reimbursement for laboratory tests. The numbers of national codes vary considerably (DAN: 303, NOR: 1612, SWE: 415). Furthermore, in Denmark >3500 local codes are used for requisition and to communicate more details with the analytical result than the NPU terminology allows. Also, in Norway the NPU codes are by many lab professionals considered insufficient for communicating all relevant information with results. However, the Norwegian reimbursement system has been a strong motivator for implementing international NPU codes. We find it necessary to add information about "how" a measurement is done to the information about "what" is measured in the laboratory report. Until this is settled otherwise, we suggest an increased pragmatism towards producing national codes including method specific information. Furthermore, we recommend that organisations responsible for classifications have heavy professional participation and decision-making competencies in order to lead and guide implementation and optimal use of the classifications., Competing Interests: Declaration of Conflict of interests The authors of this article declare that there is no conflict of interest with regard to the content of this manuscript. R. Ceder, K. Toska,, Y.B. Hansen and G. Nordin are, or have been, members of the IFCC committee on Nomenclature, Properties and Units (C-NPU) in collaboration with IUPAC., (Copyright © 2024 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Magnetosheath jets represent localized enhancements in dynamic pressure observed within the magnetosheath. These energetic entities, carrying excess energy and momentum, can impact the magnetopause and disrupt the magnetosphere. Therefore, they play a vital role in coupling the solar wind and terrestrial magnetosphere. However, our understanding of the morphology and formation of these complex, transient events remains incomplete over two decades after their initial observation. Previous studies have relied on oversimplified assumptions, considering jets as elongated cylinders with dimensions ranging from |$0.1\, R_{\rm E}$| to |$5\, R_{\rm E}$| (Earth radii). In this study, we present simulation results obtained from Amitis, a high-performance hybrid-kinetic plasma framework (particle ions and fluid electrons) running in parallel on graphics processing units (GPUs) for fast and more environmentally friendly computation compared to CPU-based models. Considering realistic scales, we present the first global, three-dimensional (3D in both configuration and velocity spaces) hybrid-kinetic simulation results of the interaction between solar wind plasma and the Earth. Our high-resolution kinetic simulations reveal the 3D structure of magnetosheath jets, showing that jets are far from being simple cylinders. Instead, they exhibit intricate and highly interconnected structures with dynamic 3D characteristics. As they move through the magnetosheath, they wrinkle, fold, merge, and split in complex ways before a subset reaches the magnetopause. [ABSTRACT FROM AUTHOR]

Background: European legislation defines as "near-patient testing" (NPT) what is popularly and in other legislations specified as "point-of-care testing" (POCT). Systems intended for NPT/POCT use must be characterized by independence from operator activities during the analytic procedure. However, tools for evaluating this are lacking. We hypothesized that the variability of measurement results obtained from identical samples with a larger number of identical devices by different operators, expressed as the method-specific reproducibility of measurement results reported in External Quality Assessment (EQA) schemes, is an indicator for this characteristic., Materials and Methods: Legal frameworks in the EU, the USA and Australia were evaluated about their requirements for NPT/POCT. EQA reproducibility of seven SARS-CoV-2-NAAT systems, all but one designated as "POCT", was calculated from variabilities in Ct values obtained from the respective device types in three different EQA schemes for virus genome detection., Results: A matrix for characterizing test systems based on their technical complexity and the required operator competence was derived from requirements of the European In Vitro Diagnostic Regulation (IVDR) 2017/746. Good EQA reproducibility of the measurement results of the test systems investigated implies that different users in different locations have no recognizable influence on their measurement results., Conclusion: The fundamental suitability of test systems for NPT/POCT use according to IVDR can be easily verified using the evaluation matrix presented. EQA reproducibility is a specific characteristic indicating independence from operator activities of NPT/POCT assays. EQA reproducibility of other systems than those investigated here remains to be determined., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter B. Luppa is member of the board of directors of INSTAND e.V., a non-profit organization, named as one of two EQA providers for Germany by the Deutsche Ärztekammer. Heinz Zeichhardt declares that he is co-chairman of the Joint Diagnostic Council of the Deutsche Vereinigung zur Bekaempfung der Viruskrankheiten e.V. (DVV e.V.) and Gesellschaft fuer Virologie (GfV e.V.) and is Advisor for the INSTAND External Quality Assessment (EQA) schemes in virus diagnostics. He is owner and managing director of IQVD GmbH - Institut fuer Qualitaetssicherung in der Virusdiagnostik, Berlin, and was majority owner and managing director of GBD Gesellschaft fuer Biotechnologische Diagnostik mbH, Berlin. He declares that he has no conflicts of interest with regard to the activities mentioned in relation to the publication. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Despite sleep disturbance and somatic symptoms being common health complaints, the relationship between these disturbances and single somatic symptoms is not well documented. The objectives of this study were to (i) identify somatic symptoms that are particularly associated with sleep disturbance, here referred to as somatic symptoms related to sleep disturbance (SS-SD), (ii) determine increased risk of sleep disturbance for each SS-SD and for a certain number of SS-SD, with and without controlling for anxiety and depression, and (iii) determine sensitivity and specificity for identifying sleep disturbance based on number of SS-SD in a general Swedish sample. Population-based, cross-sectional data based on validated questionnaire instruments were used from participants who constituted a sleep disturbance (n = 864) or a reference (n = 2340) group. Among 15 common somatic symptoms, stomach pain, back pain nausea/gas/indigestion, dizziness, and constipation/loose bowels/diarrhea were identified as SS-SD, with odds ratios of increased risk of sleep disturbance that ranged from 1.93 to 2.44 (1.36-1.79 and 1.54-1.91 when controlled for anxiety and depression, respectively). The risk of sleep disturbance increased by 1.44 times for each SS-SD (1.25 and 1.30 when controlled for anxiety and depression, respectively). A cutoff of two/three or more SS-SD had a sensitivity of 72.5/54.2% and a specificity of 50.0/69.7% for identifying sleep disturbances. When patients present with these somatic symptoms with or without a pathophysiological explanation, primary care clinicians may consider screening for sleep disturbance.

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Free light chain (FLC) measurements are important in diagnosing monoclonal gammopathies. As FLC are heterogeneous, different reagents and instruments for measuring FLC concentrations may give diverging results that affect assessment of patients with monoclonal gammopathies. Here we investigated agreement between different FLC methods using data from the Swedish external quality assurance (EQA) programme., Methods: The two main FLC assays, N Latex FLC (Siemens) and Serum Freelite (The Binding Site), using four nephelometric or turbidimetric instrument platforms, were compared. Results from 27 EQA rounds distributed to 11-16 Swedish hospital laboratories during 2015-2020 were investigated., Results: The kappa (κ) FLC measurements deviated significantly over time, but when only nephelometry was used, deviation from the mean was lower (median ranges: -5% to 13 %). The CV was significantly higher for the Freelite assay (mean CV = 8.7) than for the N latex assay (mean CV = 5.7) (p < 0.0001). The coefficient of determination between all combinations of reagents and instrument platforms used was generally good (r 2  = 0.76-0.87), and the correlation slope acceptable (0.81-1.2). For lambda (λ) FLC measurements, no concordance between combinations of instruments and reagents is apparent, deviating between -40 % to + 48 % from the mean. The CV was significantly higher for the combination with nephelometry and the Freelite assay (CV mean = 13.9 %) than nephelometry and the N latex assay (CV mean = 9.9 %) (p <0.001). The coefficient of determination varied between combinations of reagents and instrument platforms (r 2  = 0.59-0.89) and the slope ranged between 0.48 and 1.5. Significant differences between the two reagents used were sometimes noted., Conclusions: Imprecision in λFLC affects the κFLC/λFLC ratio. This may be important in clinical assessment of patients, especially differentiating between monoclonal and polyclonal gammopathies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated., Methods: We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements., Results: GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software., Conclusions: We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty., Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:, (© American Association for Clinical Chemistry 2022.)

We demonstrate a method of tuning the resonant frequencies of silicon microring resonators using a 3D-printed microfluidic chip overlaid directly on the photonic circuit with zero energy consumption following the initial tuning. Aqueous solutions with different concentrations of NaCl are used in experimentation. A shift of a full free spectral range is observed at a concentration of 10% NaCl. On a 60 µm microring resonator, this equals a resonant wavelength shift of 1.514 nm when the index of the cladding changes by 0.017 refractive index units (RIUs), or at a rate of 89.05 nm/RIU.

Sepsis represents a global health priority because of its high mortality and morbidity. The key to improving prognosis remains an early diagnosis to initiate appropriate antibiotic treatment. Procalcitonin (PCT) is a recognized biomarker for the early indication of bacterial infections and a valuable tool to guide and individualize antibiotic treatment. To meet the increasing demand for PCT testing, numerous PCT immunoassays have been developed and commercialized, but results have been questioned. Many comparison studies have been carried out to evaluate analytical performance and comparability of results provided by the different commercially available immunoassays for PCT, but results are conflicting. External Quality Assessment Schemes (EQAS) for PCT constitute another way to evaluate results comparability. However, when making this comparison, it must be taken into account that the variety of EQA materials consist of different matrices, the commutability of which has not yet been investigated. The present study gathers results from all published comparison studies and results from 137 EQAS surveys to describe the current state-of-the-art harmonization of PCT results. Comparison studies globally highlight a significant variability of measurement results that nonetheless seem to have a moderate impact on medical decision-making. For their part, EQAS for PCT provides highly discrepant estimates of the interlaboratory CV. Due to differences in commutability of the EQA materials, the results from different peer groups could not be compared. To improve the informative value of the EQA data, the existing limitations such as non-harmonized conditions and suboptimal and/or unknown commutability of the EQA materials have to be overcome. The study highlights the need for commutable reference materials that could be used to properly evaluate result comparability and possibly standardize calibration, if necessary. Such an initiative would further improve the safe use of PCT in clinical routine., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Sensitivity and specificity of rapid antigen detection tests (RADTs) for detection of group A hemolytic streptococcus (GAS) vary. The purpose is to present the first SKUP (Scandinavian evaluation of laboratory equipment for point of care testing) evaluations concerning the assessment of the diagnostic performance and user-friendliness of two RADTs for detection of GAS when used under real-life conditions in primary health care. Throat samples were collected in duplicates at primary health care centers (PHCCs) from patients with symptoms of pharyngitis. The performance of QuickVue Dipstick Strep A test (307 samples) and DIAQUICK Strep A Blue Dipstick (348 samples) was evaluated using culture results at a clinical microbiology laboratory as comparison. The user-friendliness was evaluated using a questionnaire. The diagnostic sensitivity was 92% (90% confidence interval (CI) 87-96%) and 72% (90% CI 65-79%), while the diagnostic specificity was 86% (90% CI 81-90%) and 98% (90% CI 96-99%) for QuickVue Dipstick Strep A test and DIAQUICK Strep A Blue Dipstick, respectively. Both RADTs obtained acceptable assessments for user-friendliness and fulfilled SKUP's quality goal for user-friendliness. The diagnostic sensitivity for QuickVue Dipstick Strep A test and the diagnostic specificity for DIAQUICK Strep A Blue Dipstick in this objective and supplier-independent evaluation were higher compared with previous meta-analyses of RADTs. However, the diagnostic specificity for QuickVue Dipstick Strep A test and the diagnostic sensitivity for DIAQUICK Strep A Blue Dipstick were lower compared with previous meta-analyses of RADTs.

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m 2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m 2 , whereas in elderly people it is increased at levels <45 ml/min per 1.73 m 2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable., (Copyright © 2019 by the American Society of Nephrology.)

Background Glomerular filtration is the most important kidney function. The most accurate glomerular filtration rate (GFR) estimates are based on the clearance of exogenous filtration markers. Of these, iohexol is the only exogenous marker that is included in an external quality assessment (EQA) scheme. The aim of the present study was to evaluate the performance of the European laboratories participating in Equalis' EQA scheme for iohexol. Methods Weighed amounts of iohexol (Omnipaque) were added to plasma samples and distributed to laboratories participating in the EQA scheme for iohexol. All laboratories performed the assays in a blinded fashion. Results The number of participating laboratories varied between 27 and 34 during the study period. Iohexol was determined by HPLC in 77% of the laboratories and by UPLC/MS/MS methods in 15% of the laboratories. The mean interlaboratory coefficient of variation was 4.7% for the HPLC methods and 6.4% for the UPLC/MS/MS methods. The mean bias between calculated and measured iohexol values was -1.3 mg/L (95% confidence interval ±0.3) during the first part of the study period and 0.1 mg/L (±0.3) during the later part. Conclusions The low interlaboratory variation demonstrates that iohexol can be measured reliably by many laboratories and supports the use of iohexol as a GFR marker when there is a need for high quality GFR measurements.

Background Creatinine measurement for estimation of glomerular filtration rate (GFR) is a frequently used laboratory test. Differences in analytic creatinine methods have caused large inter-laboratory variation. International and national standardization efforts have been made in the last decade. Methods This study describes the results of the standardization efforts in Sweden by summarizing data for creatinine concentration in blood plasma in the Equalis quality assessment program during 1996-2014. Results Non-compensated Jaffe methods dominated in 1996-2001 (91 of 103 laboratories; 90%) and were then gradually replaced by either compensated Jaffe methods or enzymatic creatinine methods. In 2014 a majority of Swedish hospital laboratories (139 of 159; 87%) used enzymatic methods. The reported mean creatinine value by the Swedish laboratories was about 10 μmol/L higher than the isotope dilution mass spectrometry (IDMS) assured reference value in 2003, but consistent with the reference value from 2009 to 2014. The inter-laboratory CV was 7%-9% for creatinine values until 2007, and thereafter gradually decreased to about 4%-5% in 2014. Conclusions The introduction of enzymatic methods in Swedish laboratories has contributed to achieving a low inter-laboratory variation. Also, the reported values are lower for enzymatic methods compared to Jaffe methods, and the values obtained with enzymatic methods were consistent with IDMS certified values established at reference laboratories. Thus, many Swedish hospital laboratories reported 10 μmol/L lower, and more true, creatinine concentrations in 2012 than in 2003, which may cause bias in longitudinal studies.

Many decisions within healthcare are based on results from laboratory tests. These results all have an uncertainty, which can be either neglectable or large enough to affect the clinical assessment. In external quality assessment (EQA) the laboratories make independent observations on the same control sample, with values unknown for the participants. The results can be used to determine if quality improvement is needed. We present EQA data for laboratory tests with three different measurement scales; quantitative, ordinal and nominal. Results from EQA should be used in the discussions of quality in test results and necessary analytical performance specifications should be agreed upon.

Analytical performance specifications (APS) based on outcomes refer to how 'good' the analytical performance of a test needs to be to do more good than harm to the patient. Analytical performance of a measurand affects its clinical performance. Without first setting clinical performance requirements, it is difficult to define how good analytically the test needs to be to meet medical needs. As testing is indirectly linked to health outcomes through clinical decisions on patient management, often simulation-based studies are used to assess the impact of analytical performance on the probability of clinical outcomes which is then translated to Model 1b APS according to the Milan consensus. This paper discusses the related key definitions, concepts and considerations that should assist in finding the most appropriate methods for deriving Model 1b APS. We review the advantages and limitations of published methods and discuss the criteria for transferability of Model 1b APS to different settings. We consider that the definition of the clinically acceptable misclassification rate is central to Model 1b APS. We provide some examples and guidance on a more systematic approach for first defining the clinical performance requirements for tests and we also highlight a few ideas to tackle the future challenges associated with providing outcome-based APS for laboratory testing., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)