Scandinavian Journal of Clinical & Laboratory Investigation最新文献

General practitioners (GPs) in the Region of Southern Denmark were randomly allocated to a range of interventions to optimize their use of Vitamin D tests over one year. The aim of the current survey study was to investigate GPs assessment of the interventions. Using REDCap web-platform, we invited 638 GPs to participate in a survey about their experiences of guidelines, feedback reports, non-interruptive alerts, and interruptive alerts. The questions were customized for the different interventions. We received responses from only 131 GPs (21%), but no differences in gender, age, or type of GP clinic were observed between responders and invited GPs. Approximately half of the GPs found that guidelines were helpful, and a similar proportion of GPs read the feedback reports 'often' or 'always'. The pop-up alerts were accepted when used for maximum three months for often-used tests. In contrast, alerts were accepted for long periods for rarely-used tests. The groups that were exposed to the interruptive alert found it 'problematic' that it appeared every time vitamin D was requested. Guidelines and feedback reports on tests numbers were accepted, but it was previously found, that they had little effect on improving the use of biochemical tests. Pop-up alerts in the requesting IT system can produce alert fatigue. Future research should focus on developing feedback reports that - when possible - also include relevant clinical information, and pop-up alerts should for often used tests be displayed only for weeks or a few months, but can be repeated.

Physiological changes in hemostasis during pregnancy have been reported by several authors. This study aimed at establishing reference intervals for the hemostasis biomarkers thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), thrombomodulin (TM) and tissue plasminogen activator-inhibitor complex (tPAI-C), in healthy pregnancies. After excluding outliers, a total of 496 healthy pregnant women (128 first-trimester, 142 second-trimester, 107 third-trimester and 119 pre-labor) and 103 healthy nonpregnant women were enrolled from Shenzhen Bao'an Women's and Children's Hospital. Hemostasis biomarkers, TAT, PIC, TM and tPAI-C, were measured by using a quantitative chemiluminescence enzyme immunoassay performed on HISCL automated analysers. The median and reference intervals (the 2.5th and 97.5th percentiles) were calculated to establish trimester-specific reference intervals for healthy pregnant women. The reference intervals for TAT, PIC, TM and tPAI-C in the first trimester were 0.7-7.6 1 µg/L, 0.2-0.9 mg/L, 2.8-11.0 TU/ml, and 1.2-6.5 1 µg/L, respectively. The reference intervals in the second trimester were 1.7-12.0 1 µg/L, 0.2-1.0 mg/L, 3.7-11.6 TU/ml, and 2.8-8.8 1 µg/L, respectively. The reference intervals in the third trimester were 2.7-16.1 1 µg/L, 0.1-1.4 mg/L, 2.9-12.9 TU/ml, and 1.9-8.0 1 µg/L, respectively. At pre-labor, the reference intervals were 4.8-32.9 1 µg/L, 0.2-1.9 mg/L, 4.2-12.6 TU/ml, and 2.8-15.4 1 µg/L, respectively. Gestational reference intervals for TAT, PIC, TM and tPAI-C in healthy pregnancies are provided, but only for TAT with increasing concentrations throughout pregnancy, the reference intervals for non-pregnant were not applicable.

Phosphatidylethanol (PEth) are membrane molecules formed from phosphatidylcholine and ethanol through transphosphatidylation catalyzed by phospholipase D. Measurement of the main PEth form 16:0/18:1 is used as a specific and sensitive alcohol biomarker, since its formation requires ethanol, it accumulates in the blood upon repeated ethanol exposure, and it is only slowly eliminated during abstinence. PEth formation correlates with alcohol intake at the population level, albeit with considerable inter-individual variation as for the half-life during withdrawal. Over the past decade, the use of PEth has increased significantly and the applications have broadened. In Sweden, routine decision limits and the interpretation of test results for PEth were harmonized in 2013, using < 0.05 µmol/L (∼35 µg/L) as the recommended lower reporting limit and values > 0.30 µmol/L (∼210 µg/L) to indicate regular high alcohol intake. Routine test results show a large variation with about half being < 0.05 µmol/L and some even exceeding 10 µmol/L. In 2013, an external quality assessment (EQA) scheme for PEth 16:0/18:1 measurement in whole blood was also started (Equalis, Uppsala, Sweden), presently involving 56 laboratories from 13 countries. The agreement of PEth results between the laboratories has gradually improved to a CV < 15%. The current clinical and scientific information suggests that PEth values below the lower reporting limit (typically ∼0.03-0.05 µmol/L, or ∼20-35 µg/L) indicates sobriety or only low or occasional alcohol consumption, while regular high alcohol intake at levels corresponding to harmful drinking is required in most cases to reach PEth values > 0.30 µmol/L.

When comparing two analytical results for the same analyte, the clinicians may benefit from knowing the reference change values (RCVs) of the analyte. For Fibrosis-4 Index (FIB-4), a noninvasive test used for assessing the risk of liver fibrosis, no RCVs have been published for non-cirrhotic individuals. Therefore, we estimated RCVs for adults, using retrospectively collected data from outpatients with AST, ALT, and thrombocytes within the respective reference intervals. FIB-4 was calculated as (age × AST)/(thrombocytes × ALT^0.5). From two FIB-4 values in each patient we calculated the RCVs parametrically and non-parametrically. For both methods, we estimated the limits of the central 90% of the distribution of the ratio between the second and the first measurement. We obtained data on 599 outpatients with two blood tests taken 3 - 972 (median 258) days apart. The RCVs were 0.72 - 1.40 and 0.72 - 1.43, respectively, using the parametric and non-parametric methods. The 5 and 95 percentiles were not statistically significantly associated with sex, age, level of analyte, or the time between the measurements. The within-subject biological variation of FIB-4 was estimated to be 13.9%. Conclusion: In 90% of the patients the ratio between the second and the first FIB-4 result was approximately 0.7 - 1.4.

Measurements on clinical chemistry analysers must be verified to demonstrate applicability to their intended clinical use. We verified the performance of measurements on the Siemens Atellica® Solution chemistry analysers against the clinically acceptable analytical performance specifications, CAAPS, including the component of intra-individual biological variation, CV_I. The relative standard uncertainty of measurement, i.e. analytical variation, CV_A, was estimated for six example measurands, haemoglobin A_1c in whole blood (B-HbA_1c), albumin in urine (U-Alb), and the following measurands in plasma: sodium (P-Na), pancreatic amylase (P-AmylP), low-density lipoprotein cholesterol (P-LDL-C), and creatinine (P-Crea). Experimental CV_A was calculated from single-instrument imprecision using control samples, variation between measurements on parallel instruments, and estimation of bias with pooled patient specimens. Each obtained CV_A was compared with previously developed CAAPS. The calculated CV_A was 1.4% for B-HbA_1c (CAAPS 1.9% for single diagnostic testing, CAAPS 2.0% for monitoring after duplicate tests; IFCC units), 10.9% for U-Alb (CAAPS 44.9%), 1.2% for P-Na (CAAPS 0.6%, after triplicate testing 1.5%), 8.2% for P-AmylP (CAAPS 22.9%). The CV_A was 4.9% for P-LDL-C (CAAPS for cardiovascular risk stratification 4.9% after four replicates), and 4.2% for P-Crea (CAAPS 8.0%). Three of the six measurands fulfilled the estimated clinical need. Results from P-Na measurements indicate a general need for improving the P-Na assays for emergency patients. It is necessary to consider CV_I when creating diagnostic targets for laboratory tests, as emphasised by the CAAPS estimates of B-HbA_1c and P-LDL-C.

We set out to determine the performance of the Testi Technologies enzymatic assay saliva ethanol test strips of three different detection levels: 0 g/L, 0.2 g/L and 0.5 g/L, using as the reference method a gas chromatography analyser (GC). Alcohol levels were measured in 104 volunteers at up to three points in time, using up to three test strips per measurement, while gathering blood samples and breathalyser readings in parallel. The plasma alcohol concentrations (PAC) were determined from the plasma samples using GC. The qualitative results of the test strips were compared to the quantitative results from the reference method, as well as the breathalyser readings, and the amount of true and false positive and true and false negative results were classified using predetermined cut-off levels. The best performing test strips were the 0 g/L and the 0.2 g/L strips. The 0 g/L strips had a sensitivity and specificity of 1.00, as false negatives and false positives were not detected. The 0.2 g/L strips had a sensitivity and specificity [95% confidence interval (CI)] of 0.98 (0.96 - 1.00) and 0.83 (0.62 - 1.00) respectively, an accuracy of 0.97 (0.95 - 0.99), and a diagnostic odds ratio of 205.00 (35.33 - 1189.66). The test strips perform their intended purpose of screening for alcohol consumption well, with their great sensitivity as a defining property compared to other testing methods. For them to be able to be implemented in a clinical setting however, further refinement of the tests' characteristics would be required.

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

Noreflow is a condition associated with a poor prognosis in ST segment elevation myocardial infarction patients. It has been shown that many inflammatory markers and index such as procalcitonin, C-reactive protein, neutrophil to lymphocyte ratio, systemic immune inflammatory index (SII), are associated with noreflow. We used a brand-new index pan-immune-inflammation value (PIV) to retrospectively evaluate the relationship between PIV and noreflow. A total of 1212 patients were included for analysis. Noreflow was observed in 145 patients. In multivariate analysis, PIV (odds ratio (OR): 1.025; [1.002-1.115], p < 0.001), baseline ejection fraction (OR: 0.963; [0.934-0.993], p = 0.015), stent length (OR: 1.032; [1.010-1.054], p = 0.004), age (OR: 1.034; [1.014-1.053], p = 0.001) and pain to PCI time (OR: 1.003 [1.002-1.005], p < 0.001) were observed to be the independent predictors of noreflow. ROC curve analysis showed that the best cut off value of PIV for predicting noreflow was ≥889 with 77.2% sensitivity and 77.5% specificity (AUC, 0.828; 95% CI [0.806-0.849]). A ROC curve comparison analysis was performed to compare PIV and SII. The predictive power of PIV was higher than SII (differences between areas: 0.154; p < 0.001). According to our findings, an increase in PIV is an independent predictor of noreflow in patients with STEMI.

Myocardial injury after non-cardiac surgery (MINS) is associated with a 2-3-fold increased risk of subsequent major cardiovascular events and postoperative mortality. The pathological mechanism behind MINS is not fully uncovered. We hypothesized that patients with MINS following hip fracture surgery would have an altered haemostatic balance pre- and postoperative compared with patients without MINS. This was investigated in a prospective single-centre observational study including patients consecutively. The outcomes were changes in thrombin generation, fibrinogen/fibrin turnover, tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrin structure measurements in patients developing MINS and patients who did not. Outcomes were measured preoperatively and two hours postoperatively. Seventy-two patients were included whereof 26 (36%) patients developed MINS. D-dimer delta values were significantly higher in patients developing MINS than in patients who did not (p = 0.01). After adjusting for age, sex, smoking, alcohol abuse, atrial fibrillation, anticoagulant medication preoperative CRP, preoperative creatinine and duration of surgery, the association remained significant (p = 0.04). There were no significant changes in thrombin generation, in markers of fibrinogen/fibrin turnover besides D-dimer, or in fibrin structure measurements pre- and postoperatively between patients with and without MINS. As such, a relationship between the coagulative and fibrinolytic activity and MINS cannot be ruled out in patients with MINS after hip fracture surgery. Registration: The study was an observational sub-study to a multicentre randomised clinical trial registered at ClinicalTrials.gov (NCT02344797).