Critical test result management at Danish hospital laboratories: a national survey.

Critical test results in clinical laboratories are crucial for timely patient care, serving as indicators of potentially life-threatening conditions. Despite their importance, a notable heterogeneity in management practices exists globally. This study investigates the current practices of managing critical results at Danish clinical biochemistry laboratories and identifies areas prone for improvement. A comprehensive online survey was distributed to all 21 Danish clinical biochemistry laboratories regarding their critical result management, including documentation practices, critical limit selection, and quality assurance measures. A total of 17 laboratories (81%) responded. The answers revealed a generally uniform approach to managing critical results, with all laboratories having 24-h reporting, local instructions and using the telephone as communication channel. However, variations were noted in documentation practices and critical limit selection. Notably, 23.5% of the laboratories reported that one out of every ten critical results was not reported, indicating a significant risk of delayed critical results. This is further complicated by the limited use of predefined timeframes for reporting and also, only few laboratories actively monitored response times. The findings emphasize the need for more standardized documentation and evaluation practices to align with international standards and to enhance patient safety. While the laboratories showed a commitment to standardized procedures, the study emphasizes the necessity of a National or Nordic guideline to supplement the ISO 15189:2022. This study is a step towards optimizing critical result management, not only in Danish clinical biochemistry laboratories but also across various laboratory specialties, thereby improving overall laboratory quality, efficiency, and patient safety.

General practitioners' assessment of interventions applied to optimize laboratory test utilization: a cross-sectional survey study.

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.

Using the ELF test, FIB-4 and NAFLD fibrosis score to screen the population for liver disease.

BACKGROUND & AIMS: There is a need for accurate biomarkers of fibrosis for population screening of alcohol-related and non-alcoholic fatty liver disease (ALD, NAFLD). We compared the performance of the enhanced liver fibrosis (ELF) test to the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), using transient elastography as the reference standard. METHODS: We prospectively included participants from the general population, and people at risk of ALD or NAFLD. Screening positive participants (TE ≥8 kPa) were offered a liver biopsy. We measured concomitant ELF, FIB-4, and NFS using validated cut-offs: ≥9.8, ≥1.3, ≥-1.45, respectively. RESULTS: We included 3,378 participants (1,973 general population, 953 at risk of ALD, 452 at risk of NAFLD), with a median age of 57 years (IQR: 51-63). Two hundred-and-forty-two were screening positive (3.4% in the general population, 12%/14% who were at-risk of ALD/NAFLD, respectively). Most participants with TE <8 kPa also had ELF <9.8 (88%) despite a poor overall correlation between ELF and TE (Spearman´s rho = 0.207). ELF was associated with significantly fewer false positives (11%) than FIB-4 and NFS (35% and 45%), while retaining a low rate of false negatives (<8%). A screening strategy of FIB-4 followed by ELF in indeterminate cases resulted in false positives in 8%, false negatives in 4% and the correct classification in 88% of cases. We performed a liver biopsy in 155/242 (64%) patients who screened positive, of whom 54 (35%) had advanced fibrosis (≥F3). ELF diagnosed advanced fibrosis with significantly better diagnostic accuracy than FIB-4 and NFS: AUROC 0.85 (95% CI 0.79-0.92) vs. 0.73 (0.64-0.81) and 0.66 (0.57-0.76), respectively. CONCLUSION: The ELF test alone or combined with FIB-4 for liver fibrosis screening in the general population and at-risk groups reduces the number of futile referrals compared to FIB-4 and NFS, without overlooking true cases. IMPACT AND IMPLICATIONS: We need referral pathways that are efficient at detecting advanced fibrosis from alcohol-related and non-alcoholic fatty liver disease in the population, but without causing futile referrals or excessive use of resources. This study indicates that a sequential test strategy of FIB-4 followed by the ELF test in indeterminate cases leads to few patients referred for confirmatory liver stiffness measurement, while retaining a high rate of detected cases, and at low direct costs. This two-step referral pathway could be used by primary care for mass, targeted, or opportunistic screening for liver fibrosis in the population. CLINICAL TRIAL NUMBER: Clinicaltrials.gov number NCT03308916.

Serum keratin-18 detects hepatic inflammation and predicts progression in compensated alcohol-associated liver disease.

Alcohol-associated liver fibrosis accumulates over decades, driven by hepatic inflammation and cell death. We investigated the diagnostic accuracy of keratin-18 degradation, measured using serum M30 and M65 levels, and the ActiTest for hepatic inflammatory activity in patients with compensated alcohol-associated liver disease (ALD). Furthermore, we evaluated the prognostic accuracy of markers for liver-related events and all-cause mortality. All findings were compared with routine liver function tests: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase. Our prospective, biopsy-controlled, single-center study included 265 patients with ongoing or prior excessive alcohol intake, representing the full spectrum of compensated ALD. We defined hepatic inflammatory activity as a combined score of lobular inflammation and ballooning. For severe hepatic inflammatory activity (n = 40), we found excellent diagnostic accuracy for M30 (area under the receiver operating characteristics curve [AUROC] = 0.90), M65 (AUROC = 0.86), and AST (AUROC = 0.86). Elevated M30 (M30 > 240 U/L) had the highest positive predictive value (PPV) and specificity, significantly higher than M65, ActiTest and ALT, but not AST (M30: sensitivity = 83%, specificity = 82%, positive predictive value = 45%, negative predictive value = 95%). Patients were followed up for 1445 patient-years. All markers, except for ALT, significantly predicted liver-related events and all-cause mortality. After adjusting for advanced fibrosis, drinking behavior and body mass index, M30 and M65 remained significant predictors of liver-related events, whereas M30 and AST were significant predictors of all-cause mortality. Conclusion: M30 and AST accurately detect severe hepatic inflammatory activity in patients with compensated ALD. M30 was the only significant predictor of both liver-related events and all-cause mortality after adjusting for advanced fibrosis, body mass index, and drinking behavior at inclusion.

Quantification of the anti-neoplastic polyacetylene falcarinol from carrots in human serum by LC-MS/MS.

Falcarinol is a polyacetylene which is found in carrots and known to have anti-neoplastic properties in rodents. Research in the bioactivity of falcarinol in humans require methods for quantification of falcarinol in human serum. Here we report the development of an LC-MS/MS method and its use to measure serum falcarinol concentrations in humans following intake of a carrot product. Falcarinol was measured by LC-MS/MS using the m/z 268 to m/z 182 mass transition. Six calibrator levels (0.2-20 ng/mL) and 3 control levels (0.4, 2 and 8 ng/mL) were prepared by addition of falcarinol to human serum pools. Linearity of the developed method was good with a mean R2 of 0.9942. Within-day, between-day and total coefficients of variation were 6.9-13.1%, 4.1-5.0% and 8.1-14.0%, respectively. The limits of detection and quantitation were 0.1 and 0.2 ng/mL, respectively, matrix effects 84.2%, recovery 101.4-105.4% and carry-over -0.24-0.07%. Serum falcarinol concentrations were measured in 18 healthy volunteers prior to and at 9 time-points following intake of a carrot product. Falcarinol concentrations peaked at the 1-hour time-point after intake in 15 out of 18 volunteers and declined according to a single exponential decay function with an aggregate t½ of 1.5 h. In conclusion, an LC-MS/MS method for quantification of falcarinol in human serum with acceptable performance was developed and used to measure falcarinol concentrations following intake of a carrot product.

Can the Enhanced Liver Fibrosis Score Be Used to Diagnose Children With Liver Fibrosis?

OBJECTIVES: The noninvasive Enhanced Liver Fibrosis (ELF) score is used in adults with liver fibrosis as a diagnostic aid. The ELF score combines 3 serum markers of extracellular matrix remodeling and fibrogenesis: hyaluronic acid (HA), the N-terminal pro-peptide of collagen type III (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1). We aimed to evaluate the clinical use of the ELF score in children. METHODS AND RESULTS: A reference interval for the ELF score was established using 343 liver-healthy children ages 6 to 17 years. The median ELF score of 8.9 in healthy children was significantly increased compared with healthy adults. ELF scores increased significantly in both female and male healthy controls with peak levels at puberty, driven by elevated levels of HA and PIIINP likely explained by increased growth. If adult normal values were applied to the group of liver-healthy children, only 6.4% were in the normal range. Prospectively, we analysed ELF scores in patients with possible or confirmed liver fibrosis because of autosomal recessive polycystic kidney disease (ARPKD). All ELF scores in children with ARPKD were within the reference intervals generated from the group of healthy children. CONCLUSIONS: The usual diagnostic cut-off ranges for the ELF score in adults are not applicable; instead age and gender-appropriate cut-off values should be used in children. The clinical value of ELF scores in children is questionable as children during pubertal growth showed elevated ELF scores and patients with ARPKD and liver fibrosis showed normal levels.

A randomized controlled study of biochemical tests in primary care: interventions can reduce the number of tests but usage does not become more appropriate.

OBJECTIVES: The use of laboratory tests increases worldwide, and to some extent their use is likely to be inappropriate. Although primary care is responsible for a substantial proportion of requests, this sector is less extensively investigated than hospitals. METHODS: We tested the effect of six combinations of four interventions applied to 313 primary care clinics, using vitamin D as model test (253,762 vitamin D results). We evaluated the changes in test numbers in the six intervention groups compared to the control group, and whether interventions resulted in more homogenous test use within groups or affected the distribution of test results. All interventions included information on vitamin D testing guidelines. Four groups were exposed to a non-interruptive alert in the ordering IT-system and in two groups this was supplemented by an interruptive alert. Half of the groups received monthly feedback reports. RESULTS: Application of alerts, irrespective of the combination with feedback reports, resulted in significantly reduced test numbers (maximum -46%). Guidelines either alone or combined with feedback reports did not cause significant difference from the control group. The within-group requesting pattern changed significantly for only two of the groups. The distribution of low and normal vitamin D results within groups showed no signs of more appropriate use of the test in any of the groups. CONCLUSIONS: Some of the interventions reduced the number of tests, but there were no indications of improved adherence to the guidelines. The interventions may have led to under-utilization of the test and thus should be used with care.

Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease.

BACKGROUND & AIMS: Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking. METHODS: We performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk. RESULTS: We followed 462 patients for a median of 49 months (IQR 31-70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE <10 kPa, the hazard ratios for liver-related events for TE 10-15 kPa were 8.1 (3.2-20.4), and 27.9 (13.8-56.8) for TE >15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups. CONCLUSION: TE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles. LAY SUMMARY: Alcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.

The impact of interventions applied in primary care to optimize the use of laboratory tests: a systematic review.

Laboratory tests are important tools in primary care, but their use is sometimes inappropriate. The aim of this review is to give an overview of interventions applied in primary care to optimize the use of laboratory tests. A search for studies was made in the MEDLINE and EMBASE databases. We also extracted studies from two previous reviews published in 2015. Studies were included if they described application of an intervention aiming to optimize the use of laboratory tests. We also evaluated the overall risk of bias of the studies. We included 24 studies. The interventions were categorized as: education, feedback reports and computerized physician order entry (CPOE) strategies. Most of the studies were classified as medium or high risk of bias while only three studies were evaluated as low risk of bias. The majority of the studies aimed at reducing the number of tests, while four studies investigated interventions aiming to increase the use of specific tests. Despite the studies being heterogeneous, we made results comparable by transforming the results into weighted relative changes in number of tests when necessary. Education changed the number of tests consistently, and these results were supported by the low risk of bias of the papers. Feedback reports have mainly been applied in combination with education, while when used alone the effect was minimal. The use of CPOE strategies seem to produce a marked change in the number of test requests, however the studies were of medium or high risk of bias.

Hypotension and Hypocapnia During General Anesthesia in Piglets: Study of S100b as an Acute Biomarker for Cerebral Tissue Injury.

BACKGROUND: Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA. METHODS: Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery. RESULTS: Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001). CONCLUSION: S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported.

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). METHODS: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. RESULTS: The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. CONCLUSION: In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58.

The association between uric acid levels and different clinical manifestations of coronary artery disease.

AIMS: Uric acid (UA) has been associated with the presence and severity of coronary artery disease. To further assess the role of UA role in coronary artery disease, we investigated UA levels in both healthy asymptomatic middle-aged individuals and in different subgroups of hospitalized patients with suspected or definite myocardial infarction (MI). PATIENTS AND METHODS: The severity of coronary artery calcification (CAC) was examined in asymptomatic individuals (n=1039) using a noncontrast computed tomography scan. Hospitalized patients with suspected acute MI (n=772) were grouped according to troponin I (TnI) concentrations: (i) elevated TnI concentrations (>0.03 µg/l) with subdivision according to the type of MI and other clinical conditions associated with myocardial injury, or (ii) nonelevated TnI concentrations (≤0.03 µg/l). RESULTS: UA was not associated with the severity of CAC in asymptomatic individuals when adjusting for relevant risk factors. Patients with type 2 MI and patients with myocardial injury associated with conditions of myocardial ischemia showed significantly higher UA levels (0.390 mmol/l, P=0.002 and 0.400 mmol/l, P=0.001, respectively) than patients with type 1 MI (0.329 mmol/l), after adjusting for other risk factors. CONCLUSION: UA was not correlated with the severity of CAC in asymptomatic middle-aged individuals, and patients with type 2 MI or ischemic myocardial injury were shown to have higher UA levels than type 1 MI patients. This observation is concordant with the hypothesis that UA might be involved in the pathophysiological mechanisms leading to an imbalance in the oxygen supply/demand ratio in type 2 MI and ischemic myocardial injury.

Lack of association between cystatin C and different coronary atherosclerotic manifestations.

Cystatin C (CysC) is known to be related to cardiovascular disease (CVD), including the presence and severity of coronary artery disease (CAD) and future clinical events. In this study, the association between CysC levels and (1) coronary artery calcification (CAC) in asymptomatic individuals from the general population as well as (2) different subgroups of patients with suspected or definite acute myocardial infarction (MI) was investigated. CysC levels were measured in serum from asymptomatic individuals as part of a screening study for CAC using non-contrast cardiac CT scan (N = 1039) as well as in subgroups of hospitalized patients with a suspected MI (N = 769). CysC was not associated with CAC in asymptomatic individuals after adjusting for relevant risk factors. No difference in CysC levels was observed between patients with type 1 MI (1.07 mg/L) and patients with normal troponin (with or without prior CAD: 1.14 and 1.01 mg/L, respectively). However, patients with type 2 MI and patient subgroups with elevated troponin but without MI had significantly higher CysC levels (1.24, 1.23 and 1.31 mg/L), even after adjusting for other risk factors. CysC was not associated with CAC in middle-aged asymptomatic individuals from the general population. Furthermore, CysC levels were found to be significantly lower in patients with type 1 MI compared to patients with type 2 MI and patients with elevated troponins but without MI. Thus, in two independent and clinically different populations, no association between CysC and coronary atherosclerotic manifestations could be demonstrated.

No further gain can be achieved by calculating Disease Activity Score in 28 joints with high-sensitivity assay of C-reactive protein because of high intraindividual variability of C-reactive protein: A cross-sectional study and theoretical consideration.

Disease Activity Score in 28 joints (DAS28) is commonly used to evaluate disease activity of rheumatoid arthritis (RA) and is a guide to treatment decision.The aim of this study was to evaluate the impact of lower reporting limit for C-reactive protein (CRP), with respect to intraindividual biological variability, on the calculation of DAS28 and subsequent patient classification.This study consists of 2 sections: a theoretical consideration discussing the performance of CRP in calculating DAS28 taking intraindividual biological variation and lower reporting limit for CRP into account and a cross-sectional study of RA patients applying our theoretical results. Therefore, we calculated DAS28 twice, with the actual CRP values and CRP = 9 mg/L, the latter to elucidate the positive effects of reducing the lower reporting limit of CRP from <10 to <3 mg/L.Lower-reporting limit of <10 mg/L leads to overestimate DAS28. However, reducing lower reporting limit for CRP to <3 mg/L results in optimizing DAS28 calculation. Further lowering of reporting limit for CRP to <3 mg/L does not increase the precision of DAS28 owing to the relatively large intraindividual biological variation.Five hundred twelve patients were included. There was a significant difference between recalculated and patients DAS28 (P < 0.001). One hundred nine patients had DAS28 deviation (compatible to remission to low: 66, low to moderate: 39. and moderate to high: 4).Owing to significant impact of intraindividual biologic variation on DAS28 and patient classification, special attention should be paid to calculate DAS28 when CRP values are within normal range. Furthermore, we conclude that results of different studies evaluating DAS28 and treatment response are not comparable if the reporting limits of CRP are unknown.

Therapeutic Drug Monitoring of Lithium: A Study of the Accuracy and Analytical Variation Between Laboratories in Denmark.

BACKGROUND: Serum lithium is monitored to ensure levels within the narrow therapeutic window. This study examines the interlaboratory variation and inaccuracy of lithium monitoring in Denmark. METHODS: In 16 samples consisting of (1) control materials (n = 4), (2) pooled patient serum (n = 5), and (3) serum from individual patients (n = 7), lithium was measured in 19 laboratories using 20 different instruments. The lithium concentrations were targeted by a reference laboratory. Ion-selective electrode (n = 5), reflective spectrophotometric (RSM, n = 5), and spectrophotometric (n = 10) methods were used. RESULTS: Acceptable accuracy-interpreted as total differences from target values (bias) less than or equal to ±12%-was generally found in patient samples above 0.7 mmol/L. Below 0.7 mmol/L, 8 instruments had 2 or more patient samples exceeding a difference to the targeted reference value of >12%. Seven of these instruments had a systematic positive or negative bias and more so at lower lithium concentrations. Three poorly calibrated instruments were found in the ion-selective electrode group, 3 in the spectrophotometric group, and 2 in the RSM group. The instruments using reflectance spectrophotometry (RSM) were on average 21% positively biased when measuring control materials. However, this effect was not observed in patient samples. CONCLUSIONS: Large interlaboratory variation was found below 0.7 mmol/L because of 7 instruments with a poor accuracy and 1 with poor precision. Methods should be recalibrated or substituted. Controls below 0.7 mmol/L are recommended.

Ionized calcium measurements are influenced by albumin--should ionized calcium be corrected?

Measurement of ionized calcium (CaI) has been reported to be dependent on albumin concentration. We examined the correlation between albumin and CaI measured on different ion selective electrode analyzers and in different groups of patients in a large dataset, extracted from the laboratory information system. In 17,281 outpatients and 16,194 inpatients, significantly positive correlations were found between CaI and albumin, with changes in CaI per 10 g/L change in albumin ranging from 0.007-0.043 mmol/L and 0.017-0.028 mmol/L, respectively. Correlations were found to be significantly different when using different analyzers. In order to examine whether the difference in correlations between the analyzers were really due to different patient populations investigated on the different analyzers, data analyzed on the same type of analyzer from inpatients from four different wards (intensive care unit, medical ward, surgical ward and orthopedic ward) were examined. There was no significant difference in correlations between patients from the four wards. Although, these results points towards technical causes behind the observed differences it cannot be entirely ruled out that clinical diseases or treatment might influence albumin interaction with CaI measurements. Combining all data from both out- and inpatients, a correction formula using a change in CaI of 0.03 mmol/L per 10 g/L change in albumin, was constructed. However, the albumin influence on CaI is only a minor part of the total CaI variation and, in most situations, the relatively small effect of changes in albumin on CaI-results is most likely of no clinical importance.