Implementation of high sensitivity troponin into routine clinical practice - results of the extended CARdiac MArkers guideline uptake in Europe group (CARMAGUE) survey.

BACKGROUND: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented. METHODS: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis. RESULTS: Responses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours. CONCLUSIONS: Measurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind.

The multidimensional value of natriuretic peptides in heart failure, integrating laboratory and clinical aspects.

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness.

Changing Immunochemistry Platforms: Thyroid Function Test Comparison and Reference Intervals Based on Clinical Needs.

BACKGROUND: Diagnosis of thyroid dysfunction relies on thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri-iodothyronine (FT3) tests against valid reference intervals (RIs). We changed the immunoassay platform from Abbott Architect to Siemens Atellica and aimed to establish Atellica RIs based on laboratory information system (LIS) patient data. METHODS: Atellica thyroid hormone immunoassays were verified against those of Architect. Real-life patient results were retrieved from LIS. A single result per patient dataset was used to establish the RIs by the indirect method. RESULTS: Atellica and Architect assays correlated well but Atellica showed a positive bias between 13% and 53%, the largest for FT4. Variations of the Atellica assays were ≤4%. The 95% Atellica RIs were 0.4-3.8 mU/L for TSH, 0.9-1.6 ng/dL for FT4, and 227-416 pg/dL for FT3. Considering the accumulating clinical experience with Atellica, the RIs for clinical use were adjusted as 0.5-4.0 mU/L, 0.9-1.8 ng/dL, and 169-409 pg/dL, respectively. CONCLUSIONS: We verified thyroid hormone RIs for Atellica by the indirect method for the first time. Our model proved reliable for selecting results of presumably healthy individuals from LIS data. Critical review of the RIs with local endocrinologists is essential.

How Well Do Laboratories Adhere to Recommended Guidelines for Cardiac Biomarkers Management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) Study of the European Federation of Laboratory Medicine Task Group on Cardiac Markers.

BACKGROUND: The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice. METHODS: An email link to a web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe. RESULTS: 374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.2%-42.0%. The majority of the respondents were from hospitals with proportionately more responses from central hospitals than district hospitals. Cardiac troponin was the preferred cardiac biomarker, evenly split between cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Aspartate transaminase and lactate dehydrogenase are no longer offered as cardiac biomarkers. Creatine kinase, creatine kinase MB isoenzyme, and myoglobin continue to be offered as part of the cardiac biomarker profile in approximately on 50% of respondents. There is widespread utilization of high sensitivity (hs) troponin assays. The majority of cTnT users measure hs-cTnT. 29.5% of laboratories measure cTnI by a non-hs method but there has been substantial conversion to hs-cTnI. The majority of respondents used ng/L and use the 99th percentile as the upper reference limit (71.9% of respondents). A range of diagnostic protocols are in use. CONCLUSIONS: There is widespread utilization of hs troponin methods. A significant minority do not use the 99th percentile as recommended and there is, as yet, little uptake of very rapid diagnostic strategies. Education of laboratory professionals and clinicians remains a priority.

Physical health examination in outpatients with schizophrenia: the cost effectiveness of laboratory screening tests.

BACKGROUND: Guidelines on laboratory screening in schizophrenia recommend annual monitoring of fasting lipids and glucose. The utility and the cost effectiveness of more extensive laboratory screening have not been studied. METHODS: The Living Conditions and the Physical Health of Outpatients with Schizophrenia Study provided a comprehensive health examination, including a laboratory test panel for 275 participants. We calculated the prevalence of the results outside the reference range for each laboratory test, and estimated the cost effectiveness to find an aberrant test result using the number needed to screen to find one abnormal result (NNSAR) and the direct cost spent to find one abnormal result (DCSAR, NNSAR x direct cost per test) formulas. In addition, we studied whether patients who were obese or used clozapine had more often abnormal results. RESULTS: A half of the sample had 25-hydroxyvitamin D below, and almost one-fourth cholesterol, triglycerides or glucose above the reference range. One-fifth had sodium below and gamma glutamyltransferase above the reference range. NNSAR was highest for potassium (137) and lowest for 25-hydroxyvitamin D (2). DCSAR was below 5€ for glucose, all lipids and sodium, and below 10€ for creatinine and gamma glutamyltransferase. Potassium (130€), pH-adjusted ionized calcium (33 €) and thyroid stimulating hormone (33€) had highest DCSARs. Several abnormal results were more common in obese and clozapine using patients. CONCLUSIONS: An annual laboratory screening panel for an outpatient with schizophrenia should include fasting glucose, lipids, sodium, creatinine, a liver function test and complete blood count, and preferably 25-hydroxyvitamin D.

Update on current practice in laboratory medicine in respect of natriuretic peptide testing for heart failure diagnosis and management in Europe. The CARdiac MArker guideline Uptake in Europe (CARMAGUE) study.

BACKGROUND: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines. METHODS: A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity. RESULTS: There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency. CONCLUSION: Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors.

How well do laboratories adhere to recommended guidelines for dyslipidaemia management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) study.

BACKGROUND: The CArdiac MARker Guidelines Uptake in Europe Study (CAMARGUE) initiated by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) aims to survey the current use of evidence-based guidelines for dyslipidemia testing in Europe. METHODS: In 2019 a web-based questionnaire was distributed via EFLM National Societies to clinical laboratories in Europe. Questions covered pre-analytics, analytical methods, measurement units, flagging of decision thresholds, and use of decision-enhancing comments. RESULTS: Returns were obtained from 452 laboratories from 28 countries. Most laboratories always use nonfasting blood samples for lipid assays (66%). Lipid profiles are reported in mmol/L by 59% of the laboratories, mainly from 14 countries promoting the use of SI units. Important differences in flagging of decision thresholds were observed, with less than half of the laboratories applying the guideline-recommended LDL cholesterol threshold. Only 17% of the laboratories add an alert comment when familial hypercholesterolemia is suspected and 23% when risk of pancreatitis from hypertriglyceridemia is high. CONCLUSIONS: There are marked differences among laboratories in Europe in terms of pre-analytical, analytical, and post-analytical lipid management that could have an important clinical impact. This relates to different availability of assays or different laboratory practices on reporting and flagging of lipid profiles.

Are Heart Failure Management Recommendations and Guidelines Followed in Laboratory Medicine in Europe and North America? The Cardiac Marker Guideline Uptake in Europe (CARMAGUE) Study.

BACKGROUND: The aim of this survey was to investigate how well heart failure (HF) guidelines for use of natriuretic peptides (NPs) have been implemented in laboratory practice in Europe and North America. METHODS: In 2013 and 2014, a web-based questionnaire was distributed via North American and European biochemical societies. Questions covered assay performed, reason for method choice, decision limits for HF, and laboratory accreditation status. RESULTS: There were 442 European Union and 91 North American participating laboratories with response rates of 50% and 64% from major or university hospitals, respectively. NP measurements were offered in 67% of European Union and 58% of North American respondents. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was most widely used in Europe (68%) and B-type natriuretic peptide (BNP) was more commonly used (58%) in North America. The most frequent reason for use of a specific assay was the availability of instruments that measure either NT-proBNP (51%) or BNP (67%). For diagnosis of acute HF, NT-proBNP decision limits were diverse; age-dependent limits based on the 2012 European Society of Cardiology (ESC) recommendations were used in only 17% of European sites and 26% of North American sites. For BNP, the guideline-recommended acute HF decision limit of 100 ng/L was better adhered to in Europe (48%) and North America (57%). Surprisingly, similar decision limits were stated for acute and chronic HF by >50% of respondents. CONCLUSIONS: NP measurement for HF diagnosis was available in >50% of responding laboratories. However, guideline recommended cutoff values for both acute and chronic HF were still implemented in <30% of participating medical centers.

How Well Do Laboratories Adhere to Recommended Clinical Guidelines for the Management of Myocardial Infarction: The CARdiac MArker Guidelines Uptake in Europe Study (CARMAGUE).

BACKGROUND: We undertook an assessment of current use of evidence-based guidelines for the use of cardiac biomarkers in Europe (EU) and North America (NA). METHODS: In 2013-2014 a web-based questionnaire was distributed via NA and EU biochemical societies. Questions covered cardiac biomarkers measured, analytical methods used, decision thresholds, and use of decision-making protocols. Results were collated using a central database and analyzed using comparative and descriptive nonparametric statistics. RESULTS: In EU, returns were obtained from 442 hospitals, 50% central or university hospitals, and 39% from local hospitals from 35 countries with 395/442 (89%) provided an acute service. In NA there were 91 responses (63.7% central or university hospitals, 19.8% community hospitals) with 76/91 (83.5%) providing an acute service. Cardiac troponin was the preferred cardiac biomarker in 99.5% (EU) and 98.7% (NA), and the first line marker in 97.7% (EU) and 97.4% (NA). There were important differences in the choice of decision limits and their derivations. The origin of the information was also significantly different, with EU vs NA as follows: package insert, 61.9% vs 40%; publications, 17.1% vs 15.0%; local clinical or analytical validation choice, 21.0% vs 45.0%; P = 0.0003. CONCLUSIONS: There are significant differences between EU and NA use of cardiac biomarkers. This probably relates to different availability of assays between EU and NA (such as high-sensitivity troponin assays) and different laboratory practices on assay introduction (greater local evaluation of assay performance occurred in NA).

Do laboratories follow heart failure recommendations and guidelines and did we improve? The CARdiac MArker Guideline Uptake in Europe (CARMAGUE).

BACKGROUND: Natriuretic peptides (NP) are well-established markers of heart failure (HF). During the past 5 years, analytical and clinical recommendations for measurement of these biomarkers have been published in guidelines. The aim of this follow-up survey was to investigate how well these guidelines for measurement of NP have been implemented in laboratory practice in Europe. METHODS: Member societies of the European Federation of Clinical Chemistry and Laboratory Medicine were invited in 2009 to participate in a web-based audit questionnaire. The questionnaire requested information on type of tests performed, decision limits for HF, turn-around time and frequency of testing. RESULTS: There was a moderate increase (12%) of laboratories measuring NP compared to the initial survey in 2006. The most frequently used HF decision limits for B-type NP (BNP) and N-terminal BNP (NT-proBNP) were, respectively, 100 ng/L and 125 ng/L, derived from the package inserts in 55%. Fifty laboratories used a second decision limit. Age or gender dependent decision limits were applied in 10% (8.5% in 2006). The vast majority of laboratories (80%) did not have any criteria regarding frequency of testing, compared to 33% in 2006. CONCLUSIONS: The implementation of NP measurement for HF management was a slow process between 2006 and 2009 at a time when guidelines had just been established. The decision limits were derived from package insert information and literature. There was great uncertainty concerning frequency of testing which may reflect the debate about the biological variability which was not published for most of the assays in 2009.

A pilot survey of the use and implementation of cardiac markers in acute coronary syndrome and heart failure across Europe. The CARdiac MArker Guideline Uptake in Europe (CARMAGUE) study.

BACKGROUND: Guidelines on preferred cardiac marker strategies for investigation of patients with acute coronary syndromes (ACS) are available from the laboratory medicine and cardiology communities. Therefore, implementation of these guidelines into daily clinical practice should be a joint effort of laboratory specialists and clinicians. This was investigated in this survey. METHODS: A pilot study was performed sponsored by the European Federation of Clinical Chemistry and Laboratory Medicine. A link to an online questionnaire was e-mailed to 990 laboratories from eight European countries in May 2006. The requested information included tests performed, clinical protocol development, and reference limits. RESULTS: We obtained a total of 220 responses. Out of these, 208 responses (95%) were from hospitals that provide 24-h admission of patients. The suggested turn-around-time (<60 min) was apparently met by >88% for cardiac troponin T/I and for CK-MB mass. The majority of the laboratories derive their decision limits from kit inserts provided by the manufacturers. The results revealed a worrying fact that external quality assessments are not used in all testing. CONCLUSIONS: Our survey demonstrated that cardiac troponin is the preferred biomarker for the diagnosis of ACS. Half of the participants had written protocols, mostly as a result of collaboration between laboratorians and clinicians.

Metabolic syndrome among persons with schizophrenia and other psychotic disorders in a general population survey.

OBJECTIVE: To determine the prevalence of metabolic syndrome and investigate its components in individuals with psychotic disorders and individuals using antipsychotic medication in a general population study. METHOD: The study population was a nationally representative, 2-stage cluster sample of 8028 persons aged 30 years or over from Finland. The field work for this study took place between September 2000 and June 2001. Laboratory and other measurements related to metabolic syndrome were taken in a health examination. We used the Structured Clinical Interview for DSM-IV (SCID-I) and case note data when making diagnostic assessments according to DSM-IV-TR criteria. Metabolic syndrome was diagnosed according to Adult Treatment Panel III criteria. Subjects who had not fasted the required 4 hours were excluded from the analysis. Prevalences of metabolic syndrome, adjusting for age, sex, and hours of fasting, were estimated by calculating predicted marginals, evaluated at 8 hours of fasting. RESULTS: The prevalence estimates of metabolic syndrome were 36.2% (SE = 7.3), 41.4% (SE = 6.3), and 25.0% (SE = 8.6) among subjects with schizophrenia, other nonaffective psychosis, and affective psychosis, respectively, compared with 30.1% (SE = 0.8) in subjects without psychotic disorders. Subjects with schizophrenia had significantly lower high-density lipoprotein cholesterol and higher tri-glyceride and glucose levels and larger waist circumference, but also lower systolic blood pressure, than the remaining study population (all p values < .05). While all markers of metabolic syndrome were elevated among subjects with other nonaffective psychotic disorders, only the difference in waist circumference was statistically significant (p < .05). The prevalence of metabolic syndrome was significantly elevated among users of high-potency (52.1% [SE = 6.6]; p < .001) but not low-potency (39.0% [SE = 6.9]) and atypical (23.4% [SE = 10.8]) antipsychotic medication. CONCLUSION: Nonaffective psychotic disorders are associated with abdominal obesity and glucose and lipid abnormalities. Regular monitoring and active treatment of metabolic abnormalities are essential in this patient population.