Defining laboratory medicine, or squaring the circle?

In the August 2020 issue of Clinical Chemistry and Laboratory Medicine, Giuseppe Lippi and Mario Plebani proposed a definition of laboratory medicine, which ends with this sentence: "The results of these measurements are translated into actionable information for improving the care and/or maintaining the wellness of both a single individual and an entire population". Nevertheless, the selfishness of individuals may, sometimes, jeopardize the interest of whole populations. The virtue of justice being within the reach of the entire human community more than of single individuals, the final sentence in the definition proposed by Giuseppe Lippi and Mario Plebani, should therefore, in our view, be rewritten, less selfishly, for example like this: "For a given investment, these measurements are preferably made when they bring as much beneficence, and non-maleficence, as possible to the whole population".

Practice in financial support of third party organised conferences and courses at a national level for health care professionals in Europe.

Background Ethical MedTech prescribes high standards for the participation of the in vitro diagnostics (IVD) industry in third-party organised educational events in terms of charitable donations, educational grants, scholarships and fellowships. We planned a survey to investigate the previous and current practice in terms of cooperation between professionals or professional societies and the IVD industry, as well as plans under the incorporation of the MedTech Europe Code. Methods Different questions, from general information to specific questions related to the practice and knowledge of the new Ethical MedTech Code, were included in two different surveys; for European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) National Societies' (NSs) representatives, and for their (NSs) individual members. Results Twenty-five out of 40 EFLM NS representatives replied; more than half declared that all different types of financial resources were available for supporting the continuing professional education of health care professionals (HCPs). In addition, 322 individual responses collected from 31 NSs, answered that the institutional director (50.3%) or laboratory chief (70.1%) made generally made a decision, without specific criteria. Conclusions The MedTech Europe Code is already adopted or is about to be adopted in numerous EFLM NSs, but most of them have not implemented it as yet. The use of the Code and better communication between IVD companies and HCPs are necessary to guarantee an improved and fair use of financial support, as well as better choices for the organisation and attendance at scientific events.

The economic impact of poor sample quality in clinical chemistry laboratories: results from a global survey.

Background Despite advances in clinical chemistry testing, poor blood sample quality continues to impact laboratory operations and the quality of results. While previous studies have identified the preanalytical causes of lower sample quality, few studies have examined the economic impact of poor sample quality on the laboratory. Specifically, the costs associated with workarounds related to fibrin and gel contaminants remain largely unexplored. Methods A quantitative survey of clinical chemistry laboratory stakeholders across 10 international regions, including countries in North America, Europe and Oceania, was conducted to examine current blood sample testing practices, sample quality issues and practices to remediate poor sample quality. Survey data were used to estimate costs incurred by laboratories to mitigate sample quality issues. Results Responses from 164 participants were included in the analysis, which was focused on three specific issues: fibrin strands, fibrin masses and gel globules. Fibrin strands were the most commonly reported issue, with an overall incidence rate of ∼3%. Further, 65% of respondents indicated that these issues contribute to analyzer probe clogging, and the majority of laboratories had visual inspection and manual remediation practices in place to address fibrin- and gel-related quality problems (55% and 70%, respectively). Probe maintenance/replacement, visual inspection and manual remediation were estimated to carry significant costs for the laboratories surveyed. Annual cost associated with lower sample quality and remediation related to fibrin and/or gel globules for an average US laboratory was estimated to be $100,247. Conclusions Measures to improve blood sample quality present an important step towards improved laboratory operations.

Applications of MALDI Mass Spectrometry in Clinical Chemistry.

BACKGROUND: MALDI-TOF mass spectrometry (MS) is set to make inroads into clinical chemistry because it offers advantages over other analytical platforms. These advantages include low acquisition and operating costs, ease of use, ruggedness, and high throughput. When coupled with innovative front-end strategies and applied to important clinical problems, it can deliver rapid, sensitive, and cost-effective assays. CONTENT: This review describes the general principles of MALDI-TOF MS, highlights the unique features of the platform, and discusses some practical methods based upon it. There is substantial potential for MALDI-TOF MS to make further inroads into clinical chemistry because of the selectivity of mass detection and its ability to independently quantify proteoforms. SUMMARY: MALDI-TOF MS has already transformed the practice of clinical microbiology and this review illustrates how and why it is now set to play an increasingly important role in in vitro diagnostics in particular, and clinical chemistry in general.

The future of laboratory medicine - a 2014 perspective.

Predicting the future is a difficult task. Not surprisingly, there are many examples and assumptions that have proved to be wrong. This review surveys the many predictions, beginning in 1887, about the future of laboratory medicine and its sub-specialties such as clinical chemistry and molecular pathology. It provides a commentary on the accuracy of the predictions and offers opinions on emerging technologies, economic factors and social developments that may play a role in shaping the future of laboratory medicine.

A simple and inexpensive automated technique for measurement of serum nitrite/nitrate.

OBJECTIVE: We described an automated technique for measurement of serum nitrite/nitrate (NO(x)) using the Cobas Mira clinical chemistry analyzer. DESIGN AND METHODS: NO(x) was measured by the modified Griess method. Precision, accuracy, linearity, instrument carry-over and lower limit of quantitation (LLOQ) were assessed. RESULTS: The automated technique for measurement of serum NO(x) was linear, precise, and accurate. It has a LLOQ of 2.0 µmol/L. CONCLUSION: Serum NO(x) measured by the modified Griess method can be applied easily to the Cobas Mira clinical chemistry analyzer.

Electrolyte orders in the neuroscience intensive care unit: worth the value or waste?

BACKGROUND: To assess the value of the practice of obtaining frequent electrolyte measurements in patients with extended stay in a neuroscience intensive care unit (NICU). METHODS: We identified consecutive patients 18 years or older, admitted to the NICU between January 1 and July 31, 2009 with length of stay ≥ 5 days. We collected potassium, sodium, magnesium, ionized calcium, phosphorus laboratory measurements and hemoglobin levels, and recorded electrolyte replacement orders and red blood cell transfusions. Average laboratory costs were estimated. RESULTS: 93 patients were included in the study (54 men, mean age 54 years, range 18-85 years). Mean length of stay was 10.4 days (range 5-36 days). Sodium and potassium were the electrolytes most frequently measured (averages of 14.1 and 13.1 per patient, respectively). More than 75% of the results were within normal range for all electrolytes measured and critical values were extremely uncommon. The number of phlebotomies for electrolyte measurements was strongly associated with the degree of hemoglobin drop (P < 0.0001). Electrolyte panels were ordered much more often than individual electrolytes with average cost exceeding $2200 per patient. Replacing half of these electrolyte panels with single sodium or potassium orders would have resulted in savings greater than $100,000 in our population. CONCLUSIONS: Electrolytes measurements are very frequent in the NICU, but results are most often normal and only exceptionally critical. The phlebotomies required for these tests significantly worsen hemoglobin levels. A more conservative use of electrolyte measurements can result in reduction of blood loss and substantial cost savings.

Cardiac: is this biomarker ready for the prime time?

Today, the increase of the blood concentration of cardiac troponins is designated as surrogate for cardiac necrosis and myocardial infarction, when an appropriate clinical and/or instrumental situation is present. As cardiac troponins reflect myocyte death, biomarkers of reversible myocardial damage in the absence of necrosis are, however, still needed to detect the presence of damage even before the irreversible injury is induced and identify "vulnerable" patients before major events occur, permitting adequate treatment. Markers of plaque destabilization and/or markers of myocardial ischemia could be enormously valuable in the emergency department setting if shown to contribute additional independent diagnostic information. However, a new cardiac biomarker is of definitive clinical value only if adequate assays for its measurement are available, its predictive value is defined in the right clinical context, optimal cut-off and release kinetics are known, demonstration of the marker incremental value is clear, there is consistency of marker performance across different settings, and, more importantly, there are data on the effect on patient management and outcome and on cost-effectiveness. Despite the emergence of multiple candidates, sufficient evidence for any of these has yet been demonstrated to recommend their adoption into clinical practice.

Diagnostic performance and cost effectiveness of measurements of plasma N-terminal pro brain natriuretic peptide in patients presenting with acute dyspnea or peripheral edema.

BACKGROUND: The purpose of this study was to determine the diagnostic power of a newly available assay for amino-terminal pro-brain natriuretic peptide (NT-proBNP) to identify patients with acute heart failure. In addition, the influence of initial NT-proBNP measurements on economic consequences, diagnostic procedures and staff involvement was evaluated. METHODS AND RESULTS: 401 patients presenting with acute dyspnea or peripheral edema in the emergency department were enrolled. NT-proBNP was measured after initial clinical evaluation. Clinical routine care and diagnostic assessment were blinded to NT-proBNP results. Two cardiologists independently validated the period of hospitalization, clinical examinations and medical therapies of each patient considering NT-proBNP results. The median NT-proBNP level among patients with acute congestive heart failure (CHF) (n=122) was 3497 pg/ml as compared to 320 pg/ml in patients without (n=279) (p<0.0001). An NT-proBNP cutoff level <300 pg/ml was optimal to rule out acute CHF (negative predictive value 96%; sensitivity 96%). NT-proBNP >or=300 pg/ml could strongly predict acute CHF when compared to patients' history or physical examination (odds ratio 9.5; p<0.0001) and diagnostic technical findings (odds ratio 14.7; p<0.05). In patients with NT-proBNP<300 pg/ml, 14% of the period of hospitalization could be saved, corresponding to savings of US $481 per patient. In addition, 9% of the number and time of staff involvement of clinical examinations and therapies could be saved, 10% of the costs of clinical examinations. Chest X-rays were saved in 34%, echocardiography in 9%. CONCLUSIONS: Measurement of NT-proBNP leads to multiple saving amounts and optimizes diagnostic pathways and resource allocation.

Quality of diagnostic mutation analyses for phenylketonuria.

DNA sequence analyses have become a major component in the diagnostic work-up of patients; however, limited consideration appears to be given to the possibility that reported results may in fact be wrong. Over the last four years we have carried out an External Quality Assessment scheme for mutation analysis in phenylketonuria. Each year, three DNA samples with previously characterized genotypes were mailed to participating laboratories. Indications for testing were either confirmation of diagnosis and prediction of disease severity, or carrier analysis. Each year there were several laboratories that failed to identify mutations because of methodological limitations. Of the participating laboratories that used comprehensive mutation detection methods, each year there was at least one that missed at least one mutation. Indeed, in the 2007 scheme almost 8% of reports from laboratories that used comprehensive mutation detection methods such as sequencing of all exons of the PAH gene contained incorrect genotypes. There were also serious deficiencies in the interpretation of genotype data: in the 2007 scheme, 6 out of 10 laboratories that obtained full genotyping marks for interpretation incurred a reduction of marks because information on the expected phenotype was missing or wrong. Several laboratories failed to appreciate the clinical relevance of a mutation associated with mild hyperphenylalaninaemia, which does not require treatment, and some discussed the option of prenatal diagnosis in the respective case. In conclusion, mutation analyses may be prone to errors and this demands careful interpretation of results in relation to clinical and biochemical findings.

Laboratory medicine: challenges and opportunities.

Technologic innovations have substantially improved the productivity of clinical laboratories, but the services provided by clinical laboratories are increasingly becoming commoditized. We reflect on how current developments may affect the future of laboratory medicine and how to deal with these changes. We argue that to be prepared for the future, clinical laboratories should enhance efficiency and reduce costs by forming alliances and networks; consolidating, integrating, or outsourcing; and more importantly, create additional value by providing knowledge services related to in vitro diagnostics.

Quantitative bacterial micro-assay for rapid detection of serum phenylalanine on dry blood-spots: application in phenylketonuria screening.

Phenylketonuria is an inherited metabolic disease, which is characterized by an increased level of serum phenylalanine. Quantitative measurement of phenylalanine in the serum of phenylketonuria patients is necessary to confirm the disease, and to distinguish phenylketonuria from other forms of hyperphenylalaninemia. In this study, we report a rapid and inexpensive micro-assay for simultaneous detection and quantitative measurement of serum phenylalanine on dry blood-spots. Analysis of the standard curve showed a broad linear range for phenylalanine from 120 to 1800 micromol/L. Application of this method, the standard Guthrie bacterial inhibition assay and a high-performance liquid chromatography (HPLC) method for analysis of 34 samples from phenylketonuria patients and control samples produced comparable results, with the regression equation Y = 0.994X + 0.996. The advantage of this method over the Guthrie bacterial inhibition assay is its ability to measure serum phenylalanine quantitatively without false positive results. The method was successfully applied to dried blood-spots, serum and whole blood. The cost per sample is approximately 20-50 US cents, which is much less than for HPLC and commercial enzyme kits. The method can be automated, and is thus suitable for neonatal and mass screening for phenylketonuria, especially in developing countries where funding is a limiting factor.