Daria Pašalić
Department of Medical Chemistry, Biochemistry and Clinical Chemistry
Zagreb University School of Medicine
Šalata ul 2.
10 000 Zagreb, Croatia
Phone +385 (1) 4590 205; +385 (1) 4566 940
E-mail: dariapasalic [at] gmail [dot] com

Useful links



Christenson RH.S10-1: Evidence-based laboratory medicine: Principles to practice. Biochemia Medica 2009;19(Suppl 1):S77.
University of Maryland School of Medicine, Baltimore, MD, USA
Corresponding author:rchristenson [at] umm [dot] edu
Evidence Based Laboratory Medicine (EBLM) involves providing the best possible information on which decisions are based. EBLM techniques are becoming an essential part of routine practice in laboratory medicine and are based on the “A5 cycle”. The A5 cycle signifies Ask, Aquire, Appraise, Apply and Audit. This structure will be used to illustrate how the EBLM approach is actionable in everyday problem solving.
The EBLM process begins with ASKing a clinical question, For question formulation use of “PICO”, an acronym which stands for Patient, Intervention (test), Comparator, and Outcome, is recommended. After the question is properly formulated, the PICO format can be used to Aquire the evidence for addressing the question. Acquisition can be performed at any computer connected to the internet through use of databases such as Medline (PubMED), EMBASE or the Cochrane collaboration for searching. Using key terms identified from the formulated PICO question in Boolean strategies facilitates the searching process. After key literature and other evidence are located, available checklists can be used for Appraisal of the evidence. This is necessary to determine if the information found should be included in answering the question. Applying the evidence into practice is possible by adapting the information into the practice environment. An Audit of how use of the evidence performed as expected completes the A5 cycle.
The theme throughout this lecture will involve a clinical problem involving B-type natriuretic peptide to illustrate the EBLM process and demonstrate to attendees how helpful the A5 strategy can be utilized in everyday practice. The overall objective of the session is to have attendees better understand the use of EBLM in their everyday practice.
Matijevic R. S10-2: Evidence based medicine - clinical perspective. Biochemia Medica 2009;19(Suppl 1):S78.
Medical School, University of Zagreb, Sveti Duh General Hospital, Zagreb, Croatia
Corresponding author:rmatijev [at] mef [dot] hr
Evidence based medicine – EBM is defined as continuous learning process used in order to integrate current medical knowledge into an everyday process of healthcare, both for the benefit of our patients. EBM integrates the process and ability to define clinical question and puts it in the format being suitable to find an answer on it in the available literature. As well as that, EBM concept includes knowledge of the literature search, precise and selective assessment and judgment of information find in the literature. Implementation of EBM into everyday clinical practice is important and useful. It improves the medical care of all patients and it is designed for a specific patient by the process of quality care. It minimizes the risk of medical mistake potentially opening a field of litigation process and finally, improves the use of clinical protocols and guidelines.
The whole process of EBM can be simplified in five steps:

1)         Asking and defining a clinically important question - PICO. This is a first step in solving a clinical problem. It is based on:
             P - patient or entity who had a problem
             I – intervention: or what had been done in order to solve the problem in patient or problem approach
            C – comparison: defines the way of solving the problem, the way of investigation performed or defined for the purpose of solving a problem
            O – outcome: is a result of intervention used in order to assess the benefit or otherwise for specific intervention in order to solve the problem

2)         Finding the best evidence
3)         Critical assessment of the evidence found
4)         Integration of the evidence found and setting the clinical situation and defining a guideline
5)         Assessment of clinical usefulness, data storage and results assessment
EBM approach and clinical practice based on EBM roles is impossible to explain without mentioning Cochrane collaboration and Cochrane database of systematic reviews. Currently it is present in 91 countries and it includes: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects – DARE, CENTRAL, Cochrane Database of Methodology Reviews, NHS Economic Evaluation Database and Health Technology Assessment Reports.
Cochrane Review helps in defining and formulating clinical – important question, helps to find and evaluate the studies used for the further assessment, assesses the quality of the studies, collect information for the further analysis and finally, analyses, presents and interprets the results. It is crucially important for the EBM and for maintaining a quality assessment and control.
Kralik Oguić S.S10-3: BNP and cardiovascular markers in emergency laboratory diagnostic. Biochemia Medica 2009;19(Suppl 1):S79-S80.
Clinical Institute for Laboratory Diagnostics, Zagreb Clinical Hospital Centre, Zagreb, Croatia
Corresponding author:skralik [at] kbc-zagreb [dot] hr
Down’s syndrome is the most common genetic cause of mental retardation. Trysomy 21 is present in approximately 92% of all cases. Prenatal diagnostics of Down’s syndrome includes only invasive procedures as amniocentesis and chorionic villus sampling which carrie procedure-related risk with miscarriages as the worse. In the early 90’s in the last century the development of screening methods started which provided identification of pregnancies with increased risk of Down syndrome necessary to offer prenatal diagnosis.
At the same time a great progress in Down’s syndrome screening is detected but also a proportion of women giving birth at older ages. It makes the estimation of efficacy of new screening metods more difficult.
First screening methods in second trimester of pregnancy (15-22 weeks) are still in use: double test (AFP and hCG), triple test (addition of unconjugated estriol) and quad test (addition of inhibin-A). Combined screening test in first trimester (11-14 weeks) came later. With different combinations of screening tests better sensitivity (95%) and lower false positive rate (2%) is achieved. Nevertheless the recommendations are various from country to country and efficasy is different depending on methods used. Some authors claim that the number of births of children with Down’s syndrome is not significantly reduced and that even the number of misscarriages induced with invasive diagnostic procedures is growing. There is also a question of cost-benefit ratio of different strategies.
Comparing the data from large population studies we can conclude that the introduction of a combined risk assesment in the first trimester and its integration with second trimester results reduced the number of infants born with Down’s syndrome and also the number of chorionic vilus samplings and amniocentesis. It is also proved that optimal first trimester screening test combines nuchal translucency and pregnancy associated plasma protein-A (PAPP-A) with the third marker but it is irrelevant whether is it total hCG, free beta-hCG or inhibin A, there is no difference in screening performance. Quad or triple test is the optimal choice for second trimester screening. When comparing cost effectiveness of three different strategies in combining results from first and second trimester screening (integrated test, sequential screening and contingent screening) contingent screening is the preferred option. In contingent screening the first trimester results are used to categorise women as high, intermediate or low risk. High risk women are offered early diagnosis, low risk women do not go second trimester testing and intermediate risk women are offered second trimester testing.
We can conclude that screening methods of Down’s syndrome provided today are very effective but variety of choices is too big. It is confusing for both patients and doctors but also for us who work in clinical laboratory when we have to define which type of tests will be included in screening we can offer.
Fumić K.S10-4:Rational use of the metabolic laboratory. Biochemia Medica 2009;19(Suppl 1):S80-S81.
Clinical Institute of Laboratory Diagnosis, Zagreb University School of Medicine and Clinical Hospital Center, Zagreb, Croatia
Corresponding author:ksenija [dot] fumic [at] zg [dot] htnet [dot] hr
The area of hereditary metabolic diseases develops quickly and sets even higher demands to physicians, medical biochemists, parents and the whole community that has to respond to them. Up to now we are familiar with the mechanism of development of more than 500 hereditary metabolic disorders where one can recognize changes on the level of metabolites, enzymes or genes. Metabolic laboratories for primary and/or selective search for hereditary metabolic diseases should respond with an array of the most optimal methods and procedures for detecting a disease as well as for treatment monitoring of a great number of such rare diseases. Those characteristics determine metabolic laboratories independently of their organization. In order to use the laboratory equipment and professional staff as rational as possible and thus to enable conscientious application of the best evidence for decision making in diagnostic and treatment of a certain patient with a hereditary metabolic disease, it is recommended that one metabolic laboratory covers needs of 4,000,000 citizens.
Continuous education should ease a choice of metabolic tests to less informed physicians with the aim of the earliest possible detection of a metabolic disease, what is also a precondition for a successful treatment and a decrease in number of unnecessary tests that make the work of a metabolic laboratory significantly complicated. Although a great number of test results presents one of the usual characteristics of such laboratories, it is necessary to set the indications for certain tests as well as possible. One of the principles that should be adopted by physicians in cases when patient’s life is not in danger is first to choose those tests that can detect curable and more common diseases. Only after they are not detected one should search for rare and incurable diseases. Such way of work requires and understands active physician’s cooperation with medical biochemists, what represents a prerequisite for rational utilization of metabolic laboratory.
Vučić Lovrenčić M.S10-5: In search of an ideal glycemic control indicator. Biochemia Medica 2009;19(Suppl 1):S81-S82.
Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Zagreb, Croatia
Corresponding author:vucic [at] idb [dot] hr
There is plenty of evidence implicating tight glycemic control as a key-postulate for prevention of chronic diabetic complications. However, monitoring and assessment of glycemic control is still controversial. Despite advances in technology and patient education, results of self-control glucose monitoring performed by the diabetic patients are still uncertain. Continuous subcutaneous glucose monitoring by the use of appropriate sensors is limited in use because of high costs, and accurate result interpretation needs additional evidence-based studies.
Thus, laboratory measurement of hemoglobin A1c remains an inevitable factor in the control and clinical monitoring of diabetes mellitus. A need for harmonzation of hemoglobin A1c lead to a controversial outcome: NGSP-standardization system enabled traceability of results to the landmark clinical evidence-based studies with established correlation between glycemic control, expressed as hemoglobin A1c and risk for development of chronic diabetic complications; IFCC-reference system enables traceability to the analytical reference method, giving significantly lower results due to it’s specificity which, according to the interpretation of clinical diabetologists might lead to the treatment errors and serious deterioration in the care for diabetic patients.
This controversy resulted into idea of a complete revalorization of hemoglobin A1c in terms of obtaining extended evidence of it’s correlation with an average glycemia, with an ultimate goal of expressing hemoglobin A1c results as equivalents of average glycemia. Albeit respective multicentric study results confirmed correlation and ensured enough data for the mathematical conversion of hemoglobin A1c (%) into derived average glycemia equivalents (mmol/l), a significant dispersion of values in the controlled study population made extrapolation of this model to the general population questionable. Thus, further research is needed to provide choice for an ideal indicator of glycemic control.