Diler Aslan

Use of total patient data for indirect estimation of reference intervals for 40 clinical chemical analytes in Turkey

Abstract In the present study we used patient data to calculate laboratory-specific indirect reference intervals. These values were compared with reference intervals obtained for a healthy group according to recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine and manufacturer suggestions. Laboratory results (422,919 records) from all subjects of 18–45years of age over a 1-year period were retrieved from our laboratory information system and indirect reference intervals for 40 common analytes were estimated using a modified Bhattacharya procedure. Indirect reference intervals for most of the biochemical analytes were comparable, with small differences in lower [alkaline phosphatase (ALP) (male), alanine aminotransferase (ALT), creatine kinase, iron (male), total iron-binding capacity, folic acid, calcium (female), lactate dehydrogenase (LDH), lipoprotein (a) [Lp(a)], thyroid-stimulating hormone (TSH), total triiodothyronine (T3), direct bilirubin, apolipoprotein A-I (apoA-I), glucose, homocysteine, total cholesterol, ferritin, total protein, ceruloplasmin, sodium, blood urea nitrogen (BUN) and uric acid (female)] and/or upper limits [albumin, ALP (male), amylase, apoA-I, creatine kinase-MB (CK-MB), total iron-binding capacity, phosphorus, glucose, total cholesterol, γ-glutamyltransferase (γ-GT), magnesium, total protein, high-density lipoprotein cholesterol (HDL-C), total T3, ALP (male), ALT, aspartate aminotransferase (AST) (male), direct bilirubin (male), creatine kinase, iron, folic acid (female), Lp(a), uric acid and triglycerides], to the reference intervals determined for healthy subjects in our laboratory. The indirect reference intervals, with the exception of a few parameters (creatinine, direct total bilirubin, calcium, BUN and potassium), were not similar to the reference intervals suggested by the manufacturers. We conclude that laboratory-specific reference intervals can be determined from stored data with a relatively easy and inexpensive method. Indirect reference intervals derived from stored data may be particularly suitable for the evaluation of results for the presenting population. Clin Chem Lab Med 2006;44:867–76.

Rate of T alleles and TT genotype at MTHFR 677C‐>T locus or C alleles and CC genotype at MTHFR 1298A‐>C locus among healthy subjects in Turkey: impact on homocysteine and folic acid status and reference intervals

Methylenetetrahydrofolate reductase (MTHFR) is important for folate and homocysteine (Hcy) metabolism. MTHFR 677C‐>T and 1298A‐>C MTHFR are two most common mutations which can affect folate and total homocysteine (tHcy) status. This study was designed to determine the rate of MTHFR 677C‐>T and 1298A‐>C mutations, and their influence on serum folate, Hcy and vitamin B12 status and the reference intervals in 402 healthy Turkish adults. The rate of MTHFR 677C‐>T or 1298A‐>C mutations was 50.7% or 54.7%, respectively. The MTHFR 677C‐>T mutation‐specific reference intervals for serum folate and tHcy were characterized by marked shifts in their upper limits. In homozygote subjects for MTHFR 677C‐>T serum folate concentration was lower and serum tHcy concentration was higher than those in the wild genotype; all subjects had lower serum folate and 54% of the subjects had higher tHcy concentrations than the cutoff values of ≤10 nmol/L and ≥12 µmol/L, respectively. Serum vitamin B12 status was similar in all genotypes. Serum tHcy concentrations were inversely correlated with serum folate and vitamin B12 concentrations in all genotypes. These data show that the rate of MTHFR 677C‐>T and 1298A‐>C mutations is very high in Turks and serum folate and tHcy status are impaired by these mutations. Copyright

Simple Statistics in Diagnostic Tests

Simple Statistics in Diagnostic Tests Diagnostic performance of a laboratory test is one of the key elements in decision making on diagnosis, screening, monitoring, risk assessment and prognosis of diseases. Sensitivity, specificity, likelihood ratios, diagnostic odds ratios and receiver operating characteristic curves are the measures of diagnostic accuracy of a test. The pretest probability of a disease or a target condition can be enhanced by the use of these measures, and hence the decision is made with the posttest probability. These measures are also used for analysis and critical appraisal of literature for finding the best evidence in the five-step model of evidence-based medicine approach, as well as for integrating the research results into clinical usage. In this context, the specialists in laboratory medicine should assess the diagnostic performance of a laboratory test as well as its analytical performance in order to take part in the management of health care services and health care resources. The aim of this review is to summarize the simple Statistics in diagnostic tests. Jednostavna Statistika U DijagnostiČkim Testovima Dijagnostičke performanse laboratorijskog testa jedan su od ključnih elemenata u procesu odlučivanja o dijagnozi, skriningu, praćenju, proceni rizika i prognozi bolesti. Mere dijagnostičke tačnosti jednog testa su osetljivost, specifičnost, odnosi verovatnoće, odnosi dijagnostičkih šansi i «ROC» krive. Verovatnoća bolesti ili medicinskog stanja pre testa može se uz upotrebu ovih metoda bolje proceniti, tako da se odluka donosi prema proceni verovatnoće posle testa. Te mere takođe se koriste za analizu i kritičko razmatranje literature u cilju pronalaženja najboljih dokaza u okviru modela iz oblasti medicine zasnovane na dokazima koji sadrži pet koraka, kao i za uključivanje rezultata istraživanja u kliničku upotrebu. Shodno tome, specijalisti laboratorijske medicine treba da procene dijagnostičke performanse kako bi učestvovali u upravljanju službama javnog zdravstva i resursima zdravstvene nege. Cilj ovog pregleda je da ukratko izloži primenu jednostavnih statističkih metoda u proceni dijagnostič kih testova.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers

Abstract Background: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. Methods: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). Results: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. Conclusions: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

Biomarkers for Diabetes Complications: The Results of Several Clinical Studies

Biomarkers for Diabetes Complications: The Results of Several Clinical Studies Diabetes is a common metabolic disorder. Its microvascular and macrovascular complications contribute to death, disabilities, and reduction in life expectancy in diabetes. It is a costly disease, and affects not only the patient and family, but also the public health, communities and society. It takes an increasing proportion of the national health care expenditure. The prevention of the development of diabetes and its complications is a major concern. Biomarkers have been investigated for understanding the mechanisms of the development and progression of diabetic complications. In this paper, the biomarkers which are recommended in the clinical practice and laboratory medicine guidelines, and which have been investigated for prediction or diagnosis of diabetes complications, have been reviewed. The results of several clinical studies will be summarized. Biomarkeri Komplikacija u Dijabetesu: Rezultati Nekoliko Kliničkih Studija Dijabetes predstavlja čest metabolički poremećaj, čije mikrovaskularne i makrovaskularne komplikacije doprinose smrti, invaliditetu i skraćenju očekivanog životnog veka kod obolelih. Ova bolest podrazumeva velike troškove a pored pacijenta i njegove porodice pogađa i javno zdravlje, zajednice i društvo. Dijabetes zahteva sve veći deo nacionalnih troškova zdravstva. Prevencija razvoja dijabetesa i njegovih komplikacija je važan problem. U cilju razumevanja mehanizama razvoja i progresije komplikacija u dijabetesu vrši se istraživanje biomarkera. U ovom radu dat je pregled biomarkera koji se preporučuju u kliničkoj praksi i pravilnicima za laboratorijsku medicinu i koji su istraživani radi predikcije ili dijagnostikovanja komplikacija u dijabetesu. U sažetom obliku su prikazani rezultati nekoliko kliničkih studija.

Comparison of cetylpyridinium chloride and cetyltrimethylammonium bromide extractive procedures for quantification and characterization of human urinary glycosaminoglycans.

Abstract Background: Glycosaminoglycans (GAGs) are natural complex polysaccharides that are important in several pathological processes. Urinary GAGs have long been investigated for their possible modifications in many pathological conditions. In some cases, they have been found to have diagnostic utility. As a result, the measurement of GAGs in urine is gradually gaining importance. Cetylpyridinium chloride (CPC) and cetyltrimethylammonium bromide (CETAB) are generally used to extract urinary GAGs prior to analysis. In this study, we evaluated the extraction of human urinary GAGs using CPC in comparison with CETAB. Methods: Extracted urinary GAGs were qualitatively and quantitatively analyzed by agarose-gel electrophoresis in the presence of sequential staining and densitometric scanning. This procedure was able to give more reproducible and reliable results for urinary GAGs, and high performance liquid chromatography (HPLC) was used for the evaluation of chondroitin sulfate (CS) disaccharides. Results: Differences were observed between CPC and CETAB extract protocols. The absolute amount of CS evaluated by electrophoresis was found to be similar for the two protocols. However, the heparan sulfate (HS) concentration was calculated to be approximately 3.3 times greater for CPC than CETAB. When calculated in relative percentage, 33.6% HS was determined for CPC and 10.0% for CETAB. These results show a quantitative expression for greater recovery of HS by using CPC protocol than CETAB. No significant differences were found between CS quantified by agarose-gel and HPLC. In addition, no differences were observed for the CS disaccharide composition purified by using CPC or CETAB, and quite similar results were observed for 4s/6s disaccharide ratios and charge density values. Conclusions: Extract procedures for urinary GAGs using CPC or CETAB are able to recover similar amounts of CS quantified by agarose-gel electrophoresis and HPLC. However, CPC yields greater recovery of HS than the CETAB protocol; an increase of approximately 3.3 times as evaluated by electrophoresis. This different capacity of HS extraction between CPC and CETAB should be considered when urinary GAGs of subjects affected by various diseases and related pharmacological treatments are considered, or meta-analysis is performed comparing various studies and trials performed under different experimental conditions. Clin Chem Lab Med 2010;48:1133–9.

The report of the 1st Turkey in vitro diagnostic symposium results

Abstract “The 1st Turkish in vitro Diagnostic Symposium” was organized in İzmir between the dates 18–20 February 2016 with cooperation of Turkish Biochemistry Society Izmir Branch and Dokuz Eylul University Institute of Health Sciences. This article presents a collection of the subjects, recommendations and results included in the final report of the symposium. Symposium subjects were analysed under separate titles and evaluated together with results obtained from various reports on medical devices (MD) in the last decade. According to the final report, the subjects to be considered on preferential basis include “configuration of the websites of legal authorities, standardization and accreditation institutions in a way to access work on in vitro Diagnostic (IVD)”, “activation of university-industry cooperation”, “determination of national standards parallel to international standards” and “carrying out the statistics about IVD-MD in Turkey as immediate as possible”. Drawing attention to the fact that there is a requirement for competent man power for every-stage of IVD-MD lifecycle, it is recommended that postgraduate education programmes are founded to serve these fields. Consequently, this symposium enabled to determine the basic problems about the sector by bringing together the stakeholders related to IVD-MD field and to come up with an action plan in accordance with the recommendations.