Diagnostic test accuracy systematic review in medical biochemistry

Medicinska biokemija pruža dijagnostičke zdravstvene usluge korištenjem medicinskih, laboratorijskih testova. Procjena dijagnostičke točnosti (dijagnostička osjetljivost i specifičnost) testova u određenoj bolesti temeljni je cilj dijagnostičkih sustavnih pregleda (DSP). Izrada plana istraživanja DSP zahtjeva definiranje pozicije i uloge ispitivanog testa (eng. index test) u dijagnostičkom algoritmu istraživane bolesti. Ona odražava i slaganje rezultata index testa s referentim standardom (najboljim mogućim načinom dijagnoze ispitivane bolesti). Izrada plana istraživanja, provedno istaživanje i njegovo publiciranje daje metodološke kompetencije primjenjive u daljnjem stručnom i znanstvenom usavršavanju, ali i u rutinskom laboratorijskom radu. Ujedno DSP korisna su građa kliničkih i dijagnostičkih smjernica temeljenih na dokazima koje omogućavaju primjenu medicine temeljene na dokazim u medicinsko-biokemijskom laboratoriju.Medical biochemistry offers diagnostic health service by implementation of medical, laboratory tests. The diagnostic accuracy (sensitivity and specificity) of those tests is a main aim of the diagnostic test accuracy systematic reviews (DTA SR). In the work on a protocol of DTA SR it is mandatory to define a role of test (index test) in the clinical pathway of testing disease. The role of index test reflects also an agreement in sensitivity and specificity between test and reference standard (a gold standard). The work on the protocol, producing and publishing of the DTA SR, all together give an author methodological expertise of generic kind making it feasible in his/her further research but also in the routine laboratory work. Additionally, DTA SR may be used as a source for development of the clinical and diagnostic guidelines that make possible an application of the evidence based medicine in the routine work of the medical biochemical laboratories

Celiac disease: From pathophysiology to treatment

Celiac disease, also known as “celiac sprue”, is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac diseas

Plasma Levels of Osteopontin and Vascular Endothelial Growth Factor in Association with Clinical Features and Parameters of Tumor Burden in Patients with Multiple Myeloma

The aim of this pilot study was to determine the plasma levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) and find possible association between them and main clinical features and parameters of tumor burden in patient with multiple myeloma (MM). Plasma levels of OPN and VEGF were determined in 44 newly diagnosed MM patients and 24 healthy persons by ELISA method. These values were compared with the presence of anemia, renal dysfunction, and bone lesions as myeloma related clinical manifestations and with serum beta-2 microglobulin and Durie-Salmon clinical stage as prognosticators related to tumor mass. The value of OPN was significantly higher in MM patients with evident bone lesions (P=0.03) and there was also a positive correlation with serum beta-2 microglobulin (r=0.366; P=0.04). Furthermore, patients with lower Durie-Salmon stage had significantly lower OPN and VEGF levels (P=0.05; P=0.04, resp.). Our preliminary results found positive association between plasma level of OPN, tumor burden, and bone destruction. Further analysis should provide information about the possible use of OPN as useful clinical biomarker for monitoring bone disease and tumor mass, as well as a prognostic factor, or a possible target for pharmacological intervention

Plasma Levels of Osteopontin and Vascular Endothelial Growth Factor in Association with Clinical Features and Parameters of Tumor Burden in Patients with Multiple Myeloma

The aim of this pilot study was to determine the plasma levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) and find possible association between them and main clinical features and parameters of tumor burden in patient with multiple myeloma (MM). Plasma levels of OPN and VEGF were determined in 44 newly diagnosed MM patients and 24 healthy persons by ELISA method. These values were compared with the presence of anemia, renal dysfunction, and bone lesions as myeloma related clinical manifestations and with serum beta-2 microglobulin and Durie-Salmon clinical stage as prognosticators related to tumor mass. The value of OPN was significantly higher in MM patients with evident bone lesions () and there was also a positive correlation with serum beta-2 microglobulin (; ). Furthermore, patients with lower Durie-Salmon stage had significantly lower OPN and VEGF levels (; , resp.). Our preliminary results found positive association between plasma level of OPN, tumor burden, and bone destruction. Further analysis should provide information about the possible use of OPN as useful clinical biomarker for monitoring bone disease and tumor mass, as well as a prognostic factor, or a possible target for pharmacological intervention

Values of vanillylmandelic acid and homovanillic acid in the urine as potential prognostic biomarkers in ischaemic stroke patients

Background: Suitable biomarkers that have prognostic values are one of the key points of interest in ischaemic stroke. Increased sympathetic nervous system activity in ischaemic stroke causes multiple local and systemic effects that can be detrimental to the outcome. The mechanism of action is increased secretion and activity of catecholamines, whose end metabolic products are vanillylmandelic acid and homovanilic acid. Aim of our study was to determine whether these compounds can be used as potential prognostic biomarkers in ischaemic stroke, as a unique insight into the activity of the sympathetic nervous system. Methods: Urine samples of 96 patients with ischaemic stroke and transitory ischaemic attacks were analysed. Values of vanillylmandelic and homovanillic acids in urine were tested using liquid chromatography on the first and third day post-stroke. Severity of stroke was determined using the NIHSS scale, while functional outcome was determined using the Modified Rankin Scale. Results: Values of vanillylmandelic and homovanillic acids positively correlated with functional outcome of ischaemic stroke. Favorable outcomes correlated with decreased values, on contrary to increased values, which were associated with unfavourable outcomes. Conclusion: Determining the values of these compounds in the urine is an easily available prognostic tool for the ischaemic stroke outcome, while also influencing potential therapeutic change

Evaluating performance in sweat testing in medical biochemistry laboratories in Croatia

Introduction: Sweat test has a diagnostic role in evaluation of cystic fibrosis. Its performance includes sweat stimulation, collection and analysis. All listed may be sources of inconsistencies in everyday practice. The aim of this study was an evaluation of external quality assessment (EQA) of sweat chloride measurement including sweat test performance in medical biochemistry laboratories in Croatia. Materials and methods: EQA for sweat chloride measurement was provided by Croatian Centre for Quality Assessment in Laboratory Medicine (CROQALM) in five consecutive exercises to medical biochemistry laboratories (MBL) that offered sweat testing. A questionnaire regarding all phases of testing was mailed to involved MBL (N = 10). Survey results were compared to current guidelines for sweat test performance. Results: Reported results of EQA in 2015 exercises showed coefficients of variation (CV) from 28.9%, 29.0% to 35.3%, respectively. An introduction of uniform sweat chloride measurement protocol resulted in CV of 15.5% and 14.7% reported in following two exercises in 2016. All MBL included in this study replied to the questionnaire. Results reported by MBL indicated: lack of patient information policy (7/10), use of unacceptable electrodes (6/9), misuse of minimum of acceptable sweat weight (6/9), lack of internal quality assessment (5/9) and recommended reference ranges (5/9 and 4/9). Agreements to guidelines were found in approach to unsuitable patients (9/10) and sweat collection (8/9). Conclusion: Presented results indicate major weak points of current practice in sweat test performance in Croatian MBL and stress the need for its standardization on a national level

Serological tests for primary biliary cholangitis

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To determine and compare the diagnostic accuracy in terms of sensitivity and specificity of different serological markers for diagnosis of primary biliary cholangitis in people suspected of having the disease. To investigate variation in the diagnostic accuracy of AMA, ANA, anti-M2, anti-sp100, anti-gp210, anti-PML, anti-sp140, and anti-EPO antibodies according to the following potential sources of heterogeneity. Studies at low risk of bias versus studies with unclear or high risk of bias (as assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool) (2). Full-text publications versus abstracts (this may indicate publication bias if there is an association between the results of the study and the study reaching full publication) (Eloubeidi 2001). Prospective versus retrospective studies. The prevalence of people who are symptomatic versus people who are asymptomatic (the presence of symptoms may increase the pretest probability). People who are symptomatic will be defined as people with fatigue (lasting more than three months ; anaemia and hypothyroidism excluded), pruritus, jaundice, and abdominal pain in the absence of biliary stones, oesophageal varices, ascites, and liver failure (Prince 2004 ; AASLD 2009). Studies that included 30% or less of participants with other autoimmune diseases versus studies that included more than 30% of such participants. Detection of index tests by different types of immunoassays. Diagnostic accuracy of anti-M2, ANA, anti-sp100, anti- gp210, anti-PML, anti-sp140, and anti-EPO according to the prevalence of AMA-negative participants in the included studies. Diagnostic accuracy of AMA, anti-M2, ANA, anti- sp100, anti- gp210, anti-PML, anti-sp140, and anti-EPO in participants suspected of primary biliary cholangitis referred from a general practitioner clinicversus people referred from specialist clinic. Diagnostic accuracy of AMA, anti-M2, ANA, anti-sp100, anti-gp210, anti-PML, anti- sp140, and anti-EPO in participants without liver cirrhosis versus participants with liver cirrhosis (as defined by individual studies)

An analysis of the vitamin D overtesting in a tertiary healthcare centre

Introduction: Vitamin D testing is excessively used in clinical practice, despite of the clinical guidelines statements against population screening for vitamin D deficiency. This study aimed to assess an annual number of performed 25-hydroxy vitamin D (25(OH)D) tests that were unsupported by the national guidelines for prevention, detection and therapy of vitamin D deficiency in adults and to calculate associated financial burden for the publicly funded healthcare. Materials and methods: A representative sample of requested 25(OH)D tests in 2018 (N = 474) was formed after selection and randomisation of data set (N = 5298) collected from the laboratory information system database of the Clinical Department for Laboratory Diagnostics, the Clinical Hospital Centre Rijeka. Records were classified in two groups depending on associated medical condition(s) according to the national guidelines. An annual cost of the total and group specific vitamin D testing was calculated on the base of a single test price reimbursed by the Croatian Healthcare Insurance Fund (CHIF). Results: Medical conditions with high-risk for vitamin D deficiency were detected in 43% (206/474) of vitamin D requests (group 1). Conditions not associated with vitamin D deficiency were detected in 57% (268/474) requests (group 2). A total cost of 25(OH)D testing for the CHIF was 58,729.50 EUR (25,523.79 EUR in the group 1 and 33,205.71 EUR in the group 2). Conclusions: More than half of all 25(OH)D tests performed in the clinical laboratory represent avoidable cost for the public healthcare. Prevention of population screening by vitamin D testing is needed

Laboratory medicine in arterial hypertension

In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It mainly refers to routine blood and urine tests for diagnosis and monitoring primary hypertension and its associated conditions such as asymptomatic hypertension-mediated organ damage, chronic kidney disease and hypertensive disorders of pregnancy. In addition, long term non-fatal and fatal risks for cardiovascular (CV) events in hypertension are assessed based on clinical and laboratory data. Furthermore, laboratory medicine is involved in the management of hypertension, especially in monitoring the disease progression. However, antihypertensive drugs may interfere with laboratory test results. Diuretics, especially thiazides, can affect blood and urine sodium concentrations, or angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can affect the blood biomarkers of the renin-angiotensin-aldosterone system (RAAS). It’s dysfunction plays a critical role in primary aldosteronism (PA), the most common endocrine disorder in secondary hypertension, which accounts for only small proportion of AH in relative terms but substantial proportion of hypertensives in absolute terms, affecting younger population and carrying a higher risk of CV mortality and morbidity. When screening for PA, aldosterone-to-renin ratio still contributes massively to the increased incidence of the disease, despite certain limits. In conclusion, laboratory medicine is involved in the screening, diagnosis, monitoring and prognosis of hypertension. It is of great importance to understand the preanalytical and analytical factors influencing final laboratory result

Laboratory medicine in arterial hypertension

In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It mainly refers to routine blood and urine tests for diagnosis and monitoring primary hypertension and its associated conditions such as asymptomatic hypertension-mediated organ damage, chronic kidney disease and hypertensive disorders of pregnancy. In addition, long term non-fatal and fatal risks for cardiovascular (CV) events in hypertension are assessed based on clinical and laboratory data. Furthermore, laboratory medicine is involved in the management of hypertension, especially in monitoring the disease progression. However, antihypertensive drugs may interfere with laboratory test results. Diuretics, especially thiazides, can affect blood and urine sodium concentrations, or angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can affect the blood biomarkers of the renin-angiotensin-aldosterone system (RAAS). It’s dysfunction plays a critical role in primary aldosteronism (PA), the most common endocrine disorder in secondary hypertension, which accounts for only small proportion of AH in relative terms but substantial proportion of hypertensives in absolute terms, affecting younger population and carrying a higher risk of CV mortality and morbidity. When screening for PA, aldosterone-to-renin ratio still contributes massively to the increased incidence of the disease, despite certain limits. In conclusion, laboratory medicine is involved in the screening, diagnosis, monitoring and prognosis of hypertension. It is of great importance to understand the preanalytical and analytical factors influencing final laboratory result