Moving average procedures as an additional tool for real-time analytical quality control: challenges and opportunities of implementation in small-volume medical laboratories

Introduction: Moving average (MA) is one possible way to use patient results for analytical quality control in medical laboratories. The aims of this study were to: (1) implement previously optimized MA procedures for 10 clinical chemistry analytes into the laboratory information system (LIS); (2) monitor their performance as a real-time quality control tool, and (3) define an algorithm for MA alarm management in a small-volume laboratory to suit the specific laboratory. Materials and methods: Moving average alarms were monitored and analysed over a period of 6 months on all patient results (total of 73,059) obtained for 10 clinical chemistry parameters. The optimal MA procedures were selected previously using an already described technique called the bias detection simulation method, considering the ability of bias detection the size of total allowable error as the key parameter for optimization. Results: During 6 months, 17 MA alarms were registered, which is 0.023% of the total number of generated MA values. In 65% of cases, their cause was of pre-analytical origin, in 12% of analytical origin, and in 23% the cause was not found. The highest alarm rate was determined on sodium (0.10%), and the lowest on calcium and chloride. Conclusions: This paper showed that even in a small-volume laboratory, previously optimized MA procedures could be successfully implemented in the LIS and used for continuous quality control. Review of patient results, re-analysis of samples from the stable period, analysis of internal quality control samples and assessment of the analyser malfunctions and maintenance log have been proposed for the algorithm for managing MA alarms

Laboratorijska podrška u dijagnozi hipertireoidizma

Physicians need quality laboratory testing support for the accurate diagnosis and cost-effective management of thyroid disorders. Over the past forty years, improvements in the sensitivity and specificity of biochemical thyroid tests have dramatically impacted clinical strategies for detecting and treating thyroid disorders. Improvements in the sensitivity of assays to measure the pituitary thyroid stimulating hormone, thyrotropin (TSH) now allow TSH to be used for detecting hypothyroidism. Modern-day TSH methods with their enhanced sensitivity are Most of the current methods are capable of achieving a functional sensitivity of 0.02mIU/L or less, which is a necessary detection limit for the full range of TSH values observed between hypo- and hyperthyroidism. With this level of sensitivity, it is possible to distinguish the profound TSH suppression typical of severe Graves' thyrotoxicosis (TSH lt 0.01 mlU/L) from the TSH suppression (0.01 - 0.1 mlU/L) observed with mild (subclinical) hyperthyroidism and in some patients with a non-thyroidal illness. Current thyroid tests are usually performed on serum by automated immunometric methods that employ specific antibodies. Methodology continues to evolve as performance standards are established and new technology and instrumentation are developed as laboratory support for diagnosis of hyperthyroidism.Postavljanje tačne dijagnoze i efikasno lečenje tireoidnih oboljenja zahteva kvalitetan laboratorijski servis. Poboljšanje specifičnosti i osetljivosti biohemijskih tireoidnih testova u prethodnih četrdeset godina je dramatično uticalo na kliničke strategije u detekciji i tretmanu tireoidnih oboljenja. Poboljšanje osetljivosti metoda za određivanje tireoidnog stimulišućeg hormona, tiretropina (TSH) je omogućilo detekciju hipertireoidizma. Većina tekućih metoda je u mogućnosti da postigne funkcionalnu osetljivost od 0,02 mlU/L ili manje što predstavlja neophodni detekcioni limit za ceo opseg TSH vrednosti koje se sreću od hipo do hipertireoidizma. Sa ovim nivoom osetljivosti moguće je razlikovanje velike TSH supresije koja je tipična za tešku Graves-ovu tireotoksikozu (TSH lt 0,01 mlU/L) od supresije TSH (0,01 - 0,1 mlU/L) koja se sreće kod blagog (subkliničkog) hipertireoidizma i kod nekih pacijenata sa netireoidnim oboljenjima. Današnji tireoidni testovi koji koriste serum se izvode kao automatizovane imunometrijske metode i koriste specifična antitela. Sa uspostavljanjem standarda izvođenja nastavlja se sa razvojem metodologije i novih tehnologija i instrumenata kao podrška u dijagnozi hipertiroidizma

Primena 'Šest sigma' nivoa kvaliteta u laboratorijskoj medicini

The principle of continuous improvement of working process applies to quality management itself. Six Sigma level of quality provides a quantitative definition of the desired specifications for production processes and allows those specifications to be related to the customer needs or requirements. When six-sigma performance is recognized as a fundamental goal for processes, quality can truly be measured and managed in a more quantitative way. A six-sigma process provides a better guarantee that products will be produced within the desired specifications and with a low defect rate.Princip kontinuiranog unapređenja procesa rada se primenjuje pre svega na sam menadžment kvaliteta. Šest sigma nivo kvaliteta omogućava kvantitativno definisanje željenih specifikacija proizvodnog procesa, a koje su povezane sa zahtevima ili potrebama kupca. Ukoliko je šest sigma fundamentalni cilj za proces, onda i kvalitet pouzdano može da se meri i obezbeđuje na kvantitativniji način. Proces čiji nivo kvaliteta zadovoljava šest sigma daje bolje garancije da će proizvod biti u granicama zadatih specifikacija i imaće nisku stopu defekata (nepravilnosti)

Vodiči za primenu tumorskih markera kod karcinoma dojke

The best-validated markers in breast cancer are all tissue based and include estrogen receptors (ER), progesteron receptors (PR), HER-2, urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1). Assay of ER, PR and HER-2 is now mandatory on all newly diagnosed breast cancer patients. The measurement of uPA and PAI-1, although technically and clinically validated, is not yet in widespread clinical use, mainly due to the requirement of a minimum amount of fresh or freshly frozen tissue. Assay of these proteins however, may be used to aid the selection of lymph node-negative breast cancer patients that do not need adjuvant chemotherapy. Although widely used in post-operative surveillance and monitoring therapy in advanced disease, the clinical value of CA 15-3 and other serum markers has not yet been validated by a Level I evidence study. Recent improvements in our understanding of breast cancer biology and a parallel increase in possible treatment options have led to improvements in outcome this very heterogeneous disease. Oncologists still have significant difficulty in tailoring treatment strategies to the molecular characteristics of an individual's disease.Najbolje validovani markeri karcinoma dojke pripadaju tkivnim markerima i uključuju receptore za estrogen (ER), receptore za progesteron (PR), HER-2 urokinaza plazminogen aktivator (uPA) i plazminogen aktivator inhibitor 1 (PAI-1). Kod svih novodijagnostikovanih pacijenata sa karcinomom dojke određivanje ER, PR i HER-2 je danas obavezno. Mada je merenje uPA i PAI-1 tehnički validovano, do danas nije klinički rasprostranjeno i to uglavnom zbog zahteva za minimalnom količinom svežeg ili sveže zamrznutog tkiva. Određivanje ovih proteina može da se iskoristi kao pomoć pri selekciji "limfni čvor negativnih" pacijenata s karcinomom dojke kojima nije potrebna adjuvantna hemoterapija. Mada se dosta koristi u postoperativnom praćenju i praćenju terapije u poodmaklom oboljenju, klinička vrednost CA 15-3 i drugih serumskih markera nije još uvek validovana u studijama nivoa dokaza I. Nedavna poboljšanja u razumevanju biologije karcinoma dojke i paralelno povećanje mogućih opcija tretmana treba da vode ka poboljšanju ishoda ove veoma hetrogene bolesti. Onkolozi još uvek imaju teškoće u odabiru specifičnih strategija tretmana prema molekularnim karakteristikama oboljenja svakog pacijenta ponaosob

Klinička korisnost tumorskih markera

As with all diagnostic tests, tumor markers are surrogate indicators that can be used clinically to increase or decrease the clinician’s suspicion that a future clinically important event will or will not happen, and/or that a specific treatment will reduce that risk. To determine the clinical utility of tumor markers, one of several potential uses must be designated, including risk assessment, screening, differential diagnosis, prognosis, and monitoring clinical course. Within these uses, only tumor markers for which the results effect a change that results in a more favorable clinical outcome (overall survival, disease free survival, quality of life, or decreased cost) are recommended for routine clinical use. Introduction of tumor markers into routine clinical practice has been poorly controlled, with few criteria or guidelines as to how such markers should be used. However, unlike the objective criteria established to evaluate new therapeutic agents, few guidelines have been established to determine if and/or when use of a tumor markers should become standard. Dr. Daniel Hayes of the University of Michigan, Ann Arbor, Michigan, United States and coworkers have proposed that it is appropriate to establish similar criteria for evaluation of tumor markers and to standardize the tumor marker information for clinical utility. The proposed an evidence-based system is called the Tumor Marker Utility Grading System or TMUGS. Acceptance of a tumor marker for clinical utility requires careful and thoughtful study design so that the results are meaningful in the clinical setting.Kao svi dijagnostički testovi, tumorski markeri su surogat indikatori koji klinički mogu da se upotrebe za povećanje ili smanjenje sumnje lekara o tome da se neki važan događaj u budućnosti može da dogode ili ne dogode, kao i/ili da će se specifičnim tretmanom smanjiti rizik. Da bi se odredila klinička korisnost tumorskih markera neophodno je da rezultati njihovog određivanja precizno odgovaraju situaciji rizika, "skrininga", dijagnoze, prognoze, predviđanja i praćenja kliničkog toka. Za rutinsku kliničku praksu preporučuju se oni tumorski markeri koji mogu da pomognu pri donošenju pouzdanih kliničkih odluka koje će rezultirati u poboljšanju u jednom od četiri klinička ishoda: obuhvatno preživljavanje, preživljavanje bez bolesti, kvalitet života ili koštanje lečenja. Uvođenje tumorskih markera u rutinsku kliničku praksu je loše kontrolisano uz primenu nekoliko kriterijuma ili vodiča za njihovo korišćenje. Suprotno činjenici da postoje objektivni kriterijumi za evaluaciju terapeutskih agenasa, samo nekoliko vodiča za primenu tumorskih markera je postalo standard. Dr. Daniel Hayes sa "Ann Arbor" Univerziteta u Mičigenu, SAD i saradnici su preporučili uspostavljanje sličnih kriterijuma u evaluaciji tumorskih markera i standardizaciju njihove kliničke korisnosti. Preporučeni sistem zasnovan na dokazima je nazvan Tumor Marker Utility Grading System ili TMUGS. Prihvatanje tumorskih markera u kliničkoj praksi zahteva temeljan i smisleni dizajn studije tako da rezultati budu značajni u kliničkoj situaciji

Određivanje visoko osetljivog C-reaktivnog proteina - klinički i analitički kvalitet

Inflammation plays a key role in the pathophysiology of atherosclerotic disease. A number of inflammatory markers that are measurable in blood have been investigated for their ability to predict the risk of future atherosclerotic events. High-sensitivity (hs) measurement of C-reactive protein (CRP) has received a great deal of attention recently for use as an atherosclerotic risk marker. For these reasons, CRP is currently the inflammatory marker of choice. The Centers for Disease Control and Prevention (CCDC) and the American Heart Association (AHA) issued guidelines for the utility of this marker in the primary prevention setting and in patients with stable coronary disease or acute coronary syndromes. The guidelines also included specific recommendations that pertain to the laboratory aspect of CRP and defined cut-points for clinical interpretation; CRP concentrations lt 1 mg/L are considered low, 1-3 mg/L average, and >3 mg/L high relative risk. A number of preanalytical and analytical factors including specimen type and stability, assay imprecision, commercial availability, and standardization are reviewed here. Better control of preanalytic and analytic sources of variations will undoubtedly lead to improvement in CRP measurements. Further research is required to better define the performance characteristics necessary for assays bearing the designation hsCRP. These characteristics include developing guidelines for total analytical error from a careful review of the intraindividual biological variability of the analyte under conditions that will be encountered in clinical practice, defining allowable random and systematic error limits based on this information, validating these guidelines in the clinical setting, and completing the standardization efforts.Inflamacija ima ključnu ulogu u patofiziologiji aterosklerotskih oboljenja. Vršena su ispitivanja velikog broja u krvi merljivih inflamatornih markera u njihovoj mogućnosti predviđanja rizika za nastanak aterosklerotskih događaja u budućnosti. Određivanje visoko osetljivog (high sensitivity, hs) C-reaktivnog proteina (CRP) se odskora primenjuje kao marker aterosklerotskog rizika. CRP danas predstavlja inflamatorni marker izbora. Centri za kontrolu i prevenciju oboljenja (The Centers for Disease Control and Prevention, CCDC) i Američko udruženje za srce (American Heart Association, AHA) su dali preporuke za korišćenje ovog markera u primarnoj prevenciji pacijenata sa stabilnim koronarnim oboljenjima ili akutnim koronarnim sindromom. Preporuke uključuju laboratorijski aspekt vezan za CRP i definišu "cut-off" vrednosti u kliničkoj interpretaciji koncentracije CRP pri čemu vrednosti CRP lt 1 mg/L govore o niskom, vrednosti od 1 do 3 mg/L o srednjem i vrednosti > 3 mg/L o visokom relativnom riziku. U radu je opisan veliki broj preanalitičkih i analitičkih faktora kao što su vrsta uzorka, stabilnost, nepreciznost određivanja, komercijalna dostupnost i standardizacija važnih za određivanje CRP. Bolja kontrola preanalitičkih i analitičkih izvora varijacija sigurno vodi poboljšanju određivanja CRP. Neophodna su dodatna ispitivanja vezana za definisanje karakteristika izvođenja testova za određivanje hsCRP. Ove karakteristike uključuju preporuke vezane za ukupnu analitičku grešku koja potiče od intraindividulne biološke varijacije CRP a koja mora da se uzme u obzir pri donošenju kliničkih odluka, kao i definisanje granica dozvoljene slučajne i sistematske greške, Takođe je neophodno da se izvrši validacija ovih preporuka u specifičnim kliničkim situacijama i završe započete aktivnosti vezane za standardizaciju određivanja

Antifosfolipidna antitela u zdravih srpskih osoba srednjih godina - preliminarni podaci

Background: The investigation of the prevalence of the IgG and the IgM isotypes of anticardiolipin (aCL) and antib2glycoprotein I (ab2gpI) Abs in healthy Serbian middle-aged subjects was the main goal of our study. In addition, we analyzed the potential associations of above-mentioned Abs with serum proteins and lipids/lipoproteins. Methods: Forty healthy subjects were included in our study. Obesity (BMI 30 kg/m2) was present in 8/40 (20%) subjects. Titers of analyzed Abs were measured by ELISA. Results: The prevalence of IgG and IgM ab2gpI Abs was 5% and 12.5%, respectively, while the prevalence of IgM aCL was 10%. The IgG ab2gpI Abs were significantly different between subjects with normal triglycerides levels and those with hypertriglyceridemia (Mann-Whitney, P = 0.014). The significant difference in hsCRP concentrations was observed between subjects with the increased levels of the IgM isotype of aCL Abs and those with normal IgM aCL values (Mann-Whitney, P = 0.028). Conclusions: Dyslipidemia and BMI ≥30 were associated with aPL Abs and therefore, the correction of BMI and lipid status might be beneficial in reduction or elimination of predisposing factors that might trigger thrombotic events in otherwise healthy middle-aged subjects. Larger national study is necessary to confirm our findings.Uvod: Analiza prevalentnosti IgG i IgM izotipa antikardiolip- inskih (aCL) i anti- b2glikoprotein I (ab2gpI) At kod zdravih sredove~nih stanovnika Srbije je bila glavni cilj na{e studije. Dodatno, analizirali smo potencijalnu povezanost gore- navedenih At sa serumskim proteinima i lipidima/lipopro- teinima. Metode: 40 zdravih ispitanika je bilo uklju~eno u na{u studiju. Gojaznost (BMI ≥ 30 kg/m2) je uo~ena kod 8/40 (20%) osoba. Titri analiziranih antitela su utvr|ivani ELISA testom. Rezultati: Prevalentnost IgG i IgM ab2gpIAt je bila 5% i 12.5%, redom, dok je prevalentnost IgM aCL bila 10%. Nivoi IgG ab2gpI At su se zna~ajno razlikovali izme|u ispi- tanika sa i bez hipertrigliceridemije (Mann-Whitney, P = 0.014). Zna~ajne razlike u hsCRP koncentracijama uo~ene su izme|u osoba sa povi{enim nivoima IgM aCL At i onih sa referentim vrednostima (Mann-Whitney, P = 0,028). Zaklju~ak: Dislipidemija i BMI ≥30 su bili povezani sa aPL At uprkos njihovoj niskoj prevalentnosti, i zato korekcija BMI i lipidnog statusa bi bila korisna u redukciji ili elimi- naciji predispoziraju}ih faktora koji mogu da izazovu trom- boti~ki doga|aj kod ina~e zdravih sredove~nih ispitanika. Obimnije nacionalne studije su neophodne da bi potvrdile na{e nalaze

Optimizing moving average control procedures for small-volume laboratories: can it be done?

Introduction: Moving average (MA) means calculating the average value from a set of patient results and further using that value for analytical quality control purposes. The aim of this study was to examine whether the selection, optimization and validation of MA procedures can be performed using the already described bias detection simulation method and whether it is possible to select appropriate MA procedures for a laboratory with a small daily testing volume

Bias in medical biochemistry- what laboratory professionals need to know?

In medical laboratories, bias presents quantitative expression of trueness, as analytical performance characteristic that describes systematic errors. Despite bias evaluation is an integral part of basic lessons of laboratory quality management, it is still difficult to achieve adequate bias estimation in routine laboratory practice. There are several principles that could be used to estimate bias, but fundamental for evaluating bias in routine medical laboratories is the availability of a suitable reference materials. Besides, it is important that the measuring method and measuring analytical system are in a stable state, and that they have completed an appropriate validation or verification process. This could be checked routinely by the results of internal and/or external quality control. In addition, information about the uncertainty of the certified reference material is a prerequisite for testing the bias. Significant efforts were made to minimized bias in routine laboratory practice, using reference measurement methods and commutable reference materials. Still, there are some challenges that remain for the laboratory professionals as the end users, due to remaining bias between measurement methods and systems from different and/or the same manufacturers

Difficulties in proving medical errors: Where do we stand?

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