The Cost-Effective Laboratory: Implementation of Economic Evaluation of Laboratory Testing

Laboratory testing as a part of laboratory in vitro diagnostic (IVD) has become required tool in clinical practice for diagnosing, monitoring and prognosis of diseases, as well as for prediction of treatment response. The number of IVD tests available in laboratory practice has increased over the past decades and is likely to further increase in the future. Consequently, there is growing concern about the overutilization of laboratory tests and rising costs for laboratory testing. It is estimated that IVD accounts for between 1.4 and 2.3% of total healthcare expenditure and less than 5% of total hospital cost (Lewin Group report). These costs are rather low when compared to pharmaceuticals and medical aids which account for 15 and 5%, respectively. On the other hand, IVD tests play an important role in clinical practice, as they influence from 60% to 70% of clinical decision-making. Unfortunately, constant increases in healthcare spending are not directly related to healthcare benefit. Since healthcare resources are limited, health payers are interested whether the benefits of IVD tests are actually worth their cost. Many articles have introduced frameworks to assess the economic value of IVD tests. The most appropriate tool for quantitative assessment of their economic value is cost-effectiveness (CEA) and cost-utility (CUA) analysis. The both analysis determine cost in terms of effectiveness or utilities (combine quantity and quality of life) of new laboratory test against its alternative. On the other hand, some investigators recommended calculation of laboratory test value as product of two ratios: Laboratory test value = (Technical accuracy/Turnaround time) x Utility/Costs). Recently, some researches used multicriteria decision analysis which allows comparison of diagnostic strategies in terms of benefits, opportunities, costs and risks. All analyses are constructed to identify laboratory test that produce the greatest healthcare benefit with the resources available. Without solid evidence that certain laboratory tests are cost-effective, laboratory services cannot be improved. Consequently, simple policy measures such as cost cutting may be imposed upon many laboratories while patients will have limited access to laboratory service

Promene hormonskih i lipidnih parametara u dece sa hipotiroidizmom; uticaj bolesti i supstitucione terapije

Clinical signs of thyroid gland hormones deficiency appear at different ages in infants with different concentrations of hormones. They depend on causes which had caused the hypothyroid degree of subsequents. Concentrations of hormones parameters: tT3, tT4, TSH, fT3, fT4, TBG and Tg (fluoroimmunoassay, DELFIA) and lipid parameters: total cholesterol (Chol), triglycerides (TRG), high density lipoprotein, (HDL-chol) and density lipoprotein, (LDLchol) were determined in order to establish changes that appear under the influence of the disease and replacement therapy in infants with hypothyroidism. In order to establish the influence of infant’s age on a determined parameter, all parameters where determined in the sample of healthy infants. A group of healthy infants (N=100) aged one mounth to 18 years, was devided in 5 age subgroups. The group of patients was devided into the same age groups as healthy group of the moment of diagnosis (N=56). Metabolic condition of an infant was established according to found by ANOVA test according to Tudey Snedecor method for the following parameters; T3 (d=0.35 p lt 0.001), fT3 (d=1.63 p lt 0.001) fT4 (d=2.59 p lt 0.001), TSH (d=2.27 p lt 0.001), TBG (d=90.82 p lt 0.001), Tg (d=4.59 p lt 0.02), Cho. (d=0.48 p lt 0.001) and LDL-chol. (d=0.51 p lt 0.001). These findings must be taken into account when the influence of replacement therapy on the observed parameters concentration changes is interpreted. The average concentration values were compared by Student’s t-test in infant before replacement therapy with that of the control subgroup of infants of the same age in order to evaluate the influence on values of the examined parameters. The average concentration values in infants after the replecement therapy were compared that before the replacement therapy as well as the control group, findings in order to the influence on the examined parameters. We observed significant changes hormone parameters in all agesubgroups under hypothyroid condition and return to control levels, except for T4 where the values were significantly higher in all age groups (p lt 0.05) in comparison to the control group. As for lipids, we found significantly higher values in all age subgroups for chol (p lt 0.01) and LDL-chol (p lt 0.001); they did not differ from that in control group after the replacement therapy. Patients were classified at the moment of clinical examination into the following categories: normometabolic (NM) and hypometabolic (HM). They were compared by Student’s T-test of different pairs with the condition before the replacement therapy. The percentage share in the change of TRG concentrations (p lt 0.02), LDL-chol (p lt 0.025) and T3 (p lt 0.001) was significantly different between NM and HM, and the long-lasting replacement therapy caused significant individual differences in Chol concentrations (NM ’ 37.90% p lt 0.001, HM ’ 15.14% p lt 0.001), HDL-chol (NM ’ 7.81% p lt 0.001, HM ’ 12.05% p lt 0.001), LDL-chol (NM ’ 50.15% P lt 0.001 HM 20.03 p lt 0.01) and T3 (NM ’ 105.04% p lt 0.001, HM 32.18% p>0.005). We conclude that hypothyroidism caused significant hormonal and metabolic changes in infants; however there is no clinical and laboratory index regarding the results of replacement therapy; this is the reason why the patient’s condition must be evaluated individually.Zavisno od uzroka koji su doveli do hipotiroidnog stanja kod deteta (dishormonogeneza, hipoplazija, ektopija, atireoza), a time i težine poremećaja, klinički znaci deficita hormona štitne žlezde ispoljavaju se u različitom uzrastu deteta, s različitim koncentracijama ispitivanih hormona. U cilju utvrđivanja promena nastalih pod uticajem bolesti i supstitucione terapije kod dece s hipotiroidizmom određene su koncentracije hormonskih parametara: tT3, tT4, TSH, fT3, fT4, TBG i Tg (fluoroimunotest DELFIA), kao i lipidnih: ukupni holesterol, trigliceridi, HDL-holesterol i LDL-holesterol. Za utvrđivanje uticaja starosti deteta na ispitivani parametar isti su obrađeni u uzorku zdrave dece. Grupa zdrave dece N=100 uzrasta od 1 meseca do 18 godina podeljena je u 5 starosnih podgrupa. Posebnu grupu sačinjava uzorak uzet iz pupčane vrpce, zdravo rođene dece. Grupa obolele dece je podeljena po istim starosnim grupama kao i zdrava grupa i to: u momentu otkrivanja bolesti (N=58) i u momentu kasnijeg pregleda, posle dugovremene supstitucione terapije sa L-T4 (N=56). Metaboličko stanje deteta utvrđeno je po kriterijumu specifičnih klinički znakova i simptoma. ANOVA testom po metodi Tudey Snedecor-a utvrđena je statistički značajna razlika između starosnih podgrupa za sledeće parametre: T3 (d=0,35 p lt 0,001), fT3 (d=1,63 p lt 0,001) fT4 (d=2,59 p lt 0,001), TSH (d=2,27 p lt 0,001), TBG (d=90,82 p lt 0,001), Tg (d=4,59 p lt 0,02), holesterola (d=0,48 p lt 0,001) i LDL-holesterola (d=0,51 p lt 0,001), što se mora uzeti u obzir kod tumačenja uticaja supstitucione terapije na izmenu koncentracija posmatranih parametara. Koncentracije svih hormonskih parametara u uzorku pupčane vrpce se razlikuje od koncentracija u ostalim starosnim grupama dece, osim za T4. Da bi se procenio uticaj bolesti na vrednosti ispitivanih parametara, upoređene su vrednosti srednjih koncentracija Studentovim T-testom podgrupa dece pre supstitucije sa kontrolnim grupama dece iste starosne dobi. Za procenu uticaja supstitucije na ispitivane parametre upoređene su srednje koncentracije ispitivanih parametara, grupe dece posle supstitucije sa grupom dece pre supstitucije kao i sa kontrolnom grupom. Za posmatrane hormonske parametre imamo značajne izmene u svim starosnim podgrupama, sa nastankom hipotiroidnog stanja i vraćanje na nivo vrednosti kontrolne grupe sem za T4 kada su vrednosti značajno više u svim starosnim grupama (p lt 0,05) u odnosu na kontrolu. Kod lipida značajno veće vrednosti nađene su u svim starosnim podgrupama za holesterol (p lt 0,01) i LDL-holesterol (p lt 0,001) koje se ne razlikuju od kontrolne grupe posle supstitucione terapije. Pacijente su u momentu kliničkog pregleda razvrstali u kategorije normometabolični (NM) i hipometabolični (HM) i upoređeni Studentovim T-testom razlike parova sa sopstvenim stanjem pre supstitucione terapije. Procentualni udeo u izmeni koncentracija triglicerida (p lt 0,02) LDL-holesterola (p lt 0,025) i T3 (p lt 0,001) je značajno različit između NM I HM, a dugogodišnja supstituciona terapija dovodi do značajnih interindividualnih razlika u koncentracijama holesterola (NM ’ 37,90% p lt 0.001, HM - 15,14% p lt 0,001) HDL-holesterola (NM - 7,81% p lt 0.001, HM - 12,0,05% p lt 0.001), LDL-holesterola (NM - 50,15% P lt 0,001 HM 20,03 p lt 0,01) i T3 (NM 105,04% p lt 0,001, HM - 32,18% p>0,005). Zaključujemo da hipotiroidizam dovodi do značajnih hormonskih i metaboličkih promena kod obolele dece, ali ne postoji generalni klinički i laboratorijski indeks postignutog rezultata supstitucione terapije, te zbog toga se individualno procenjuje stanje bolesnika

Economic evaluation of different screening alternatives for patients with clinically suspected acute deep vein thrombosis

Introduction: We examined the cost-effectiveness of the three different D-dimer measurements in the screening of DVT in models with and without calculation of pre-test probability (PTP) score. Moreover, we calculated the minimal cost in DVT detection. Material and methods: In the group of 192 patients with clinically suspected acute DVT, we examined the three different D-dimer measurements (Innovance D-dimer, Hemosil D-dimer HS and Vidas D-dimer Exclusion II) in combination with and without PTP assessment. Results: The diagnostic alternative employing Vidas D-dimer Exclusion II assay without and with PTP calculation gave lower incremental cost-effectiveness ratio (ICER) than the alternative employing Hemosil D-dimer HS assay (0.187 Euros vs. 0.998 Euros per one additional DVT positive patient selected for CUS in model without PTP assessment and 0.450 vs. 0.753 Euros per one DVT positive patient selected for CUS in model with PTP assessment). According to sensitivity analysis, the Hemosil D-dimer HS assay was the most cost effective alternative when one patient was admitted to the vascular ambulance per day. Vidas D-dimer Exclusion II assay was the most cost effective alternative when more than one patient were admitted to the vascular ambulance per day. Cost minimisation analysis indicated that selection of patients according to PTP score followed by D-dimer analysis decreases the cost of DVT diagnosis. Conclusions: ICER analysis enables laboratories to choose optimal laboratory tests according to number of patients admitted to laboratory. Results support the feasibility of using PTP scoring and D-dimer measurement before CUS examination in DVT screening

Impact of discounting in pharmacoeconomic modeling. A case study

Discounting adjusts future costs and benefits in terms of their present value. The purpose of this study was to present the effect of discounting on Markov model prepared for the evaluation of the different antihypertensive treatments in Serbia. The Markov model consisting of eight states with the cycle length of six months was constructed. Comparator strategies were diuretic, beta blocker; calcium channel blocker and ACE inhibitors. All therapeutic strategies were compared with strategy no intervention". Complications of hypertension (acute myocardial infraction, angina pectoris or stroke alone or in combinations) and total mortality were observed as outcomes. Time horizon of the study was lifetime of the patient or 100 years old, due to assumption that 99% of the cohort would die at that age. Analyses were performed from the third-party payer perspective. Annual discount rate of 5% was applied at all future costs and effects. Undiscounted results showed that patients who started treatment with a beta blocker had the highest life expectancy (49.00 QALY) and being the most cost-effective strategy (ICER = (sic)46.63/QALY compared to no intervention). In the case of discounting the highest gain in the QALY had patients who were on beta blocker, 23.7 QALY. After the discounting cost-effective strategies were ACE inhibitor (ICER = (sic)253.08/QALY compared to no intervention) and diuretic (ICER = (sic)262.54/QALY compared to no intervention). The results of the study showed that the discounting could change the choice of cost-effective therapeutic strategy Biotechnol. & Biotechnol. Eq. 2011, 25(3), 2555-255

Indirect reference intervals for haematological parameters in capillary blood of pre-school children

Introduction: Indirect estimation of reference intervals (RIs) is straightforward and inexpensive procedure for determination of intra-laboratory RIs. We applied the indirect approach to assess RIs for haematological parameters in capillary blood of pre-school children, using results stored in our laboratory database. Materials and methods: We extracted data from laboratory information system, for the results obtained by automatic haematology analyser in capillary blood of 154 boys and 146 girls during pre-school medical examination. Data distribution was tested, and logarithmic transformation was applied if needed. Reference intervals were calculated by the nonparametric percentile method. Results: Reference intervals were calculated for: RBC count (4.2-5.4 x1012/L), haemoglobin (114-146 g/L), MCH (25.0-29.4 pg), MCHC (321-368 g/L), RDW-SD (36.1-43.5 fL), WBC count (4.5-12.3 x109/L), neutrophils count (1.7-6.9 x109/L) and percentage (29.0-69.0%), lymphocytes count (1.6-4.4 x109/L) and percentage (21.9-60.7%), PLT (165-459 x109/L), MPV (8.1-11.4 fL) and PDW (9.2-14.4%). Gender specific RIs were calculated for mo-nocytes count (male (M): 0.2-1.6 x109/L; female (F): 0.1-1.4 x109/L) and percentage (M: 2.5-18.3%; F: 1.8-16.7%), haematocrit (M: 0.34-0.42 L/L; F: 0.34-0.43 L/L), MCV (M: 73.4-84.6 fL; F: 75.5-84.2 fL) and RDW (M: 12.1-14.3%; F: 11.7-13.9%), due to observed gender differences in these parameters (P = 0.031, 0.028, 0.020, 0.012 and 0.001; respectively). Estimated RIs markedly varied from the literature based RIs that are used in the labora-tory. Conclusions: Indirect method employed in this study enables straightforward assessment of RIs in pre-school children. Herein derived RIs differed from the literature-based ones, indicating the need for intra-laboratory determination of RIs for specific populations and sample types

Obstructive sleep apnea and cardiometabolic risk

Opstruktivna apneja u snu (OSA) je hronično progresivno oboljenje sa visokom prevalencom u populaciji koje, bez pravovremene dijagnoze i terapije, može dovesti do značajnih posledica po kvalitet života pacijenata. OSA je čest komorbiditet kod pacijenata sa metaboličkim sindromom (MS) i kardiovaskularnim bolestima (KVB) i predstavlja važan faktor rizika za nastanak ovih oboljenja, a prisustvo nelečenog, teškog oblika OSA povezano je sa porastom ukupnog i mortaliteta usled koronarnih događaja. Brojne studije su ukazale na vezu između MS i OSA, te je ovaj fenomen opisan kao poseban poremećaj - sindrom Z. Istraživanje uzročno-posledične veze između OSA i KVB je u velikoj meri otežano kompleksnom prirodom samog oboljenja. Smatra se da je kardiometabolički rizik u OSA udružen sa arterijskom hipertenzijom, insulinskom rezistencijom, endotelnom disfunkcijom, inflamacijom, dislipidemijom i oksidativnim stresom. Lečenje OSA se danas najefikasnije sprovodi neinvazivnom ventilacijom, pomoću uređaja koji obezbeđuje pozitivan pritisak u gornjim disajnim putevima (eng. continuous positive airway pressure, CPAP) i na taj način sprečava pojavu apneja tokom spavanja. Rezultati kliničkih studija su pokazali da CPAP terapija značajno poboljšava hemodinamske parametre, reguliše hipertenziju, povećava osetljivost na insulin i koriguje dislipidemiju. Buduća istraživanja bi trebalo da rasvetle da li je apneja u snu faktor rizika za KVB per se ili je ta veza posledica šireg patofiziološkog procesa, čiji je deo i OSA.Obstructive sleep apnea (OSA) is a chronic, progressive disorder with a high prevalence in the population. Without timely diagnosis and therapy OSA can significantly affect the quality of life of the patients. OSA is a common co-morbidity in patients with metabolic syndrome (MS) and cardiovascular disease (CVD) and is an important risk factor for their development. The presence of untreated, severe OSA is associated with an increase in total and cardiovascular mortality. Numerous studies have pointed to the relationship between MS and OSA, and this phenomenon was described as syndrome Z. Investigation of the causal relationship between OSA and CVD has been greatly confounded by the complex nature of the disease itself. Cardiometabolic risk in OSA is associated with arterial hypertension, insulin resistance, endothelial dysfunction, inflammation, dyslipidemia, and oxidative stress. The treatment of OSA is now most effectively performed by continuous positive airway pressure (CPAP), a type of non-invasive ventilation which prevents the onset of sleep apnea. The results of clinical studies have shown that CPAP therapy significantly improves haemodynamic parameters, regulates hypertension, increases insulin sensitivity, and corrects dyslipidemia. Future investigations should clarify whether sleep apnea is a risk factor for CVD per se or is a consequence of a broader pathophysiological process, of which OSA is part

The cost-effectiveness of hypertension pharmacotherapy in Serbia: A Markov model

To date there is no Markov model to evaluate the cost-effectiveness of antihypertensive pharmacotherapies at national level in developing countries. The aim of our study was to evaluate different antihypertensives and determine their cost-effectiveness as mono therapy treatment in primary care in Serbia. We developed a Markov model to estimate quality-adjusted life years (QALY), lifetime costs and incremental cost-effectiveness of different antihypertensive medicines used in the clinical practice in Serbia (diuretic, beta blocker Ca channel blocker and ACE inhibitors) to strategy "no intervention". Cohort of 55-year-old patients with hypertension (systolic and diastolic blood pressure >= 140 and 90 mmHg), without cardiovascular complications was run through the model. Acute myocardial infarction, angina pectoris, heart failure, stroke, and total mortality were observed as outcomes. The time horizon was over a lifetime, and the perspective was that of a third-party payer Annual discount rate of 5% was applied to all future costs and effects. The results showed small differences in QALY in strategies ACE inhibitor, beta blockers, and diuretic. The incremental cost-effectiveness ratio (ICER) for diuretic, compared to no intervention, was (sic)74.27/QALY. The ICER for beta blocker compared to diuretic was (sic)75.58/QALY. ACE inhibitor was extended dominated by diuretic and beta blocker, while Ca channel blocker had higher costs and less effectiveness compared to all previous strategies. The results of the probabilistic sensitivity analysis showed that application of antihypertensive therapy is cost-effective even at small values of willingness to pay. It could be concluded that for individuals aged 55 the diuretics are the most cost-effective strategy to start monotherapy of hypertension

Obesity and dyslipidemia

Obesity, a pandemic of the modern world, is intimately associated with dyslipidemia, which is mainly driven by the effects of insulin resistance and pro-inflammatory adipokines. However, recent evidence suggests that obesity-induced dyslipidemia is not a unique pathophysiological entity, but rather has distinct characteristics depending on many individual factors. In line with that, in a subgroup of metabolically healthy obese (MHO) individuals, dyslipidemia is less prominent or even absent. In this review, we will address the main characteristics of dyslipidemia and mechanisms that induce its development in obesity. The fields, which should be further investigated to expand our knowledge on obesity-related dyslipidemia and potentially yield new strategies for prevention and management of cardiometabolic risk, will be highlighted. Also, we will discuss recent findings on novel lipid biomarkers in obesity, in particular proprotein convertase subtilisin/kexin type 9 (PCSK9), as the key molecule that regulates metabolism of low-density lipoproteins (LDL), and sphingosine-1-phosphate (S1P), as one of the most important mediators of high-density lipoprotein (HDL) partides function. Special attention will be given to microRNAs and their potential use as biomarkers of obesity-associated dyslipidemia

Dislipidemija u dijabetes melitusu tip 2

Type 2 diabetes mellitus is a chronic high-prevalence metabolic disease, which is characterized by hyperglycaemia, but also with lipid and protein metabolism disorders. Patients with type 2 diabetes have a high risk for cardiovascular disease (CVD) development and dyslipidemia is considered as a key marker of this increased risk. Hypertriglyceridemia, reduced high density lipoprotein cholesterol (HDL-c) concentrations, and a shift in low-density lipoprotein particles (LDL) distribution toward the small, triglycerides-rich particles, are the most important changes in the lipid profile in diabetes.Type 2 diabetes is a metabolic disorder associated with low grade inflammation and oxidative stress, so in this condition high density lipoprotein particles (HDL) also undergo structural and functional changes and, as a consequence, lose their atheroprotective role. Dyslipidemia treatment in type 2 diabetes patients younger than 40 and without any other risk factor for CVD development starts with changes in a lifestyle, but in patients older than 40 years, first line medications are statins.Glycemic and lipid control in type 2 diabetes patients significantly reduces CVD risk.Dijabetes melitus tip 2 je hronično oboljenje sa visokom prevalencom, koje se karakteriše hiperglikemijom, ali i poremećajima u metabolizmu lipida i proteina. Pacijenti sa tipom 2 dijabetesa imaju visok rizik za razvoj kardiovaskularnih bolesti (KVB) i upravo se dislipidemija smatra ključnim uzročnikom ovog povećanog rizika. Hipertrigliceridemija, snižena koncentracija holesterola u lipoproteinskim česticama visoke gustine (HDL-h) i promena u raspodeli lipoproteinskih čestica niske gustine (LDL) u smeru većeg udela malih čestica, bogatih trigliceridima, predstavljaju najvažnije promene lipidnog profila koje se odnose na dislipidemiju u dijabetesu. Kako je dijabetes stanje kontinuirane blage inflamacije niskog stepena i stalne produkcije slobodnih radikala, HDL lipoproteinske čestice takođe podležu strukturnim i funkcionalnim promenama, usled čega gube svoje ateroprotektivne osobine. Terapija dislipidemije kod pacijenata mlađih od 40 godina bez prisutnih drugih faktora rizika za razvoj KVB počinje promenom životnog stila, a kod pacijenata starijih od 40 godina lekovi izbora u terapiji su statini. Glikemijska i lipidna kontrola kod pacijenata sa tipom 2 dijabetesa značajno umanjuje rizik od nastanka KVB

Circulating resistin protein and mRNA concentrations and clinical severity of coronary artery disease

Introduction: Previous studies have implicated a strong link between circulating plasma resistin and coronary artery disease (CAD). The aim of this study was to evaluate the differences in peripheral blood mononuclear cells (PBMC) resistin mRNA and its plasma protein concentrations between the patients with CAD of different clinical severity. Material and methods: This study included 33 healthy subjects as the control group (CG) and 77 patients requiring coronary angiography. Of the latter 30 was CAD negative whereas 47 were CAD positive [18 with stable angina pectoris (SAP) and 29 with acute coronary syndrome (ACS)]. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by real-time PCR. Results: Resistin protein was significantly higher in the ACS group compared to the CG (P = 0.001) and the CAD negative group (P = 0.018). Resistin mRNA expression did not vary across the study groups, despite the positive correlation seen with plasma resistin (rho = 0.305, P = 0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (rho = -0.404, P lt 0.001 and rho = -0.257, P = 0.032, respectively). Furthermore, the highest plasma resistin tertile showed the lowest HDL-C (P = 0.006). Plasma resistin was positively associated with serum creatinine (rho = 0.353, P = 0.002). Conclusion: Significant increase of plasma resistin in patients with ACS compared to CG and CAD negative patients was observed. Despite no change in PBMC resistin mRNA in different disease conditions a positive association between resistin mRNA and resistin plasma protein was evident. Both plasma resistin and PBMC resistin mRNA were negatively associated with plasma HDL-C, and plasma resistin positively with serum creatinine