Abbott Diagnostics Research Articles

High-Sensitivity Troponin I and Rhythm Outcome after Electrical Cardioversion for Persistent Atrial Fibrillation

Objectives: We hypothesised that high-sensitivity troponin I (hs-TnI) might predict long-term rhythm outcome after cardioversion for persistent atrial fibrillation (AF), and that maintenance of sinus rhythm and/or treatment with the angiotensin II type 1 receptor blocker candesartan would reduce hs-TnI levels. Methods: In a double-blind, placebo-controlled study, 171 patients referred for electrical cardioversion for AF were randomised to receive candesartan or placebo for 3-6 weeks before cardioversion and for 6 months after electrical cardioversion. Blood samples for analysis of hs-TnI (Abbott Diagnostics) were available in 129 patients at baseline and in 60 successfully cardioverted patients at study end. Results: Hs-TnI was detectable in all subjects, with a median value of 5.3 ng/l (25th percentile 3.7, 75th percentile 7.2). hs-TnI at baseline was not predictive of rhythm outcome 6 months after electrical cardioversion for persistent AF. Treatment with candesartan did not influence the levels of hs-TnI. hs-TnI was unchanged from baseline to study end in patients who maintained sinus rhythm [4.9 (3.7, 7.0) and 5.0 (4.0, 6.4) ng/l, respectively; p = 0.699). Conclusions: hs-TnI did not predict AF recurrence after cardioversion. hs-TnI levels were unchanged in patients maintaining sinus rhythm for 6 months after electrical cardioversion. hs-TnI levels were not influenced by treatment with candesartan.

Continuous renal replacement therapy in critically ill patients does not affect urinary neutrophil gelatinase-associated lipocalin levels

In the present study, we assessed urinary neutrophil gelatinase-associated lipocalin (uNGAL) during 24-hour continuous renal replacement therapy (CRRT) in critically ill patients. The study was performed in accordance with the Declaration of Helsinki and was approved by the Scientific Council and the Ethics Committee of Evangelismos Hospital in Athens, Greece. Informed consent was provided by family members of the patients included in the study. Eighteen critically ill patients (13 men and five women with a mean age of 69 ± 14 years) in an interdisciplinary intensive care unit underwent continuous veno-venous hemodiafiltration (CVVHD). Three had oliguria (urine output of less than 200 mL per 12 hours). Patient characteristics at enrollment are shown in Table 1. Table 1 Patient characteristics (n = 18) uNGAL was determined before CRRT onset and at 6 and 24 hours during CVVHD. uNGAL was measured by using a chemiluminescent assay with ARCHITECT technology (Abbott Diagnostics Inc., Abbott Park, IL, USA). For CVVHD, pump-driven machines - from Prisma (a brand of Gambro, Deerfield, IL, USA), Kimal (Dormagen, Germany), or Nephro-Tech (Shawnee, KS, USA) - were used with a 0.9 m2 polysulfone filter. uNGAL levels did not change, whereas serum creatinine and serum cystatin C significantly decreased (Table 2). No correlation was found between uNGAL levels and the illness severity scores at inclusion. Table 2 Renal function biomarkers during continuous renal replacement therapy In a study by Schilder and colleagues [1] in a previous issue of Critical Care, plasma NGAL (pNGAL) in critically ill patients was similarly not affected by RRT. No net removal of pNGAL was established, although absorption by the filter with concomitant production could not be definitively excluded. Besides an insufficient clearance through the filter, other causes could be implicated for the remaining NGAL levels. Whereas pNGAL can come from an extra-renal source (as in sepsis [2]), uNGAL may derive mostly from local synthesis in the kidney [3]. NGAL that has been synthesized in the kidney and can be detected in urine may not efficiently enter the systemic circulation to be cleared by the filter. Another possible explanation concerns the significance of NGAL function. It has been shown that NGAL has some physiological functions such as carrying out antimicrobial activity and a protective role in the kidney [4,5]. Substituting the function of the kidney with the artificial filter does not mean that the reasons leading to the increased levels of NGAL are eliminated (for example, sepsis or, specifically for the uNGAL, the kidney damage). So regardless of the possibility that the filter cleanses the factor, the production of NGAL might be purposely preserved to carry out its physiological role.

HBV carriage in children born from HIV-seropositive mothers in Senegal: The need of birth-dose HBV vaccination.

Hepatitis B is a major public health problem in Senegal, a country with high prevalence and a transmission occurring mainly during infancy. Only, one 6-8 weeks vaccination campaign was initiated in 2005 and it was part of the expanded program of immunization. The aim of this study was to determine the prevalence of HBsAg in children born from HIV-seropositive mothers by using dried blood specimens. Specimens were collected between July 2007 and November 2012 from children aged 2-48 weeks in Dakar and decentralized sites working on HIV mother-to-child transmission prevention. HBsAg detection was performed using Architect HBsAg Qualitative II kit (Abbott Diagnostics, Ireland) and for all reactive samples confirmation was done using Architect HBsAg Qualitative II Confirmatory kit (Abbott Diagnostics, Ireland). Nine hundred thirty samples were collected throughout the country with 66% out of Dakar, the capital city. The median age was 20 weeks and 88% of children were less than 1 year of age with a sex ratio of 1.27 in favor of boys. HBsAg was detected in 28 cases giving a global prevalence of 3%. According to age, HBsAg prevalences were 5.1% for children less than 6 weeks, 4.1% and 4.6%, respectively, for those aged 12-18 weeks and 18-24 weeks of age. The HIV prevalence was 2.6% with no HIV/HBV co-infection. This study showed a high rate of HBV infection in children under 24 months, highlighting the need to promote birth-dose HBV vaccination as recommended by WHO.

Evaluation of analytical performance and comparison of clinical results of the new generation method AccuTnI + 3 for the measurement of cardiac troponin I using both patients and quality control plasma samples

The study aims are to evaluate the analytical performance and the clinical results of the chemiluminescent Access AccuTnI+3 immunoassay for the determination of cardiac troponin I (cTnI) with DxI 800 and Access2 platforms and to compare the clinical results obtained with this method with those of three cTnI immunoassays, recently introduced in the European market. The limits of blank (LoB), detection (LoD), and quantitation (LoQ) at 20% CV and 10% CV were 4.5ng/L and 10.9ng/L, 17.1 and 30.4ng/L, respectively. The results of STAT Architect high Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI third generation (Tosoh Bioscience), and Access AccuTnI+3 (Beckman Coulter Diagnostics) showed very close correlations (R ranging from 0.901 to 0.994) in 122 samples of patients admitted to the emergency department. However, on average there was a difference up to 2.4-fold between the method measuring the highest (ADVIA method) and lowest cTnI values (AccuTnI+3 method). The consensus mean values between methods ranged from 6.2% to 29.6% in 18 quality control samples distributed in an external quality control study (cTnI concentrations ranging from 29.3ng/L to 1557.5ng/L). In conclusion, the results of our analytical evaluation concerning the AccuTnI+3 method, using the DxI platform, are well in agreement with those suggested by the manufacturer as well as those reported by some recent studies using the Access2 platform. Our results confirm that the AccuTnI+3 method for the Access2 and DxI 800 platforms is a clinically usable method for cTnI measurement.

009.3 Relibale genotypic tropism tests for the major hiv-1 subtypes

Introduction Human immunodeficiency virus (HIV) infects immune system cells by binding cell-surface CD4 and one of two coreceptors, CCR5 or CXCR4. Maraviroc (MVC) is an anti-HIV drug that binds to CCR5 and blocks HIV entry. Because MVC is ineffective against CXCR4-using viruses, it is only prescribed to patients shown to exclusively harbour CCR5-using viruses. The major obstacles to MVC being more widely used in anti-HIV therapies are (i) traditional pre-treatment prognostic “tropism tests” to determine CCR5- or CXCR4-usage are expensive and time consuming, and (ii) cheaper and rapid genotypic tropism tests have been developed only for subtype B viruses, which account for only 10% of infections worldwide. We developed PhenoSeq, a suite of reliable genotypic tropism tests for the major HIV subtypes; A, B, C, D and circulating recombinant forms of AE (CRF01_AE) and AG (CRF02_AG), which together account for 95% of infections worldwide. Methods Development of genotypic tropism tests was informed by analysis of all previously published HIV genetic sequences with corresponding coreceptor usage and subtype data (n = 2257; 630 CXCR4-using and 1637 CCR5-using), to elucidate statistically significant mutations that distinguish CXCR4- from CCR5-using viruses. The accuracy of PhenoSeq was validated against independent HIV sequences from patients previously enrolled in phase III MVC clinical trials (A4001064 and MERIT), relative to phenotypic tropism tests results. Results PhenoSeq genotypic algorithms exhibited more favourable sensitivity and specificity profiles for establishing CCR5- or CXCR4-usage of HIV subtypes A, B, C, D, CRF01_AE and CRF02_AG than alternative algorithms, including in-use algorithms geno2pheno and WebPSSM (two tailed t-test, p ≤ 0.05 considered significant). Conclusion As the only platform of algorithms that reliably infer tropism of all major global HIV subtypes, PhenoSeq may inform the use of MVC and future CCR5 blocking drugs, in particular for regions burdened most by the HIV pandemic, where non-B HIV predominates. Disclosure of interest statement JFD and FD are employees of ViiV Healthcare. PRG is a former member of the ViiV Australia scientific advisory board and has received honoraria. KC and PRG have received funding from ViiV Healthcare Australia for conference travel. KC and PRG presently receive research funding from ViiV Healthcare to further develop PhenoSeq algorithms. PRH is supported by CIHR/GSK Research Chair in Clinical Virology and has consulted and/or received grant funding from a variety pharmaceutical diagnostic companies and has received grants from, served as an ad hoc advisor to, or spoke at various events sponsored by: Pfizer, Glaxo-Smith Kline, Abbott, Merck, Selah, Tobira, Virco and Quest Diagnostics.

P07.08 Designing of molecular beacon based polymerase chain reaction method as an unconventional low cost diagnostic assay for sexually transmitted diseases

Introduction About 300 million new infections of gonorrhoea, Chlamydia, or trichomoniasis occur each year. Young adults, population with health inequities and people in resource poor settings bear the significant proportion of sexually transmitted infections (STI). Therefore, rapid, inexpensive and acceptable tests are needed to address STIs in developing countries. PCR based tests are recommended for diagnosis of several STIs, but such tests require sophisticated infrastructure, need to be imported and hence cannot be used in resource limited settings. Affordability can be countered by the development of in house diagnostic assays which are practical and easy to use, and produced within country to further lower the cost. Methods Endocervical swabs were collected from patients visiting gynaecology department of hospitals in Delhi. In-house PCR based assay was developed for C. trachomatis , N. gonorrhoeae and T. vaginalis and modified to visual assay using molecular beacon for end-point detection. Results The molecular beacon based PCR assay was developed for C. trachomatis , N. gonorrhoeae and T. vaginalis and evaluated against different commercial kits viz; Roche AMPLICOR NG/CT kit and qPCR kit of Abbott and fast-track diagnostics. Specificity of molecular beacon was confirmed by competition experiments. Diagnostic tests were more than 95% specific and 99.0% sensitive for all the three pathogens and negative and positive predicted values were around 98.5% and 97.5%, respectively at 95% CI for these three pathogens. We also observed that dry swab samples gave concordant results with that of wet swabs. Assay reagents were stable for more than 6 months at room temperature. We also report, high rates of co-infection for C. trachomatis + N. gonorrhoeae , C. trachomatis + T. vaginalis , N. gonorrhoeae + T. vaginalis amongst women patients in India. Conclusions Development of a rapid, sensitive, specific and PCR based visual diagnostic assay, suitable for developing countries will provide a better disease management.

Performance characteristics of six automated 25-hydroxyvitamin D assays: Mind your 3s and 2s

BackgroundMeasurement of 25(OH)D has evolved rapidly, with an increased number of high-throughput automated immunoassays becoming available in recent years. The aim of this study was to fully evaluate six commercially available automated 25(OH)D immunoassays, including 2 newly available (Beckman Coulter) and one recalibrated (Siemens) assay. Comparisons were made to specifically identify the effect of the absence or presence of 25(OH)D2 on these assays. Design and methodsAccess2 and UniCel DxI 800 (Beckman Coulter), ARCHITECT i2000SR (Abbott Diagnostics), ADVIA Centaur XP (Siemens), Liaison XL (DiaSorin) and MODULAR E170 (Roche Diagnostics) assays were assessed for accuracy, imprecision, interference, limit of blank, and linearity. All were compared to an in-house LC-MS/MS method (traceable to NIST SRM 972) using Passing–Bablok regression and Bland–Altman bias plots. Method comparisons used residual serum samples with both endogenous 25(OH)D2 and 25(OH)D3 (n=50) or 25(OH)D3 only (n=86). Comparisons with all 136 samples were intended to simulate real-world laboratory testing. ResultsThe majority of assays under-recovered 25(OH)D in comparison to LC-MS/MS, with three of six immunoassays affected by the presence of 25(OH)D2. Imprecision was greatest at 25(OH)D concentrations near the decision limits used to assess deficiency. Only two of six immunoassays would meet the recommended bias criteria of <5%. ConclusionsAlthough standardization efforts continue, these differences in performance remain a concern. Clinicians should be aware when comparing results among assays and using them to determine adequacy of 25(OH)D stores in various patient populations.

Use of rapid tests for perinatal HIV infection in resource-limited settings

Early testing strategies such as human immunodeficiency virus (HIV) DNA and RNA assays have become popular, cheaper and reliable, however the measures of success of Prevention of Mother-to-Child Transmission (PMTCT) programs in predominantly breastfeeding populations often depend on long term follow-up and HIV testing of children. Diagnosis in PMTCT programs in resource-poor countries therefore remains dependent on serological assays. The use of rapid HIV tests in perinatal HIV diagnosis, as recommended by the WHO, was based on the sensitivity and specificity of the enzyme-linked immuno-assay (ELISA) in children and not guided by an independent evaluation of rapid tests. For the purpose of ensuring a reliable diagnosis of perinatal HIV infection in predominantly breastfed children and largely resource-poor settings in Sub-Saharan Africa, we evaluated a HIV rapid test against the ELISA in serial plasma samples. We tested stored plasma samples for HIV antibodies, using a rapid test (Abbott Determine HIV1/2, Abbott Diagnostics, Wiesbaden, Germany) from a cohort of children between 12 and 18 months of age, enrolled in the PETRA (perinatal transmission) study at the Durban site, and compared to pre-determined real-time ELISA results. Using the ELISA results at 18 months as gold standard, the sensitivity of the ELISA at 12 and 15 months was 100% (95% CI 79–100), and specificity improved from 90.4% (95% CI 86–94) at 12 months to 99.5% (95% CI 97–100) at 15 months. The sensitivity of the rapid HIV test when compared to ELISA results at 18 months was 100% (95% CI 46–98) at 12 and 15 months, and the specificity was 89% (95% CI 80–94) and 99% (95% CI 92–100) at 12 and 15 months respectively. The negative predictive values for the rapid test at 12, 15 and 18 months were 100% (95% CI 94–100). Using the 18 month ELISA as the gold standard, the rapid test at 12 and 15 months demonstrated similar specificities to the corresponding ELISA tests. We concluded that the sensitivity and specificity of the rapid HIV test remained optimal (100%) for the diagnosis of HIV infection in children at 18 months. The earlier use of a rapid test at 15 months correctly excluded HIV infection in 99% of the children. Any earlier use of rapid tests without subsequent confirmation could result in an estimated 10% or more children misdiagnosed as HIV infected.

Usefulness of measuring urine neutrophil gelatinase-associated lipocalin (NGAL) and calculating NGAL to creatinine ratio as early predictors of kidney dysfunction in patients with type 2 diabetes

The aim of the study was to assess the usefulness of measuring concentrations of NGAL in first morning urine and calculating NGAL/creatinine ratio (uNGAL/uCr) among patients with early stage diabetic kidney disease (DKD) in course of type 2 diabetes (DMt2) and to assess the correlations between these markers and routine biochemical and blood count parameters. Material and Methods: The studied group consisted of 55 patients with DKD in course of DMt2 and 22 controls without diabetes; the study included patients with estimated glomerular filtration rate &gt;60ml/min/1,73m2 without overt proteinuria. NGAL was measured with chemiluminescence microparticle immunoassay (CMIA) with ARCHITECT analyzer (Abbott Diagnostics). Results: Studied group had higher values of uNGAL/uCr than controls (median 21.3 vs. 12.2 μg/g; p=0.014). Among studied group, women presented higher uNGAL/uCr comparing to men (38.6 vs. 11.7 μg/g; p=0.001). Both in patients and controls, uNGAL concentrations were positively correlated with urine creatinine. In studied group, we observed positive correlations of uNGAL and uNGAL/uCr with urine albumin and albumin/creatinine retaio (UACR); in control group, only the correlation between uNGAL and albuminuria was statistically significant. Additionally, in studied group, positive correlations were observed between uNGAL and uNGAL/uCr and serum cholesterol, LDL-cholesterol and triglycerides concentrations. In multiple regression, albuminuria and LDL-cholesterol significantly predicted uNGAL and UACR and triglycerides significantly predicted uNGAL/uCr in the studied group. Conclusions: The obtained results confirm the usefulness of measuring uNGAL and calculating uNGAL/uCr as early markers of kidney dysfunction in patients with DMt2. The results of the study should be confirmed in larger group of patients.

Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL)

Acute pyelonephritis is a severe disease which is sometimes difficult to recognize based on clinical symptoms and routinely available diagnostic tests, especially in young children. The aim of this study was to assess the diagnostic value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a biomarker of acute pyelonephritis. In this case-control study we analyzed 134 children (median age 2.5 years) who were admitted to the Pediatric Clinic of University Hospital Centre Osijek, Croatia. Eighty of them had acute pyelonephritis, while 54 children had febrile state of different etiology including cystitis and they represented the control group. uNGAL, white blood cells, C-reactive protein, urinanalysis, urine culture, kidney ultrasound and a dimercaptosuccinic acid scintigraphic scan were done for each child. uNGAL was measured using chemiluminiscent microparticle immunoassay on ARHITECT i1000SR (Abbott Diagnostics, IL, USA). uNGAL values were significantly higher in children with acute pyelonephritis compared to the control groups (113.6 ng/mL vs. 10.2 ng/mL, p<0.001). A receiver operating characteristic curve comparison was done for tested parameters and encouraging results were obtained for uNGAL (AUC=0.952). A cut-off value of 29.4 ng/mL had 92.5% sensitivity and 90.7% specificity. We showed that uNGAL can also serve in differentiating acute pyelonephritis from cystitis (cut-off 38.5 ng/mL), and for differentiation of cystitis from febrile states with etiology other than urinary tract infection (UTI) (cut-off 20.4 ng/mL). uNGAL can be a useful diagnostic biomarker in acute pyelonephritis in children, but also in differentiating cystitis from febrile states other than UTI.

Seroprevalence of Toxoplasma, Rubella, and Cytomegalovirus among pregnant women in Van.

Objective:To determine the seroprevalence of anti-Toxoplasma, anti-Rubella, and anti-Cytomegalovirus (CMV) antibodies among pregnant women receiving prenatal care at Van Training and Research Hospital.Materials and Methods:In developing countries, various infectious agents encountered in the gestational period are important because they influence both maternal and fetal health. Among these, Toxoplasma gondii, Rubella and CMV are quite prevalent. In the present study, anti-Toxoplasma, anti-Rubella and anti-CMV antibodies were analyzed in the serum samples obtained from women receiving prenatal care at Van Training and Research Hospital between June 2012 and July 2013, and positive serum samples were retrospectively evaluated. Anti-Toxoplasma, anti-Rubella and anti-CMV antibodies were analyzed using ELISA with Cobas 4000 e411 (Roche, Germany) and Architect i2000SR (Abbott Diagnostics, Germany) analyzers.Results:Over the course of the study period, the results of a total of 9809 patients were investigated in terms of anti-Toxoplasma, anti-Rubella, and anti-CMV antibodies. Anti-Toxoplasma, anti-Rubella, and anti-CMV IgM and IgG antibody positivity rates were 1.1%, 0.5% and 2.6%, and 37.6%, 86.5% and 100%, respectively.Conclusion:Anti-Toxoplasma IgG antibody positivity rates determined in the present study were lower as compared with the results of the other studies reported from Turkey. However, CMV IgM and IgG antibody positivity rates were be higher as compared with those reported in the literature.

New ARCHITECT plasma pro-gastrin-releasing peptide assay and lung cancer: Implications for diagnosis, follow-up, and prognosis.

7570 Background: Pro-gastrin-releasing peptide (proGRP) is a precursor of the neuropeptide hormone produced by small cell lung cancer (SCLC) and considered as a potential serum marker for this disease. However, proGRP was shown to be more stable in plasma compared to serum. In this prospective study we evaluated the new proGRP assay in plasma format. Methods: Plasma proGRP was determined using the ARCHITECT i System (Abbott Diagnostics, Wiesbaden, Germany) in four cohorts: healthy individuals (n = 100) and patients with benign lung diseases (BLD, n = 102), non-small cell lung carcinoma (NSCLC, n = 241), and SCLC (n = 90). Results: The median (95 percentile) concentrations of plasma proGRP in healthy, BLD, NSCLC and SCLC were: 38 (64), 39 (64), 40 (121) and 680 (17695) pg/ml, respectively. There was no association with age, gender or smoking. The proGRP assay proved to be effective in distinguishing SCLC from NSCLC with area under the curve 0.941, 95%CI 0.906-0.975, 84.4% sensitivity, 95% specificity, at a...

Impact of atrial fibrillation on levels of high-sensitivity troponin I in a 75-year-old population

Purpose. Atrial fibrillation (AF) has been associated with elevated levels of cardiac troponins; however, it is not clear if this association is independent of underlying cardiovascular disease. The aim of this study was to investigate the impact of AF on cardiac troponin I levels in a 75-year-old cohort from the general population, using a recently introduced, highly sensitive assay. Methods. All 75-year-old citizens in Asker and Baerum counties were invited to participate in a prevalence study of AF. High-sensitive troponin I (hs-TnI) levels were measured (Abbott Diagnostics) in serum samples collected from 62 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. Results. Hs-TnI was detectable in all subjects (median 7.3 ng/L [range 3.0–88.7]). Patients with AF had higher levels than subjects in sinus rhythm (8.3 ng/L [3.7–88.7] vs. 6.8 ng/L [3.0–77.5]; p = 0.011). Male gender (p = 0.002), hypertension (p = 0.001), coronary heart disease (p < 0.001), heart failure (p < 0.001), prior stroke or transient ischemic attack (p = 0.013) and serum creatinine (p < 0.001) were all associated with higher levels of hs-TnI in univariate analysis. Heart failure and coronary heart disease remained significantly associated with hs-TnI in multivariate analysis, whereas the relation between AF and hs-TnI was no longer statistically significant. Conclusion. All subjects had detectable levels of hs-TnI. AF patients had higher hs-TnI levels than subjects in sinus rhythm; however, this difference was not statistically significant after adjustment for heart failure and coronary heart disease.

Clinical significance of serum HBsAg levels, HBsAg/HBV DNA ratio, and association with liver inflammation activity in HBeAg-positive chronic hepatitis B

To study the clinical significance of hepatitis B surface antigen (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver inflammation in HBeAg-positive chronic hepatitis B (CHB). One hundred and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive status were enrolled in the study.Quantitative measurements were made for HBsAg levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by real-time fluorescence quantitative PCR.Levels of liver function markers were measured by standard methods.Liver biopsy specimens were obtained from all patients and used to score the histology (liver inflammation) activity index (HAI) and grade (G) the extent of necroinflammation.Statistical correlation analysis was performed to determine the association of HBsAg titre or HBsAg/HBV DNA ratio with the various parameters of liver injury. HBsAg titre and HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than 0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was found between HBsAg titre and HBV DNA load, and a significant negative correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001) and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P less than 0.0001).Patients with G less than 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G more than or equal to 2 as the positive index provided the following area under the curve (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level, 0.713.When the random chance AUC was 0.5, all levels of AUC were statistically significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio (specificity =81.33%) was more specific than ALT level (specificity =81.33%).Youden's index for comprehensive evaluation using ALT was higher than those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%. HBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the index for judging the degree of liver inflammation in HBeAg-positive CHB patients.Higher sensitivity and specificity are attained when HBsAg and ALT are used in series or parallel.

Evaluation of a next generation direct whole blood enzymatic assay for hemoglobin A1c on the ARCHITECT c8000 chemistry system.

The utility of HbA1c for the diagnosis of type 2 diabetes requires an accurate, precise and robust test measurement system. Currently, immunoassay and HPLC are the most popular methods for HbA1c quantification, noting however the limitations associated with some platforms, such as imprecision or interference from common hemoglobin variants. Abbott Diagnostics has introduced a fully automated direct enzymatic method for the quantification of HbA1c from whole blood on the ARCHITECT chemistry system. Here we completed a method evaluation of the ARCHITECT HbA1c enzymatic assay for imprecision, accuracy, method comparison, interference from hemoglobin variants and specimen stability. This was completed at three independent clinical laboratories in North America and Europe. The total imprecision ranged from 0.5% to 2.2% CV with low and high level control materials. Around the diagnostic cut-off of 48 mmol/mol, the total imprecision was 0.6% CV. Mean bias using reference samples from IFCC and CAP ranged from -1.1 to 1.0 mmol/mol. The enzymatic assay also showed excellent agreement with HPLC methods, with slopes of 1.01 and correlation coefficients ranging from 0.984 to 0.996 compared to Menarini Adams HA-8160, Bio-Rad Variant II and Variant II Turbo instruments. Finally, no significant effect was observed for erythrocyte sedimentation or interference from common hemoglobin variants in patient samples containing heterozygous HbS, HbC, HbD, HbE, and up to 10% HbF. The ARCHITECT enzymatic assay for HbA1c is a robust and fully automated method that meets the performance requirements to support the diagnosis of type 2 diabetes.

The evaluation of B-type Natriuretic Peptide and Troponin I in acute myocardial infarction and unstable angina

Introduction: The diagnostic utility of B-type natriuretic peptide (BNP) has prompted interest in its use as an aid in the detection of early heart failure and assessment of diseases. The first objective of this study was measurement of BNP and troponin I (TnI) blood levels in patients with acute myocardial infarction (AMI) and unstable angina. The second objective of this study was to find a correlation between TnI and BNP in blood.Methods: The concentrations of BNP and TnI in 150 blood levels were determined using CMIA (chemiluminescent microparticle immunoassay) Architect and 2000 (Abbott diagnostics). The retrospective study included 100 patients who were hospitalized at the Department of Internal Medicine of the University Clinical Center Sarajevo and 50 healthy control. The reference blood range of BNP is 0-100 pg/mL and TnI is 0.00-0.4 ng/mL.Results: In the patients with AMI the mean value of BNP is 764.48 ± 639.52 pg/mL and TnI is 2.50 ± 2.28ng/mL. The patients with unstable angina have BNP 287.18 ± 593.20 pg/mL and TnI 0.10 ± 0.23 ng/mL. Our studies have shown that the correlation between BNP and TnI was statistically significant for p&lt; 0.05 using Student t test with correlation coefficient r = 0.36. Conclusions: BNP and TnI levels can help to identify the patients with a high risk for cardiovascular diseases.

Quantification of hepatitis B surface antigen with the novel DiaSorin LIAISON XL Murex HBsAg Quant: Correlation with the ARCHITECT quantitative assays

BackgroundRecent technologic innovations allow for quantitative assessment of hepatitis B surface antigen (HBsAg) levels in serum; this has been used to monitor the course of chronic HBV hepatitis (CHB) and predict treatment response. LIAISON-XL Murex HBsAg Quant assay (DiaSorin, Saluggia, I) is the newest immunoassay CE approved to quantify HBsAg. ObjectivesTo compare LIAISON-XL performances with ARCHITECT-QT HBsAg (Abbott Diagnostics, IL, USA), as reference test. Study designSequential serum samples (n=152) from 14 HBe-negative patients with CHB, the majority of them infected by HBV genotype D undergoing antiviral treatment, were retrospectively tested with both assays. The 2nd WHO Standard 00/588 for HBsAg was used as reference. ResultsLIAISON-XL and ARCHITECT-QT correlated by r=0.95, p<0.0001; by Bland–Altman analysis agreement of mean difference was 0.21±0.15log10IU/mL, 95% CI: −0.07 to 0.5). Performance of LIAISON-XL against the 2nd WHO Standard was r=0.998, p<0.0001 (95% CI: 0.993–0.999) with results nearer to the expected WHO values compared to ARCHITECT-QT. Median baseline HBsAg level was similar with the two methods before antiviral treatment, throughout fluctuations of HBsAg level in treatment non-responders and during the decrease of HBsAg titer in treatment responders. Correlation between HBsAg levels and HBV DNA was statistically significant for both the two immunoassays (LIAISON-XL: r=0.4988, 95% CI: 0.3452–0.6264, p<0.0001; ARCHITECT-QT: r=0.480, 95% CI: 0.3233–0.6111, p<0.0001). ConclusionsCorrelation between HBsAg measurement with LIAISON-XL and ARCHITECT-QT was high. LIAISON-XL accurately quantified HBsAg in clinical samples at baseline or during antiviral therapy; it can be applied for HBsAg quantification in clinical practice and decision making in CHB.

Weekly and 90-Minute Biological Variations in Cardiac Troponin T and Cardiac Troponin I in Hemodialysis Patients and Healthy Controls

Myocardial infarction (MI) is diagnosed by the finding of a single cardiac troponin value above the 99th percentile and a significant time-dependent change in cardiac troponin concentration. The aim of this study was to determine the 90-min and weekly biological variations, the reference change value (RCV), and the index of individuality (II) of high-sensitivity cardiac troponin T (hs-cTnT) (Roche Diagnostics) and hs-cTnI (Abbott Diagnostics) in patients receiving hemodialysis (HD) and in healthy individuals. Blood samples were collected from 19 HD patients (on an HD-free day) and 20 healthy individuals at 90-min intervals over a 6-h period (between 08:30 and 14:30) and before the midweek HD treatment for 10 weeks. The within-person variation (CVi), between-person variation, RCV, and II were calculated. During the 6-h sampling period, the concentrations of hs-cTnT (both groups) and hs-cTnI (HD patients only) decreased on average by 0.8% to 1.7% per hour, respectively. These declining trends were included in the calculation of a 90-min asymmetric RCV: -8%/+5% in HD patients (hs-cTnT), -18%/+21% in HD patients (hs-cTnI), -27%/+29% in healthy individuals (hs-cTnT), and -39%/+64% in healthy individuals (hs-cTnI). The II was low in both groups for both assays. The weekly CVi values were approximately 8% (hs-cTnT) and 15% (hs-cTnI) in both groups. When using a cardiac troponin change of 20%-50% to diagnose an MI, the false-positive rate is likely to be lower for the hs-cTnT assay than for the hs-cTnI assay. The low II suggests that use of a diagnostic cutoff value can be omitted.

Use of Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values

Many patients presenting to the emergency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS. We used the hs-cTnI assay from Abbott Diagnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CV(T)) and, knowing the assay analytical CV (CV(A)), we could calculate within-person biological variation (CV(i)), reference change values (RCVs), and absolute RCV delta cTnI concentrations. We had data sets on 283 patients. Men and women had similar CV(i) values of approximately 14%, which was similar at all concentrations <40 ng/L. The biological variation was not dependent on the time interval between sample collections (t = 1.5-17 h). The absolute delta critical reference change value was similar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value <5 ng/L, and 97% had values of <10 ng/L. With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS.

Development of NuQ nucleosome blood tests for the detection of colon cancer.

Dr Jake Micallef speaks to Hannah L Wilson, Commissioning Editor: Dr Micallef has 20 years of experience in research and development and in the management of early-stage biotechnical companies, including the manufacture of biotechnology products and the establishment of manufacturing operations. Dr Micallef gained this experience while working for WHO over a 10-year period from 1985. While working for WHO, Dr Micallef developed new diagnostic products in the areas of reproductive health and cancer. In 1990 he commenced development of a new diagnostic technology platform for WHO that was launched in 1992 and supported 13 tests. Dr Micallef also initiated and implemented in-house manufacture (previously outsourced to Abbott Diagnostics Inc., Dartford, UK) and worldwide distribution of these products for WHO. In 1990, he started a 'not-for-profit' WHO company, Immunometrics Ltd (London, UK), which marketed and distributed those diagnostic products worldwide. In 1999 Dr Micallef studied for an MBA and went on to co-found Gene Expression Technologies Ltd (London, UK) in 2001 where he successfully lead the development of the chemistry of the GeneICE technology and implemented the manufacture of GeneICE molecules. He also played a major role in business development and procured a GeneICE contract with Bayer Pharmaceuticals (Leverkusen, Germany). From 2004 to 2007, he taught 'science and enterprise' to science research workers from four universities at CASS Business School (London, UK) before joining Cronos Therapeutics (London, UK) in 2004. In 2006 Cronos was listed in the UK on AIM, becoming ValiRx. Dr Micallef continued to work as Technical Officer for ValiRx, where he in-licensed the Hypergenomics and Nucleosomics technologies and co-founded ValiBio SA (Namur, Belgium), which is now Belgian Volition SA, a subsidiary of Singapore Volition. Dr Micallef was educated at King's College London (UK; BSc, Biology and Chemistry, 1977; PhD Physical Chemistry, 1981), St Thomas' Hospital Medical School, London (UK; MSc Chemical Pathology, 1985) and Imperial College Management School (UK; MBA, 2000).