Abbott GmbH Research Articles

Evaluation and experience from routine use of chemiluminescence assays for serological screening of blood and plasma donations on the Alinity s system and the Alinity i system, two new fully-automated immunoassay systems in Poland

In Poland, independent evaluations under the auspices of the Institute of Hematology and Transfusion Medicine (IHTM) are mandated for any new device, assay, systems for screening samples from whole blood and plasma donors prior to implementation by Blood Transfusion Center (BTC). In last 5 years, two new systems were introduced to the market by Abbott GmbH, namely the Alinity s and the Alinity i. The evaluations performed for these two systems included the assessment of sensitivity, specificity and precision for each of the four mandatory serological screening markers in Poland: Hepatitis B Surface Antigen (HBsAg), Hepatitis C virus antibodies (Anti-HCV), HIV antibodies (anti-HIV) and Syphilis antibodies (anti-Treponema pallidum, anti-TP). Sensitivity was assessed by testing seroconversion panels, HBsAg international reference standard, well characterized local samples, and dilution panels. Specificity was assessed by testing routine donor samples. The results from Alinity i assays were compared to the results from Abbott ARCHITECT i2000SR and Ortho VITROS 3600 assays, while the results from Alinity s assays were compared to the results of ARCHITECT i2000SR assays. The evaluation of the Alinity s and Alinity i assays for sensitivity (100 %), specificity (99,92–100 %) and precision generated results that were as good as or better than generated by routinely used systems, were within acceptance criteria, and met all requirements for screening blood donor samples in accordance with Polish regulations. The specificity of the assays in routine use by BTCs, analyzed after approximately 150,000 donations on both systems, was comparable to the specificity observed during the evaluations at IHTM.

Applying sigma metrics to assess quality control processes in the transfusion transmissible infection screening laboratory of a blood center.

In the field of healthcare, quality and efficiency are of paramount importance to ensure the provision of safe and reliable diagnostic services. Blood screening laboratories play a critical role in detecting and preventing the spread of infectious diseases, ensuring the safety of blood transfusions, and supporting medical diagnoses. To enhance the quality of processes in such laboratories, the Six Sigma methodology has gained significant recognition for its ability to systematically identify and minimize variations, thereby improving overall efficiency and reducing errors. This retrospective study aims to explore the application of Six Sigma metrics in the context of blood screening laboratories, providing an in-depth analysis of its implementation, benefits, and challenges. The performance of three serology assays, i.e., anti-HCV, HIV Ag/Ab combo, and HBsAg, using internal quality control (IQC) daily data extracted from six Alinity i instruments (Abbott GmbH, Germany), from February to April 2023, was evaluated. Mean, standard deviation (SD), and coefficient of variation (CV%) was calculated for positive controls. Bias was calculated using peer group data. Sigma metrics were calculated using allowable total error (TEa %) based on difference between the observed mean of the positive control and the s/co cut-off of assay. The observed CV% for positive controls was ≤10%. The TEa% ranged from 66% to 79% for the analytes using the observed mean. All the assays showed Six Sigma performance (σ>6) with and without bias. The study observed that the serology assays showed very high sigma values (σ>6) and thus, simplified statistical quality control (SQC) design based on Westgard Sigma rules could be implemented without compromising blood safety.

Influence of infectious diseases on detection of antibodies to treponema pallidum

The problem of the spread of syphilis is becoming acute due to the rapid increase in the number of initially detected cases of the disease. When analyzing and interpreting the obtained laboratory data, there is always the possibility of obtaining contradictory results, both false positive and false negative, which do not coincide with the clinical picture of the patient. Since in practice false positive results of serological tests for syphilis are detected more often than false negative ones, special importance is attached to the identification and study of the causes of their occurrence. At the analysis stage, the cause may be the cross-reactivity of the test system with various ‘particles’ in the analyzed samples, due to the peculiarities of its design and antigenic composition. For this work, sets of reagents Abbott GmbH (CMIA), Mindray (CLIA), as well as reagents produced by Vector-Best (ELISA) were used. During the study, it was found that one of the possible ‘particles’ leading to cross-reactivity of test systems may be IgG antibodies to cytomegalovirus.

Therapeutic Drug Monitoring of Carbamazepine: A 20-Year Observational Study.

Background: Carbamazepine (CBZ) is a first-generation anticonvulsant drug. Hence, in certain cases, therapeutic drug monitoring (TDM) supports pharmacotherapy. Methods: The presented research was based on a retrospective analysis including 710 ambulatory and hospitalized patients treated with CBZ between the years 1991 and 2011. The method used for the determination of the CBZ concentration was fluorescence polarization immunoassay (FPIA) performed using an Abbott GmbH TDx automatic analyzer, with the therapeutic range for carbamazepine being 4–12 µg/mL. Results: The therapeutic range was observed more often in patients between 3 and 17 years of age compared with the population ≥18 years of age (73.5% vs. 68.8%). The therapeutic level was exceeded less frequently in the population between 3 and 17 years of age despite them being given a significantly higher dose per kilogram of body weight than in the population ≥18 years of age (13.64 mg/kg vs. 10.43 mg/kg, p < 0.0001). Patients ≥18 years of age were statistically significantly more likely to be in the group with a suspected drug overdose (73.9% vs. 26.1%), and suicide attempts only occurred in elderly patients (100.0% vs. 0.0%, p = 0.003). Conclusion: The results of the TDM of CBZ showed that only 71% of all samples were at the therapeutic level. To ensure the maximum efficacy and safety of the therapy, it is necessary to monitor the concentration of CBZ regardless of sex and age.

Association of anti-HBc and liver inflammation in HBeAg-negative chronic hepatitis B virus-infected patients with normal ALT and detectable HBV DNA.

Serum hepatitis B core antibody (anti-HBc) is associated with liver inflammation in chronic hepatitis B patients. This study aimed to investigate whether anti-HBc could serve as a predictor of significant liver inflammation in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infected patients with normal alanine aminotransferase (ALT) and detectable HBV DNA. Treatment-naïve HBeAg-negative chronic HBV infected patients with normal ALT and detectable HBV DNA who underwent liver biopsy were retrospectively included from two medical centers. Liver inflammation grade was evaluated using the Scheuer scoring system and significant liver inflammation was defined as ≥G2. Serum anti-HBc levels were measured by commercial immunoassays (Abbott GmbH & Co. KG). A total of 117 patients were included and 50 (42.7%) patients showed significant liver inflammation. Serum anti-HBc levels in patients with significant liver inflammation were significantly higher than patients with no or mild liver inflammation (<G2) (p < 0.001). High serum anti-HBc (odds ratio 1.562, 95% confidential interval 1.157-2.110, p = 0.004) was an independent risk factor of significant liver inflammation. The area under the receiver operating characteristic curve of serum anti-HBc in predicting significant liver inflammation was 0.769 and the optimal cut-off value was 10.87 S/CO, with a sensitivity of 59.2% and a specificity of 87.9%. Our data revealed that a substantial of HBeAg-negative chronic infection patients with normal ALT and detectable HBV DNA showed significant liver inflammation. Serum anti-HBc can predict significant liver inflammation in these patients.

Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies.

The plaque reduction neutralization test (PRNT) is a preferred method for the detection of functional, SARS-CoV-2 specific neutralizing antibodies from serum samples. Alternatively, surrogate enzyme-linked immunosorbent assays (ELISAs) using ACE2 as the target structure for the detection of neutralization-competent antibodies have been developed. They are capable of high throughput, have a short turnaround time, and can be performed under standard laboratory safety conditions. However, there are very limited data on their clinical performance and how they compare to the PRNT. We evaluated three surrogate immunoassays (GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit (GenScript Biotech, Piscataway Township, NJ, USA), the TECO® SARS-CoV-2 Neutralization Antibody Assay (TECOmedical AG, Sissach, Switzerland), and the Leinco COVID-19 ImmunoRank™ Neutralization MICRO-ELISA (Leinco Technologies, Fenton, MO, USA)) and one automated quantitative SARS-CoV-2 Spike protein-based IgG antibody assay (Abbott GmbH, Wiesbaden, Germany) by testing 78 clinical samples, including several follow-up samples of six BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA) vaccinated individuals. Using the PRNT as a reference method, the overall sensitivity of the examined assays ranged from 93.8 to 100% and specificity ranged from 73.9 to 91.3%. Weighted kappa demonstrated a substantial to almost perfect agreement. The findings of our study allow these assays to be considered when a PRNT is not available. However, the latter still should be the preferred choice. For optimal clinical performance, the cut-off value of the TECO assay should be individually adapted.

Effect of the oxytocin receptor antagonist nolasiban on pregnancy rates in women undergoing embryo transfer following IVF: analysis of three randomised clinical trials.

Does a single oral dose of nolasiban 900 mg administered 4 h before embryo transfer (ET) increase pregnancy rates in women undergoing IVF? In an individual patient data (IPD) meta-analysis of three clinical trials, a single oral dose of nolasiban 900 mg was associated with an increased ongoing pregnancy rate of an absolute 5% (relative 15%). Several clinical studies have shown that blocking activation of oxytocin receptors by an oxytocin receptor (OTR) antagonist has the potential to decrease uterine contractions, increase endometrial perfusion and enhance endometrial decidualisation and other parameters of endometrial receptivity. It has been hypothesised that antagonism of oxytocin receptors could improve the likelihood of successful embryo implantation and thus increase pregnancy and live birth rates following ET. This is an analysis of three randomised, double-blind, placebo-controlled trials, which randomised 1836 subjects between 2015 and 2019. We describe the results of a meta-analysis of individual participant data (IPD) from all three trials and the pre-specified analyses of each individual trial. Participants were patients undergoing ET following IVF/ICSI in 60 fertility centres in 11 European countries. Study subjects were below 38 years old and had no more than one previously failed cycle. They were randomised to a single oral dose of nolasiban 900 mg (n = 846) or placebo (n = 864). In IMPLANT 1, additional participants were also randomised to nolasiban 100 mg (n = 62) or 300 mg (n = 60). Fresh ET of one good quality embryo (except in IMPLANT 1 where transfer of two embryos was allowed) was performed on Day 3 or Day 5 after oocyte retrieval, approximately 4 h after receiving the study treatment. Serum hCG levels were collected at 14 days post oocyte retrieval (Week 2) and for women with a positive hCG result, ultrasound was performed at Week 6 post-ET (clinical pregnancy) and at Week 10 post-ET (ongoing pregnancy). Pregnant patients were followed for maternal (adverse events), obstetric (live birth, gestational age at delivery, type of delivery, incidence of twins) and neonatal (sex, weight, height, head circumference, Apgar scores, congenital anomalies, breast feeding, admission to intensive care and specific morbidities e.g. jaundice, respiratory distress syndrome) outcomes. In an IPD meta-analysis of the clinical trials, a single oral dose of nolasiban 900 mg was associated with an absolute increase of 5.0% (95% CI 0.5, 9.6) in ongoing pregnancy rate and a corresponding increase of 4.4% (95% CI -0.10, 8.93) in live birth rate compared to placebo. Similar magnitude increases were observed for D3 or D5 transfers but were not significantly different from the placebo. Population pharmacokinetics (PK) demonstrated a correlation between higher exposures and pregnancy. The meta-analysis was not a pre-specified analysis. While the individual trials did not show a consistent significant effect, they were not powered based on an absolute increase of 5% in ongoing pregnancy rate. Only a single dose of up to 900 mg nolasiban was administered in the clinical trials; higher doses or extended regimens have not been tested. Only fresh ET has been assessed in the clinical trials to date. The finding support the hypothesis that oxytocin receptor antagonism at the time of ET can increase pregnancy rates following IVF. The overall clinical and population PK data support future evaluation of higher doses and/or alternate regimens of nolasiban in women undergoing ET following IVF. The trials were designed, conducted and funded by ObsEva SA. A.H., O.P., E.G., E.L. are employees and stockholders of ObsEva SA. E.L. is a board member of ObsEva SA. G.G. reports honoraria and/or non-financial support from ObsEva, Merck, MSD, Ferring, Abbott, Gedeon-Richter, Theramex, Guerbet, Finox, Biosilu, Preglem and ReprodWissen GmbH. C.B. reports grants and honoraria from ObsEva, Ferring, Abbott, Gedeon Richter and MSD. P.P. reports consulting fees from ObsEva. H.T. reports grants and or fees from ObsEva, Research Fund of Flanders, Cook, MSD, Roche, Gedeon Richter, Abbott, Theramex and Ferring. H.V. reports grants from ObsEva and non-financial support from Ferring. P.T. is an employee of Cytel Inc., who provides statistical services to ObsEva. J.D. reports consulting fees and other payments from ObsEva and, Scientific Advisory Board membership of ObsEva. ClinicalTrials.gov: NCT02310802, NCT03081208, NCT03758885. December 2014 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885). January 2015 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885).

False-positive high sensitivity troponin I on Alinity i

Background: High sensitivity troponin I (Hs troponin I) is a precise and sensitive marker of myocardial injury. However, interferences by antibodies are not uncommon in immunoassays. Macrotroponin is one such phenomenon, in which immune complexes are formed between troponin and circulating antibodies, giving rise to false-positive results. Case Presentation: This is a case of a 30-year-old male with elevated high sensitivity troponin I results of 419 ng/l (99th percentile upper reference limit for males is 34.2 ng/l). The test was performed on Abbott Alinity i immunoassay analyzer (Abbott Gmbh &amp; Co. KG, Wiesbaden, Germany). Electrocardiogram, exercise tolerance test, and echocardiogram were all unremarkable. The results of creatinine kinase-myocardial component, troponin T, and conventional troponin I on VITROS ECi Immunodiagnostics System (Ortho-Clinical Diagnostics, Rochester, NY) were within normal limits. Laboratory experiments were carried out to evaluate the case, and the investigations conducted indicated the presence of macrotroponins in the specimen, which demonstrated cross immunoreactivity with the Alinity (Abbott) assay but not with the VITROS (Ortho) assay. Conclusion: Clinicians and laboratorians should be aware of the possible interference by macrotroponin in their assays and should be alerted when there is a discordance between the laboratory and clinical findings.

Delayed Diagnosis of Hidradenitis Suppurativa and Its Effect on Patients and Healthcare System

Background: Hidradenitis suppurativa (HS) is a neglected chronic inflammatory disease affecting the skin of axillary, inguinal, gluteal, and perianal body areas. Besides pain, purulent discharge, and destruction of skin architecture, HS patients experience metabolic, musculoskeletal, and psychological disorders. This study determined the delay in HS diagnosis and its consequences. Methods: A prospective, multi-center, epidemiologic, non-interventional clinical trial based on real-world data in Germany. Self-explanatory questionnaires and medical examinations performed by dermatologists of 394 patients with HS, regardless of therapy, were considered. Findings: The average duration from manifestation of first symptoms until HS diagnosis was 10·0±9·6 (mean±SD) years. During this time, HS patients consulted on average more than three different physicians - most frequently general practitioners, dermatologists, surgeons, gynecologists - and faced more than three misdiagnoses. Diagnosis delay was longer in younger and non-smoking patients. In most cases, HS was correctly diagnosed by dermatologists. The longer the delay of diagnosis, the greater the disease severity at diagnosis. Delayed HS diagnosis was also associated with an increased number of surgical interventions, concomitant diseases, and days of work missed. Interpretation: This study demonstrates an enormous delay in the diagnosis of HS, which results in more severe disease. It also shows for the first time that a delay in diagnosis of a chronic inflammatory disease leads to a higher number of concomitant systemic disorders. In addition to the impaired health status, delayed diagnosis of HS impairs the professional life of affected people. Trial Registration: German Clinical Trials Register (DRKS-ID: DRKS00013778). Funding Statement: AbbVie Deutschland GmbH & Co. KG. Declaration of Interests: G.K. has received honoraria for participation in advisory boards, in clinical trials and/or as speaker from AbbVie Deutschland GmbH & Co. KG, Abbott GmbH, Actelion Pharmaceuticals Ltd., Basilea Pharmaceutica Ltd., Bayer AG, Biogen IDEC GmbH, Celgene GmbH, JanssenCilag GmbH, LEO Pharma GmbH, Lilly Deutschland GmbH, MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Parexel International GmbH, Pfizer Deutschland GmbH, and UCB Pharma GmbH. K.W. has received research grants, travel grants, consulting honoraria and/or lecturer honoraria from AbbVie Inc., AbbVie Deutschland GmbH & Co. KG, Bayer Schering Pharma AG, Celgene GmbH, Flexopharm GmbH & Co. KG, Generon Corporation Ltd., Janssen Pharmaceutica NV, Johnson & Johnson Pharmaceutical Services LLC, Novartis Pharma GmbH, Pfizer Deutschland GmbH, and UCB Pharma GmbH. S.S.-B. has received honoraria for participation in advisory boards, in clinical trials and/or as speaker from AbbVie Inc., AbbVie Deutschland GmbH & Co. KG, Novartis Pharma GmbH, and Pfizer Deutschland GmbH. S.K. has no conflicts of interest to declare. S.G.-K. and S.B. are employees of Abbvie Deutschland GmbH & Co. KG and my own AbbVie stocks. R.S. has received research grants, scientific awards or honoraria for participation in advisory boards, clinical trials or as speaker for one or more of the following: AbbVie Inc., AbbVie Deutschland GmbH & Co. KG, Bayer Schering Pharma AG, Biogen IDEC GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Celgene GmbH, Celgene International II Sarl, Charite Research Organisation GmbH, Dr. Willmar Schwabe GmbH & Co. KG, Flexopharm GmbH & Co. KG, Generon Corporation ltd., JanssenCilag GmbH, La Roche-Posay Laboratoire Dermatologique Deutschland, Novartis Pharma GmbH, Parexel International GmbH, Pfizer Deutschland GmbH, Sanofi -Aventis Deutschland GmbH, TFS Trial Form Support GmbH, UCB Pharma GmbH. Ethics Approval Statement: The Ethics Committee of Charite-Universitatsmedizin Berlin approved the study protocol. All patients provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research.

The Effect of Prophylactic Doses of Reviparin on the Postoperative Value of Platelets.

Introduction:Low molecular weight heparin (LMWH) is used as anticoagulant in diseases characterized by possible thrombosis, as well as for thromboprophylaxis in surgery. The administration of LMWH preoperatively and postoperatively allows satisfactory thromboprophylaxis of patients undergoing surgery. Their application can reduce the number of platelets.Aim:To determine what effect Reviparin has on platelet values postoperatively in patients undergoing open cholecystectomy.Methods:The study was conducted at the Clinic for Anesthesia and Resuscitation of the Clinical Center of the University of Sarajevo. A retrospective study was performed that included data analysis for 33 patients undergoing open cholecystectomy over a two-year period. There were 22 male and 11 female patients out of a total of 33 patients. Platelet values from laboratory findings of patient’s medical history were monitored for 5 days. The values found were recorded in a table containing the patient’s first and last name, gender, age and platelet value. All patients had the same endotracheal anesthesia with Propofol, Fentanyl, and Atracurium supplemented with oxygen and nitric oxide at the appropriate dose. All of the patients received same dose of 0.25ml (1432 IU) Reviparin (Clivarin) from Abbott GmbH & Co.KG, preoperatively and postoperatively. Patients undergoing laparoscopic surgery as well as patients receiving other low-molecular-weight heparin or receiving higher doses of Reviparin were excluded from the study. Statistical analysis was performed using the MedCalc v12.7 statistical package for biomedical research.Results:An analysis of gender representation in the total sample shows that there was 22 or 66.7% of males while there was 11 or 33.3% of female patients. Analysis of platelet values indicates that there is no statistically significant correlation with gender, but that there is a statistically significant correlation between platelet values between samples, ie. that patients who had higher preoperative values retained more platelet values even during postoperative measurements.Conclusion:Platelet values do not change significantly postoperatively with the use of prophylactic doses of Reviparin, after an open cholecystectomy.

Prevalence of Hepatitis B Virus (HBV) Among Blood Donors in Eastern Saudi Arabia: Results From a Five-Year Retrospective Study of HBV Seromarkers.

BackgroundTransfusion-transmissible hepatitis B virus (HBV) infection is a major problem worldwide. Recently, confirmatory nucleic acid tests (NATs) for HBV DNA have been employed in several countries. We assessed the prevalence and yearly trends of HBV infection in blood donors in the Eastern Province of Saudi Arabia, screening for HBV surface antigen (HBsAg), antibody against HBV core antigen (anti-HBc), and HBV DNA.MethodsBetween 2011 and 2015, a total of 22,842 donors were screenedfor HBsAg, anti-HBc, and HBV DNA using the HBsAg Qualitative II kit (Abbott, Ireland Diagnostics Division, Sligo, Ireland), ARCHITECT Anti-hepatitis B core antigen antibody (HBc) II Assay kit (Abbott GmbH & Co. KG, Wiesbaden, Germany), and NAT Procleix Ultrio Elite Assay kit (Grifols Diagnostic Solutions Inc., Los Angeles, CA, USA), respectively.ResultsA total of 739 (3.24%) donors were HbsAg(+), anti-HBc(+), or HBV DNA(+); 63 (0.28%) were HbsAg(+), anti-HBc(+), and HBV DNA(+). Twelve (0.05%) were anti-HBc(+) and HBV DNA(+) but HBsAg(−); they were considered to have occult infection. Further, 664 (2.91%) were HBsAg(−) but anti-HBc(+), indicating chronic or resolving infection. HBV prevalence increased significantly from 2011 to 2012, increased marginally till 2013, and showed a decreasing trend from 2013 (P>0.05).ConclusionsThe five-year prevalence of HBV infection among blood donors in the Eastern Province of Saudi Arabia (3.24%) is lower than that reported for other regions in the country. The occult HBV infection rate of 0.05% emphasizes the importance of NATs in isolating potential infectious blood units.

Therapeutic drug monitoring of digoxin-20 years of experience.

Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1-2ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood. The presented research was based on a retrospective analysis including 2149 patients treated with digoxin and hospitalized between 1980 and 2000. Was used for the determination of SCD automatic analyzer TDX ABBOTT GmbH - fluorescence polarization immunoassay (FPIA), with therapeutic range for digoxin of 0.8-2.0ng/ml. Average SCD result in the study population was located within the therapeutic range and amounted 1.06ng/ml (55.7% of patients). Statistically significant differences in digoxin level were observed depending on the way of medicine administration (p=0.000001) and the daily amount (p=0.001). Moreover, statistically significant differences in digoxin level were observed depending on sex (p=0.00002). An elevated level of digoxin was observed in the case of patients who received the medication both orally and intravenously, together with an increase in the daily amount of digoxin doses. It was confirmed that an elevated digoxin level occurs in the course of treatment in the case of women.

A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.

STUDY QUESTION Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? SUMMARY ANSWER Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. WHAT IS KNOWN ALREADY MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. STUDY DESIGN, SIZE, DURATION Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to <42 years of age; body mass index (BMI) ≥18 to ≤30 kg/m2) with a documented history of infertility who were planning to undergo IVF. A centralized electronic system was used for randomization, and the study investigators, sponsor's study team, and subjects remained blinded throughout the study. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 1031 subjects were randomized to receive either oral dydrogesterone (n = 520) or MVP (n = 511). Luteal support was started on the day of oocyte retrieval and continued until 12 weeks of gestation (Week 10), if a positive pregnancy test was obtained at 2 weeks after embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set (FAS), 497 and 477 subjects in the oral dydrogesterone and MVP groups, respectively, had an embryo transfer. Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates at 12 weeks of gestation of 37.6% and 33.1% in the oral dydrogesterone and MVP treatment groups, respectively (difference 4.7%; 95% CI: -1.2-10.6%). Live birth rates of 34.6% (172 mothers with 213 newborns) and 29.8% (142 mothers with 158 newborns) were obtained in the dydrogesterone and MVP groups, respectively (difference 4.9%; 95% CI: -0.8-10.7%). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP. LIMITATIONS, REASONS FOR CAUTION The analysis of the results was powered to consider the clinical pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the differences between treatments in live birth rate, observed in this study, should therefore be made with caution. WIDER IMPLICATIONS OF THE FINDINGS Oral dydrogesterone may replace MVP as the standard of care for luteal phase support in IVF, owing to the oral route being more patient-friendly than intravaginal administration, as well as it being a well tolerated and efficacious treatment. STUDY FUNDING/COMPETING INTEREST(S) Sponsored and supported by Abbott Established Pharmaceuticals Division. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Besins, Ferring and Mithra (now Allergan) and H.T. has received consultancy fees from Finox, Ferring, Abbott, ObsEva and Ovascience. G.S. has nothing to disclose. E.K. is an employee of Abbott GmbH. G.G. has received investigator fees from Abbott during the conduct of the study; outside of this submitted work, G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC. TRIAL REGISTRATION NUMBER NCT01850030 (clinicaltrials.gov). TRIAL REGISTRATION DATE 19 April 2013. DATE OF FIRST PATIENT'S ENROLLMENT 23 August 2013.

Short communication: Repeatability of β-hydroxybutyrate measurements in capillary blood obtained from the external vulvar skin

The primary objective of this study was to evaluate the repeatability of measurements of β-hydroxybutyrate (BHB) concentrations in capillary blood obtained from minimal-invasive puncturing of different sites at the external vulva skin of dairy cows. A total of 240 multiparous cows sampled once within 21 d in milk were enrolled in the study. Capillary blood samples were obtained from the right and left labium of the external vulva skin and additionally from a site close to the first puncture. Samples were analyzed by using an electronic hand-held device [FreeStyle Precison Neo (FSP-Neo), Abbott GmbH & Co., Wiesbaden, Germany)]. Additionally, samples from a coccygeal vessel were analyzed as reference in a laboratory. Mean deviations (± standard deviation) between the 3 capillary sampling sites ranged from 0.01 ± 0.14 (left vs. right labium) to 0.02 ± 0.13 mmol/L (left or right labium vs. additional site). The BHB concentrations in capillary blood compared with the reference showed a mean deviation of 0.14 ± 0.18 mmol/L. The Spearman correlation coefficient between BHB concentrations in capillary blood and coccygeal blood was 85.4%. Mixed model analyses showed no significant effect of sampling site or squeezing the skin during sampling procedures on the differences toward the reference. Based on laboratory BHB concentrations of ≥1.2 and ≥1.4 mmol/L, respectively, the prevalence of hyperketonemia was 10.4 (n = 25) and 5.0% (n = 12). Thresholds to detect hyperketonemia with the FSP-Neo were optimized by receiver operating characteristic analyses. Based on a laboratory BHB concentration of ≥1.2 mmol/L thresholds were determined as 1.1 (left labium, 2nd puncture) and 1.0 mmol/L (right labium), with sensitivities between 94 and 99% and specificities between 89 and 97%. Based on a serum BHB concentration of 1.4 mmol/L, receiver operating characteristic analyses resulted in optimized cutoffs of 1.4 mmol/L for all sampling sites at the vulva, with sensitivities of 100% and specificities between 96 and 99%. In conclusion, vulvar capillary blood is suitable for accurate measuring of BHB concentrations by using the FSP-Neo. After adjusting the thresholds, the FSP-Neo provides very good test characteristics independent of the capillary sampling site or squeezing the skin and allows a practical and reliable screening tool for dairy cows.

Measurement of β-hydroxybutyrate in capillary blood obtained from an ear to detect hyperketonemia in dairy cows by using an electronic handheld device

The primary objective of the present study was to test whether capillary blood obtained by puncturing the skin of an ear with a minimal invasive lancet technique is able to detect hyperketonemia (HYK) in dairy cows. Furthermore, test characteristics of a new available handheld device, the FreeStyle Precision Neo (FSP-Neo, Abbott GmbH & Co. KG, Wiesbaden, Germany) for determination of β-hydroxybutyrate (BHB) concentrations in bovine blood were evaluated by comparing the measurements with a laboratory reference. The BHB concentration was determined with the FSP-Neo device in 720 capillary blood samples from 3 different sampling sites (left, right ear, and repeated measurement) and in 240 samples from a coccygeal vessel. The concentration of BHB in serum harvested from the coccygeal blood samples was analyzed at the laboratory and was used as reference. The Spearman correlation coefficient (ρs) between the BHB concentrations in capillary blood measured with the handheld device and the reference test was between 0.76 and 0.81. Using capillary blood, the mean ± standard deviation BHB difference compared with the reference test was 0.20±0.47 mmol/L for all 3 sampling locations at the ears. The receiver operating characteristic analyses for the FSP-Neo device resulted in an optimized threshold for the detection of subclinical ketosis (SCK) in capillary blood of 1.3 mmol/L (left and right ear) and 1.2 mmol/L (repeated measurements). Applying these adjusted threshold sensitivities (Se) for all 3 capillary sampling sites at the ear were 100%, and specificities (Sp) ranged between 93 and 94%. Hence, we conclude that all sampling locations were suitable to identify cows suffering from SCK. The reference test compared with BHB measurements in coccygeal blood resulted in a ρs of 0.92 with a mean ± standard deviation of 0.02±0.21 mmol/L. The receiver operating characteristic analyses for the FSP-Neo device resulted in an optimized threshold for the detection of SCK in coccygeal blood of 1.1 mmol/L, with a corresponding Se and Sp of 100 and 95%, respectively. Because capillary blood is easily achievable from an ear, particularly if animals are fixed in headlocks for routine checkups, this technique is considered as an additional minimally invasive method for the identification of dairy cows suffering from HYK.

A novel ELISA using a recombinant outer membrane protein, rTp0663, as the antigen for serological diagnosis of syphilis.

The lack of Treponema pallidum-specific antigens with highly accurate diagnosis makes the diagnosis of syphilis challenging. A soluble recombinant version of a new diagnostic protein Tp0663 has been produced. The serodiagnostic potential of this protein was assessed by screening 3326 serum samples simultaneously evaluated by rapid plasma reagin and T. pallidum particle agglutination tests. Kappa (κ) coefficients were used to compare the concordance between clinical diagnosis and the Tp0663-based ELISA or the ARCHITECT Syphilis TP chemiluminescent immunoassay (Abbott GmbH and Co. KG). Using the results of clinical diagnosis as the gold standard, the sensitivity and specificity of Tp0663 were found to be 98.83% (95% confidence interval (CI) 96.61-99.60%) and 100% (95% CI 99.88-100%), respectively. In comparison, the ARCHITECT Syphilis TP assay was found to have a lower sensitivity (97.27%, 95% CI 94.46-98.67%) and specificity (99.61%, 95% CI 99.32-99.78%). In particular, the ARCHITECT Syphilis TP exhibited a false-positive rate of 0.39%. Moreover, the ELISA was in perfect agreement with the gold standard, with a κ value of 0.99, comparable to that of ARCHITECT Syphilis TP (0.96). These results identified Tp0663 as a novel serodiagnostic candidate with great potential for developing novel tests for the diagnosis of syphilis.

Successful therapy with anakinra in a patient with generalized pustular psoriasis carryingIL36RNmutations

U.H. and M.W. contributed equally to this work. Funding sources: none. Conflicts of interest: R.M. and M.P.S. have received payments for conduction of clinical trials, as invited speaker or advisor, or for travel grants from the following companies: Abbott GmbH & Co. KG, Biogen IDEC GmbH, Essex Pharma GmbH, Janssen‐Cilag, LEO Pharma GmbH, Merck Serono GmbH, Novartis Pharma GmbH, Pfizer GmbH and Wyeth Pharma GmbH. M.P.S. has received research grants from Abbott and BiogenIdec, and has received consulting fees from Abbott, BiogenIdec, Janssen‐Cilag, LEO Pharma, Novartis Pharma and Pfizer. Dear Editor, Generalized pustular psoriasis (GPP) may be caused by homozygous or compound heterozygous mutations in the gene IL36RN, which codes for interleukin‐36 receptor antagonist (IL‐36Ra).1 2 Such mutations are present in approximately 40% of patients with GPP in Germany.3 Anakinra, an interleukin (IL)‐1 receptor antagonist, has been described as an effective treatment against GPP in several cases.4 However, there are no published data on whether anakinra is also effective in the subgroup of patients with GPP carrying IL36RN mutations. Here, we report the first case of a patient with GPP carrying IL36RN mutations who responded well to therapy with anakinra.

122-P: A NOVEL ALLELE: HLA-B∗13:01:06, IDENTIFIED BY SEQUENCE- BASED TYPING IN A CHINESE INDIVIDUAL

Here we reported the identification and characterization of a novel allele: HLA-B∗13:01:06. In an ongoing research project studying the association with cancer susceptibility and HLA allele diversity in Southern Chinese Han population, blood samples collected from patients and health controls have been sent to HLA typing lab routinely. Genomic DNA had been extracted by using Qiagen DNA extraction kit (Qiagen, Valencia, CA),following the manufacturer’s instructions. Polymerase chain reaction (PCR)/ sequence-based typing (SBT) methods were used to obtain HLA—A,-B,-C and –DRB1 nucleotide sequences (AlleleSEQR Combikits, Abbott GmbH& Co. KG, Wiesbaden, Germany). HLA high-resolution typing results have been identified by using ABI Sequence Analysis program (Assign 3.5 SBT software, Conexio Genomics, Applecross, Australia). One of these samples was found a mismatched in HLA allele database while the result was assigned for “R” with one nucleotide mismatched showing symbol, which suggested there was G or A at position 218 at codon49 in exon2. This sample was typing again by using another direct sequence-based typing kit (HLAssure SBT Typing Kit, Texas BioGene Inc, Richardson, Texas, U.S.A). The result showed there was a nucleotide mutation changing from G to A at the position 219. The nucleotide sequences of this sample are identical to those of HLA-B∗13:01:01, except one nucleotide acid changed (G → A) at position218, at codon49(GCG → GCA) in exon2 (Fig 1). It is a silent mutation, the amino acid remains the same(Ala → Ala). The nucleotide sequence has been submitted to the GenBank nucleotide sequence database and the submission number is HQ873872, The name HLA-B∗13:01:06 has been officially assigned by the WHO Nomenclature Committee in January 2011.

Comparison of 2 electronic cowside tests to detect subclinical ketosis in dairy cows and the influence of the temperature and type of blood sample on the test results

The objective of this study was to determine the suitability of 2 electronic hand-held devices [FreeStyle Precision (FSP), Abbott GmbH & Co. KG, Wiesbaden, Germany and GlucoMen LX Plus (GLX), A. Menarini GmbH, Vienna, Austria] for measuring β-hydroxybutyrate (BHBA) in dairy cows. Three experiments were conducted to evaluate (1) the diagnostic performance of the devices, (2) the effect of the type of blood sample, and (3) the influence of the ambient temperature on the determined results. A total of 415 blood samples from lactating Holstein and Simmental cows were collected and analyzed with both devices (whole blood) and in a laboratory (serum). Correlation coefficients between whole-blood and serum BHBA concentrations were highly significant, with 94% for the FSP and 80% for the GLX device. Based on thresholds for subclinical ketosis of 1.2 and 1.4 mmol of BHBA/L, results obtained with the hand-held devices were evaluated by receiver operating characteristics analyses. This resulted in adjusted thresholds of 1.2 and 1.4mmol/L for the FSP and 1.1 and 1.3mmol/L for the GLX device. Applying these thresholds, sensitivities were 98 and 100% for the FSP and 80 and 86% for the GLX device, respectively. Corresponding specificities were 90 and 97% for the FSP and 87 and 96% for the GLX device, respectively. Additionally, concentrations of BHBA were tested with both devices in whole blood, EDTA-added whole blood, and in their resulting serum and plasma, collected from 65 animals. Determined BHBA concentrations were similar within each device for whole and EDTA-added blood, and in serum and plasma, but differed between whole blood and serum and between EDTA-added blood and plasma. Blood samples with low (0.4mmol/L), medium (1.1mmol/L), and high (1.6mmol/L) BHBA concentrations were stored between +5 to +32°C and analyzed repeatedly at temperature levels differing by 4°C. Additionally, devices and test strips were stored at equal conditions and used for measurement procedures. Storage temperature of the devices and test strips did not influence the differences between the results of the laboratory and the devices, whereas the temperature of the blood samples caused significant differences. Although the level of agreement between the laboratory and the GLX device was lower than for the laboratory and the FSP device, both devices are useful tools for monitoring subclinical ketosis in dairy cows. Due to their effects on the determined results, the type and temperature of the tested sample should be considered.

OP0145 Induction therapy with adalimumab plus methotrexate versus methotrexate monotherapy in recent onset rheumatoid arthritis (RA) – an investigator initiated randomized controlled trial

BackgroundTo study the prolonged effect on disease activity by an early induction therapy with adalimumab (ADA) plus methotrexate (MTX) versus MTX alone in DMARD naïve patients (pts) with early RA...