Methodology to Evaluate Clinical Impact of 0/3 Hour High-Sensitivity Cardiac Troponin T Protocol on Managing Acute Coronary Syndrome in Daily Emergency Department Practice.

OBJECTIVE: Sex-/age-differentiated cutoffs and the magnitude of serial changes in high-sensitivity cardiac troponins (hs-cTn) for acute coronary syndrome (ACS) diagnosis algorithms are still under discussion. This study presents a methodology to evaluate decision-making limits and to assess whether sex-specific cutoffs could improve diagnostic accuracy. METHODS: A high-sensitivity cardiac troponin T (hs-cTnT) 0-/3-hour protocol was adopted, applying the 2015 European Society of Cardiology Guidelines. Decision-making limits (99th percentile: 14 ng/L; delta change ≥ 30%) were agreed upon with the emergency department (ED) at the University Hospital of Siena in Siena, Italy. One-year requests (5177) for hs-cTnT serial determination were compared with the final International Classification of Diseases, 9th revision, clinical modifications diagnosis (contingency tables; receiver operating characteristic curves). RESULTS: The algorithm's capability to exclude or confirm ACS was verified by remarkable negative predictive value (97%) and high areas under the curve for the first troponin sampling (0.712), troponin sampling at 3 hours (0.789), and delta (0.744). The clinical utility for the general population-even those with comorbidities-accessing the ED was verified. Our data did not support a sex-differentiated cutoff utility because it would not have affected patient management. CONCLUSION: This methodology allowed us to confirm the effectiveness of our decision-making limits.

Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience.

BACKGROUND: Autoantibodies against-phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (iMN). Enzyme-linked immunosorbent assay (ELISA) is becoming the preferred method in many laboratories for the determination of anti-PLA2R antibodies, because it provides quantitative results, and is not prone to subjective interpretation, as is the case with indirect immunofluorescence assay. METHODS: The purpose of our study was to determine the diagnostic performance of serum PLA2R antibodies detected by commercially available ELISA in a large Italian multicenter cohort of patients with biopsy-proven iMN and in patients with other renal diseases, with special focus on evaluating the optimal cut-off value to discriminate positive and negative results. A total of 495 consecutive patients were recruited. Renal biopsies were performed in all patients, and blood samples were taken before the initiation of immunosuppressive treatment. RESULTS: According to the clinical diagnosis and to kidney biopsy, 126 patients were diagnosed with iMN and 369 had other non-membranous nephropathies. Anti-PLA2R autoantibodies were detected using a commercial anti-PLA2R ELISA. At a cut-off value of 20 relative units (RU)/ml indicated by the manufacturer for positive classification, sensitivity was 61.1% and specificity 99.7%. At a cut-off value of 14 RU/ml indicated by the manufacturer for borderline results, sensitivity was 63.5% and specificity remained the same (99.7%). At a cut-off of 2.7 RU/ml, selected as the optimal cut-off on the basis of ROC curve analysis, sensitivity was 83.3% and specificity 95.1%. The best overall efficiency of the test was observed at 2.7 RU/ml; however, the highest positive likelihood ratio and diagnostic odds ratio were achieved at 14 RU/ml. A cut-off threshold higher than 14 RU/ml or lower than 2.7 RU/ml entailed worse test performance. CONCLUSION: Depending on the clinical use (early diagnosis or as a support to confirm clinical diagnosis), nephrologists may take advantage of this evidence by choosing the most convenient cut-off. However, renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity.

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs.

BACKGROUND: Although experts agree that strict dietary compliance is fundamental for the health of celiac patients, there are no evidence-based recommendations on the best way to assess dietary compliance. Detection of gluten immunogenic peptides (GIPs) in feces was recently proposed as an effective method of assessing the dietary compliance of celiac patients. METHODS: Fifty-five consecutive celiac patients (27 adults and 28 children, age 6-72 years), who had been on a gluten-free diet for at least 2 years, were enrolled. All patients were evaluated clinically for symptoms, physical parameters and laboratory parameters. Dietary compliance was assessed with the Biagi questionnaire and serum anti-tissue transglutaminase (tTG) IgA antibodies were measured. GIPs were determined by immunoenzymatic assay on an automated Chorus analyzer (DIESSE Diagnostica Senese), after extraction of fecal samples by the method developed by DIESSE. RESULTS: Eight patients tested positive for GIPs (GIPs+); 71.4% of GIP-positive patients were asymptomatic; tTG antibodies were detected in 3/8 GIP+ patients. The Biagi score was significantly associated with fecal positivity for GIPs (P=0.02). However, according to the Biagi score, 57.1% of GIP+ patients followed the diet strictly and 5.4% of GIP- subjects did not comply with the diet or made substantial mistakes. CONCLUSIONS: Assay of fecal GIPs identified more patients who did not comply with the diet than did the Biagi questionnaire, evaluation of symptoms or anti-tTG antibodies. Detection of fecal GIPs offers a direct, objective, quantitative assessment of even occasional exposure to gluten and is confirmed as a practical way to check dietary compliance.

Fecal gluten immunogenic peptides as indicators of dietary compliance in celiac patients.

BACKGROUND: It is important to have methods for evaluating dietary compliance in patients with celiac disease (CD). Determination of fecal gluten immunogenic peptides (GIPs) was recently proposed as a method of detecting gluten intake. The aim of this study was to evaluate whether determination of GIPs can be used as an indicator of compliance with a gluten-free diet (GFD). METHODS: Twenty-five persons with CD on a gluten-free diet for at least one year were enrolled in the study. Compliance with the diet was assessed by the Biagi questionnaire, evaluation of symptoms and assay of IgA anti-tissue transglutaminase antibodies (IgA anti-tTG). GIPs were determined by iVYLISA GIP-S test (Biomedal S.L., Seville, Spain) on an automated Chorus analyzer (DIESSE Diagnostica Senese, Siena, Italy), after extraction of fecal samples by the method developed by DIESSE. RESULTS: Four patients tested positive for GIPs (GIP+), two of whom complied strictly with the gluten-free diet according to the Biagi questionnaire. None of the four GIP-positive patients manifested symptoms. IgA anti-tTG was significantly higher in GIP+ than in GIP- subjects. CONCLUSIONS: Assay of fecal GIPs identified more patients who were not complying with the diet than the Biagi questionnaire or evaluation of symptoms. The anti-tTG and GIP results agreed perfectly; however, since anti-tTG antibodies remain high for longer and are not a completely reliable marker of GFD intake, detection of fecal GIPs offers a direct, objective, quantitative assessment of exposure, even occasional, to gluten and could be used to check dietary compliance.

A computer model for professional competence assessment according to ISO 15189.

Background As defined by ISO 15189 competence is the "demonstrated ability to apply knowledge and skills" thus, its assessment is fundamental for ensuring the quality of the total testing process in order to reduce the risk for the patient. We have developed a functional software for the measurement of professional competences in order to standardize the procedure and to collect all the data in a single platform, avoiding redundancy and dispersion. Methods Our model objectively assesses the skills, as they become measurable and comparable with appropriate standards and involves both managers and operators, to increase their active engagement. The assessment concerns everyone, but the standards to be met (numerical values) can vary according to the responsibilities. Several subjective and objective criteria are evaluated: each parameter can contribute in a variable proportion to the total skills measured according to the needs of the organization. Results The data are automatically analyzed and can be easily monitored in real time in the form of indicators, thanks to dashboards. The comparison between the skills required and those measured allows highlighting the gap useful for planning personalized training paths. Conclusions Our tool is reliable and highly adaptable to laboratories about competences to track criteria, standards and monitored indicators. The computerized management is a strategic action as it fulfills the requirements of registration, traceability, communication, data analysis and indicators development, which are the tenets of continuous improvement, and allows planning to be made on the basis of the actual training needs.

Defining and Managing the Preanalytical Phase With FMECA: Automation and/or "Human" Control.

OBJECTIVE: Our scope is to provide methodological elements on how to manage effectively the preanalytical phase in the laboratory testing process, by objectively measuring the risk connected to the phases handled by man with respect to those managed by machines. BACKGROUND: Preanalytical errors account for most of the mistakes related to laboratory testing and can affect patient care. Hence, it is necessary to manage the risk connected to the preanalytical phase, as required by certification and accreditation bodies. The risk assessment discloses the steps at greater risk and gives indications to make decisions. METHOD: We have reviewed the state of art in the automation of the preanalytical phase, addressing needs and problems. We have used the proactive risk assessment methodology FMECA (Failure Mode, Effects, and Criticality Analysis) to identify the most critical phases in our preanalytical process and have calculated the risk associated. RESULTS: The most critical phases were the human controlled ones. In particular, the highest risk indexes were associated to manual acceptance of test orders, identification of the patients, tube labeling, and sample collection. CONCLUSION: Automation in the preanalytical phase is fundamental to replace, support, or extend the human contribution. Nevertheless each organization is different about workloads and competencies, so the most suitable management must be tailor-made in each context. APPLICATION: We present a method by which each organization is able to find its best balance between automation and human contribution in the control of the preanalytical phase.

A study on the association of mood disorders and gluten-related diseases.

Our study aimed to evaluate the presence of antibodies related to gluten intolerance in patients with mood disorders. A total of 60 patients with a diagnosis of bipolar disorder or depressive disorder were recruited. Fourty-eight subjects randomly selected among unrelated family members were included as controls. Celiac disease-associated antibodies were assayed both in the patients and controls. Mean values of IgA/IgG anti-gliadin antibodies, IgA/IgG anti-deamidated gliadin peptide antibodies and IgA anti-transglutaminase (tTG) antibodies were not different between patients and controls. However, a significant difference was found for anti-tTG IgG antibodies. Even if both in controls and in patients the mean anti-tTG IgG value was below the cutoff, the estimates produced by the statistical model showed that each unit increase in the anti-tTG IgG antibody value corresponded to an approximately 5% increased chance of having a mood disorder. The patient group showed a more frequent presence of symptoms associated to non-celiac gluten sensitivity. However, as there was neither any correlation between antibody levels and gastrointestinal symptoms, nor with the intensity of the psychiatric symptoms, it may be conceivable that the increase in anti-tTG IgG antibodies is not disorder-related but possibly an outcome of the psychiatric disorder itself.