Association between serum 25-hydroxyvitamin D and prostate-specific antigen: a retrospective study in men without prostate pathology.

Objectives: Recently, vitamin D status has been associated with prostate cancer risk. However, some studies argue that there is no association of vitamin D with prostate cancer risk and serum prostate-specific antigen (PSA) concentrations. No clear conclusions can be drawn from the studies found in the literature. Our aim was to assess the relationship between PSA and 25-hydroxyvitamin D [25(OH)D]. Methods: We selected 415 individuals without prostate pathologies and subgroups were generated according to age and 25(OH)D. Statistical analyses were performed using Shapiro-Wilk test, Student's t and ANOVA tests, and Pearson's correlation. Besides, the minimum sample size needed to obtain statistically significant results between groups according to 25(OH)D concentration was calculated and a Student's t-test for paired samples was performed to study individuals with two PSA measurements over time, where 25(OH)D concentration increased or decreased more than 25 %. Results: We observed a slight correlation between age and PSA concentration (r=0.379, p<0.001). However, we found no significant differences when we compared PSA concentrations between groups according to 25(OH)D concentrations (p=0.891): 1.25 ± 1.32 µg/L (group with 25(OH)D<50 nmol/L) and 1.17 ± 0.90 (group with 25(OH)D≥50 nmol/L). Pearson's correlation coefficient was close to 0. The minimum samples size to obtain statistically significant results was 815,346 men, and we observed no differences in PSA concentrations in individuals with two measurements. Conclusions: Our findings show no association in men without prostate pathologies, based on 25(OH)D levels.

Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser.

Introduction: The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Materials and methods: Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer's cut-offs. Sample turnaround time (TAT) was examined. Results: Imprecision repeatability CVs were 1.1-4.7% and within-lab imprecision were 1.8-7.6% (10.0-25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer's values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Conclusions: Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

Humoral Response after Three Doses of mRNA-1273 or BNT162b2 SARS-CoV-2 Vaccines in Hemodialysis Patients.

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases; however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non- or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters.

Notification of biochemistry critical results and its clinical impact on outpatient care: experience in a Spanish tertiary hospital.

OBJECTIVES: The communication of critical results (CR) is considered an essential role in clinical laboratories to ensure patient safety. This is especially relevant to outpatients, who are non-hospitalized and more difficult to locate. In our laboratory, there is a specific protocol for CR management that sets up the communication pathway to adequately provide these results to clinicians. The aim of this study is to evaluate the impact of CR reporting on outpatient care. METHODS: This is a retrospective study focused on CR for biochemistry parameters in a clinical laboratory of a Spanish tertiary hospital during 2019. A total of 156 CR were determined and properly provided to clinicians. We collected CR, age, gender, and the requesting department. We also collected the medical action data resulting from the communication of the CR. RESULTS: Seventy-six outpatients (49%) were properly treated because of effective CR communication. Hypoglycemia was the most frequent event (33%), however, the greatest clinical impact was observed for patients with hyponatremia (100%), hyperkalemia (62%), hypokalemia (60%), and hypercalcemia (57%). Based on these findings, we evaluated new glucose alert thresholds depending on whether or not the outpatient was diabetic (1.7 and 2.2 mmol/L, respectively). Based on these new thresholds, we established a CR reporting protocol with 69% effectiveness in outpatients. CONCLUSIONS: We demonstrate that CR communication in outpatients has a significant clinical impact. To increase the effectiveness of the CR reporting protocol, we propose to adjust alert thresholds according to pathology, department, and patient population.

Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients.

RATIONALE & OBJECTIVE: Patients with kidney failure who are receiving maintenance dialysis have a higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and worse clinical outcomes after coronavirus disease 2019 (COVID-19) than the general population. Therefore, immunization against SARS-CoV-2 with effective vaccines is an important component of health-maintenance strategies for these patients. This study evaluated the humoral and cellular responses to messenger RNA (mRNA) SARS-CoV-2 vaccines in this population. STUDY DESIGN: Observational prospective multicenter cohort study. SETTING & PARTICIPANTS: 205 patients treated at 3 dialysis units at the Hospital Clínic of Barcelona (Spain) were vaccinated from February 3 to April 4, 2021, and followed until April 23, 2021. EXPOSURE: Immunization with either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine. OUTCOME: Seroconversion, defined as the detection of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG), and the identification of activated CD4+T cells 3 weeks after completing vaccination. Anti-S1-RBD IgG levels were also analyzed as a secondary outcome. ANALYTICAL APPROACH: Univariate and multivariable logistic and multiple linear regression models were used to evaluate the associations between vaccination and study outcomes. RESULTS: We found that 97.7% of 175 vaccinated patients who were seronegative at baseline developed a response (humoral, cellular, or both); 95.4% of these patients seroconverted, while 62% of those tested for cellular immunity had a positive response. Greater age and immunosuppressive treatment were associated with lower antibody levels. LIMITATIONS: Mandatory vaccine administration by health authorities. Anti-S1-RBD IgG levels were reported up to 150U/mL and cellular immune responses were characterized qualitatively. Antibody assay and cellular response assessment may not be comparable with previously published laboratory approaches. CONCLUSIONS: Immunization with mRNA vaccines generated a humoral and cellular immune response in a high proportion of patients with kidney failure receiving maintenance dialysis. These findings as well as the high risk of infection and poor clinical outcomes among these patients make their vaccination a health priority.

Value of clinical laboratory test for early prediction of mortality in patients with COVID-19: the BGM score.

BACKGROUND: COVID-19 causes high mortality and long hospitalization periods. The aim of this study was to search for new early prognostic strategies accessible to most health care centers. METHODS: Laboratory results, demographic and clinical data from 500 patients with positive SARS-CoV-2 infection were included in our study. The data set was split into training and test set prior to generating different multivariate models considering the occurrence of death as the response variable. A final computational method called the BGM score was obtained by combining the previous models and is available as an interactive web application. RESULTS: The logistic regression model comprising age, creatinine (CREA), D-dimer (DD), C-reactive protein (CRP), platelet count (PLT), and troponin I (TNI) showed a sensitivity of 47.3%, a specificity of 98.7%, a kappa of 0.56, and a balanced accuracy of 0.73. The CART classification tree yielded TNI, age, DD, and CRP as the most potent early predictors of mortality (sensitivity = 68.4%, specificity = 92.5%, kappa = 0.61, and balanced accuracy = 0.80). The artificial neural network including age, CREA, DD, CRP, PLT, and TNI yielded a sensitivity of 66.7%, a specificity of 92.3%, a kappa of 0.54, and a balanced accuracy of 0.79. Finally, the BGM score surpassed the prediction accuracy performance of the independent multivariate models, yielding a sensitivity of 73.7%, a specificity of 96.5%, a kappa of 0.74, and a balanced accuracy of 0.85. CONCLUSIONS: The BGM score may support clinicians in managing COVID-19 patients and providing focused interventions to those with an increased risk of mortality.

A novel point-of-care device for blood potassium detection of patients on dialysis: Comparison with a reference method / Un nuevo dispositivo de punto de atención para la detección de potasio en sangre de pacientes en diálisis: comparación con un método de referencia

No disponible

Multi-site performance evaluation and Sigma metrics of 20 assays on the Atellica chemistry and immunoassay analyzers.

Background The Atellica Solution comprises chemistry (CH) and immunoassay (IM) analyzers. Recently, six early adopter clinical laboratories across Europe evaluated the analytical performance of 20 CH and IM assays. To measure analytical performance quality, Sigma metrics were calculated for individual-site and pooled-site results. Methods Precision, detection capability, linearity, and method comparison studies were performed according to Clinical Laboratory Standards Institute protocols. Global Sigma metrics across sites were calculated from pooled data at the medical decision level using total allowable error (TEa) goals from CLIA for CH assays, and TEa goals from RiliBÄK for IM assays; and, the equation: Sigma metrics=%TEa-%bias/%CV. A pooled %CV was calculated by combining the imprecision obtained from individual sites. Bias calculations were performed against the ADVIA Chemistry system or ADVIA Centaur system using Deming regression analysis (Passing-Bablok regression for electrolytes) on the pooled-site data. The 103 individual-site Sigma metric calculations used individual-site imprecision and pooled-bias. Results The limits of blank and detection results agreed with the manufacturer's claims. Most assays were linear across the assay range tested. Pooled Sigma metrics were good or better (>4 Sigma) for 18 of 20 assays; and, acceptable for urea nitrogen (3.1) and sodium (3.9), the latter values attributable to higher imprecision at one of five sites. Conclusions Sigma metrics for data generated across multiple real-world sites evaluating the Atellica Solution demonstrated good or better performance of greater than 4 Sigma for 18 of 20 assays tested. Overall, results verified the manufacturer's claims that methods were fit for use in clinical laboratories.

Filling the gap between lab and clinical impact: An open randomized diagnostic trial comparing urinary ethylglucuronide and ethanol in alcohol dependent outpatients.

BACKGROUND: Efforts aimed at reducing alcohol-related harm include early detection of risky drinkers as well as detection of early relapse in patients with alcohol dependence. Ethyl glucuronide (EtG) has been proven to be a reliable biomarker for the detection of recent drinking; however, no randomized, diagnostic trial to date has tested its impact on drinking outcomes. The aim of this study was to assess, in a randomized design, the implications of EtG screening on alcohol outcomes, compared to screening with a low sensitivity biomarker such as ethanol. METHODS: Alcohol dependent outpatients were randomized to either 24 weeks of continuous screening with EtG or ethanol. Patients were aware of screening methods and results. After 24 weeks, all participants were screened with EtG. Self-reports were also gathered. A logistic regression compared the rate of EtG positive results at study end between groups. Generalized estimating equations evaluated the descending monthly rate of EtG positive patients in the EtG group. RESULTS: A total of 162 patients were randomized. During the study period, the ethanol group showed less patients with positive screens (19/64 (29.7%) vs 58/98 (59%)). After 24 weeks, the EtG group showed a greater number of patients having a negative screening test compared to ethanol subjects when they were all screened with EtG (5/62 (8.1%) vs 13/39 (33.3%)). A significant decrease in the rate of EtG positive patients was found for the first three months of the study. CONCLUSIONS: Routine screening with EtG seems to reduce drinking and improve abstinence rates in alcohol dependent outpatients.

The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure.

OBJECTIVE: We tested the hypothesis that early measurement of galectin-3 at the emergency department (ED) during an episode of acute heart failure (AHF) allows predicting short- and long-term outcomes. METHODS: We performed an exploratory study including 115 patients consecutively diagnosed with AHF in a single ED. Clinical and analytical variables were recorded. The primary endpoint was 30-day all-cause mortality, and secondary endpoints were 30-day composite outcome (death, rehospitalization or ED reconsultation, whichever first) and 1-year mortality. RESULTS: Seven patients (6.1%) died within 30 days and 43 (37.4%) within 1 year. The 30-day composite endpoint was observed in 21.1% of patients. Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512-0.953; p = 0.041) but not for 1-year mortality (0.521; 0.408-0.633; p = 0.722). Patients with galectin-3 concentrations >42 µg/L had an OR = 7.67(95%CI = 1.57-37.53; p = 0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive capacity for 1-year mortality (0.642; 0.537-0.748; p = 0.014). Patients with NT-proBNP concentrations >5400 ng/L had an OR = 4.34 (95%CI = 1.93-9.77; p < 0.001) for 1-year mortality. These increased short- (galectin-3) and long-term (NT-proBNP) risks remained significant after adjustment for age or renal function. s-cTnI failed in both short- and long term death prediction. No biomarker predicted the short-term composite endpoint. CONCLUSION: These results suggest that galectin-3 could help to monitor the risk of short-term mortality in unselected patients with AHF attended in the ED.

Verificación e implantación en un laboratorio de urgencias de un sistema de medición de los índices séricos (hemólisis, ictericia y lipidemia) en un Dimension® EXL(TM) / Verification and implementation of a serum index measurement system (haemolysis, icterus, and lipaemia) in a Dimension® EXL(TM) in an emergency laboratory

Introducción. La hemólisis, ictericia y lipidemia son los principales interferentes que pueden producir errores analíticos en la medición de magnitudes bioquímicas. Muchos analizadores incorporan sistemas de detección de interferentes, sin embargo no suelen estar verificados. El objetivo del estudio es verificar el sistema de medición HIL del analizador Dimension® EXL(TM) y comprobar la adecuada asignación por el proveedor de los valores de alerta. Material y métodos. Se ha evaluado el efecto de la hemoglobina, bilirrubina y triglicéridos en los resultados, comparando el valor de la magnitud en la muestra sin interferente con los valores obtenidos en la misma muestra con concentraciones crecientes del mismo. Se ha seguido el procedimiento recomendado por la Comisión de Metrología y Sistemas Analíticos de la SEQC. Asimismo, se ha elaborado un algoritmo de cuándo informar la presencia de interferencias (criterios clínicos y técnicos). Resultados. Todos los resultados de los índices hemolíticos incluyeron la concentración esperada del interferente, para la ictericia hubo ligeras diferencias, mientras que para la lipidemia el analizador proporcionó resultados más bajos de los esperados. En el estudio de los índices de alerta HIL hubo diferencias entre los resultados obtenidos y la información del fabricante. Se presenta el algoritmo para informar la presencia de estas interferencias. Conclusiones. La incorporación de estos índices de alerta sin una previa verificación de los mismos puede llevar a cometer errores. Una correcta verificación de estos sistemas permitiría detectar la falta de veracidad en la medición de estos interferentes o el inadecuado establecimiento de algunos índices de alerta (AU)

Introduction. Haemolysis, icterus (bilirubin) and lipaemia (triglycerides) (HIL) are the main interferences that can lead to analytical errors in the measurement of biological substances. Many analysers incorporate interference detection systems, which nonetheless are often not verified. The main objective is to verify the HIL measurement system of the Dimension® EXL(TM) analyser, and to check the correct assignment of the alert values by the supplier. Material and methods. The effect of the haemolysis, bilirubin and triglycerides on the results has been assessed by comparing the value of the quantity in a sample without interference with the values obtained in the same sample with increasing concentrations of interfering substances. The procedure recommended by the Comisión de Metrología y Sistemas Analíticos of the SEQC has been followed. An algorithm to inform of interferences, based on clinical and technical aspects, has been developed. Results. All haemolytic index results included the expected concentration of the interfering substance. Few errors were found for icterus, while for lipaemia the analyser gave results lower than expected. In the study of the HIL alert indexes, differences were found between the results obtained and the information provided by the supplier. Finally the algorithm followed in our laboratory to inform the presence of interfering substances is presented. Conclusions. The introduction of these alert indexes without a prior verification of them can lead to potential errors. Proper verification of these systems would enable detecting the lack of trueness in the measurement of the interfering substances or the inadequate establishment of some alert indexes (AU)

Eight-Year Experience with Nocturnal, Every-Other-Day, Online Haemodiafiltration.

BACKGROUND: New haemodialysis therapeutic regimens are required to improve patient survival. Longer and more frequent dialysis sessions have produced excellent survival and clinical advantages, while online haemodiafiltration (OL-HDF) provides the most efficient form of dialysis treatment. METHODS: In this single-centre observational study, 57 patients on 4-5-hour thrice-weekly OL-HDF were switched to nocturnal every-other-day OL-HDF. Inclusion criteria consisted of stable patients with good prospects for improved occupational, psychological and social rehabilitation. The aim of this study was to report our 8-year experience with this schedule and to evaluate analytical and clinical outcomes. RESULTS: Nocturnal, every-other-day OL-HDF was well tolerated and 56% of patients were working. The convective volume increased from 26.7 ± 2 litres at baseline to 46.6 ± 6.5 litres at 24 months (p < 0.01). Increasing the dialysis dose significantly decreased bicarbonate, blood-urea-nitrogen and creatinine values. Predialysis phosphate levels fell markedly with complete suspension of phosphate binders from the second year of follow-up. Although haemoglobin was unchanged, there was a 50.4% reduction in darbepoetin dose at 24 months and a significant decrease in the erythropoietin resistance index. Blood pressure significantly decreased in a few months. Antihypertensive medication requirements were decreased by 60% after 3 months and by 73% after 1 year and this difference was maintained thereafter. CONCLUSIONS: Nocturnal, every-other-day OL-HDF could be an excellent therapeutic alternative since it is well tolerated and leads to clinical and social-occupational rehabilitation with satisfactory morbidity and mortality. These encouraging results strengthen us to continue and invite other clinicians to join this initiative.

Urine Ethyl Glucuronide Unraveling the Reality of Abstinence Monitoring in a Routine Outpatient Setting: A Cross-Sectional Comparison with Ethanol, Self Report and Clinical Judgment.

AIMS: To test the screening performance of urinary ethyl glucuronide (EtG) under routine clinical conditions in a sample of alcohol-dependent outpatients, comparing it against urinary ethanol, self reports and clinical judgment. METHODS: A cross-sectional study under routine conditions was conducted in February 2015, where 613 consecutive urinary samples, provided by 188 outpatients with alcohol use disorders, were analyzed for ethanol and EtG (cut-off level = 500 ng/ml). Clinical variables such as the presence of aversive medication, comorbidities and clinician judgment were also collected. The discrepancy between the number of alcohol and EtG positives was recorded. A logistic regression analysis including clinical variables was conducted to assess for predictors of EtG positivity. RESULTS: Urinary alcohol yielded 9 positives (1.5% of all urine samples) belonging to 8 patients. EtG yielded 136 positives (22% of all urine samples) belonging to 74 patients. Of these, 93.4% (127 of 136) were negative for alcohol. All urinary alcohol positives resulted in EtG positives. The clinician judged 48 samples from 26 patients as belonging to not abstinent patients and 550 samples from 178 patients as belonging to abstinent patients. She was unsure in 15 samples from 15 patients. When comparing it against EtG as the gold standard, the area under the curve was 0.592. Self reports were extremely unreliable in this study, with only 5 patients reporting drinking in a total of 6 urine samples. In the logistic regression model, only aversive medications (OR 2.1, 95% CI 1.3-3.3) and clinician judgment (OR 2, 95% CI 1.4-2.9) resulted in significant effects. CONCLUSIONS: EtG performed largely better than ethanol for urine screening in alcohol outpatients, detecting an extra 20.4% (125 out of 613) of positives. It means that for each alcohol-positive sample, there were 15 EtG-positive samples. Although better than ethanol, clinician judgment was also not performed efficiently. If routinely implemented in the screening of alcohol outpatients, EtG might bring relevant changes that merit further research.

Assessment of patient safety culture in clinical laboratories in the Spanish National Health System.

INTRODUCTION: There is increasing awareness of the importance of transforming organisational culture in order to raise safety standards. This paper describes the results obtained from an evaluation of patient safety culture in a sample of clinical laboratories in public hospitals in the Spanish National Health System. MATERIAL AND METHODS: A descriptive cross-sectional study was conducted among health workers employed in the clinical laboratories of 27 public hospitals in 2012. The participants were recruited by the heads of service at each of the participating centers. Stratified analyses were performed to assess the mean score, standardized to a base of 100, of the six survey factors, together with the overall patient safety score. RESULTS: 740 completed questionnaires were received (88% of the 840 issued). The highest standardized scores were obtained in Area 1 (individual, social and cultural) with a mean value of 77 (95%CI: 76-78), and the lowest ones, in Area 3 (equipment and resources), with a mean value of 58 (95%CI: 57-59). In all areas, a greater perception of patient safety was reported by the heads of service than by other staff. CONCLUSIONS: We present the first multicentre study to evaluate the culture of clinical safety in public hospital laboratories in Spain. The results obtained evidence a culture in which high regard is paid to safety, probably due to the pattern of continuous quality improvement. Nevertheless, much remains to be done, as reflected by the weaknesses detected, which identify areas and strategies for improvement.