SARS-CoV-2 Seropositivity and HIV Viral Load Among Mozambican Pregnant Women.

INTRODUCTION: Prevalence estimates of SARS-CoV-2 infection in Africa are limited, particularly among pregnant women and in those living with HIV. This study assessed the seroprevalence of SARS-CoV-2 antibodies among Mozambican HIV-infected pregnant women during the first year of the pandemic, before COVID-19 vaccines were deployed in the country. SETTING: The study was conducted in Manhiça district, a semirural area in southern Mozambique. METHODS: A prospective cohort study including pregnant women living with HIV was conducted from November 2019 to June 2021. Women were enrolled at the first antenatal care clinic visit and followed until postpartum. HIV viral load and IgM/IgG antibodies against SARS-CoV-2 were determined in blood samples at first antenatal care clinic visit and at delivery. Associations between SARS-CoV-2 serostatus and maternal characteristics at enrolment were analyzed. RESULTS: A total of 397 women were enrolled. SARS-CoV-2 IgG/IgM antibodies were detected in 7.1% of women at enrolment and in 8.5% of women at delivery. Overall, SARS-CoV-2 antibodies were detected in 45 women (11.3%; 95% confidence interval 8.4 to 14.9%) during the study period; the first seropositive sample was identified in September 2020. Having undetectable HIV viral load was associated with seropositivity of SARS-CoV-2 IgG/IgM [odds ratio 3.35 (1.10 to 11.29); P = 0.039]. CONCLUSION: Seroprevalence of SARS-CoV-2 antibodies in this cohort of Mozambican unvaccinated pregnant women was similar to reported global estimates of approximately 10% in pregnancy for 2021. The findings also suggest that pregnant women with high HIV viral load may have an impaired immune response against SARS-CoV-2 and might need to be carefully managed in case of COVID-19.

Optimization of dialysate bicarbonate in patients treated with online haemodiafiltration.

BACKGROUND: Metabolic acidosis is a common problem in haemodialysis patients, but acidosis overcorrection has been associated with higher mortality. There is no clear definition of the optimal serum bicarbonate target or dialysate bicarbonate. This study analysed the impact of reducing dialysate bicarbonate from 35 to 32 mEq/L on plasma bicarbonate levels in a cohort of patients treated with online haemodiafiltration (OL-HDF). METHODS: We performed a prospective cohort study with patients in a stable chronic OL-HDF programme for at least 12 months in the Hospital Clinic of Barcelona. We analysed pre- and post-dialysis total carbon dioxide(TCO2) before and after dialysate bicarbonate reduction from 35 to 32 mEq/L, as well as the number of patients with a pre- and post-dialysis TCO2 within 19-25 and ≤29 mEq/L, respectively, after the bicarbonate modification. Changes in serum sodium, potassium, calcium, phosphorous and parathyroid hormone (PTH) were also assessed. RESULTS: We included 84 patients with a 6-month follow-up. At 6 months, pre- and post-dialysis TCO2 significantly decreased (26.78 ± 1.26 at baseline to 23.69 ± 1.92 mEq/L and 31.91 ± 0.91 to 27.58 ± 1.36 mEq/L, respectively). The number of patients with a pre-dialysis TCO2 >25 mEq/L was significantly reduced from 80 (90.5%) to 17 (20.2%) and for post-dialysis TCO2 >29 mEq/L this number was reduced from 83 (98.8%) to 9 (10.7%). PTH significantly decreased from 226.09 (range 172-296) to 182.50 (125-239) pg/mL at 6 months (P < 0.05) and post-dialysis potassium decreased from 3.16 ± 0.30 to 2.95 ± 0.48 mEq/L at 6 months (P < 0.05). Sodium, pre-dialysis potassium, calcium and phosphorous did not change significantly. CONCLUSIONS: Reducing dialysate bicarbonate concentration by 3 mEq/L significantly and safely decreased pre- and post-dialysis TCO2, avoiding acidosis overcorrection and improving secondary hyperparathyroidism control. An individualized bicarbonate prescription (a key factor in the adequate control of acidosis) according to pre-dialysis TCO2 is suggested based on these results.

Analytical performance assessment and improvement by means of the Failure mode and effect analysis (FMEA).

INTRODUCTION: Laboratories minimize risks through quality control but analytical errors still occur. Risk management can improve the quality of processes and increase patient safety. This study aims to use the failure mode and effect analysis (FMEA) to assess the analytical performance and measure the effectiveness of the risk mitigation actions implemented. MATERIALS AND METHODS: The measurands to be included in the study were selected based on the measurement errors obtained by participating in an External Quality Assessment (EQA) Scheme. These EQA results were used to perform an FMEA of the year 2017, providing a risk priority number that was converted into a Sigma value (σFMEA). A root-cause analysis was done when σFMEA was lower than 3. Once the causes were determined, corrective measures were implemented. An FMEA of 2018 was carried out to verify the effectiveness of the actions taken. RESULTS: The FMEA of 2017 showed that alkaline phosphatase (ALP) and sodium (Na) presented a σFMEA of less than 3. The FMEA of 2018 revealed that none of the measurands presented a σFMEA below 3 and that σFMEA for ALP and Na had increased. CONCLUSIONS: Failure mode and effect analysis is a useful tool to assess the analytical performance, solve problems and evaluate the effectiveness of the actions taken. Moreover, the proposed methodology allows to standardize the scoring of the scales, as well as the evaluation and prioritization of risks.

Performance evaluation of Siemens Atellica enhanced estradiol assay.

Background: Serum estradiol (E2) levels may be used in the diagnostic and/or monitoring of a broad variety of clinical conditions. The aims of this study were to evaluate the Siemens enhanced estradiol assay (eE2) on Atellica IM 1600 (Siemens Healthineers) and to perform a sample comparison with the Siemens ADVIA Centaur XP (Siemens Healthineers). Methods: Within-day and between-day coefficient of variation (CV) were determined using serum sample pools and quality control materials. Six serum samples with decreasing concentrations of E2 were used to assess the limit of quantification. Linearity was evaluated using two different serum samples. Accuracy was evaluated by measuring three certified reference materials. Passing-Bablok regression and Bland-Altman plot were used for comparing Atellica and Centaur XP in 119 serum samples ranging from 45 to 10,059 pmol/L. Results: Within-day and between-day imprecision was <6.6%. Accuracy was <6.0% for all values except for 114 pmol/L (22%). The study of limit of quantification resulted in an interday imprecision <20%. High correlation between measured and expected estradiol dilution results was observed (R = 0.99), with recoveries ranging from 77 to 93%. Comparison study showed good agreement and no significant bias. Conclusions: The study shows that Atellica eE2 assay presents acceptable imprecision and accuracy and correlates well with Centaur XP.

Study of the analytical performance at different concentrations of hematological parameters using Spanish EQAS data.

Background External quality assessment programs are one of the currently available tools to evaluate the analytical performance of clinical laboratories, where the measurement error (ME) obtained can be compared with quality specifications to evaluate possible deviations. The objective of this work was to analyze the ME behavior over the analytical range to assess the need to establish concentration-dependent specifications. Methods A total of 389,000 results from 585 laboratories and 2628 analyzers were collected from the Spanish external quality assessment schemes (EQAS) in hematology during the years 2015-2016. The parameters evaluated included white blood cells, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, prothrombin time, activated partial thromboplastin time, neutrophils, lymphocytes, monocytes, eosinophils, basophils, reticulocytes, hemoglobin A2, antithrombin, factor VIII, protein C and von Willebrand factor. The 90th percentile of ME was calculated for every concentration evaluated of each parameter. Results We found a significant variation in the analytical performance of leukocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils, prothrombin time, reticulocytes, hemoglobin A2, antithrombin and protein C. Furthermore, this ME variation may not allow complying with the same biological variability requirements within the whole analytical range studied. Conclusions Our work shows the importance of implementing concentration-dependent specifications which can help laboratories to use proper criteria for quality specifications selection and for a better external quality control results evaluation.

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy

ABSTRACT Background In people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60 mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60-89 mL/min). Objective The present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. Methods Cross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60-89 mL/min). Results Among the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58-3.55), female sex (OR 1.23, 95% CI 1.02-1.48), baseline hypertension (OR 1.57, 95% CI 1.25-1.97) or dyslipidemia (OR 1.48, 95% CI 1.17-1.87), virologic suppression (OR 1.88, 95% CI 1.39-2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33-2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03-1.39). Conclusions Females and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease.

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy.

BACKGROUND: In people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60-89mL/min). OBJECTIVE: The present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. METHODS: Cross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60-89mL/min). RESULTS: Among the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58-3.55), female sex (OR 1.23, 95% CI 1.02-1.48), baseline hypertension (OR 1.57, 95% CI 1.25-1.97) or dyslipidemia (OR 1.48, 95% CI 1.17-1.87), virologic suppression (OR 1.88, 95% CI 1.39-2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33-2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03-1.39). CONCLUSIONS: Females and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease.

Analytical verification and method comparison of the ADVIA Centaur® Intact Parathyroid Hormone assay.

OBJECTIVES: This study is the first verification of the novel iPTH Siemens ADVIA Centaur® Intact Parathyroid Hormone (iPTHm) chemiluminescence immunoassay based on monoclonal antibodies. We also compared the iPTH results obtained using this assay with the previous ADVIA Centaur® Parathyroid Hormone assay (iPTHp) based on polyclonal antibodies. DESIGN AND METHODS: The analytical performance study of iPTHm assay included LoD, LoQ, intra- and inter-assay reproducibility, and linearity. A comparison study was performed on 369 routine plasma samples. The results were analyzed independently for patients with normal and abnormal GFR, as well as patients on hemodialysis. In addition, clinical concordance between assays was assessed. Finally, we studied PTH stability of plasma samples at 4°C. RESULTS: For the iPTHm assay LoD and LoQ were 0.03pmol/L and 0.10pmol/L, respectively. Intra- and inter-assay CV were between 2.3% and 6.2%. Linearity was correct in the range from 3.82 to 203.08pmol/L. Correlation studies showed a good correlation (r=0.99) between iPTHm and iPTHp, with bias of -2.55% (IC -3.48% to -1.62%) in the range from 0.32 to 117.07pmol/L. Clinical concordance, assessed by Kappa Index, was 0.874. The stability study showed that differences compared to basal iPTH concentration did not exceed 20% in any of the samples analyzed. CONCLUSIONS: The iPTHm assay demonstrated acceptable performance and a very good clinical concordance with iPTHp assay, currently used in our laboratory. Thus, the novel iPTHm assay can replace the previous iPTHp assay, since results provided by both assays are very similar. In our study, the stability of iPTH is not affected by storage up to 14days.

Improvement in the stability of serum samples stored in an automated refrigerated module.

OBJECTIVES: In clinical laboratories it is necessary to know for how long the analytes are stable in the samples with specific storage conditions. Our laboratory has implemented the new Aptio Automation System (AAS) (Siemens Healthcare Diagnostics) where the analyzed samples are stored in a refrigerated storage module (RSM) after being sealed. The aim of the study was to evaluate the stability of serum samples with the AAS and comparing the results with a previous study using a conventional refrigerated system. DESIGN AND METHODS: Serum samples from a total of 50 patients were collected and for each of them 27 biochemical analytes were analyzed. The samples were divided in 5 sets of 10 samples. Each set was re-analyzed at one of the following times: 24, 48, 72, 96 and 120h. Stability was evaluated according to the Total Limit of Change (TLC) criteria, which combine both analytical and biologic variation. RESULTS: A total of 26 out of 27 analytes were stable at the end of the study according to TLC criteria. Lactate dehydrogenase was not stable at 48h observing a decrease in its concentration until the end of the study. In the previous study (conventional storage system) 9 biochemical analytes were not stable with an increase of their levels due to the evaporation process. CONCLUSIONS: The RSM connected to the AAS improves the stability of serum samples. This system avoids the evaporation process due to the sealing of samples and allows better control of the samples during their storage.

Evaluation of a portable hemoglobinometer (HemoCue) to control anemia in hepatitis C liver transplant recipients undergoing antiviral therapy.

BACKGROUND: Monitoring of anemia, the most frequent side-effect of antiviral therapy in hepatitis C virus (HCV)-infected liver transplant recipients, requires frequent blood tests and medical visits. AIMS: The primary aim of this study was to assess the usefulness and the accuracy of a portable hemoglobinometer (HemoCue) in patients receiving antiviral therapy after liver transplantation due to severe hepatitis C recurrence in the graft. The secondary aim was to evaluate the usefulness of this device in terms of cost-saving and time-saving benefits. METHODS: Multiple simultaneous hemoglobin measurements were obtained in venous blood by the reference method (ADVIA 120) and in capillary blood using HemoCue in 16 patients receiving antiviral therapy after liver transplantation. In addition, paired HemoCue measurements were taken to assess the reproducibility of this method, and correlation coefficients (CC) were calculated between them. Time requirements and cost of both procedures were recorded and compared. RESULTS: HemoCue showed an excellent reproducibility (CC 0.92) and very high correlation with the standard method (CC 0.89). Its accuracy in detecting anemia (hemoglobin ≤10 mg/dl) was excellent as well (area under the receiver operator characteristic curve, 0.96). The application of HemoCue in this cohort of patients resulted in a significant reduction in the economical expense and labor (i.e., time) per patient during follow-up. CONCLUSION: HemoCue is accurate and reproducible in measuring hemoglobin levels, and could be effectively used in this cohort of patients to control anemia during antiviral therapy. It could also help to reduce both overall costs and displacements, thereby improving the quality of life of these patients.

Impact of ultrasensitive cardiac troponin I dynamic changes in the new universal definition of myocardial infarction.

We evaluated the impact of using the new universal definition of myocardial infarction (MI) criteria implemented with a 20% increment between 2 cardiac troponin I (cTnI) measurements. The study included 284 consecutive episodes of patients admitted to the emergency department with suspected acute coronary syndrome (ACS) and an initial cTnI measurement of 0.10 ng/mL (0.10 microg/L) or less followed by 1 or more measurements within 24 hours. Episodes with a maximum cTnI above the 99th percentile (0.04 ng/mL [0.04 microg/L]) and a dynamic increase between 2 measurements of 20% or more were considered to meet MI criteria. Of the 284 episodes, 109 (38.4%) had a maximum cTnI higher than 0.04 ng/mL (0.04 microg/L). However, only 66 episodes (23.2%) also had an increase of 20% or more in the cTnI concentration and met MI criteria. These 66 episodes included 37 patients diagnosed with an MI and 29 patients not diagnosed with an MI. The 29 patients who also met MI criteria were more frequently readmitted for ACS within 6 months.

Evaluation of a new ultrasensitive assay for cardiac troponin I.

OBJECTIVES: We evaluated the analytical and clinical performance of a new ultrasensitive cardiac troponin I assay (cTnI) on the ADVIA Centaur system (TnI-Ultra). DESIGN AND METHODS: The evaluation included the determination of detection limit, within-assay and between-assay variation and comparison with two other non-ultrasensitive methods. Moreover, cTnI was determined in 120 patients with acute chest pain with three methods. To evaluate the ability of the new method to detect MI earlier, it was assayed in 8 MI patients who first tested negative then positive by the other methods. RESULTS: The detection limit was 0.009 microg/L and imprecision was <10% at all concentrations evaluated. In comparison with two other methods, 10% of the anginas diagnosed were recategorized to MI. CONCLUSIONS: The ADVIA Centaur TnI-Ultra assay presented high reproducibility and high sensitivity. The use of the recommended lower cutpoint (0.044 microg/L) implied an increased and earlier identification of MI.

[Forearm ischemic exercise test. Standardization and diagnostic value in the identification of McArdle disease]. / Prueba de ejercicio con isquemia en el antebrazo. Estandarización y valor diagnóstico en la identificación de la enfermedad de McArdle.

BACKGROUND AND OBJECTIVE: The forearm ischemic exercise test (FIET) with serial lactate determinations is used worldwide for the screening of McArdle's disease and other glucogenosis. Yet there is no uniformity with regard to the intensity of the work and the ischemia time. The aim of this study was to standardize the test conditions in normal people and to check its efficacy in our population. PATIENTS AND METHOD: In a first stage, we included 9 healthy persons in whom four different conditions were applied regarding the cuff pressure and ischemia time. In a second stage, 5 previously known McArdle disease patients, 30 normal individuals and 25 patients with a diagnosis of myopathy other than glucogenosis underwent FIET with the conditions standardized in the first stage. RESULTS: The best curve profile was obtained with a cuff pressure 20 mm Hg above systolic blood pressure and with exercise until fatigue o cramps without time limitation. With a cut-point at 200% of the basal values of ammonium and lactate, the sensitivity and specificity of FIET were 100% and 96%, respectively, for McArdle's disease. No major side effects were recorded in any case. CONCLUSIONS: Conditions of FIET have been standardized. Taking into account the high sensitivity and specificity of the test, its use should be considered in the screening of anaerobic metabolic myopathies.