Applying the Milan models to setting analytical performance specifications - considering all the information.

Analytical performance specifications (APS) are used for decisions about the required analytical quality of pathology tests to meet clinical needs. The Milan models, based on clinical outcome, biological variation, or state of the art, were developed to provide a framework for setting APS. An approach has been proposed to assign each measurand to one of the models based on a defined clinical use, physiological control, or an absence of quality information about these factors. In this paper we propose that in addition to such assignment, available information from all models should be considered using a risk-based approach that considers the purpose and role of the actual test in a clinical pathway and its impact on medical decisions and clinical outcomes in addition to biological variation and the state-of-the-art. Consideration of APS already in use and the use of results in calculations may also need to be considered to determine the most appropriate APS for use in a specific setting.

Outcome-based analytical performance specifications: current status and future challenges.

Analytical performance specifications (APS) based on outcomes refer to how 'good' the analytical performance of a test needs to be to do more good than harm to the patient. Analytical performance of a measurand affects its clinical performance. Without first setting clinical performance requirements, it is difficult to define how good analytically the test needs to be to meet medical needs. As testing is indirectly linked to health outcomes through clinical decisions on patient management, often simulation-based studies are used to assess the impact of analytical performance on the probability of clinical outcomes which is then translated to Model 1b APS according to the Milan consensus. This paper discusses the related key definitions, concepts and considerations that should assist in finding the most appropriate methods for deriving Model 1b APS. We review the advantages and limitations of published methods and discuss the criteria for transferability of Model 1b APS to different settings. We consider that the definition of the clinically acceptable misclassification rate is central to Model 1b APS. We provide some examples and guidance on a more systematic approach for first defining the clinical performance requirements for tests and we also highlight a few ideas to tackle the future challenges associated with providing outcome-based APS for laboratory testing.

Effect of lactase supplementation on infant colic: Systematic review of randomized controlled trials.

To systematically review evidence on the efficacy and safety of using a lactase supplementation for managing infant colic. The MEDLINE, EMBASE, and Cochrane Library databases were searched (up to September 2023) for randomized controlled trials (RCTs) comparing oral lactase supplementation with placebo or no intervention in infants younger than 6 months old with infant colic. The risk of bias was assessed using the revised version of the Cochrane risk-of-bias tool. Outcomes measured were selected according to a standardized core outcome set. Five RCTs involving a total of 391 infants were identified. Three RCTs reported reduced crying duration, but one showed effect only in a compliant group (40.4%, p = 0.0052). A meta-analysis of two RCTs found no difference in crying duration and fussing time during 1 week of lactase treatment compared with placebo (mean difference [MD] -17.66 min/day, 95% confidence interval [CI], -60.8 to 25.5; I2 = 68% and MD 2.75, 95% CI, -58.2 to 57.2; I2 = 80%, respectively). Other outcomes were assessed only in individual studies or not reported. The risk of bias was low in only one RCT, high in three, and raised some concerns in one. While individual trials have shown some promise, the overall evidence for the efficacy of lactase supplementation in treating infant colic remain inconclusive. Further well-designed RCTs are necessary to determine the effects of lactase on managing infant colic.

Nutritional status and feeding difficulties in children up to 2 years of age with cow's milk allergy.

BACKGROUND/OBJECTIVES: To assess the nutritional status and incidence of feeding difficulties in Polish children up to 2 years of age with cow's milk allergy (CMA) on cow's milk proteins-free diet. METHODS: A cross-sectional, multi-center study included children aged 6 months to 2 years with confirmed or suspected (without oral food challenge) diagnosis of CMA on the elimination diet for at least 1 month. The primary outcomes were an assessment of proportion of children with impaired nutritional status (with the weight for length and body mass index (BMI) z-score > 1 and <-1), and feeding difficulties according to the Montreal Children's Hospital Feeding Scale. Children with confirmed and suspected CMA were assessed separately. RESULTS: A 144 children with confirmed CMA and 88 with suspected CMA were included (57 and 78% with multiple food allergies, respectively). Among children with confirmed CMA, one-third (35.5%) of participants had any nutritional status impairment regardless of definition. Among those, most of children had mild malnutrition (10.4 vs. 9%) and possible risk of overweight (11.1 vs. 9.7%; following respectively BMI for age and weight for length z-scores). Only 16.0% of children had feeding difficulties. Feeding difficulties was identified to be a risk factor for moderate malnutrition compared to children without feeding difficulties (odds ratio 10, 95% confidence interval: 4-27). CONCLUSIONS: Mild malnutrition and possible risk of overweight are concern in children up to 2 years of age on cow's milk proteins-free diet. Feeding difficulties are less common, however, may affect the nutritional status.

Gastrointestinal Comorbidities Associated with Atopic Dermatitis-A Narrative Review.

The current understanding of atopic dermatitis (AD) seems to be extending beyond a skin-confined condition frequently associated with allergic comorbidities, as in a number of epidemiological studies, the prevalence rate of a range of illnesses has been determined to be greater in patients with AD, or inversely. In most cases, the reasons for this are vague. A subset of these conditions are gastrointestinal disorders, including food sensitization (FS) and food allergy (FA), eosinophilic esophagitis (EoE) (it is of mixed background, both IgE-dependent and independent), food protein-induced enterocolitis syndrome (FPIES) (it exemplifies an IgE-independent food allergy), Crohn's disease (CD), colitis ulcerosa (CU), celiac disease, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD). In this review, we performed a comprehensive search of the literature using the PubMed database. We addressed the epidemiology of the increased co-occurrence of these diseases with AD and discussed potential causes for this subject. Multiple gastroenterological comorbidities appear to be more common in patients with AD, according to our review. The mechanisms that underlie this phenomenon are largely unknown, highlighting the need for further study in this field.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

BACKGROUND: Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. APPROACH: An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association of Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. CONTENT: Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (Hb A1c) in the blood. Glycemic control is monitored by the people with diabetes measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring (CGM) devices and also by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. SUMMARY: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

Executive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

BACKGROUND: Numerous laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. An expert committee compiled evidence-based recommendations for laboratory analysis in patients with diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments in the full version of the guideline). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association of Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. CONTENT: Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (Hb A1c) in the blood. Glycemic control is monitored by the patients measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring devices and also by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring; genetic testing; and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. SUMMARY: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

Analytical and Non-Analytical Variation May Lead to Inappropriate Antimicrobial Dosing in Neonates: An In Silico Study.

BACKGROUND: Therapeutic drug monitoring (TDM) of aminoglycosides and vancomycin is used to prevent oto- and nephrotoxicity in neonates. Analytical and nonanalytical factors potentially influence dosing recommendations. This study aimed to determine the impact of analytical variation (imprecision and bias) and nonanalytical factors (accuracy of drug administration time, use of non-trough concentrations, biological variation, and dosing errors) on neonatal antimicrobial dosing recommendations. METHODS: Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration-time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing. RESULTS: Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3-12.1% (amikacin), 16.2-19.0% (tobramycin), 12.2-45.8% (gentamicin), and 9.6-19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin). CONCLUSIONS: Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.

Plasma arginine metabolites in health and chronic kidney disease.

BACKGROUND: Elevated plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) are risk factors for chronic kidney disease (CKD) and cardiovascular disease. Using plasma cystatin C (pCYSC)-based estimated glomerular filtration rate (eGFR) trajectories, we identified a cohort at high risk of poor kidney-related health outcomes amongst members of the Dunedin Multidisciplinary Health and Development Study (DMHDS). We therefore examined associations between methylarginine metabolites and kidney function in this cohort. METHODS: ADMA, SDMA, L-arginine and L-citrulline were measured in plasma samples from 45-year-olds in the DMHDS cohort by liquid chromatography-tandem mass spectrometry. RESULTS: In a healthy DMHDS subset (n = 376), mean concentrations were: ADMA (0.40 ± 0.06 µmol/L), SDMA (0.42 ± 0.06 µmol/L), L-arginine (93.5 ± 23.1 µmol/L) and L-citrulline (24.0 ± 5.4 µmol/L). In the total cohort (n = 857), SDMA correlated positively with serum creatinine (Pearson's r = 0.55) and pCYSC (r = 0.55), and negatively with eGFR (r = 0.52). A separate cohort of 38 patients with stage 3-4 CKD (eGFR 15-60 mL/min/1.73 m2) confirmed significantly higher mean ADMA (0.61 ± 0.11 µmol/L), SDMA (0.65 ± 0.25 µmol/L) and L-citrulline (42.7 ± 11.8 µmol/L) concentrations. DMHDS members classified as high-risk of poor kidney health outcomes had significantly higher mean concentrations of all four metabolites compared with individuals not at risk. ADMA and SDMA individually predicted high-risk of poor kidney health outcomes with areas under the ROC curves (AUCs) of 0.83 and 0.84, and together with an AUC of 0.90. CONCLUSIONS: Plasma methylarginine concentrations facilitate stratification for risk of CKD progression.

Discrepancy between Guidelines and Clinical Practice in the Management of Cow's Milk Allergy in Children: An Online Cross-Sectional Survey of Polish Physicians.

The aim of this study was to assess the compliance between current guidelines on the diagnosis and management of children with cow's milk allergy (CMA) and clinical practice by a survey of Polish physicians. An online cross-sectional survey involving a convenience series of participants was performed from January 15 to March 20, 2020. Data provided by 605 physicians (74.2% of them pediatricians working in general practice) were analyzed. Contrary to the current recommendations, only a minority of respondents (27.4%) reported performing oral food challenge (OFC) to confirm the diagnosis of CMA. Among those who reported performing OFC (n = 160 respondents), the majority performed an open challenge (82.5%). Most respondents (79.2%) correctly recommended as the first-line treatment extensively hydrolyzed cow's milk formula for a child with mild-to-moderate CMA. Less than half of participants (43.8%) recommended amino acid-based formula for a child with severe CMA (anaphylaxis). Only half of respondents (50.8%) reassessed tolerance to cow's milk proteins. For assessing tolerance acquisition, more respondents recommended challenge to baked milk compared with fresh cow's milk (60.5% vs. 39.5%, respectively). This survey study found that only a minority of responding physicians follow current guidelines for diagnosis and management of children with CMA in Poland.

Lot-to-lot reagent verification: challenges and possible solutions.

Lot-to-lot verification is an important laboratory activity that is performed to monitor the consistency of analytical performance over time. In this opinion paper, the concept, clinical impact, challenges and potential solutions for lot-to-lot verification are exained.

Interference by macroprolactin in assays for prolactin: will the In Vitro Diagnostics Regulation lead to a solution at last?

Cross reactivity with high molecular weight complexes of prolactin known as macroprolactin is a common cause of positive interference in assays for serum prolactin. All prolactin assays currently available are affected with 5-25% of results indicating hyperprolactinaemia falsely elevated due to macroprolactinaemia - hyperprolactinaemia due to macroprolactin with normal concentrations of bioactive monomeric prolactin. Macroprolactinaemia has no pathological significance but, if it is not recognised as the cause, the apparent hyperprolactinaemia can lead to clinical confusion, unnecessary further investigations, inappropriate treatment and waste of healthcare resources. Macroprolactinaemia cannot be distinguished from true hyperprolactinaemia on clinical grounds alone but can be detected by a simple laboratory test based on the precipitation of macroprolactin with polyethylene glycol. Laboratory screening of all cases of hyperprolactinaemia to exclude macroprolactinaemia has been advised as best practice but has not been implemented universally and reports of clinical confusion caused by macroprolactinaemia continue to appear in the literature. Information provided by manufacturers to users of assays for prolactin regarding interference by macroprolactin is absent or inadequate and does not comply with the European Union Regulation covering in vitro diagnostic medical devices (IVDR). As the IVDR is implemented notified bodies should insist that manufacturers of assays for serum prolactin comply with the regulations by informing users that macroprolactin is a source of interference which may have untoward clinical consequences and by providing an estimate of the magnitude of the interference and a means of detecting macroprolactinaemia. Laboratories should institute a policy for excluding macroprolactinaemia in all cases of hyperprolactinaemia.

Harmonization of LC-MS/MS Measurements of Plasma Free Normetanephrine, Metanephrine, and 3-Methoxytyramine.

BACKGROUND: Plasma-free normetanephrine and metanephrine (metanephrines) are the recommended biomarkers for testing of pheochromocytoma and paraganglioma (PPGL). This study evaluated the status of harmonization of liquid chromatography-tandem mass spectrometry-based measurements of plasma metanephrines and methoxytyramine and clinical interpretation of test results. METHODS: 125 plasma samples from patients tested for PPGLs were analyzed in 12 laboratories. Analytical performance was also assessed from results of a proficiency-testing program. Agreement of test results from different laboratories was assessed by Passing-Bablok regression and Bland-Altman analysis. Agreement in clinical test interpretation based on laboratory specific reference intervals was also examined. RESULTS: Comparisons of analytical test results by regression analysis revealed strong correlations for normetanephrine and metanephrine (R ≥ 0.95) with mean slopes of 1.013 (range 0.975-1.078), and 1.019 (range 0.963-1.081), and intercepts of -0.584 (-53.736 to 54.790) and -3.194 (-17.152 to 5.933), respectively. The mean bias between methods was 1.2% (-11.6% to 16.0%) for metanephrine and 0.1% (-18.0% to 9.5%) for normetanephrine. Measurements of 3-methoxytyramine revealed suboptimal agreement between laboratories with biases ranging from -32.2% to 64.0%. Interrater agreement in test interpretation was >94% for metanephrine and >84% for normetanephrine; improvements in interrater agreement were observed with use of harmonized reference intervals, including age-specific cut-offs for normetanephrine. CONCLUSIONS: Analytical methods for metanephrines are well harmonized between laboratories. However, the 16% disagreement in test interpretation for normetanephrine suggests use of suboptimal method-dependent reference intervals for clinical decision-making for this metabolite. Improved analytical methods and reference interval harmonization are particularly required for 3-methoxytyramine.

Reference intervals for venous blood gas measurement in adults.

OBJECTIVES: Venous blood gas (VBG) analysis is becoming a popular alternative to arterial blood gas (ABG) analysis due to reduced risk of complications at phlebotomy and ease of draw. In lack of published data, this study aimed to establish reference intervals (RI) for correct interpretation of VBG results. METHODS: One hundred and 51 adult volunteers (101 females, 50 males, 18-70 years) were enrolled after completion of a health questionnaire. Venous blood was drawn into safePICO syringes and analysed on ABL827 blood gas analyser (Radiometer Pacific Pty. Ltd.). A non-parametric approach was used to directly establish the VBG RI which was compared to a calculated VBG RI based on a meta-analysis of differences between ABG and VBG. RESULTS: After exclusions, 134 results were used to derive VBG RI: pH 7.30-7.43, partial pressure of carbon dioxide (pCO2) 38-58 mmHg, partial pressure of oxygen (pO2) 19-65 mmHg, bicarbonate (HCO3-) 22-30 mmol/L, sodium 135-143 mmol/L, potassium 3.6-4.5 mmol/L, chloride 101-110 mmol/L, ionised calcium 1.14-1.29 mmol/L, lactate 0.4-2.2 mmol/L, base excess (BE) -1.9-4.5 mmol/L, saturated oxygen (sO2) 23-93%, carboxyhaemoglobin 0.4-1.4% and methaemoglobin 0.3-0.9%. The meta-analysis revealed differences between ABG and VBG for pH, HCO3-, pCO2 and pO2 of 0.032, -1.0 mmol/L, -4.2 and 39.9 mmHg, respectively. Using this data along with established ABG RI, calculated VBG RI of pH 7.32-7.42, HCO3- 23 - 27 mmol/L, pCO2 36-49 mmHg (female), pCO2 39-52 mmHg (male) and pO2 43-68 mmHg were formulated and compared to the VBG RI of this study. CONCLUSIONS: An adult reference interval has been established to assist interpretation of VBG results.

IFCC interim guidelines on rapid point-of-care antigen testing for SARS-CoV-2 detection in asymptomatic and symptomatic individuals.

With an almost unremittent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections all around the world, there is a compelling need to introduce rapid, reliable, and high-throughput testing to allow appropriate clinical management and/or timely isolation of infected individuals. Although nucleic acid amplification testing (NAAT) remains the gold standard for detecting and theoretically quantifying SARS-CoV-2 mRNA in various specimen types, antigen assays may be considered a suitable alternative, under specific circumstances. Rapid antigen tests are meant to detect viral antigen proteins in biological specimens (e.g. nasal, nasopharyngeal, saliva), to indicate current SARS-CoV-2 infection. The available assay methodology includes rapid chromatographic immunoassays, used at the point-of-care, which carries some advantages and drawbacks compared to more conventional, instrumentation-based, laboratory immunoassays. Therefore, this document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 aims to summarize available data on the performance of currently available SARS-CoV-2 antigen rapid detection tests (Ag-RDTs), providing interim guidance on clinical indications and target populations, assay selection, and evaluation, test interpretation and limitations, as well as on pre-analytical considerations. This document is hence mainly aimed to assist laboratory and regulated health professionals in selecting, validating, and implementing regulatory approved Ag-RDTs.

Effect of a low-FODMAP diet for the management of functional abdominal pain disorders in children: a study protocol for a randomized controlled trial.

BACKGROUND: Evidence from studies in adults documents that fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may be triggers of symptoms in individuals with functional abdominal pain disorders (FAPDs). However, in children, the evidence is very limited. We aim to assess the effects of a low-FODMAP diet compared with a regular diet for the management of children with FAPDs. METHODS: We will perform a randomized, quadruple-blinded, controlled trial. Seventy-four children aged 8 to 18 years with a FAPD (Irritable Bowel Syndrome or Functional Abdominal Pain-Not Otherwise Specified), diagnosed according to the Rome IV criteria, will be randomly allocated to receive either a low-FODMAP diet or a regular diet for 4 weeks. The primary outcome will be the percentage of the responders, defined as the participants who have at least 30% improvement in abdominal pain intensity on a Visual Analogue Scale (VAS) during the last week of the trial compared with baseline, that is at least equal to the Reliable Change Index (≥ 25 mm change on VAS). Other outcomes will include changes in stool consistency, abdominal pain frequency, total scores on the Gastrointestinal Symptom Rating Scale, KIDSCREEN-10 Index and World Health Organization Five Well-Being Index, child's school attendance and parents' work absenteeism, and BMI-for-age z-score. Compliance, tolerability of the low-FODMAP diet, and adverse events also will be evaluated. Each FAPD subtype will be assessed separately. DISCUSSION: There is a need for high-quality evidence regarding the dietary management of children with FAPDs. This randomized controlled trial (RCT) of rigorous methodological design will help to establish the effectiveness, if any, of a low-FODMAP diet for the management of FAPDs in the pediatric population. The findings of this RCT will assist with the development of guidelines and influence the direction of further research. TRIAL REGISTRATION: NCT04528914 Data and protocol version identifier: 24/08/2020.

Detection of silent cerebral microcirculatory abnormalities in patients with manifest ischemic coronary disease: a perfusion brain MRI study combined with dipyridamole stress.

OBJECTIVES: Intravenous dipyridamole (DP) can induce transient perfusion abnormalities in the heart but also the brain indicated by brain SPECT. L-arginine can regulate the vascular tone via nitric oxide (NO). Therefore, we examined cerebral blood volume (CBV) by perfusion MRI and L-arginine level before and after DP stress in patients, who developed transient neurological signs, and compared these to unaffected patients. DESIGN: A total of nine patients with ischemic coronary disease after myocardial perfusion scintigraphy were selected for this prospective pilot study. Four had DP-induced transient mild neurologic signs during myocardial perfusion scintigraphy, while five had no neurological signs. By using perfusion MRI in both groups in a second stage, we examined CBV in identical areas of the two hemispheres before and during DP stress. Besides, pre-and post-stress L-arginine serum levels were also analyzed by high-performance liquid chromatography. Trial registration: NCT03688815. RESULTS: CBV in the sensory-motor area at baseline was significantly higher in patients with DP-induced transient neurological signs compared to patients without signs (p = 0.028). Intravenous DP normalized the higher perfusion by decreasing CBV, and also increased serum L-arginine level (p = 0.001). CONCLUSIONS: Intravenous DP changed the CBV accompanied by a systemic elevation of L-arginine: this indicates a direct vasorelaxing effect on brain vessels, and an indirect vasodilator effect through L-arginine release presumably via NO. In areas with decreased CBV before DP, such double effects caused transient neurological symptoms presumably due to steal phenomenon. Therefore, intravenous DP may have a potential to identify patients with high risk for cerebral ischemia.

The kinetic estimated glomerular filtration rate ratio predicts acute kidney injury.

AIM: Kinetic estimated Glomerular Filtration Rate (KeGFR) approximates GFR under non-steady-state conditions. We investigated whether the ratio of KeGFR difference to baseline eGFR could predict acute kidney injury (AKI) earlier than a creatinine-based algorithm that triggered an AKI electronic Alert (eAlert). METHODS: This retrospective, single-centre, proof-of-concept cohort study assessed all patients diagnosed with AKI by an automated serum creatinine-based eAlert. The kinetic eGFR, the kinetic eGFR difference from baseline and the ratio of difference to baseline was calculated in subjects with at least two serum creatinine (sCr) measurements within 72 h of AKI. RESULTS: Patients in the AKI cohort (n = 140) had a significant decline in KeGFR ratio (AKI: 17% IQR 7% to 29%, Non-AKI: 0 IQR -12% to 9%; P-value <.0001). A decrease of the ratio greater than 10% predicted AKI with a sensitivity of 66%, a specificity of 77%, a positive predictive value of 63%, and negative predictive value of 80%. The median lead time between KeGFR ratio decrease and AKI was 24 h (IQR: 19-27 h). CONCLUSIONS: KeGFR ratio is a cheap, simple method that predicted AKI 24 h before laboratory detection. KeGFR may facilitate triaging patients to increased monitoring or intervention.

Efficacy and safety of hydrolyzed formulas for cow's milk allergy management: A systematic review of randomized controlled trials.

OBJECTIVE: To summarize evidence on the efficacy and safety of the use of extensively hydrolyzed formulas (EHFs) for the treatment of children with cow's milk allergy (CMA). DESIGN: Systematic review of randomized controlled trials (RCTs) per PRISMA guidelines. The risk of bias of included RCTs was assessed using the Cochrane Collaboration's risk of bias tool. In general, a narrative synthesis of the findings was performed. When sufficient data were available, a meta-analysis using the random-effect model was performed. DATA SOURCES: The Cochrane Library, MEDLINE, and EMBASE databases were searched up to February 2020. ELIGIBILITY CRITERIA: RCTs, including cross-over trials, assessing children of any age with any type of CMA that compared use of a formula containing extensively hydrolyzed bovine proteins (whey and/or casein) with use of any other formula for CMA management, were eligible for inclusion. Each type of EHF was evaluated separately. Outcome measures included allergic reactions (ie gastrointestinal, dermatological, and respiratory symptoms), growth, tolerance acquisition to cow's milk proteins, health-related quality of life, and safety. RESULTS: Fifteen trials reported in 18 publications (1285 children) fulfilled the inclusion criteria. The study findings were limited by numerous methodological issues, including differences in outcome measures and their definitions, lack of pre-specified protocols and/or trial registration, and poor reporting of adverse events, methods of sequence generation and allocation concealment. The EHF products evaluated to date appear to be well-tolerated by most children with CMA. However, published studies do not allow for any conclusion to be reached regarding the benefit of one formula over another formula intended for CMA management. CONCLUSIONS: This systematic review highlights the need for standardized treatment protocols, including an agreed-upon standardized set of outcomes that should be measured and reported in all clinical trials of specialized milk formula for the management of CMA.

Biosafety measures for preventing infection from COVID-19 in clinical laboratories: IFCC Taskforce Recommendations.

Coronavirus disease 2019 (COVID-19) is the third coronavirus outbreak that has emerged in the past 20 years, after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). One important aspect, highlighted by many global health organizations, is that this novel coronavirus outbreak may be especially hazardous to healthcare personnel, including laboratory professionals. Therefore, the aim of this document, prepared by the COVID-19 taskforce of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), is to provide a set of recommendations, adapted from official documents of international and national health agencies, on biosafety measures for routine clinical chemistry laboratories that operate at biosafety levels 1 (BSL-1; work with agents posing minimal threat to laboratory workers) and 2 (BSL-2; work with agents associated with human disease which pose moderate hazard). We believe that the interim measures proposed in this document for best practice will help minimazing the risk of developing COVID-19 while working in clinical laboratories.