Accuracy of point-of-care testing devices for haemoglobin in the operating room: meta-analysis.

BACKGROUND: Point-of-care tests (POCT) for haemoglobin are increasingly used to guide intraoperative transfusion. However, their accuracy compared to central laboratory tests is unknown. The objective was to perform a systematic review and meta-analysis of method comparison studies assessing the accuracy of POCT versus central laboratory haemoglobin tests in patients undergoing surgery. METHODS: Electronic databases were searched from inception to April 2020 (updated August 2023). Any methodological approach comparing haemoglobin measurements between POCT and central laboratory in patients undergoing surgery under anaesthesia in the operating room were included. Data abstraction was guided by PRISMA and risk of bias was assessed by QUADAS-2. Data were extracted independently and in duplicate by two reviewers. Outcomes included mean differences between POCT and central laboratory haemoglobin with associated standard deviations and 95% limits of agreement (LOA). RESULTS: Of 3057 citations, 34 studies were included (n = 2427, 6857 paired measurements). Several devices were compared (pulse co-oximetry, n = 25; HemoCue, n = 10; iSTAT, n = 6; blood gas analysers, n = 10; haematology analyser, n = 2). Median sample size was 41 patients, and 11 studies were funded by device manufacturers. Fifteen of 34 studies had low risk of bias. Pooled mean differences (95% LOA) were: pulse co-oximeters 2.3 g/l (-25.2-29.8), HemoCue -0.3 g/l (-11.1-10.5), iSTAT -0.3 g/l (-8.4-7.8) and blood gas analysers -2.6 g/l (-17.8-12.7). CONCLUSION: All POCT examining intraoperative haemoglobin measurement yielded pooled mean difference LOAs larger than the allowable limit difference of ±4 g/dl. Intraoperative haemoglobin measured by POCT should not be considered interchangeable with central laboratory values and caution is necessary when using these tests to guide intraoperative transfusion.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups.

OBJECTIVES: Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. METHODS: Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. RESULTS: The percentage of POCT glucose tests performed without valid PPID ranged from 0-87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0-50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. CONCLUSIONS: Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

High-Anion-Gap Metabolic Acidosis During a Prolonged Hospitalization Following Perforated Diverticulitis: An Educational Case Report.

Rationale: The metabolic acidoses are generally separated into 2 categories on the basis of an anion gap calculation: high-anion-gap and normal anion-gap metabolic acidosis. When a high-anion-gap metabolic acidosis (HAGMA) is not clearly explained by common etiologies and routine confirmatory testing, specialized testing can definitively establish rare diagnoses such as 5-oxoproline, d-lactate accumulation, or diethylene glycol toxicity. Presenting Concerns of the Patient: A 56-year-old woman had a prolonged hospital admission following perforated diverticulitis requiring sigmoid resection. Her hospitalization was complicated by feculent peritonitis and surgical wound dehiscence needing prolonged broad-spectrum antibiotics and wound debridements. She developed acute kidney injury and HAGMA in the hospital. Diagnoses: Chart review showed that she received a large cumulative dose of acetaminophen during her hospital stay. Laboratory studies showed markedly increased serum 5-oxoproline causing HAGMA. Interventions Including Prevention and Lifestyle: Patient was admitted to the intensive care unit and treated with N-acetylcysteine and renal replacement therapy. Outcomes: After admission to the intensive care unit, the patient continued to require vasopressor and ventilatory support for septic shock and a ventilator-associated pneumonia. After an initial recovery and resolution of her HAGMA, she subsequently suffered recurrent aspirations which were fatal. Teaching points: 1. The acronym GOLD MARK is useful when assessing patients with HAGMA and most causes of HAGMA can be established with routine testing.2. When the etiology of HAGMA remains unclear, additional testing can be required to diagnose rare causes of HAGMA.3. Rare causes of HAGMA are diethylene glycol, 5-oxoproline, and d-lactate accumulation.4. Acidosis secondary to 5-oxoproline accumulation can occur even with "therapeutic" doses of acetaminophen in patients receiving it regularly for a prolonged period and who have depleted glutathione stores.5. Risk factors for glutathione depletion include malnutrition, older age, sepsis, pregnancy, multiple chronic illnesses, and chronic kidney disease.

Justification: Les acidoses métaboliques sont généralement classées en deux catégories sur la base d'un calcul de trou anionique : les acidoses métaboliques à trou anionique élevé (HAGMA ­ High anion gap metabolic acidosis) et les acidoses métaboliques à trou anionique normal. Lorsque l'acidose métabolique à trou anionique élevé n'est pas clairement expliquée par des étiologies courantes et des tests de confirmation de routine, des tests spécialisés peuvent établir de façon définitive des diagnostics rares tels que l'accumulation de 5-oxoproline, l'accumulation de D-lactate ou une toxicité du diéthylène glycol. Présentation du cas: Une femme de 56 ans hospitalisée de façon prolongée à la suite d'une diverticulite perforée nécessitant une résection du sigmoïde. L'hospitalisation a été compliquée par une péritonite purulente et une déhiscence de la plaie chirurgicale ayant nécessité un débridement de la plaie et une antibiothérapie à large spectre prolongée. La patiente a développé une insuffisance rénale aiguë (IRA) et une HAGMA durant son séjour à l'hôpital. Diagnostic: L'examen du dossier a montré que la patiente avait reçu une dose cumulative importante d'acétaminophène pendant son séjour à l'hôpital. Des analyses en laboratoire ont montré une augmentation marquée de la 5-oxoproline sérique ayant causé l'HAGMA. Interventions y compris prévention et mode de vie: La patiente a été admise à l'unité des soins intensifs et traitée par N-acétylcystéine et thérapie de remplacement rénal (TRR). Résultats: Après son admission à l'USI, la patiente a continué d'avoir besoin de vasopresseur et d'assistance respiratoire en raison d'un choc septique et d'une pneumonie associée au ventilateur. Après un rétablissement initial et la résolution de son HAGMA, la patiente a ensuite dû subir des aspirations récurrentes qui lui ont été fatales. Enseignements tirés: 1. L'acronyme GOLD MARK est utile lors de l'évaluation des patients atteints d'HAGMA; la plupart des causes d'HAGMA peuvent être établies avec des tests de routine.2. Lorsque l'étiologie de l'HAGMA reste incertaine, des tests supplémentaires peuvent être nécessaires pour diagnostiquer les causes rares de l'HAGMA.3. Les causes rares de HAGMA sont une accumulation de diéthylène glycol, de 5-oxoproline et de D-lactate.4. L'acidose secondaire à une accumulation de 5-oxoproline peut se produire même avec des doses « thérapeutiques ¼ d'acétaminophène chez les patients qui l'ont reçu régulièrement pendant une période prolongée et qui ont épuisé leurs réserves de glutathion.5. Les facteurs de risque pour l'épuisement des réserves de glutathion incluent la malnutrition, l'âge plus avancé, la septicémie, la grossesse, les maladies chroniques multiples et l'insuffisance rénale chronique.

Point of care molecular and antigen detection tests for COVID-19: current status and future prospects.

INTRODUCTION: Detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been critical to support and management of the COVID-19 pandemic. Point of care testing (POCT) for SARS-CoV-2 has been a widely used tool for detection of SARS-CoV-2. AREAS COVERED: POCT nucleic acid amplification tests (NAATs) and rapid antigen tests (RATs) have been the most readily used POCT for SARS-CoV-2. Here, current knowledge on the utility of POCT NAATs and RATs for SARS-CoV-2 are reviewed and discussed alongside aspects of quality assurance factors that must be considered for successful and safe implementation of POCT. EXPERT OPINION: Use cases for implementation of POCT must be evidence based, regardless of the test used. A quality assurance framework must be in place to ensure accuracy and safety of POCT.

Routine Screening for Central and Primary Adrenal Insufficiency during Immune-Checkpoint Inhibitor Therapy: An Endocrinology Perspective for Oncologists.

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated hypothalamic-pituitary-adrenal axis disruption can lead to hypocortisolism. This is a life-threatening but difficult to diagnose condition, due to its non-specific symptoms that overlap with symptoms of malignancy. Currently, there is no consensus on how to best screen asymptomatic patients on ICI therapy for hypophysitis with serum cortisol. METHODS: A retrospective chart review of patients treated with ICI in a tertiary care centre was conducted to assess the rate of screening with cortisol and whether this had an impact on diagnosis of ICI-hypophysitis in the preclinical stage. Patients were identified as having hypophysitis with an adrenocorticotropin hormone (ACTH) deficiency based on chart review of patients with cortisol values ≤ 140 nmol/L (≤5 mcg/dL). We also assessed what proportion of cortisol values were drawn at the correct time for interpretation (between 6 AM and 10 AM). RESULTS: Two hundred and sixty-five patients had 1301 cortisol levels drawn, only 40% of which were drawn correctly (between 6 and 10 AM). Twenty-two cases of hypophysitis manifesting with ACTH deficiency were identified. Eight of these patients were being screened with cortisol following treatment and were detected in the outpatient setting. The remaining 14 patients were not screened and were diagnosed when symptomatic, after an emergency room visit or hospital admission. Sixty percent of the cortisol tests were uninterpretable as they were not drawn within the appropriate time window. CONCLUSION: Measuring morning serum cortisol in asymptomatic patients on ICI therapy is a fast and inexpensive way to screen for hypophysitis and should become the standard of care. Random serum cortisol measurement has no clinical value. Education needs to be provided on when to correctly perform the test and how to interpret it and we provide an algorithm for this purpose. The adoption and validation of such an algorithm as part of routine practice could significantly reduce morbidity and mortality in patients, especially as ICI therapy is becoming increasingly commonplace.

Identifying and Reducing Errors in Point-of-Care Testing.

Point-of-care testing (POCT) refers to diagnostic testing performed outside of the central laboratory, near to the patient and often at the patient bedside. This testing is generally performed by clinical staff who are not laboratory trained and, as such, often do not appreciate the importance of quality assurance (QA) activities aimed at ensuring the quality of testing performed. Within hospital environments, it is typically the central laboratory that oversees POCT and that ensures QA practices are in-place. Audits for compliance of POCT users with policies and procedures in place are key to informing quality improvement initiatives. Here, audit and follow-up data and the results from three quality improvement initiatives are discussed. These examples demonstrate where QA audit practices led to a reduction in POCT errors and improved the quality of result interpretation.

Evaluation of the Abbott PanbioTM COVID-19 Ag rapid antigen test for the detection of SARS-CoV-2 in asymptomatic Canadians.

Several rapid testing methodologies have been approved for testing of symptomatic individuals but have not been validated for asymptomatic screening. We evaluated performance of the Abbott PanbioTM COVID-19 rapid antigen assay in the asymptomatic setting. We conducted a prospective study in an urban assessment center and in the context of long-term care staff screening. A total of 3014 individuals submitted paired nasopharyngeal samples, which were tested in parallel with the rapid antigen and laboratory-based, RT-PCR assays SARS-CoV-2 detection. There was 54.5% concordance in positive results between the rapid antigen assay and RT-PCR. All positive rapid antigen assay results were confirmed by RT-PCR. The negative predictive value of the rapid antigen assay minimally improved on the negative pre-test probability of SARS-CoV-2 infection. The Abbott PanbioTM COVID-19 rapid antigen test allowed for faster identification of infected individuals but cannot be used to rule-out SARS-CoV-2 infection.

Rapid COVID-19 testing: Speed, quality and cost. Can you have all three?

KEY MESSAGES.

Canadian Society of Clinical Chemists (CSCC) consensus guidance for testing, selection and quality management of SARS-CoV-2 point-of-care tests.

OBJECTIVES: A consensus guidance is provided for testing, utility and verification of SARS-CoV-2 point-of-care test (POCT) performance and implementation of a quality management program, focusing on nucleic acid and antigen targeted technologies. DESIGN AND METHODS: The recommendations are based on current literature and expert opinion from the members of Canadian Society of Clinical Chemists (CSCC), and are intended for use inside or outside of healthcare settings that have varied levels of expertise and experience with POCT. RESULTS AND CONCLUSIONS: Here we discuss sampling requirements, biosafety, SARS-CoV-2 point-of-care testing methodologies (with focus on Health Canada approved tests), test performance and limitations, test selection, testing utility, development and implementation of quality management systems, quality improvement, and medical and scientific oversight.

Quality assurance practices for point of care testing programs: Recommendations by the Canadian society of clinical chemists point of care testing interest group.

Point of Care Testing (POCT) refers to clinical laboratory testing performed outside the central laboratory, nearer to the patient and sometimes at the patient bedside. The testing is usually performed by clinical staff, such as physicians or nurses, who are not laboratory trained. This document was developed by the POCT Interest group of the Canadian Society of Clinical Chemists (CSCC) as practical guidance for quality assurance practices related to POCT performed in hospital and outside hospital environments. The aspects of quality assurance addressed in this document include: (1) device selection, (2) initial device verification, (3) ongoing device verification, (4) ongoing quality assurance including reagent and quality control (QC) lot changes, and (5) quality management including operator and document management.

Practical challenges related to point of care testing.

Point of care testing (POCT) refers to laboratory testing that occurs near to the patient, often at the patient bedside. POCT can be advantageous in situations requiring rapid turnaround time of test results for clinical decision making. There are many challenges associated with POCT, mainly related to quality assurance. POCT is performed by clinical staff rather than laboratory trained individuals which can lead to errors resulting from a lack of understanding of the importance of quality control and quality assurance practices. POCT is usually more expensive than testing performed in the central laboratory and requires a significant amount of support from the laboratory to ensure the quality testing and meet accreditation requirements. Here, specific challenges related to POCT compliance with accreditation standards are discussed along with strategies that can be used to overcome these challenges. These areas include: documentation of POCT orders, charting of POCT results as well as training and certification of individuals performing POCT. Factors to consider when implementing connectivity between POCT instruments and the electronic medical record are also discussed in detail and include: uni-directional versus bidirectional communication, linking patient demographic information with POCT software, the importance of positive patient identification and considering where to chart POCT results in the electronic medical record.

Pharmacogenetics of chronic pain management.

OBJECTIVE: The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical practice. Drug metabolism and responses are affected by many factors, with genetic variations offering only a partial explanation of an individual's response. There is a paucity of evidence for the benefits of pharmacogenetic testing in the context of pain management. DESIGN AND METHODS: We reviewed the literature between 2000 and 2013, and references cited therein, using various keywords related to pain management, pharmacology and pharmacogenetics. RESULTS: Opioids continue to be the mainstay of chronic pain management. Several non-opioid based therapies, such as treatment with cannabinoids, gene therapy and epigenetic-based approaches are now available for these patients. Adjuvant therapies with antidepressants, benzodiazepines or anticonvulsants can also be useful in managing pain. Currently, laboratory monitoring of pain management patients, if performed, is largely through urine drug measurements. CONCLUSIONS: Drug half-life calculations can be used as functional markers of the cumulative effect of pharmacogenetics and drug-drug interactions. Assessment of half-life and therapeutic effects may be more useful than genetic testing in preventing adverse drug reactions to pain medications, while ensuring effective analgesia. Definitive, mass spectrometry-based methods, capable of measuring parent drug and metabolite levels, are the most useful assays for this purpose. Urine drug measurements do not necessarily correlate with serum drug concentrations or therapeutic effects. Therefore, they are limited in their use in monitoring efficacy and toxicity.

Validity of establishing pediatric reference intervals based on hospital patient data: a comparison of the modified Hoffmann approach to CALIPER reference intervals obtained in healthy children.

OBJECTIVES: To compare pediatric reference intervals calculated using hospital-based patient data with those calculated using samples collected from healthy children in the community as part of the CALIPER study. METHODS: Hospital-based data for 13 analytes (calcium, phosphate, iron, ALP, cholesterol, triglycerides, creatinine, direct bilirubin, total bilirubin, ALT, AST, albumin and magnesium), measured on the Vitros 5600, collected between 2007 and 2011 were obtained. The data for each analyte were partitioned by age and gender as previously defined by the CALIPER study. Outliers in each partition were removed using the Tukey method. The cumulative distribution function (cdf) was then determined for each analyte value following which, the inverse cdf values of a standard Gaussian distribution were calculated. The analyte values were plotted against the inverse cdf of the standard Gaussian distribution. Piece-wise regression determined the linear portion of the resulting graph using the statistical software R. Linear regression determined an equation for the linear portion in each partition and reference intervals were calculated by extrapolating to identify the 2.5th and 97.5th centiles in each partition based on the inverse cdf values (which would correspond to the values -1.96 and 1.96 of the Gaussian distribution). Using the 90% confidence intervals for the reference intervals defined by CALIPER and the Reference Change Value (RCV) as the criteria, these calculated reference intervals were compared to those reported previously by CALIPER. Reference samples were also measured on the Vitros 5600 analyzer in an attempt to validate the calculated reference intervals. RESULTS: In general, the reference intervals calculated from hospital-based data were generally wider than those calculated by CALIPER. None of the reference intervals calculated using the Hoffmann approach fell completely within the 90% confidence intervals calculated by CALIPER. CONCLUSIONS: These results suggest that calculating pediatric reference intervals from hospital-based data may be useful, as a guide, in some cases but will likely not replace the need to establish reference intervals in healthy pediatric populations.

Pediatric reference intervals: challenges and recent initiatives.

The clinical laboratory plays a critical role in healthcare delivery by providing objective data on specific biomarkers that directly aid in the diagnosis and monitoring of a wide range of clinical disorders. Reliable and accurate reference intervals for laboratory analyses are integral for correct interpretation of clinical laboratory test results and, therefore, for appropriate clinical decision-making. Ideally, reference intervals should be established based on a healthy population and stratified for key covariates including age, gender and ethnicity. However, establishing reference intervals can be challenging as it requires the collection of large numbers of samples from healthy individuals. This challenge is further augmented in pediatrics, where dynamic changes due to child growth and development markedly affect circulating levels of disease biomarkers. As a result, even larger reference populations are required to reliably calculate reference intervals. In this review, we outline the challenges specific to establishing pediatric reference intervals and highlight recent initiatives aimed at closing existing gaps in current knowledge. We also outline recommended approaches to the development of reference intervals and detail several alternative approaches. Finally, reference intervals for emerging and novel biomarkers of pediatric disease are discussed along with a number of potential alternative sample types.

Characterization of the temporal and spatial expression of a disintegrin and metalloprotease 17 in the human endometrium and fallopian tube.

Metalloproteinases are thought to mediate shedding of mucins from the endometrium surface, exposing oligosaccharide ligands involved in implantation. We hypothesized that a disintegrin and metalloprotease 17 (ADAM17) is upregulated during the "window of implantation" in human endometrium but not in fallopian tube (FT) where implantation is pathological. Endometrial and FT expression of ADAM17 throughout the menstrual cycle was determined using quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. The ADAM17 transcription was significantly downregulated (P < .01) during the early-midsecretory phase in the endometrium but not in the FT. The ADAM17 was localized to the surface of epithelial cells and was also detected in the endometrial stroma during the late luteal and proliferative phase of the cycle. Physiological levels of estradiol significantly (P < .05) upregulated ADAM17 transcription in vitro. Our observations do not support the role of ADAM17 in shedding of mucins during the window of implantation. The precise role of ADAM17 in the female reproductive tract requires further investigation.

Development of a multiplex selected reaction monitoring assay for quantification of biochemical markers of down syndrome in amniotic fluid samples.

Down syndrome (DS) is one of the most common chromosomal abnormalities affecting about 1 of every 700 fetuses. Current screening strategies have detection rates of 90-95% at a 5% false positive rate. The aim of this study was to discover new biomarkers of DS in amniotic fluid by using a multiplex selected reaction monitoring assay. Nine proteins were analyzed: CEL, CPA1, MUC13, CLCA1, MUC5AC, PLUNC, and HAPLN1, and CGB as positive control and serotransferrin as negative control. One proteotypic peptide for each protein was selected, and internal heavy isotope-labeled peptide standards were spiked into the samples. Fifty-four samples from pregnant women carrying normal (n = 37) or DS-affected (n = 17) fetuses were analyzed. The median protein concentrations for DS and normal samples, respectively, were as follows: 20 and 49 ng/mL (p < 0.01) for CEL; 3.7 and 14 ng/mL (p < 0.001) for CPA1; 80 and 263 ng/mL (p < 0.001) for MUC13; 46 and 135 ng/mL (p < 0.001) for CLCA1; 0.65 and 0.93 µg/mL (p < 0.05) for MUC5AC; 61 and 73 ng/mL (p > 0.05) for PLUNC; 144 and 86 ng/mL (p < 0.01) for HAPLN1; 0.89 and 0.54 µg/mL (p = 0.05) for CGB; 91 and 87 µg/mL (p > 0.05) for serotransferrin. Statistically significant differences were found in six out of the seven candidate proteins analyzed, reflecting a different regulation in DS.