Point-of-care testing performed by healthcare professionals outside the hospital setting: consensus based recommendations from the IFCC Committee on Point-of-Care Testing (IFCC C-POCT).

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Point-of-Care Testing (C-POCT) supports the use of point-of-care testing (POCT) outside of the hospital setting performed by healthcare professionals without formal laboratory education because of its numerous benefits. However, these benefits are associated with risks that must be managed, to ensure the provision of reliable test results and minimize harm to the patient. Healthcare professionals, local regulatory bodies, accredited laboratories as well as manufacturers should actively be engaged in education, oversight and advice to ensure that the healthcare professional selects the appropriate equipment and is able to analyze, troubleshoot and correctly interpret the point-of-care (POC) test results.

An approach for determining allowable between reagent lot variation.

Clinicians trust medical laboratories to provide reliable results on which they rely for clinical decisions. Laboratories fulfil their responsibility for accurate and consistent results by utilizing an arsenal of approaches, ranging from validation and verification experiments to daily quality control procedures. All these procedures verify, on different moments, that the results of a certain examination procedure have analytical performance characteristics (APC) that meet analytical performance specifications (APS) set for a particular intended use. The APC can in part be determined by estimating the measurement uncertainty component under conditions of within-laboratory precision (uRw), which comprises all components influencing the measurement uncertainty of random sources. To maintain the adequacy of their measurement procedures, laboratories need to distinguish aspects that are manageable vs. those that are not. One of the aspects that may influence uRw is the momentary significant bias caused by shifts in reagent and/or calibrator lots, which, when accepted or unnoticed, become a factor of the APC. In this paper, we postulate a model for allocating a part of allowable uRw to between-reagent lot variation, based on the need for long-term consistency of the measurement variability for that specific measurand. The allocation manages the ratio between short-term and long-term variation and indicates laboratories when to reject or correct certain variations due to reagent lots.

Comparison of ultrasound with biomarkers to identify large-for-gestational age in women screened for gestational diabetes mellitus.

OBJECTIVE: Large-for-gestational-age (LGA) is associated with both fetal and maternal complications. One of the few modifiable risk factors for LGA is Gestational Diabetes Mellitus (GDM); for this reason, fetal growth is usually monitored by ultrasound in the third trimester. This prospective study compared a panel of ten established biomarkers measured at the time of selective screening for GDM at 26-28 weeks gestation with the ultrasound prediction of LGA. METHOD: Women were recruited using convenience sampling and consented at the first antenatal visit. Women with maternal risk factors for GDM attended for the one-step 75 g oral glucose tolerance test. An additional blood sample was taken for biomarker measurement. GDM was diagnosed according to the 2013 World Health Organization (WHO) criteria. Fetal biometry, including the abdominal circumference (AC) and the fetal abdominal subcutaneous tissue (FAST) thickness, were measured at 37 weeks gestation. RESULTS: Of the 195 women included, 105 (53.8%) had GDM. Of the 195 babies, 36 (18.5%) were LGA. Whether the woman had GDM or not, fetal biometry was strongly predictive of LGA but none of the following biomarkers measured at 26-28 weeks gestation alone or in combination were predictive: c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin. CONCLUSIONS: In women diagnosed with GDM, surveillance of fetal growth to identify LGA by ultrasound should continue in the third trimester. None of the ten established maternal biomarkers measured at the time of the OGTT was as strongly predictive of LGA as ultrasound.

Improving the laboratory result release process in the light of ISO 15189:2012 standard.

The ISO 15189:2012 standard section 5.9.1 requires laboratories to review results before release, considering quality control, previous results, and clinical information, if any, and to issue documented procedures about it. While laboratory result reporting is generally regarded as part of the post-analytical phase, the result release process requires a general view of the total examination process. Reviewing test results may follow with troubleshooting and test repetition, including reanalyzing an individual sample or resampling. A systematic understanding of the result release may help laboratory professionals carry out appropriate test repetition and ensure the plausibility of laboratory results. In this paper, we addressed the crucial steps in the result release process, including evaluation of sample quality, critical result notification, result reporting, and recommendations for the management of the result release, considering quality control alerts, instrument flags, warning messages, and interference indexes. Error detection tools and plausibility checks mentioned in the present paper can support the daily practice of results release.

Exposure to tobacco smoke measured by urinary nicotine metabolites increases risk of p16/Ki-67 co-expression and high-grade cervical neoplasia in HPV positive women: A two year prospective study.

BACKGROUND: Human papillomavirus (HPV) is considered the strongest epidemiologic risk factor for cervical cancer. However, it is not a sufficient cause given the high prevalence of transient infections. We examined the relationship between exposure to tobacco smoke, measured using urinary nicotine metabolite concentrations, and p16/Ki-67 co-expression in cervical smears and subsequent risk of developing CIN2+/CIN3+ lesions in HPV positive women. METHODS: This prospective longitudinal study enrolled women presenting to colposcopy with cytological abnormalities LSIL/ASCUS at the National Maternity Hospital, Dublin. Women gave a urine sample which was used to perform the Nicotine Metabolite Assay (Siemens). HPV positive (HC2) cervical smears were stained by immunocytochemistry for p16/Ki-67 (CINtec PLUS, Roche). Two year follow-up data, including histological diagnosis, was collected for each woman. Crude and adjusted odds ratios were calculated using logistic regression to investigate associations between tobacco smoke, p16/Ki-67 positivity and CIN2+/CIN3 + . RESULTS: In total, 275 HPV positive women were included. Women with nicotine metabolite concentrations above 500 ng/mL, indicative of smoking, were classified as smokers. Smokers were at an increased risk of testing positive for p16/Ki-67 (OR 1.678; 1.027-2.740) and CIN2+ and CIN3+ (OR 1.816; 1.107-2.977 and OR 2.453; 1.200-5.013) in compared to non-smokers. In p16/Ki-67 positive women, smoking further increased their risk of CIN2+/CIN3+ (OR 2.290; 1.017-5.159 and OR 3.506 (1.534-8.017). CONCLUSION: HPV positive women exposed to tobacco smoke are at a higher risk of testing positive for p16/Ki-67 co-expression. Risk of high-grade disease is almost doubled in women who are exposed to tobacco smoke.

The use of biomarkers at the end of the second trimester to predict Gestational Diabetes Mellitus.

OBJECTIVE: Previous studies that investigated the relationship between biomarkers and gestational diabetes mellitus (GDM) generally focused on individual biomarkers with significant heterogeneity in terms of the screening methodologies, diagnostic criteria for GDM and sample handling of glucose within these studies. This prospective study used an established panel of ten biomarkers to determine if they could predict the diagnosis of GDM. STUDY DESIGN: Women with risk factors for GDM were recruited at their first antenatal visit. They attended for an oral glucose tolerance test at 26-28 weeks' gestation with strict preanalytical handling of glucose samples to minimise glycolysis. A fasting plasma sample taken simultaneously was stored at -80 °C and analysed in bulk for 10 biomarkers (insulin, c-peptide, glucagon, ghrelin, gastric inhibitory polypeptide (GIP), glucagon like peptide-1 (GLP-1), leptin, visfatin, resistin and plasminogen activator inhibitor-1 (PAI-1)) using the Bio-plex-pro Human Diabetes Assay. RESULTS: Insulin and C-peptide levels in the third tertile were associated with the development of GDM (adjusted odds ratio (aOR) 2.6, 95 % CI 1.3-5.0, p = 0.005 and aOR 3.7, 95 % CI 1.8-7.4, p < 0.001 respectively, adjusted for maternal obesity). Elevated levels of ghrelin were associated with a lower odds of developing GDM, after adjustment for maternal obesity. However, approximately half of the women with GDM who were in the obesity category did not have insulin or c-peptide levels in the third tertile. CONCLUSIONS: While three of the ten biomarkers were statistically associated with an increased risk of GDM, the large overlap in values between those with normal and abnormal glucose tolerance meant that the biomarkers (alone or in combination) were not useful clinically.

A Prospective Evaluation of Point-of-Care Measurements of Maternal Glucose for the Diagnosis of Gestational Diabetes Mellitus.

BACKGROUND: Point-of-care (POC) measurement of glucose is currently recommended only for the monitoring of gestational diabetes mellitus (GDM). This prospective observational study evaluated the use of POC measurements of maternal glucose to diagnose GDM in women being screened selectively with a 1-step 75 g oral glucose tolerance test (OGTT). METHODS: The strictest preanalytic and analytic international laboratory standards were applied to measure maternal plasma glucose at fasting and at 1 and 2 h post glucose load. The recent International Association of Diabetes and Pregnancy Study Groups diagnostic criteria were used. At the same time, maternal capillary glucose was measured. Because of differences in plasma and capillary glucose measurements, regression analysis of POC capillary glucose results vs laboratory plasma glucose results was conducted. The regression equations for plasma glucose were derived in a derivation cohort (n = 102). These equations were applied in the validation cohort (n = 100). Predicted and actual plasma glucose values were compared. RESULTS: Of the 202 women screened, 36.6% were nulliparous, 56.4% were obese, and 81.2% were Irish-born. Two thirds had a single risk factor for GDM, and a third had multiple risk factors. Based on the plasma measurements, 53.5% had GDM. As a predictor of GDM, the diagnostic accuracy of POC measurement was 83.0% (95% confidence interval, 74.2-89.8). CONCLUSIONS: In high-resource settings where measures to inhibit glycolysis are implemented, the use of POC measurements for the diagnosis of GDM is not justified based on this study. In low- and medium-resource settings, where measures to inhibit glycolysis are not achievable, regression analysis using POC measurements may be acceptable compared with plasma samples subject to glycolysis.

Maternal obesity and dyslipidemia associated with gestational diabetes mellitus (GDM).

OBJECTIVE: The association between gestational diabetes mellitus (GDM) and maternal dyslipidemia is well established, however, the role of obesity in this relationship is not well defined. We examined the relationship between maternal obesity at the first prenatal visit and fasting lipids measured at the time of the oral glucose tolerance test (OGTT) in women screened selectively for GDM. STUDY DESIGN: This prospective observational study was conducted in a large university maternity hospital. Women were recruited at the first prenatal visit following measurement of their weight and height. Clinical and sociodemographic details were recorded. Women with maternal risk factors for GDM were screened selectively with a one-step 75 g OGTT at 26-28 weeks gestation. GDM was diagnosed based on the World Health Organization (WHO) 2013 criteria. Fasting lipids were measured simultaneously. Maternal lipid levels and their relationship with GDM and obesity were analysed with linear and logistic models. RESULTS: Of the 275 women recruited at the first antenatal visit 202 attended for their OGTT at 26-28 weeks' and 53.5 % (108) had GDM based on the WHO criteria. The women with GDM were more likely to have obesity (70.4 % vs. 42.6 %, P < 0.001). Compared with women with a normal OGTT (n=94), women with GDM had higher triglycerides (P=0.023) and a lower HDL-Cholesterol (P = 0.013). However, when the cohort with GDM were stratified according to obesity, this trend was only seen in the women who had a BMI >29.9kg/m2. Based on tertiles, women with GDM had a higher odds ratio of increased triglycerides (odds ratio 3.2 (95 % confidence interval; 1.4-6.9), P = 0.004) and lower HDL-Cholesterol (odds ratio 2.2, (95 % confidence interval; 1.1-4.7), P = 0.036) and an increased TG:HDL-cholesterol ratio (odds ratio 2.3, (95 % confidence interval; 1.1-4.9), P = 0.026), only if they had obesity. CONCLUSION: Our findings suggest that the epidemiological association between GDM and dyslipidemia is mediated through maternal obesity. Women with obesity alone or GDM alone did not have an elevated OR for dyslipidemia. Interventions designed to optimise maternal lipids should prioritise women with obesity and it may be preferable for these interventions to start prior to conception.

Time and temperature affect glycolysis in blood samples regardless of fluoride-based preservatives: a potential underestimation of diabetes.

Background The inhibition of glycolysis prior to glucose measurement is an important consideration when interpreting glucose tolerance tests. This is particularly important in gestational diabetes mellitus where prompt diagnosis and treatment is essential. A study was planned to investigate the effect of preservatives and temperature on glycolysis. Methods Blood samples for glucose were obtained from consented females. Lithium heparin and fluoride-EDTA samples transported rapidly in ice slurry to the laboratory were analysed for glucose concentration and then held either in ice slurry or at room temperature for varying time intervals. Paired fluoride-citrate samples were received at room temperature and held at room temperature, with analysis at similar time intervals. Results No significant difference was noted between mean glucose concentrations when comparing different sample types received in ice slurry. The mean glucose concentrations decreased significantly for both sets of samples when held at room temperature (0.4 mmol/L) and in ice slurry (0.2 mmol/L). A review of patient glucose tolerance tests reported in our hospital indicated that 17.8% exceeded the recommended diagnostic criteria for gestational diabetes mellitus. It was predicted that if the results of fasting samples were revised to reflect the effect of glycolysis at room temperature, the adjusted diagnostic rate could increase to 35.3%. Conclusion Preanalytical handling of blood samples for glucose analysis is vital. Fluoride-EDTA is an imperfect antiglycolytic, even when the samples are transported and analysed rapidly provides such optimal conditions. The use of fluoride-citrate tubes may offer a viable alternative in the diagnosis of diabetes mellitus.

The role of preanalytical glycolysis in the diagnosis of gestational diabetes mellitus in obese women.

OBJECTIVE: The objective of this prospective observational study was to determine whether the preanalytical management of maternal plasma glucose samples had a significant effect on glucose measurements in obese pregnant women. STUDY DESIGN: Based on the accurate calculation of body mass index in the first trimester, obese women were recruited at their convenience. In 1 cohort, fasting glucose level was measured in early pregnancy; in the other cohort, an oral glucose tolerance test was performed at 24-28 weeks' gestation. Paired samples were taken from all women in both cohorts. The first sample was transferred to the laboratory in iced water for immediate analysis (fast-tracked analysis). The second sample was not placed on ice and transferred according to established hospital practices (hospital-tracked analysis). RESULTS: Of the 24 women who had a fasting glucose test in early pregnancy, the result was abnormal (≥5.1 mmol/L) in 7 women (29%) with hospital-tracked analysis compared with 16 women (67%) with fast-tracked analysis (P < .01). The mean phlebotomy-analysis interval was 119 minutes for the hospital-tracked samples compared with 23 minutes for the fast-tracked samples (P < .001). Of the 24 women who had a glucose tolerance test, the fasting glucose level was abnormal in 4 women (17%) after hospital-tracked analysis compared with 13 women (54%) after fast-tracked analysis (P < .01). The hospital-tracked phlebotomy-analysis interval for the fasting sample of the 24-28 week oral glucose tolerance test cohort was 166 minutes compared with 25 minutes for the fast-tracked samples (P < .001). CONCLUSION: Unless maternal fasting glucose samples are transported on ice and analyzed immediately in the laboratory, gestational diabetes mellitus will be underdiagnosed in obese women.

Serial N-terminal pro-brain natriuretic peptide measurement as a predictor of significant patent ductus arteriosus in preterm infants beyond the first week of life.

UNLABELLED: The aim of the study was to assess the role of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration as a predictor of patent ductus arteriosus (PDA) in very low birth weight infants beyond the first week of life. This was a prospective observational study; newborns with a birth weight < 1500 g were eligible for enrolment. Enrolled infants were screened by echocardiography on day seven of life for the presence of a PDA. This was paired with a blood sample for NT-proBNP level. Echocardiography and NT-proBNP levels were repeated at weekly intervals. The primary outcome was correlation between PDA and NT-proBNP level and between measurements of PDA significance and NT-proBNP. Sixty-nine neonates were enrolled following parental consent. The mean birth weight was 1119 ± 257 g and mean gestational age was 28.6 ± 2.6 weeks. Median NT-proBNP level on day seven was 11469 ng/l in infants with a PDA vs. 898 ng/l in infants without a PDA (p < 0.0001). There was a statistically significant correlation between PDA diameter and NT-proBNP level on day seven, day 14 and day 21. CONCLUSION: NT-proBNP concentration is significantly increased in infants with a PDA and correlates well with PDA diameter in the first three weeks of life.

The role of thromboxane A(2) in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy.

BACKGROUND: To examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction. METHODS: Prospective case control study enrolled smoking and non-smoking women at ≤14 weeks gestation. Maternal urine samples were obtained at ≤14, 28 and 36 weeks. High performance liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to quantify 11-dehydrothromboxane B(2) (TX-M) and 2,3 dinor-6-ketoprostaglandin F1α (PG-M), stable urinary metabolites of thromboxane A(2) and prostacyclin I2. Confirmation of the smoking status was performed by quantitation of urinary nicotine metabolites. Data was analysed using SPSS and Stata(®). RESULTS: Thirty five were enrolled in the smoking group and 32 in the non-smoking group. Smoking resulted higher levels of TX-M at ≤14, 28 and 36 weeks gestation. There was no difference in PG-M at any gestational time point between the two groups. The median customised birthweight centile in the smoking group was 17.0 (0-78) compared to 55.5 (4-100) in the non-smoking group (P<0.001). A causal relationship between elevated TX-M and IUGR could not be established. CONCLUSIONS: Maternal smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A(2) which occurs early in the first trimester.