Screening for hypoglycemia at the bedside in the neonatal intensive care unit (NICU) with the Abbott PCx glucose meter

BACKGROUND: Point of care (POC) glucose meters are routinely used as a screening tool for hypoglycemia in a neonatal setting. Glucose meters however, lack the same accuracy as laboratory instruments for glucose measurement. In this study we investigated potential reasons for this inaccuracy and established a cut off value for confirmatory testing. METHODS: In this prospective study, all patients in the neonatal intensive care unit who had a plasma glucose test ordered were eligible to participate. Demographic information, sample collection information (nine variables) and a recent hematocrit value were recorded for each sample. Glucose measurements were taken at the bedside on the glucose meter (RN PCx) as well as in the laboratory on both the glucose meter (LAB PCx) and the laboratory analyzer (PG). Data were analyzed by simple and mixed-effects regression analysis and by analysis of a receiver operator characteristics (ROC) curve. RESULTS: There were 475 samples analyzed from 132 patients. RN PCx values were higher than PG values (mean = 4.9%), while LAB PCx results were lower (mean = -5.2%) than PG values. Only 31% of the difference between RN PCx – PG and 46% of the difference for LAB PCx – PG could be accounted for by the variables tested. The largest proportion of variance between PCx and PG measurements was explained by hematocrit (about 30%) with a greater effect seen at glucose concentrations ≤4.0 mmol/L (≤72 mg/dL)(48% and 40% for RN PCx and LAB PCx, respectively). The ROC analysis showed that for detection of all cases of hypoglycemia (PG < 2.6 mmol/L)(PG < 47 mg/dL) the PCx screening cut off value would need to be set at 3.8 mmol/L (68 mg/dL) requiring 20% of all samples to have confirmatory analysis by the laboratory method. CONCLUSION: The large difference between glucose results obtained by PCx glucose meter compared to the laboratory analyzer can be explained in part by hematocrit and low glucose concentration. These results emphasize that the glucose meter is useful only as a screening device for neonatal hypoglycemia and that a screening cut off value must be established

ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats

Immune-mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune-mediated erythrocyte destruction, and adverse consequences of long-term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence-based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Haemorheology in Gaucher disease

In Gaucher disease, a deficiency of glucocerebrosidase results in the accumulation of glucocerebroside within the lysosomes of the monocyte–macrophage system. Prior to the availability of enzyme replacement therapy (ERT), splenectomy was often indicated for hypersplenism. Haemorheological abnormalities could be expected in view of the anaemia and abnormal lipid metabolism in these patients and the role of the spleen in controlling erythrocyte quality. Objectives: To investigate the effect of Gaucher disease on blood and plasma viscosity, erythrocyte aggregation and erythrocyte deformability, and to determine whether observed rheological differences could be attributed to splenectomy. Methods: Haematological and haemorheological measurements were made on blood collected from 26 spleen-intact patients with Gaucher disease, 16 splenectomised patients with Gaucher disease, 6 otherwise healthy asplenic non-Gaucher disease subjects and 15 healthy controls. Results: No haemorheological differences could be demonstrated between spleen-intact patients with Gaucher disease and the control group. Compared to controls, both asplenic Gaucher disease and asplenic non-Gaucher disease study groups had a reduced MCHC (P = 0.003 and 0.005, respectively) and increased whole blood viscosity at 45% haematocrit (Hct), relative viscosity and red cell aggregation index – all measured at low shear (P < 0.05 for all). Additionally, asplenic patients with Gaucher disease alone showed an increased MCV (P = 0.006), an increased whole blood viscosity at 45% Hct measured at high shear (P = 0.019), and a reduced relative filtration rate (P = 0.0001), compared to controls. Conclusion: These observations demonstrate a direct and measurable haemorheological abnormality in Gaucher disease only revealed when there is no functioning spleen to control erythrocyte quality

Blood viscosity and its relationship to iron deficiency, symptoms, and exercise capacity in adults with cyanotic congenital heart disease

Objectives This study sought to determine the relationship between blood viscosity and iron deficiency and their impact on symptoms and exercise function in adults with cyanotic congenital heart disease. Background Iron deficiency is believed to raise whole blood viscosity in cyanotic congenital heart disease, although available data are inconsistent. Methods Thirty-nine cyanotic adults were prospectively assessed for iron deficiency (transferrin saturation ≤5%), hyperviscosity symptoms, and exercise capacity. Same-day measurement of whole blood viscosity and hematocrit (Hct) adjusted viscosity (cells resuspended in autologous plasma to Hct of 45%) was performed at shear rates ranging from 0.277 s−1 to 128.5 s−1. Results Viscosity did not differ between patients with iron deficiency (n = 14) and those without (n = 25). Whole blood viscosity correlated with Hct (r = 0.63, p < 0.001 at low shear and r = 0.84, p < 0.001 at high shear) but not with red blood cell size or iron indices. Hyperviscosity symptoms were independent of iron indices but directly correlated with increased Hct-adjusted viscosity (r = 0.41, p = 0.01). Exercise capacity did not differ in iron-deficient patients. However, peak oxygen consumption was higher in those with Hct ≥ 65% (12.6 ± 3.4 ml/kg/m2 vs. 9.8 ± 2.6 ml/kg/m2, mean ± SD, p = 0.036) despite higher whole blood viscosity in these same individuals (p < 0.01 for all shear rates). Conclusions Iron deficiency is common in cyanotic adults but does not alter viscosity. Hyperviscosity symptoms are associated with a higher Hct-adjusted viscosity independent of cell size or iron stores. Higher Hct is associated with better exercise capacity. Further work to understand the origin of hyperviscosity symptoms is warranted