Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site M^Hgb and URIT-12 Point-of-Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in Durban, South Africa

<div><p>In South Africa, various point-of-care hemoglobin meters are used. However, the regulatory framework for approval, implementation and oversight of use of point-of-care hemoglobin meters is suboptimal. We assessed the diagnostic accuracy of the HemoCue Hb 301, STAT-Site M^Hgb and URIT-12 point-of-care hemoglobin meters, compared to a central laboratory based reference assay, in a central laboratory and a community based clinic in Durban, South Africa. Differences in performance of the point-of-care assays, compared to the reference assay, were more pronounced in the community based clinic. Results were reasonable for the HemoCue Hb 301, but poor for the STAT-Site M^Hgb and the URIT-12. Poor test performance of point-of-care hemoglobin meters, and inadequate evaluations and oversight in South Africa, leads to suboptimal clinical care and clinical research, and increased costs. There is a need for proper evaluation and quality assurance of point-of-care tests, the results of which should be made widely available to key stakeholders.</p></div

Correlation of the 3 point-of-care assays with values within the dynamic range of the reference Hemoglobin meter in 60 samples in a central laboratory (phase 1), and 100 samples in a community based clinical setting (phase 2).

<p>In phase 1 of the study the STAT-Site had a high failure rate. It seems that this was related to uneven migration of the sample through the sample strip, resulting in the sample migration time exceeding the maximum time specified by the manufacturer.</p

Correlation of the 3 point-of-care assays with values within the dynamic range of the reference hemoglobin meter in 100 samples in a community based clinical setting in phase 2 of the study.

<p>Dots in the blue quadrant indicate that the point-of-care assay missed anemia, i.e., misclassified a finger prick sample as non-anemic where the venous blood sample was classified as anemic according to the reference assay in a central laboratory. Dots in the red quadrant indicate that the point-of-care assay misclassified as anemic a sample that was non-anemic according to the reference assay.</p

Phase 2 (community based clinical setting) sensitivity, specificity, and predictive values for the 3 point-of-care tests to detect or exclude anemia.

<p>Phase 2 (community based clinical setting) sensitivity, specificity, and predictive values for the 3 point-of-care tests to detect or exclude anemia.</p

Bland-Altman plots comparing the reference laboratory test with the 3 point-of-care assays in phase 1 (left column) and phase 2 (right column).

<p>In phase 1 of the study the STAT-Site had a high failure rate. It seems that this was related to uneven migration of the sample through the sample strip, resulting in the sample migration time exceeding the maximum time specified by the manufacturer.</p

Unciaphenol, an Oxygenated Analogue of the Bergman Cyclization Product of Uncialamycin Exhibits Anti-HIV Activity

Unciaphenol (<b>2</b>), an oxygenated analogue of the Bergman cyclization product of the enediyne uncialamycin (<b>1</b>), has been isolated along with <b>1</b> from cultures of the actinomycete Streptomyces uncialis. It is proposed that the C-22 OH substituent in <b>2</b> might arise from the attack of a nucleophilic oxygen species on the <i>p</i>-benzyne diradical intermediate <b>IA</b> in the Bergman cyclization of <b>1</b>. <b>2</b> shows in vitro anti-HIV activity against viral strains that are resistant to clinically utilized anti-retroviral therapies

Gag expression in Jurkat cells transfected with <i>gag</i> mRNA.

<p>A. Gag production correlates with mRNA concentration. Jurkat cells were transfected by electroporation with increasing doses of synthetic codon-optimized gag mRNA. After 24 hours, the amount of Gag in the supernatant was determined by ELISA. The line shows linear fit (R²>0.99). B. The amount of Gag in cell supernatants is representative of the median Gag production in electroporated cells. Jurkat cells were transfected with varying doses of gag mRNA; after 24 hours, cell supernatants were harvested for ELISA, and cell pellets were fixed, permeabilized, and stained with anti-Gag/p24 antibody. Gag production as measured by ELISA is shown on the Y axis; Gag production as measured by MFI (median fluorescence intensity) is shown on the X axis. Line shows linear fit (R² = 0.93). ELISA values are the average of triplicate wells.</p

Putative HIV-1 Vpu inhibitors identified from virtual screening of the p-ANAPL.

<p><b>A,</b> Structures of four molecules predicted to interact with the Vpu ion channel [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121099#pone.0121099.ref020" target="_blank">20</a>]. <b>B,</b> Alignment of four molecules. Chemical substituents that define a shared pharmacophore are highlighted. <b>C,</b> Eight p-ANAPL molecules containing aspects of the shared pharmacophore. For each compound, root mean square deviation (RMSD) values are shown in parentheses.</p

Effects of p-ANAPL compounds on cell viability and <i>in vitro</i> HIV-1 replication.

<p><b>A,</b> CEM-GXR cell viability at Day 4 in the presence of p-ANAPL compounds at defined concentrations. Data are normalized to the percent of viable cells in an HIV-1_NL4-3-infected culture plus 0.1% DMSO. <b>B,</b> HIV-1 replication in CEM-GXR cells at Day 4 in the presence of compounds. Data are normalized to percent HIV-1_NL4-3-infected cells plus 0.1% DMSO. Dose-response plots of ixoratannin A-2 and boldine are highlighted with blue and green arrows, respectively. <b>C</b>, PBMC viability at Day 5 in the presence of p-ANAPL compounds. Data are normalized to the percent of viable cells in an uninfected culture plus 0.1% DMSO. <b>D</b>, HIV-1 replication in PBMCs at Day 12 in the presence of p-ANAPL compounds, as measured by p24^Gag levels in cell culture supernatants. Data are normalized to percent HIV-1_NL4-3-infected cells plus 0.1% DMSO.</p

Replication of HIV-1_NL4-3, HIV-1_Δvpu, and drug-resistant HIV-1 strains in CEM-GXR cells.

<p>Data shown are at Day 4 in the presence of 0.1 μM of established ARVs, relative to the replication rate of each HIV-1 strain in the presence of 0.1% DMSO vehicle control. *, p < 0.004 vs. HIV-1_NL4-3 replication.</p