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Rapid point-of-care tests provide plausible diagnostic strategy for hepatitis B surface antigen (HBsAg) in low resource areas. However, their utility depends upon their overall performance. Our objective was to meta-analyze the diagnostic accuracy of rapid point-of-care tests for HBsAg.
Literature search was done with the help of a metasearch engine Mettā, a query interface for retrieving articles from five leading medical databases. Studies that employed rapid point-of-care tests for detection of HBsAg and compared the results with reference test were included. Two reviewers performed quality assessment of the studies and extracted data for estimating test accuracy. Twenty-seven studies were meta-analyzed and stratified by multiple parameters.
Twenty-seven studies had evaluated 49 test brands and generated 76 data points. Sensitivity of individual tests varied widely and were heterogeneous (range 43.5%-99.8%); while specificity estimates were more robust and close to 100% (range 90%-100%). Overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio for all tests were 97.1% (95% CI, 96.1%-97.9%), 99.9% (CI, 99.8%-100%), 118.4 (CI, 84.7-165.5), 0.032 (CI, 0.023-0.045) and 4094.7 (CI, 2504.1-6600.8) respectively. This suggested high pooled accuracy for all studies. We found substantial heterogeneity between studies. Three factors (study location, reference standard and study score) appeared most strongly associated with test estimates and observed heterogeneity. The Determine test showed consistency in performance in studies done across developed and developing countries and the Determine and the BinaxNOW tests had significantly higher estimates than pooled estimates of remaining tests. Tests revealed analytical sensitivity of 4 IU/ml against manufacturer’s claim of 0.5 IU/ml; reduced sensitivity with HBsAg mutants and poor performance in seroconversion panels.
Tests with better analytical sensitivity need to be developed and their feasibility and outcomes in various clinical settings need to be addressed.
HBsAg, rapid test, performance evaluation, meta-analysis
Accuracy of Rapid Point-of-Care Diagnostic Tests for Hepatitis B Surface Antigen—A Systematic Review and Meta-analysis
Mehnaaz S. Khuroo,∗ Naira S. Khuroo,† and Mohammad S. Khuroo†∗
The nature of spontaneous mutations, including their rate, distribution across the genome, and fitness consequences, is of central importance to biology. However, the low rate of mutation has made it difficult to study spontaneous mutagenesis, and few studies have directly addressed these questions. Here, we present a direct estimate of the mutation rate and a description of the properties of new spontaneous mutations in the unicellular green alga Chlamydomonas reinhardtii. We conducted a mutation accumulation experiment for ∼350 generations followed by whole-genome resequencing of two replicate lines. Our analysis identified a total of 14 mutations, including 5 short indels and 9 single base mutations, and no evidence of larger structural mutations. From this, we estimate a total mutation rate of 3.23 × 10−10/site/generation (95% C.I. 1.82 × 10−10 to 5.23 × 10−10) and a single base mutation rate of 2.08 × 10−10/site/generation (95% C.I., 1.09 × 10−10 to 3.74 × 10−10). We observed no mutations from A/T → G/C, suggesting a strong mutational bias toward A/T, although paradoxically, the GC content of the C. reinhardtii genome is very high. Our estimate is only the second direct estimate of the mutation rate from plants and among the lowest spontaneous base-substitution rates known in eukaryotes.
Estimate of the Spontaneous Mutation Rate in Chlamydomonas reinhardtii
Rob W. Ness,1,2 Andrew D. Morgan,1 Nick Colegrave, and Peter D. Keightley
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have been associated with worse patient outcomes and higher costs of care than methicillin-susceptible (MSSA) infections. However, since prior studies found these differences, the healthcare landscape has changed, including widespread dissemination of community-associated strains of MRSA. We sought to provide updated estimates of the excess costs of MRSA infections.
We conducted a retrospective analysis using data from the National Inpatient Sample from the Agency for Healthcare Research and Quality for the years 2010-2014. We calculated costs for hospitalizations, including MRSA- and MSSA-related septicemia and pneumonia infections, as well as MRSA- and MSSA-related infections from conditions classified elsewhere and of an unspecified site (“other infections”). Differences in the costs of hospitalization were estimated using propensity score-adjusted mortality outcomes for 2010-2014.
In 2014, estimated costs were highest for pneumonia and sepsis-related hospitalizations. Propensity score-adjusted costs were significantly higher for MSSA-related pneumonia ($40725 vs $38561; P = .045) and other hospitalizations ($15578 vs $14792; P < .001) than for MRSA-related hospitalizations. Similar patterns were observed from 2010 to 2013, although crude cost differences between MSSA- and MRSA-related pneumonia hospitalizations rose from 25.8% in 2010 to 31.0% in 2014. Compared with MSSA-related hospitalizations, MRSA-related hospitalizations had a higher adjusted mortality rate. Conclusions Although MRSA infections had been previously associated with higher hospitalization costs, our results suggest that, in recent years, costs associated with MSSA-related infections have converged with and may surpass costs of similar MRSA-related hospitalizations.
hospitalization costs, national inpatient sample, excess cost of resistant infections, propensity score-adjusted costs, antimicrobial resistance
National Costs Associated With Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Hospitalizations in the United States, 2010-2014
Eili Y Klein,1,4,5 Wendi Jiang,5 Nestor Mojica,5 Katie K Tseng,5 Ryan McNeill,6,7 Sara E Cosgrove,2,3 and Trish M Perl8
2019 Jan 1;