Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18), and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5-12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.
The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.
Background The aim of this study is to quantify the effects of the SARS-CoV-2 pandemic on health services utilization in China using over four years of routine health information system data. Methods We conducted a retrospective observational cohort study of health services utilization from health facilities at all levels in all provinces of mainland China. We analyzed monthly all-cause health facility visits and inpatient volume in health facilities before and during the SARS-CoV-2 outbreak using nationwide routine health information system data from January 2016 to June 2020. We used interrupted time series analyses and segmented negative binomial regression to examine changes in healthcare utilization attributable to the pandemic. Stratified analyses by facility type and by provincial Human Development Index (HDI) – an area-level measure of socioeconomic status – were conducted to assess potential heterogeneity in effects. Findings In the months before the SARS-CoV-2 outbreak, a positive secular trend in patterns of healthcare utilization was observed. After the SARS-CoV-2 outbreak, we noted statistically significant decreases in all indicators, with all indicators achieving their nadir in February 2020. The magnitude of decline in February ranged from 63% (95% CI 61–65%; p <0•0001) in all-cause visits at hospitals in regions with high HDI and 71% (95% CI 70–72%; p <0•0001) in all-cause visits at primary care clinics to 33% (95% CI 24–42%; p <0•0001) in inpatient volume and 10% (95% CI 3–17%; p = 0•0076) in all-cause visits at township health centers (THC) in regions with low HDI. The reduction in health facility visits was greater than that in the number of outpatients discharged (51% versus 48%; p <0•0079). The reductions in both health facility visits and inpatient volume were greater in hospitals than in primary health care facilities ( p <0•0001) and greater in developed regions than in underdeveloped regions ( p <0•0001). Following the nadir of health services utilization in February 2020, all indicators showed statistically significant increases. However, even by June 2020, nearly all indicators except outpatient and inpatient volume in regions with low HDI and inpatient volume in private hospitals had not achieved their pre-SARS-COV-2 forecasted levels. In total, we estimated cumulative losses of 1020.5 (95% CI 951.2- 1089.4; P <0.0001) million or 23.9% (95% CI 22.5–25.2%; P <0.0001) health facility visits, and 28.9 (95% CI 26.1–31.6; P <0.0001) million or 21.6% (95% CI 19.7–23.4%; P <0.0001) inpatients as of June 2020. Interpretation Inpatient and outpatient health services utilization in China declined sig...
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