COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research

6.4 Transfusion management and haemostatic changes in major obstetric haemorrhage in the UK.

UNLABELLED: : Blood transfusion is fundamental to improving outcomes during major obstetric haemorrhage (MOH). Current guidelines recommend that fresh frozen plasma (FFP), cryoprecipitate and platelets are transfused when PT/APTT is >1.5 × baseline, fibrinogen 1.5x baseline, fibrinogen <1.0 g/dL and platelet <50 × 10(9)/L respectively. FFP, cryoprecipitate and platelets were transfused in 99%, 61% and 77% of women. The median (IQR) RBC, FFP and cryoprecipitate transfused were: 10 (8-1), 6 (4-8), and 2 units (2-4), with the first FFP and cryoprecipitate transfused after a median of 4 (3-6) and 7 RBC units (6-9) respectively. 45% of women underwent hysterectomy, 2 died, 82% were admitted to ITU/HDU, and 28% developed additional major morbidity. CONCLUSION: Guideline criteria for plasma/platelet transfusion were fulfilled in only 25% of these severe cases, indicating that further research is needed to define transfusion triggers in MOH

A prospective randomized trial of long term azithromycin (AZM) versus placebo in cystic fibrosis (CF): Impact on clinical, laboratory and quality of life (QOL) outcomes

No abstrac

6.4 Transfusion management and haemostatic changes in major obstetric haemorrhage in the UK.

UNLABELLED: : Blood transfusion is fundamental to improving outcomes during major obstetric haemorrhage (MOH). Current guidelines recommend that fresh frozen plasma (FFP), cryoprecipitate and platelets are transfused when PT/APTT is &gt;1.5 × baseline, fibrinogen &lt;1 g/dL and platelet count &lt;50 × 10(9)/L, respectively. However, these recommendations are not evidence-based. AIMS: to describe coagulation abnormalities and transfusion requirements during MOH (defined as transfusion of ≥8 units of RBC within 24 hrs of delivery). METHODS: Cases were identified using the UK Obstetric Surveillance System, between July 2012 and June 2013. RESULTS: We identified 181 cases; 68% delivered by caesarean. The median estimated blood loss was 6000 mL (IQR: 4500-8000). The main causes for MOH were uterine atony (40%) and placenta accreta/increta/percreta (16%). The median (IQR) platelet count, APTT-ratio and fibrinogen (worst values) were 68 x 10(9)/L (50-95), 1.3 (1.0-1.9) and 1.4 (0.8-2.2) respectively. In 33%, 27% and 25% of cases APTT-ratio was &gt;1.5x baseline, fibrinogen &lt;1.0 g/dL and platelet &lt;50 × 10(9)/L respectively. FFP, cryoprecipitate and platelets were transfused in 99%, 61% and 77% of women. The median (IQR) RBC, FFP and cryoprecipitate transfused were: 10 (8-1), 6 (4-8), and 2 units (2-4), with the first FFP and cryoprecipitate transfused after a median of 4 (3-6) and 7 RBC units (6-9) respectively. 45% of women underwent hysterectomy, 2 died, 82% were admitted to ITU/HDU, and 28% developed additional major morbidity. CONCLUSION: Guideline criteria for plasma/platelet transfusion were fulfilled in only 25% of these severe cases, indicating that further research is needed to define transfusion triggers in MOH

Authors' reply re: The epidemiology and outcomes of women with postpartum haemorrhage requiring massive transfusion with eight or more units of red cells: a national cross-sectional study

We thank Dr Killicoat and colleagues for their interest in our paper. We agree that it is important that both trainee and consultant obstetricians and mid- wives are skilled in recognising and managing obstetric haemorrhage

Re: The epidemiology and outcomes of women with postpartum haemorrhage requiring massive transfusion with eight or more units of red cells: a national cross-sectional study Reply

We thank Dr Killicoat and colleagues for their interest in our paper. We agree that it is important that both trainee and consultant obstetricians and mid- wives are skilled in recognising and managing obstetric haemorrhage

Disease-modifying and susceptibility genes in copd

Chronic obstructive pulmonary disease (COPD), the 3rd leading cause of disease burden in Australia, involves cigarette smoke-induced airway inflammation. Elucidating its molecular pattiophysiology is important for advancing the treatment of this disease. Critical inflammatory and defence mediators have now been identified, together with the discovery of natural genetic variation in their encoding genes. Aim: To examine how variations in ( 1 ) pro-inflammatory (TNFa, IL-6, TGFβf), (2) anti-inflammatory (IL-IRa) and (3) host defence (myelopemxidase IMPO). mamose-binding lectin (MBL), P450 CYPIA1, glutathione-S-tramferases IGST)) genes affect the COPD phenotype. Methods: Genotypes of these variants were determined by PCR in an Australian cohort of 237 COPD subjects (mean age 69y, FEVj 43 pred) and compared to 2 control groups: 76 smokers with normal lung function and 207 healthy blood donors. Detailed lung function was measured, together with TNFa levels and HRCT in a subset. Results: Susceptibility to COPD was associated with the CYPIAI variant (OR 2.7, p=0.017). Furthermore, susceptibility to chronic bronchitis was predicted by variant TGF] and TNFa genes (OR 4.0 and 1.6 respectively, p0.05). Moreover, COPD subjects with the MBL variant were more likely to be chronic bronchitics (OR 1.8, p=0.05). Lower KCO (55% vs. 62% pred.) was associated with the null GSTMl genotype (p=0.026). We also found that TNFa gene variation resulted in differences in the level of peripheral blood monocyte TNFa levels (364 vs 207 pg/ml. p=0.02). Conclusions: This is the first report in COPD of (1) novel associations between variations in key genes with susceptibility and disease phenotype, and (2) significant differences in TNFa levels due to interindividual TNFa gene variation. The identification of genes relevant to COPD should lead to biologically-based, targeted prevention and intervention strategies for at-risk individuals.</p