Protein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies (PCSK9mab) in Clinical Practice at Secondary Care - Real World Multicentre Experience.

Background and Aims Protein convertase subtilisin/Kexin type 9 monoclonal antibodies (PCSK9mab) are a novel addition to the therapeutic options for managing hyperlipidemia. Various guidelines have advocated the addition of these agents if the target low-density lipoprotein-cholesterol ( LDL-C) is not achieved by maximum lipid-lowering therapy. They have shown a robust and consistent reduction in LDL-C in clinical trials. However, the translation of these results in a real-world setting is limited and confined mainly to tertiary lipid centers. This service evaluation aimed to assess their efficacy in a real-world outpatient setting of secondary care centers. Methods Data was collected retrospectively from four hospitals in the North-West of England. Patients were required to attend a lipid clinic for follow-up investigations to continue with the prescription of PCSK9mab. Results A total of 175 patients were identified. Efficacy outcomes were measured in 169 patients. 6 discontinued the agent within 3 months of initiation and were excluded from the efficacy outcomes. 19.5% (n=33) had confirmed familial hypercholesterolemia. 61% (n=103) of the patients were intolerant to statins. 53.2% (n=90) of the patients have been prescribed Alirocumab. Mean LDL-C reduction was 50.6% at 6-month which was sustained at 48.9% at 12 months. There was no difference in % reduction of LDL-C between Alirocumab and Evolocumab. LDL-C reduction was more significant in patients who were on concomitant statins. 9.1% of patients experienced side effects, and 5.1% discontinued the PCSK9mab during treatment. Conclusion The efficacy of lipid reduction and the side effect profile of PCSK9mab from these secondary care services are similar to randomized clinical trials and real-world observational studies from tertiary lipid centers.

Comparison of four high-throughput, automated immunoassays for the detection of SARS-CoV-2 antibodies.

BACKGROUND: A number of immunoassays have been developed to measure antibodies specific to SARS-CoV-2. More data is required on their comparability, particularly among those with milder infections and in the general practice population. The aim of this study was to compare four high-throughput automated anti-SARS-CoV-2 assays using samples collected from hospitalized patients and healthcare workers with confirmed SARS-CoV-2 infection. In addition, we collected general practice samples to compare antibody results and determine seroprevalence. METHODS: Samples were collected from 57 hospitalized patients and nine healthcare workers at 14 days and at 28 days following confirmed SARS-CoV-2 infection. Samples were also collected from 225 patients presenting to general practice. Four assays were used: Abbott Architect IgG, Beckman Coulter DxI 800 IgG, Roche Cobas e801 total antibody and Siemens Advia Centaur XPT total antibody. RESULTS: All four assays showed concordance at 14 days in 83.9% of hospitalized patients and in 66.7% of healthcare workers. All four assays showed concordance at 28 days in 88.4% of hospitalized patients and 77.8% of healthcare workers. The sensitivity to detect recent infection was higher for the IgG assays than the total assays. All four assays showed concordance of 95.1% in the general practice population. Seroprevalence ranged from 4.9 to 5.8% depending on the assay used. CONCLUSIONS: All four assays showed excellent comparability, but it may be possible to obtain a negative result for any of the anti-SARS-CoV-2 assays in patients with confirmed previous SARS-CoV-2 infection. An equivocal range would be useful for all anti-SARS-CoV-2 assays.

Seroprevalence of SARS-CoV-2 infection in healthcare workers in a large teaching hospital in the North West of England: a period prevalence survey.

OBJECTIVES: Since its emergence in late 2019, SARS-CoV-2 has caused a global pandemic that has significantly challenged healthcare systems. Healthcare workers have previously been shown to have experienced higher rates of infection than the general population. We aimed to assess the extent of infection in staff working in our healthcare setting. DESIGN: A retrospective analysis of antibody results, compared with staff demographic data, and exposure to patients with COVID-19 infection. SETTING: A large teaching hospital in the North West of England. PARTICIPANTS: 4474 staff in diverse clinical and non-patient facing roles who volunteered for SARS-CoV-2 antibody testing by the Roche Elecsys assay between 29 May and 4 July 2020. RESULTS: Seroprevalence was 17.4%. Higher rates were seen in Asian/Asian British (OR 1.61, 95% CI 1.27 to 2.04) and Black/Black British (OR 2.08, 95% CI 1.25 to 3.45) staff. Staff working in any clinical location were more likely to be seropositive (OR 2.68, 95% 2.27 to 3.15). Staff were at an increased risk of seropositivity as the 'per 100 COVID-19 bed-days change' increased in the clinical area in which they worked (OR 1.12, 95% 1.10 to 1.14). Staff working in critical care were no more likely to have detectable antibodies than staff working in non-clinical areas. Symptoms compatible with COVID-19 were reported in 41.8% and antibodies were detected in 30.7% of these individuals. In staff who reported no symptoms, antibodies were detected in 7.7%. In all staff who had detectable antibodies, 25.2% reported no symptoms. CONCLUSIONS: Staff working in clinical areas where patients with COVID-19 were nursed were more likely to have detectable antibodies. The relationship between seropositivity in healthcare workers and the increase in 'per 100 COVID-19 bed-days' of the area in which they worked, although statistically significant, was weak, suggesting other contributing factors to the risk profile. Of staff with detectable antibodies and therefore evidence of prior infection, a quarter self-reported that they had experienced no compatible symptoms. This has implications for potential unrecorded transmission in both staff and patients.

Verification of placental growth factor and soluble-fms-like tyrosine kinase 1 assay performance in late pregnancy and their diagnostic test accuracy in women with reduced fetal movement.

BACKGROUND: Placental growth factor (PlGF) and soluble-fms-like tyrosine kinase 1 (sFlt-1) are biomarkers of placental function used to aid the diagnosis and prediction of pregnancy complications. This work verified the analytical performance of both biomarkers and provides preliminary diagnostic accuracy data to identify adverse pregnancy outcome in women with reduced fetal movement. METHODS: Verification of sFlt-1 and PlGF assays included a comparative accuracy assessment of 24 serum samples analysed at six different sites and laboratory-specific precision estimates. The sFlt-1/PlGF ratio was assessed in serum samples obtained prospectively from 295 women with reduced fetal movement ≥36 weeks' gestation; diagnostic accuracy was evaluated using 2 × 2 tables and area under the receiver operator characteristic (AUROC) curve. RESULTS: Regression analysis showed that performance between sites was good with Passing-Bablok slopes ranging from 0.96 to 1.05 (sFlt-1) and 0.93 to 1.08 (PlGF). All sites had a mean bias <15%, although there was poorer agreement at the lowest PlGF concentrations. All within- and between-batch coefficients of variation were <10%. In 289 women with an appropriately grown fetus, an sFlt-1/PlGF ratio ≥38 had a sensitivity of 0.20 (95% confidence interval [CI] 0.07, 0.41), specificity of 0.88 (95% CI 0.83, 0.92) and AUROC curve of 0.58 (95% CI 0.47, 0.68) to identify adverse pregnancy outcome. CONCLUSIONS: Analytical performance of the sFlt-1 and PlGF assays was comparable across different sites. The sensitivity of sFlt-1/PlGF to identify adverse pregnancy outcome in women with reduced fetal movement was considered acceptable, in the absence of other tests, to progress to a pilot randomized controlled trial.

Predicting short term mortality after investigation for venous thromboembolism.

INTRODUCTION: Deaths following diagnosis of venous thromboembolism (VTE) often result from another concurrent illness. The specificity of mortality markers predicting death from pulmonary embolism is unknown. The aim of this analysis was to compare blood predictors of death in patients with confirmed VTE to patients with negative investigations for VTE. MATERIALS AND METHODS: Consecutive patients investigated for VTE were prospectively consented from a single hospital over 9months. VTE was diagnosed and excluded with a standard diagnostic algorithm. Blood was drawn for biomarker analysis and analyzed in batches for NT-proBNP, high sensitivity troponin T, C-reactive protein (CRP), fatty acid binding protein (FABP) and ischemia modified albumin (IMA). Participants were followed for 3months. The cohort was analyzed in two groups: those diagnosed with VTE and those who had thrombosis excluded. Regression analysis for 3-month mortality was performed for each group. RESULTS: 16/153 patients diagnosed with VTE died within three months (10.5%) as did 23/606 patients who had negative investigations for VTE (3.8%). Predictors for death following VTE included cancer, NT-proBNP, troponin T, FABP, and Hb<95g/L. NT-proBNP>500pg/ml in acute cancer associated VTE predicted death with C-statistic of 0.89 (0.80-0.99). Cancer, NT-proBNP and troponin T also predicted death in patients with negative investigations for VTE. CONCLUSION: Several blood markers are not specific for death from PE and may be surrogate markers of global declining health.