The Influence of COVID-19 Disease on Pre-Analytical Blood Sample Haemolysis Rates in Three Acute Medical Units: An Interrupted Time Series Analysis.

The COVID-19 pandemic impacted delivery of health services. The aim of our study was to determine the impact of COVID-19 disease on pre-analytical blood sample haemolysis by modelling the daily haemolysis rates variations pre and post COVID-19 infections. Ethics approval was obtained prior to study commencing. Interrupted Time Series data analysis was conducted on UK National Health Service Acute Admissions Unit 25-month (1 February 2019 to 28 February 2021) biochemistry (total and haemolysed) blood sample dataset. Interruption was set on 23 March 2021, the start of the first UK lockdown. Daily haemolysis rate (% samples haemolysed) data were fitted with a spline curve to determine influence of haemolysis rates on short or medium-term temporal trends. Linear regression was performed so as to determine long-term temporal trends pre- and post-intervention. There were 32,316 biochemistry blood sample results: 19,058 pre and 13,258 (342 days) from the post-intervention period. Overall median daily haemolysis rate was 7.3% (range: 0-30.6%), 7.7% pre-intervention versus 6.5% post-intervention (p<0.0001). The proportion of haemolysis cases negatively correlated with the number of samples processed (rho=0.09; p=0.01). The pre-intervention slope was -1.70 %.y-1, y intercept 9.04%; post-intervention slope was -1.88%.y-1, y intercept was 10.2%; with no difference in either the slope (p=0.87) or intercept (p=0.16). There was no association between short-term variation in haemolysis rates with changes in practice due to COVID-19 disease and the disease itself. The negative correlation between haemolysis rate and the number of samples processed highlights the importance of continued venepuncture practice to facilitate haemolysis rate reduction.

Portable, low cost and sensitive cavity enhanced absorption (CEA) detection.

Absorption is a widely used technique for a range of different applications. It has lower sensitivity than many other techniques such as fluorescence which has 100 to 1000 times higher sensitivity than absorption. Optical cavity approaches have been developed where the light passes back and forth, within the sample, between two high reflectivity mirrors to increase the pathlength and sensitivity. These approaches have not yet, however, been widely used for analytical applications and for point-of-care diagnostics. Here we show a portable cavity enhanced absorption (CEA) spectrometer and a low cost point-of-care (POC) reader with CEA detection with mechanical elements fabricated using 3D printing. The CEA spectrometer can be used in both single pass and multi-pass cavity enhanced mode to provide measurements in the visible region that are very sensitive and over a wide dynamic range. The CEA mode was shown for Rhodamine B dye to increase the pathlength 57.8 fold over single pass measurements and an LOD of 7.1 × 10-11 M. The cost of the CEA POC reader was reduced by use of narrow band LEDs, photodiodes and removal of fibre optic coupling and with a 14 fold increase in the pathlength over conventional single pass microplate readers. The CEA POC reader was demonstrated for immunoassay of C-Reactive Protein (CRP), Procalcitonin (PCT) and Interleukin 6 (IL-6), towards a three biomarker panel to aid the diagnosis of sepsis. The CEA POC reader can be integrated with wireless connectivity for cloud based data sharing. We show here the potential for the wider use of optical cavity approaches where there is a need for sensitive absorption measurements and also for low cost point-of-care diagnostics.

Biomarkers for Point-of-Care Diagnosis of Sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In 2017, almost 50 million cases of sepsis were recorded worldwide and 11 million sepsis-related deaths were reported. Therefore, sepsis is the focus of intense research to better understand the complexities of sepsis response, particularly the twin underlying concepts of an initial hyper-immune response and a counter-immunological state of immunosuppression triggered by an invading pathogen. Diagnosis of sepsis remains a significant challenge. Prompt diagnosis is essential so that treatment can be instigated as early as possible to ensure the best outcome, as delay in treatment is associated with higher mortality. In order to address this diagnostic problem, use of a panel of biomarkers has been proposed as, due to the complexity of the sepsis response, no single marker is sufficient. This review provides background on the current understanding of sepsis in terms of its epidemiology, the evolution of the definition of sepsis, pathobiology and diagnosis and management. Candidate biomarkers of interest and how current and developing point-of-care testing approaches could be used to measure such biomarkers is discussed.

Utility of biomarkers in the differential diagnosis of heart failure in older people: findings from the heart failure in care homes (HFinCH) diagnostic accuracy study.

BACKGROUND: The performance of biomarkers for heart failure (HF) in older residents in long-term care is poorly understood and has not differentiated between left ventricular systolic dysfunction (LVSD) and HF with preserved ejection fraction (HFpEF). METHODS: This is the first diagnostic accuracy study in this population to assess the differential diagnostic performance and acceptability of a range of biomarkers against a clinical diagnosis using portable echocardiography. A total of 405 residents, aged 65-100 years (mean 84.2), in 33 UK long-term care facilities were enrolled between April 2009 and June 2010. RESULTS: For undifferentiated HF, BNP or NT-proBNP were adequate rule-out tests but would miss one in three cases (BNP: sensitivity 67%, NPV 86%, cut-off 115 pg/ml; NT-proBNP: sensitivity 62%, NPV 87%, cut-off 760 pg/ml). Using higher test cut-offs, both biomarkers were more adequate tests of LVSD, but would still miss one in four cases (BNP: sensitivity 76%, NPV 97%, cut-off 145 pg/ml; NT-proBNP: sensitivity 73%, NPV 97%, cut-off 1000 pg/ml). At these thresholds one third of subjects would test positive and require an echocardiogram. Applying a stricter 'rule out' threshold (sensitivity 90%), only one in 10 cases would be missed, but two thirds of subjects would require further investigation. Biomarkers were less useful for HFpEF (BNP: sensitivity 63%, specificity 61%, cut-off 110 pg/ml; NT-proBNP: sensitivity 68%, specificity 56%, cut-off 477 pg/ml). Novel biomarkers (Copeptin, MR-proADM, and MR-proANP) and common signs and symptoms had little diagnostic utility. CONCLUSIONS: No test, individually or in combination, adequately balanced case finding and rule-out for heart failure in this population; currently, in-situ echocardiography provides the only adequate diagnostic assessment. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN19781227.