A retrospective analysis of 20,178 adult neurological infection admissions to United Kingdom critical care units from 2001 to 2020.

BACKGROUND: Neurological infection is an important cause of critical illness, yet little is known on the epidemiology of neurological infections requiring critical care. METHODS: We analysed data on all adults with proven or probable neurological infection admitted to UK (NHS) critical care units between 2001 and 2020 reported to the Intensive Care National Audit and Research Centre. Diagnoses, physiological variables, organ support and clinical outcomes were analysed over the whole period, and for consecutive 5-year intervals within it. Predictors of in-hospital mortality were identified using a backward stepwise regression model. RESULTS: We identified 20,178 critical care admissions for neurological infection. Encephalitis was the most frequent presentation to critical care, comprising 6725 (33.3%) of 20,178 cases. Meningitis- bacterial, viral or unspecified cases - accounted for 10,056 (49.8%) of cases. In-hospital mortality was high, at 3945/19,765 (20.0%) overall. Over the four consecutive 5-year periods, there were trends towards higher Glasgow Coma Scale scores on admission, longer critical care admissions (from median 4 [IQR 2-8] to 5 days [IQR 2-10]), and reduced in-hospital mortality (from 24.9 to 18.1%). We identified 12 independent predictors of in-hospital death which when used together showed good discrimination between patients who die and those who survive (AUC = 0.79). CONCLUSIONS: Admissions with neurological infection to UK critical care services are increasing and the mortality, although improving, remains high. To further improve outcomes from severe neurological infection, novel approaches to the evaluation of risk stratification, monitoring and management strategies are required

Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial

Background Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. Methods This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. Results 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. Conclusion Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. Trial registration number ISRCTN66148745 and NCT01247870

Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterized samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries

Monitoring drug therapy

It is important to monitor drug therapy because the effects of a particular drug regimen can vary significantly between individuals. Wherever possible, therapeutic effect should be monitored using a clinical endpoint (i.e. a measure that directly reflects how the patient feels, functions or survives). In practice, it is often not feasible to use a clinical endpoint to guide therapy, particularly for preventive treatments. The next best option is to use a surrogate endpoint: a measure that changes so as to predict whether the clinical endpoint will be achieved. For a few drugs, neither a clinical nor a surrogate endpoint is available. In these instances, if the drug has a narrow therapeutic index and there is a predictable relationship between its concentration and its effects, it may be appropriate to measure its concentration in the blood. This article discusses approaches to monitoring drug therapy using clinical and surrogate endpoints, and plasma concentration monitoring. Specific guidance is provided for plasma concentration monitoring of digoxin, gentamicin, vancomycin, phenytoin, lithium and theophylline

Determining the volume of toxic liquid ingestions in adults: accuracy of estimates by healthcare professionals and members of the public.

CONTEXT: Ingestion of toxic liquids is common, and the volume ingested is often important for clinical decision-making. However, the accuracy and interpretation of volume estimates in the context of toxicological exposures is poorly characterised in adult practice. OBJECTIVE: To inform the interpretation of volume estimates when expressed in forms commonly encountered in toxicological practice: (1) semi-quantitative volume descriptors, such as 'mouthfuls'; (2) quantitative self-estimates of ingestion volume, for example, millilitres; and (3) estimates of residual volume in containers. METHODS: In the first part of the study, 50 members of the public ingested water in response to requests to take a 'small mouthful', 'large gulp' and 'five mouthfuls'. They estimated the amount ingested, and actual volumes were measured. In part 2, 15 members of the public and 15 healthcare professionals estimated the volumes contained in 12 opaque and transparent bottles. RESULTS: The mean age of participants in part 1 was 37 years, and in part 2 it was 34 years. The mean volume (95% prediction interval) of a 'small mouthful' was 43 (3-137) mL; 'large gulp', 77 (20-168) mL; and 'five mouthfuls', 157 (25-375) mL. The mean error (95% limits of agreement) for self-estimates of ingestion volume was an underestimate of - 52% (- 90% to + 124%). Volume contained in bottles was underestimated by - 5% (- 38% to + 27%). This varied according to the container type (mean difference: opaque, - 10%; transparent, - 1%; P < 0.01) and participant type (members of the public, - 8%; healthcare professionals, - 3%; P = 0.02). CONCLUSIONS: Volume estimates derived from semi-quantitative descriptors are not a reliable basis for clinical decision-making. Self-estimates provided in a quantitative form are inaccurate and prone to underestimation. Estimates of residual volume in containers should be regarded as suspect if the container is opaque. Where clinical decisions hinge on the volume ingested, efforts should be made to quantify this using measurement

A retrospective analysis of 20,178 adult neurological infection admissions to United Kingdom critical care units from 2001 to 2020.

BACKGROUND: Neurological infection is an important cause of critical illness, yet little is known on the epidemiology of neurological infections requiring critical care. METHODS: We analysed data on all adults with proven or probable neurological infection admitted to UK (NHS) critical care units between 2001 and 2020 reported to the Intensive Care National Audit and Research Centre. Diagnoses, physiological variables, organ support and clinical outcomes were analysed over the whole period, and for consecutive 5-year intervals within it. Predictors of in-hospital mortality were identified using a backward stepwise regression model. RESULTS: We identified 20,178 critical care admissions for neurological infection. Encephalitis was the most frequent presentation to critical care, comprising 6725 (33.3%) of 20,178 cases. Meningitis- bacterial, viral or unspecified cases - accounted for 10,056 (49.8%) of cases. In-hospital mortality was high, at 3945/19,765 (20.0%) overall. Over the four consecutive 5-year periods, there were trends towards higher Glasgow Coma Scale scores on admission, longer critical care admissions (from median 4 [IQR 2-8] to 5 days [IQR 2-10]), and reduced in-hospital mortality (from 24.9 to 18.1%). We identified 12 independent predictors of in-hospital death which when used together showed good discrimination between patients who die and those who survive (AUC = 0.79). CONCLUSIONS: Admissions with neurological infection to UK critical care services are increasing and the mortality, although improving, remains high. To further improve outcomes from severe neurological infection, novel approaches to the evaluation of risk stratification, monitoring and management strategies are required