Objective To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery.Design Systematic review and meta-analysis.Data sources Randomised controlled trials involving a threshold for red blood cell transfusion in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL, PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible.Trial selection Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease.Data extraction and synthesis Data extraction was completed in duplicate. Risk of bias was assessed using Cochrane methods. Relative risk ratios with 95% confidence intervals were presented in all meta-analyses. Mantel-Haenszel random effects models were used to pool risk ratios.Main outcome measures 30 day mortality, and cardiovascular events.Results 41 trials were identified; of these, seven included data on patients with cardiovascular disease. Data from a further four trials enrolling patients with cardiovascular disease were obtained from the authors. In total, 11 trials enrolling patients with cardiovascular disease (n=3033) were included for meta-analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519). The pooled risk ratio for the association between transfusion thresholds and 30 day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with little heterogeneity (I2=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I2=0%).Conclusions The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease. Effects on mortality and other outcomes are uncertain. These data support the use of a more liberal transfusion threshold (>80 g/L) for patients with both acute and chronic cardiovascular disease until adequately powered high quality randomised trials have been undertaken in patients with cardiovascular disease.Registration PROSPERO CRD42014014251.

Background The impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood. Methods PHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function. Findings We report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity. Interpretation We identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services. Funding: UKRI and NIHR

In Scotland, elderly and older ICU admission rates are decreasing, with regional geographic variation. Although limited by an absence of a measure of frailty, patient characteristics and treatment intensity suggest selection of less comorbid elderly patients, indicating possible rationing based on chronologic age.

Structured Abstract Objectives: The long-term consequences of severe Covid-19 requiring hospital admission are not well characterised. The objective of this study was to establish the long-term effects of Covid-19 following hospitalisation and the impact these may have on patient reported outcome measures. Design: A multicentre, prospective cohort study with at least 3 months follow-up of participants admitted to hospital between 5th February 2020 and 5th October 2020. Setting: 31 hospitals in the United Kingdom. Participants: 327 hospitalised participants discharged alive from hospital with confirmed/high likelihood SARS-CoV-2 infection. Main outcome measures and comparisons: The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, new or increased disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). We compared these outcome measures across age, comorbidity status and in-hospital Covid-19 severity to identify groups at highest risk of developing long-term difficulties. Multilevel logistic and linear regression models were built to adjust for the effects of patient and centre level risk factors on these outcomes. Results: In total 53.7% (443/824) contacted participants responded, yielding 73.8% (327/443) responses with follow-up of 90 days or more from symptom onset. The median time between symptom onset of initial illness and completing the participant questionnaire was 222 days (Interquartile range (IQR) 189 to 269 days). In total, 54.7% (179/327) of participants reported they did not feel fully recovered. Persistent symptoms were reported by 93.3% (305/325) of participants, with fatigue the most common (82.8%, 255/308), followed by breathlessness (53.5%, 175/327). 46.8% (153/327) reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24.2% (79/327) of participants. Overall (EQ5D-5L) summary index was significantly worse at the time of follow-up (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Conclusions: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present even in young, previously healthy working age adults, and were most common in younger females. Policymakers should fund further research to identify effective treatments for long-Covid and ensure healthcare, social care and welfare support is available for individuals with long-Covid.

Anaemia is common in critical illness, and standard treatment is red blood cell (RBC) transfusion, typically using a restrictive transfusion threshold of 70 g L . However, there are subgroups of patients in whom it is biologically plausible that a higher transfusion threshold may be beneficial, namely, acute sepsis, traumatic brain injury and coexisting cardiovascular disease. In this review article, we will discuss the pathophysiology of anaemia, as well as its prevalence and time course. We will explore the limitations of using haemoglobin concentration as a surrogate for oxygen delivery and the concept of the critical haemoglobin concentration. We will then discuss transfusion thresholds for the general intensive care unit (ICU) population and specific subgroups.

BackgroundTroponin I (TnI) is frequently elevated in critical illness, but its interpretation is unclear. Our primary objectives in this study were to evaluate whether TnI is associated with hospital mortality and if this association persists after adjusting for potential confounders. We also aimed to ascertain whether addition of TnI to the Acute Physiological and Chronic Health Evaluation II (APACHE II) risk prediction model improves its performance in general intensive care unit (ICU) populations.MethodsWe performed an observational cohort study with independent derivation and validation cohorts in two general level 3 ICU departments in the United Kingdom. The derivation cohort was a 4.5-year cohort (2010–2014) of general ICU index admissions (n = 1349). The validation cohort was used for secondary analysis of a prospective study dataset (2010) (n = 145). The primary exposure was plasma TnI concentration taken within 24 h of ICU admission. The primary outcome was hospital mortality. We performed multivariate regression, adjusting for components of the APACHE II model. We derived the risk prediction score from the multivariable model with TnI.ResultsHospital mortality was 37.3% (n = 242) for patients with detectable TnI, compared with 14.6% (n = 102) for patients without detectable TnI. There was a significant univariate association between TnI and hospital mortality (OR per doubling TnI 1.16, 95% CI 1.13–1.20, p < 0.001). This persisted after adjustment for APACHE II model components (TnI OR 1.05, 95% CI 1.01–1.09, p = 0.003). TnI correlated most strongly with the acute physiology score (APS) component of APACHE II (r = 0.39). Addition of TnI to the APACHE II model did not improve discrimination (APACHE II concordance statistic [c-index] 0.835, 95% CI 0.811–0.858; APACHE II + TnI c-index 0.837, 95% CI 0.813–0.860; p = 0.330) or other measures of model performance.ConclusionsTnI is an independent predictor of hospital mortality and correlates most highly with the APS component of APACHE II. It does not improve risk prediction. We would not advocate the adoption of routine troponin analysis on admission to ICU, and we recommend that troponin be measured only if clinically indicated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1800-4) contains supplementary material, which is available to authorized users.

Big data have the potential to improve medical care and reduce costs, both by individualizing medicine, and bringing together multiple sources of data about individual patients. As big data become increasingly mainstream, it will be important to maintain public confidence by safeguarding data security, governance and confidentiality.

Background Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods Plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months. Nasal and plasma anti-S IgG remained elevated for at least 12 months with high plasma neutralising titres against all variants. Of 180 with complete data, 160 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal. Samples 12 months after admission showed no association between nasal IgA and plasma IgG responses, indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.