BACKGROUND:New-onset atrial fibrillation, a condition associated with adverse outcomes in the short and long term, is common in patients admitted to intensive care units (ICUs). Identifying patients at high risk could inform trials of preventive interventions and help to target such interventions. We aimed to develop and externally validate a prediction model for new-onset atrial fibrillation in patients admitted to ICUs. METHODS:We conducted a multicentre, retrospective cohort study in three ICUs across the UK and four ICUs across the USA. Patients aged 16 years and older admitted to an ICU for more than 3 h without a history or presentation of clinically significant arrhythmia were eligible for inclusion. We analysed clinical variables to investigate the associations between predetermined candidate variables and risk of new-onset atrial fibrillation and to develop a model to estimate these risks. We developed the METRIC-AF model, a machine learning model incorporating dynamic variables. Model performance was assessed through internal-external cross-validation during model development and externally validated by use of multicentre data from ICUs across the UK. We then developed a simple graphical prediction tool using three important predictors. FINDINGS:Among 39 084 eligible patients admitted to an ICU between 2008 and 2019, 2797 (7·2%) developed new-onset atrial fibrillation during the first 7 days of their ICU stay. We identified multiple non-linear associations between candidate variables and risk of new-onset atrial fibrillation, including hypomagnesaemia at serum concentrations below 0·70 mmol/L. The final METRIC-AF model contained ten routinely collected clinical variables. Compared with a published logistic regression model, the METRIC-AF model showed superior calibration, net benefit across clinically relevant risk thresholds, and discriminative performance (C statistic 0·812 [95% CI 0·805-0·822] vs 0·786 [0·778-0·801]; p=0·0003). The simple graphical tool performed well in attributing the risk of new-onset atrial fibrillation in the external validation dataset (C statistic 0·727 [95% CI 0·716-0·739]). INTERPRETATION:The METRIC-AF model and its companion graphical tool could support the identification of patients at increased risk of developing new-onset atrial fibrillation during ICU admission, informing targeted prophylactic strategies and trial enrichment by use of routinely available clinical data. An online app also developed as part of the study allows for the exploration of prediction generation among individuals and external validation in prospective studies. FUNDING:National Institute for Health and Care Research (NIHR) and NIHR Oxford Biomedical Research Centre.

ImportanceEvidence indicates that preexisting neuropsychiatric conditions confer increased risks of severe outcomes from COVID-19 infection. It is unclear how this increased risk compares with risks associated with other severe acute respiratory infections (SARIs).ObjectiveTo determine whether preexisting diagnosis of and/or treatment for a neuropsychiatric condition is associated with severe outcomes from COVID-19 infection and other SARIs and whether any observed association is similar between the 2 outcomes.Design, Setting, and ParticipantsPrepandemic (2015-2020) and contemporary (2020-2021) longitudinal cohorts were derived from the QResearch database of English primary care records. Adjusted hazard ratios (HRs) with 99% CIs were estimated in April 2022 using flexible parametric survival models clustered by primary care clinic. This study included a population-based sample, including all adults in the database who had been registered with a primary care clinic for at least 1 year. Analysis of routinely collected primary care electronic medical records was performed.ExposuresDiagnosis of and/or medication for anxiety, mood, or psychotic disorders and diagnosis of dementia, depression, schizophrenia, or bipolar disorder.Main Outcomes and MeasuresCOVID-19–related mortality, or hospital or intensive care unit admission; SARI-related mortality, or hospital or intensive care unit admission.ResultsThe prepandemic cohort comprised 11 134 789 adults (223 569 SARI cases [2.0%]) with a median (IQR) age of 42 (29-58) years, of which 5 644 525 (50.7%) were female. The contemporary cohort comprised 8 388 956 adults (58 203 severe COVID-19 cases [0.7%]) with a median (IQR) age of 48 (34-63) years, of which 4 207 192 were male (50.2%). Diagnosis and/or treatment for neuropsychiatric conditions other than dementia was associated with an increased likelihood of a severe outcome from SARI (anxiety diagnosis: HR, 1.16; 99% CI, 1.13-1.18; psychotic disorder diagnosis and treatment: HR, 2.56; 99% CI, 2.40-2.72) and COVID-19 (anxiety diagnosis: HR, 1.16; 99% CI, 1.12-1.20; psychotic disorder treatment: HR, 2.37; 99% CI, 2.20-2.55). The effect estimate for severe outcome with dementia was higher for those with COVID-19 than SARI (HR, 2.85; 99% CI, 2.71-3.00 vs HR, 2.13; 99% CI, 2.07-2.19).Conclusions and RelevanceIn this longitudinal cohort study, UK patients with preexisting neuropsychiatric conditions and treatments were associated with similarly increased risks of severe outcome from COVID-19 infection and SARIs, except for dementia.

Data corrected and figures revised.

Key Points Question What are the risks of neuropsychiatric disorders in adults surviving COVID-19 hospitalization, and how do these compare with non-COVID severe respiratory infections? Findings In this cohort study of data from more than 8 million adults in England, during the COVID-19 pandemic, risks of new anxiety disorder, dementia, psychotic disorder, and bipolar disorder diagnoses were significantly increased in adults surviving hospitalization for COVID-19 or other severe acute respiratory infections compared with the general population. Risks of neuropsychiatric illnesses or commencement of related medications were similar for COVID-19 and non-COVID severe respiratory infections. Meaning The results of this study suggest that disease severity, rather than pathogen, is a relevant factor associated with neuropsychiatric ramifications after severe respiratory infections.

PURPOSE:Many intensive care units (ICUs) have transitioned from systemic heparin anticoagulation (SHA) to regional citrate anticoagulation (RCA) for continuous kidney replacement therapy (CKRT). We evaluated the clinical and health economic impacts of ICU transition to RCA. MATERIALS AND METHODS:We surveyed all adult general ICUs in England and Wales to identify transition dates and conducted a micro-costing study in eight ICUs. We then conducted an interrupted time-series analysis of linked, routinely collected health records. RESULTS:In 69,001 patients who received CKRT (8585 RCA, 60,416 SHA) in 181 ICUs between 2009 and 2017, transition to RCA was not associated with a change in 90-day mortality (adjusted odds ratio 0.98, 95% CI 0.89-1.08) but was associated with step-increases in duration of kidney support (0.53 days, 95% CI 0.28-0.79), advanced cardiovascular support (0.23 days, 95% CI 0.09-0.38) and ICU length of stay (0.86 days, 95% CI 0.24-1.49). The estimated one-year incremental net monetary benefit per patient was £ - 2376 (95% CI £ - 3841-£ - 911), with an estimated likelihood of cost-effectiveness of <0.1%. CONCLUSIONS:Transition to RCA was associated with significant increases in healthcare resource use, without corresponding clinical benefit, and is highly unlikely to be cost-effective over a one-year time horizon.

Background A more transmissible variant of SARS-CoV-2, the variant of concern 202012/01 or lineage B.1.1.7, has emerged in the UK. We aimed to estimate the risk of critical care admission, mortality in patients who are critically ill, and overall mortality associated with lineage B.1.1.7 compared with non-B.1.1.7. We also compared clinical outcomes between these two groups. Methods For this observational cohort study, we linked large primary care (QResearch), national critical care (Intensive Care National Audit & Research Centre Case Mix Programme), and national COVID-19 testing (Public Health England) databases. We used SARS-CoV-2 positive samples with S-gene molecular diagnostic assay failure (SGTF) as a proxy for the presence of lineage B.1.1.7. We extracted two cohorts from the data: the primary care cohort, comprising patients in primary care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 26, 2021, and known SGTF status; and the critical care cohort, comprising patients admitted for critical care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 27, 2021, and known SGTF status. We explored the associations between SARS-CoV-2 infection with and without lineage B.1.1.7 and admission to a critical care unit (CCU), 28-day mortality, and 28-day mortality following CCU admission. We used Royston-Parmar models adjusted for age, sex, geographical region, other sociodemographic factors (deprivation index, ethnicity, household housing category, and smoking status for the primary care cohort; and ethnicity, body-mass index, deprivation index, and dependency before admission to acute hospital for the CCU cohort), and comorbidities (asthma, chronic obstructive pulmonary disease, type 1 and 2 diabetes, and hypertension for the primary care cohort; and cardiovascular disease, respiratory disease, metastatic disease, and immunocompromised conditions for the CCU cohort). We reported information on types and duration of organ support for the B.1.1.7 and non-B.1.1.7 groups. Findings The primary care cohort included 198 420 patients with SARS-CoV-2 infection. Of these, 117 926 (59.4%) had lineage B.1.1.7, 836 (0.4%) were admitted to CCU, and 899 (0.4%) died within 28 days. The critical care cohort included 4272 patients admitted to CCU. Of these, 2685 (62.8%) had lineage B.1.1.7 and 662 (15.5%) died at the end of critical care. In the primary care cohort, we estimated adjusted hazard ratios (HRs) of 2.15 (95% CI 1.75-2.65) for CCU admission and 1.65 (1.36-2.01) for 28-day mortality for patients with lineage B.1.1.7 compared with the non-B.1.1.7 group. The adjusted HR for mortality in critical care, estimated with the critical care cohort, was 0.91 (0.76-1.09) for patients with lineage B.1.1.7 compared with those with non-B.1.1.7 infection. Interpretation Patients with lineage B.1.1.7 were at increased risk of CCU admission and 28-day mortality compared with patients with non-B.1.1.7 SARS-CoV-2. For patients receiving critical care, mortality appeared to be independent of virus strain. Our findings emphasise the importance of measures to control exposure to and infection with COVID-19. (C) 2021 The Author(s). Published by Elsevier Ltd.

The authors regret that part (b) of Fig. 3 was omitted from the published paper. The correct complete Fig. 3 is shown below: The authors would like to apologise for any inconvenience caused. Trajectories of vital signs in patients with COVID-19ResuscitationVol. 156PreviewThe global pandemic of coronavirus disease 2019 (COVID-19) has placed a huge strain on UK hospitals. Early studies suggest that patients can deteriorate quickly after admission to hospital. The aim of this study was to model changes in vital signs for patients hospitalised with COVID-19. Full-Text PDF Open Access

ABSTRACTBackgroundA new, more transmissible variant of SARS-CoV-2, variant of concern (VOC) 202012/01 or lineage B.1.1.7, has emerged in the UK. We estimate the risk of critical care admission, mortality in critical ill patients, and overall mortality associated with VOC B.1.1.7 compared with the original variant. We also compare clinical outcomes between these variants ‘ groups.MethodsWe linked a large primary care (QResearch), the national critical care (ICNARC CMP) and the COVID-19 testing (PHE) database and extracted two cohorts. The first was used to explore the association between VOC B.1.1.7 and critical care admission and 28-day mortality. The second to determine the risk of mortality in critically ill patients with VOC B.1.1.7 compared to those without. We used Royston-Parmar models adjusted for age, sex, region, other socio-demographics and comorbidities (asthma, COPD, type I and II, hypertension). We reported information on types and duration of organ supports for the two variants ‘ groups.FindingsThe first cohort included 198,420 patients. Of these, 80,494 had VOC B.1.1.7, 712 were critically ill and 630 died by 28 days. The second cohort included 3432 critically ill patients. Of these, 2019 had VOC B.1.1.7 and 822 died at the end of critical care. Using the first cohort, we estimated adjusted hazard ratios for critical care admission and mortality to be 1.99 (95% CI: 1.59, 2.49) and 1.59 (95% CI: 1.25-2.03) for VOC B.1.1.7 compared with the original variant group, respectively. The adjusted hazard ratio for mortality in critical care, estimated using the second cohort, was 0.93 (95% CI 0.76-1.15) for patients with VOC B.1.1.7, compared to those without.InterpretationVOC B.1.1.7 appears to be more severe. Patients with VOC B.1.1.7 are at increased risk of critical care admission and mortality compared with patients without. For patients receiving critical care, mortality appears independent of virus strain.RESEARCH IN CONTEXTEvidence before this studyA new variant of the SARS-CoV-2 virus, variant of concern (VOC) 202012/01, or lineage B.1.1.7, was detected in England in September 2020. The characteristics and outcomes of patients infected with VOC B.1.1.7 are not yet known. VOC B.1.1.7 has been associated with increased transmissibility. Early analyses have suggested infection with VOC B.1.1.7 may be associated with a higher risk of mortality compared with infection with other virus variants, but these analyses had either limited ability to adjust for key confounding variables or did not consider critical care admission. The effects of VOC B.1.1.7 on severe COVID-19 outcomes remain unclear.Added value of this studyThis study found a 60% higher risk of 28-day mortality associated with infection with VOC B.1.1.7 in patients tested in the community in comparison with the original variant, when adjusted for key confounding variables. The risk of critical care admission for those with VOC B.1.1.7 is double the risk associated with the original variant. For patients receiving critical care, the infecting variant is not associated with the risk of mortality at the end of critical care.Implications of all the available evidenceThe higher mortality and rate of critical care admission associated with VOC B.1.1.7, combined with its known increased transmissibility, are likely to put health care systems under further stress. These effects may be mitigated by the ongoing vaccination programme.

Purpose: New onset atrial fibrillation (NOAF) in critically ill patients has been associated with increased short-term mortality. Analyses that do not take into account the time-varying nature of NOAF can underestimate its association with hospital outcomes. We investigated the prognostic association of NOAF with hospital outcomes using competing risks methods. Materials and methods: We undertook a retrospective cohort study in three general adult intensive care units (ICUs) in the UK from June 2008 to December 2015. We excluded patients with known prior atrial fibrillation or an arrhythmia within four hours of ICU admission. To account for the effect of NOAF on the rate of death per unit time and the rate of discharge alive per unit time we calculated subdistribution hazard ratios (SDHRs). Results: Of 7541 patients that fulfilled our inclusion criteria, 831 (11.0%) developed NOAF during their ICU admission. NOAF was associated with an increased duration of hospital stay (CSHR 0.68 (95% CI 0.63-0.73)) and an increased rate of in-hospital death per unit time (CSHR 1.57 (95% CI 1.37-1.1.81)). This resulted in a strong prognostic association with dying in hospital (adjusted SDHR 2.04 (1.79-2.32)). NOAF lasting over 30 min was associated with increased hospital mortality. Conclusions: Using robust methods we demonstrate a stronger prognostic association between NOAF and hospital outcomes than previously reported. (C) 2020 Published by Elsevier Inc.

Abstract Background Survivors of critical illness have significant psychopathological comorbidity. The treatments offered by primary health care professionals to affected patients are unstudied. Aim To report the psychological interventions after GPs received notification of patients who showed severe symptoms of anxiety, depression or Post-Traumatic Stress Disorder. Methods Design: Multi-centre prospective cohort sub-study of the ICON study. Setting: NHS primary care in the United Kingdom. Participants: Adult patients, November 2006–October 2010 who had received at least 24 h of intensive care, where the general practitioner recorded notification that the patient had reported severe symptoms or caseness using the Hospital Anxiety and Depression Scale (HADS) or the Post-Traumatic Stress Disorder Check List-Civilian (PCL-C). Interventions: We notified general practitioners (GPs) by post if a patient reported severe symptoms or caseness and sent a postal questionnaire to determine interventions after notification. Main outcome measure: Primary or secondary healthcare interventions instigated by general practitioners following notification of a patient’s caseness. Results Of the 11,726 patients, sent questionnaire packs containing HADS and PCL-C, 4361 (37%) responded. A notification of severe symptoms was sent to their GP in 25% (1112) of cases. Of notified GPs, 65% (725) responded to our postal questionnaire. Of these 37% (266) had no record of receipt of the original notification. Of the 459 patients where GPs had record of notification (the study group for this analysis), 21% (98) had pre-existing psychopathology. Of those without a pre-existing diagnosis 45% (162) received further psychological assessment or treatment. GP screening or follow-up alone occurred in 18% (64) whilst 27% (98) were referred to mental health services or received drug therapy following notification. Conclusions Postal questionnaire identifies a burden of psychopathology in survivors of critical illness that have otherwise gone undiagnosed following discharge from an intensive care unit (ICU). After being alerted to the presence of psychological symptoms, GPs instigate treatment in 27% and augmented surveillance in 18% of cases. Trial registration ISRCTN69112866 (assigned 02/05/2006).

Purpose: We report the use and effect of prophylactic platelet transfusions in critically ill thrombocytopaenic patients, comparing patients with or without bone marrow failure as a cause of thrombocytopaenia. Methods: A retrospective observational study of admissions to three intensive care units (ICU) in the UK. We identified thrombocytopaenic patients who received a platelet transfusion and extracted the platelet count prior and subsequent to platelet transfusion. We grouped patients with or without suspected bone marrow failure, defined by a total white cell count =1.0 x 109/L. Results: Of 11,757 admissions, 399 (3.4%) patients received a platelet transfusion for thrombocytopaenia. The median [IQR] platelet count prior to transfusion in patients without bone marrow failure was 42 [28-64] x 109/L versus 14 [7-24] x 109/L (p b.0001) in those with. The median [IQR] increment in platelets following transfusion was lower in patients with marrowfailure (12 [-1-23] x 109/L) compared to those without (18 [5-36] x 109/L) (p =.006). Conclusions: Platelet transfusions were given at a higher median platelet count than suggested by guidelines. Patients with bone marrow failure were transfused at a lower threshold and experienced a smaller increment in platelet count when compared to patients without marrow failure. (c) 2020 Published by Elsevier Inc.

Critical Care Medicine: March 2020 - Volume 48 - Issue 3 - p e269 doi: 10.1097/CCM.0000000000004275

Background: The global pandemic of coronavirus disease 2019 (COVID-19) has placed a huge strain on UK hospitals. Early studies suggest that patients can deteriorate quickly after admission to hospital. The aim of this study was to model changes in vital signs for patients hospitalised with COVID-19. Methods: This was a retrospective observational study of adult patients with COVID-19 admitted to one acute hospital trust in the UK (CV) and a cohort of patients admitted to the same hospital between 2013-2017 with viral pneumonia (VI). The primary outcome was the start of continuous positive airway pressure/non-invasive positive pressure ventilation, ICU admission or death in hospital. We used non-linear mixed-effects models to compare changes in vital sign observations prior to the primary outcome. Using observations and FiO(2) measured at discharge in the VI cohort as the model of normality, we also combined individual vital signs into a single novelty score. Results: There were 497 cases of COVID-19, of whom 373 had been discharged from hospital. 135 (36.2%) of patients experienced the primary outcome, of whom 99 died in hospital. In-hospital mortality was over 4-times higher in the CV than the VI cohort (26.5% vs 6%). For those patients who experienced the primary outcome, CV patients became increasingly hypoxaemic, with a median estimated FiO(2) (0.75) higher than that of the VI cohort (estimated FiO(2) of 0.35). Prior to the primary outcome, blood pressure remained within normal range, and there was only a small rise in heart rate. The novelty score showed that patients with COVID-19 deteriorated more rapidly that patients with viral pneumonia. Conclusions: Patients with COVID-19 who deteriorate in hospital experience rapidly-worsening respiratory failure, with low SpO(2) and high FiO(2), but only minor abnormalities in other vital signs. This has potential implications for the ability of early warning scores to identify deteriorating patients.

Objectives: Prolonged admissions to an ICU are associated with high resource utilization and personal cost to the patient. Previous reports suggest increasing length of stay may be associated with poor outcomes. Conditional survival represents the probability of future survival after a defined period of treatment on an ICU providing a description of how prognosis evolves over time. Our objective was to describe conditional survival as length of ICU stay increased. Design: Retrospective observational cohort study of three large intensive care databases. Setting: Three intensive care databases, two in the United States (Medical Information Mart for Intensive Care III and electronic ICU) and one in United Kingdom (Post Intensive Care Risk-Adjusted Alerting and Monitoring). Patients: Index admissions to intensive care for patients 18 years or older. Interventions: None. Measurements and Main Results: A total of 11,648, 38,532, and 165,125 index admissions were analyzed from Post Intensive Care Risk-Adjusted Alerting and Monitoring, Medical Information Mart for Intensive Care III and electronic ICU databases respectively. In all three cohorts, conditional survival declined over the first 5–10 days after ICU admission and changed little thereafter. In patients greater than or equal to 75 years old conditional survival continued to decline with increasing length of stay. Conclusions: After an initial period of 5–10 days, probability of future survival does not decrease with increasing length of stay in unselected patients admitted to ICUs. These findings were consistent between the three populations and suggest that a prolonged admission to an ICU is not a reason for a pessimism in younger patients but may indicate a poor prognosis in the older population.

The effects of postal questionnaire burden on return rates and answers given are unclear following treatment on an intensive care unit (ICU). We aimed to establish the effects of different postal questionnaire burdens on return rates and answers given.

A46-year-old male presented acutely to hospital following trauma to the left lower limb. Past medical history included a significant history of alcohol use, established atrial fibrillation and a possible cardiomyopathy that was currently under investigation. On admission he was hypotensive, hypoxic, delirious and had sustained a closed compound proximal tibial fracture on the left side. Further investigations revealed a transaminitis, initially attributed to established alcoholic liver disease. Considering the nature of the injury and the degree of hypoxia the diagnosis of fat embolus was also considered. In view of the degree of organ dysfunction on admission his initial management was conservative. The patient was resuscitated and admitted to a higher monitoring area and subsequently a trauma ward. The limb was reduced and placed into a cast. Admission to the intensive care department occurred four weeks post initial presentation for respiratory failure secondary to hospital-acquired pneumonia. Management consisted of intubation, positive pressure ventilation, intravenous antibiotics and inotropic support. Subsequent CT scan revealed bilateral pulmonary emboli, bilateral consolidation and small bilateral effusions. The initial transaminitis had now completely resolved and in retrospect was likely the result of a hypotensive liver injury rather than chronic alcoholism. The patient was started on therapeutic tinzaparin; Angel Catheter for urgent orthopaedic surgery in a patient anti-coagulated for pulmonary emboli

INTRODUCTION:The socio-economic impact of critical illnesses on patients and their families in Europe has yet to be determined. The aim of this exploratory study was to estimate changes in family circumstances, social and economic stability, care requirements and access to health services for patients during their first 12 months after ICU discharge.METHODS:Multi-center questionnaire-based study of survivors of critical illness at 6 and 12 months after ICU discharge.RESULTS:Data for 293 consenting patients who spent greater than 48 hours in one of 22 UK ICUs were obtained at 6 and 12 months post-ICU discharge. There was little evidence of a change in accommodation or relationship status between pre-admission and 12 months following discharge from an ICU. A negative impact on family income was reported by 33% of all patients at 6 months and 28% at 12 months. There was nearly a 50% reduction in the number of patients who reported employment as their sole source of income at 12 months (19% to 11%) compared with pre-admission. One quarter of patients reported themselves in need of care assistance at 6 months and 22% at 12 months. The majority of care was provided by family members (80% and 78%, respectively), for half of whom there was a negative impact on employment. Amongst all patients receiving care, 26% reported requiring greater than 50 hours a week. Following discharge, 79% of patients reported attending their primary care physician and 44% had seen a community nurse. Mobility problems nearly doubled between pre-admission and 6 months (32% to 64%). Furthermore, 73% reported moderate or severe pain at 12 months and 44% remained significantly anxious or depressed.CONCLUSIONS:Survivors of critical illness in the UK face a negative impact on employment and commonly have a care requirement after discharge from hospital. This has a corresponding negative impact on family income. The majority of the care required is provided by family members. This effect was apparent by 6 months and had not materially improved by 12 months. This exploratory study has identified the potential for a significant socio-economic burden following critical illness.