The incidence of cancer following hospitalisation for a burn injury in Scotland 2009-2019: A retrospective cohort study.

BACKGROUND: Studies suggest increased occurrence of cancer in persons who have experienced a burn injury with hospital admission. OBJECTIVE: To determine the incidence of cancer among those hospitalised for burn injuries in Scotland compared with a similar group without a history of burn injury hospitalisation. METHOD: A retrospective cohort design was used to compare cancer (ICD10 C00-97, excluding C44) incidence in two groups: 6805 burn injury patients discharged from Scottish hospitals between 2009 and 2019, and 25,946 subjects from the general population who were matched to burn patients by sex, year of birth, and degree of social deprivation. Cancer incidence was identified from the Scottish cancer registry. Cox proportional hazard regression was used to model time to cancer incidence adjusting for age, sex, degree of deprivation and presence of a comorbidity. Cancer risk was presented as standardised incidence ratios (SIRs) and hazard ratios (HR). RESULTS: We found a higher prevalence of pre-existing conditions, particularly alcohol abuse among patients with burns. Pre-existing cancers were more common in the burn cohort (3.5%) than the comparison group (1.7%) and were excluded from further analysis. Over a median follow-up of 4-5 years, a total of 236 (3.5%) burn patients and 969 (3.7%) persons in the comparison group were diagnosed with cancer. At 0-6 months the cancer SIR for burn patients was 1.88 95% CI (1.40-2.52). After excluding the first six months of follow-up, the overall incidence of cancer was marginally elevated in burn patients (SIR 1.04, 95% CI 0.90-1.19, p = 0.62) and not statistically different from the incidence in comparison subjects (adjusted HR 1.03, 95% CI 0.88-1.21, p = 0.71). CONCLUSIONS: Patients that suffer burn injury have a higher incidence of cancer than the general population and a group matched by age, sex and degree of deprivation. A higher incidence of adverse health-related behaviours such as smoking, alcohol use and pre-existing health conditions among many patients that suffer a burn most likely explain this observed increase. Any persisting inflammatory or immune dysfunction following burn injury is unlikely to account for the increase in cancers in this study.

Long term opioid use after burn injury: a retrospective cohort study.

BACKGROUND: Patients who have survive a burn injury might be at risk of opioid dependence after discharge. This study examined the use of opioids in patients who suffer burn injury and explored factors associated with persistent opioid use after hospital discharge. METHODS: This retrospective cohort study compared adults admitted with a burn injury from 2009 to 2019 with two matched comparison cohorts from the general population and adults with a diagnosis of acute pancreatitis. Pre-admission prescription opioid use was determined, and a multivariable negative binomial regression analysis used to explore post-discharge opioid use. RESULTS: A total of 7147 burn patients were matched with 6810 pancreatitis patients and with 28 184 individuals from the general population. Pre-admission opioid use was higher in the burn and pancreatitis cohorts (29% and 40%, respectively) compared with the general population (17%). Opioid use increased in both burn and pancreatitis cohorts after discharge (41% and 53%, respectively), although patients with pancreatitis were at even higher risk of increased opioid use in an adjusted analysis (incidence rate ratio 1.43). Female sex, lower socioeconomic status, ICU admission, pre-injury opioid use, and a history of excess alcohol use were all associated with an increase in opioid prescriptions after discharge. CONCLUSIONS: Opioid use is high in those admitted with a burn injury or acute pancreatitis when compared with the general population, increasing further after hospital discharge. Female sex and socioeconomic deprivation are among factors that make increased opioid use more likely, although this phenomenon seems even more pronounced in those with acute pancreatitis compared with burn injuries.

Platelet transfusions in adult thrombocytopenic ICU patients: Protocol for a sub-study of the PLOT-ICU cohort.

INTRODUCTION: Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. METHODS: This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the 'Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)'. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively. CONCLUSIONS: The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.

Impact of acute kidney injury on major adverse cardiovascular events in intensive care survivors.

Background: Acute kidney injury commonly occurs in patients admitted to ICU. After acute kidney injury, kidney function may not completely recover leading to increased risk of future cardiovascular events. We sought to ascertain the rates of cardiovascular events in ICU survivors and if these rates were affected by the presence of acute kidney injury whilst in ICU. Methods: This retrospective observational cohort study utilised routinely collected data to identify patients who had survived an admission to one of two ICUs between July 2015 and June 2018. Baseline serum creatinine and subsequent values were used to identify acute kidney injury. Major adverse cardiovascular events described were myocardial injury, coronary artery intervention, or radiological evidence of stroke. Results: Of the 3994 ICU survivors, major adverse cardiovascular events were identified in 385 patients (9.6%; 95% confidence interval [CI] 8.8-10.6%). Presence of acute kidney injury whilst in ICU was significantly associated with future major adverse cardiovascular events (hazard ratio=1.38; 95% CI 1.12-1.70; P-value=0.003) and future biochemical myocardial injury (hazard ratio=1.48; 95% CI 1.16-1.89; P-value=0.001). Acute kidney injury did not have a statistically significant association with future coronary artery interventions or future cerebrovascular events. Conclusions: One in 10 ICU survivors experiences a major adverse cardiovascular event after discharge. Acute kidney injury whilst in ICU was associated with an increased risk of major adverse cardiovascular events and specifically myocardial injury. Further research is warranted on whether ICU survivors with acute kidney injury merit enhanced strategies for cardiovascular protection.

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Post-hospital recovery trajectories of family members of critically ill COVID-19 survivors: an international qualitative investigation.

PURPOSE: The immediate impact of coronavirus disease 2019 (COVID-19) visiting restrictions for family members has been well-documented. However, the longer-term trajectory, including mechanisms for support, is less well-known. To address this knowledge gap, we aimed to explore the post-hospital recovery trajectory of family members of patients hospitalised with a critical care COVID-19 admission. We also sought to understand any differences across international contexts. METHODS: We undertook semi-structured interviews with family members of patients who had survived a COVID-19 critical care admission. Family members were recruited from Spain and the United Kingdom (UK) and telephone interviews were undertaken. Interviews were analysed using a thematic content analysis. RESULTS: Across the international sites, 19 family members were interviewed. Four themes were identified: changing relationships and carer burden; family health and trauma; social support and networks and differences in lived experience. We found differences in the social support and networks theme across international contexts, with Spanish participants more frequently discussing religion as a form of support. CONCLUSIONS: This international qualitative investigation has demonstrated the challenges which family members of patients hospitalised with a critical care COVID-19 admission experience following hospital discharge. Specific support mechanisms which could include peer support networks, should be implemented for family members to ensure ongoing needs are met.

Use of protracted CPAP as supportive treatment for COVID-19 pneumonitis and associated outcomes: a national cohort study.

BACKGROUND: Continuous positive airway pressure (CPAP) has been increasingly deployed to manage patients with COVID-19 and acute respiratory failure, often for protracted periods. However, concerns about protracted CPAP have been raised. This study aimed to examine the use of CPAP for patients with COVID-19 and the outcomes after protracted use. METHODS: This was a national cohort study of all adults admitted to Scottish critical care units with COVID-19 from March 1, 2020 to December 25, 2021 who received CPAP. Protracted CPAP was defined as ≥ 5 continuous days of CPAP. Outcomes included CPAP failure rate (institution of invasive mechanical ventilation [IMV] or death), mortality, and outcomes after institution of IMV. Multivariable logistic regression was performed to assess the impact of protracted CPAP on mortality after IMV. RESULTS: A total of 1961 patients with COVID-19 received CPAP for COVID-19 pneumonitis, with 733 patients (37.4%) receiving protracted CPAP. CPAP failure occurred in 891 (45.4%): 544 patients (27.7%) received IMV and 347 patients (17.7%) died in critical care without IMV. Hospital mortality rate was 41.3% for the population. For patients who subsequently commenced IMV, hospital mortality was 58.7% for the standard duration CPAP group and 73.9% for the protracted duration CPAP group (P=0.003); however, there was no statistical difference in hospital mortality after adjustment for confounders (odds ratio 1.4, 95% confidence interval 0.84-2.33, P=0.195). CONCLUSIONS: Protracted CPAP was used frequently for managing patients with COVID-19. Whilst it was not associated with worse outcomes for those patients who subsequently required IMV, this might be due to residual confounding and differences in processes of care.

Extracorporeal membrane oxygenation in adults receiving haematopoietic cell transplantation: an international expert statement.

Combined advances in haematopoietic cell transplantation (HCT) and intensive care management have improved the survival of patients with haematological malignancies admitted to the intensive care unit. In cases of refractory respiratory failure or refractory cardiac failure, these advances have led to a renewed interest in advanced life support therapies, such as extracorporeal membrane oxygenation (ECMO), previously considered inappropriate for these patients due to their poor prognosis. Given the scarcity of evidence-based guidelines on the use of ECMO in patients receiving HCT and the need to provide equitable and sustainable access to ECMO, the European Society of Intensive Care Medicine, the Extracorporeal Life Support Organization, and the International ECMO Network aimed to develop an expert consensus statement on the use of ECMO in adult patients receiving HCT. A steering committee with expertise in ECMO and HCT searched the literature for relevant articles on ECMO, HCT, and immune effector cell therapy, and developed opinion statements through discussions following a Quaker-based consensus approach. An international panel of experts was convened to vote on these expert opinion statements following the Research and Development/University of California, Los Angeles Appropriateness Method. The Appraisal of Guidelines for Research and Evaluation statement was followed to prepare this Position Paper. 36 statements were drafted by the steering committee, 33 of which reached strong agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and expert panel, and rephrased before an additional round of voting. At the conclusion of the process, 33 statements received strong agreement and three weak agreement. This Position Paper could help to guide intensivists and haematologists during the difficult decision-making process regarding ECMO candidacy in adult patients receiving HCT. The statements could also serve as a basis for future research focused on ECMO selection criteria and bedside management.

Clinician perceptions of the impact of ICU family visiting restrictions during the COVID-19 pandemic: an international investigation.

PURPOSE: To guarantee the safety of the public, clinicians and patients during the COVID-19 pandemic, hospital visits were severely restricted internationally. There are limited data on the precise impact of these visiting restrictions on Intensive Care Unit clinicians. Our objectives therefore were to explore the impact of family visitation restrictions on clinicians and care delivery and describe innovation alongside areas for potential improvement. METHODS: A qualitative approach using focus groups was employed. We recruited members of the multi-disciplinary team from Spain, France and the UK. Framework analysis was used to synthesize and interpret data. RESULTS: In total, 28 staff from multiple international sites contributed to data across six focus groups: 12 from the UK, 9 from France and 7 from Spain. In relation to the key aims, we derived four themes: the emergence of new technologies, relationships and rapport establishment, communication challenges and end-of-life care provision. Across each theme, the overarching concepts of clinician emotional exhaustion and emotional distress emerged alongside the negative impact on job satisfaction. CONCLUSION: The impact of COVID-19 family visitation restrictions is far reaching. Future research should examine the wider impact of family presence in the ICU.

Platelet transfusions and thrombocytopenia in intensive care units: Protocol for an international inception cohort study (PLOT-ICU).

INTRODUCTION: Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. METHODS: We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109 /L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. CONCLUSION: The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway.

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.

Prevalence, characteristics, and longer-term outcomes of patients with persistent critical illness attributable to COVID-19 in Scotland: a national cohort study.

BACKGROUND: Patients with COVID-19 can require critical care for prolonged periods. Patients with persistent critical Illness can have complex recovery trajectories, but this has not been studied for patients with COVID-19. We examined the prevalence, risk factors, and long-term outcomes of critically ill patients with COVID-19 and persistent critical illness. METHODS: This was a national cohort study of all adults admitted to Scottish critical care units with COVID-19 from March 1, 2020 to September 4, 20. Persistent critical illness was defined as a critical care length of stay (LOS) of ≥10 days. Outcomes included 1-yr mortality and hospital readmission after critical care discharge. Fine and Gray competing risk analysis was used to identify factors associated with persistent critical Illness with death as a competing risk. RESULTS: A total of 2236 patients with COVID-19 were admitted to critical care; 1045 patients were identified as developing persistent critical Illness, comprising 46.7% of the cohort but using 80.6% of bed-days. Patients with persistent critical illness used more organ support, had longer post-critical care LOS, and longer total hospital LOS. Persistent critical illness was not significantly associated with long-term mortality or hospital readmission. Risk factors associated with increased hazard of persistent critical illness included age, illness severity, organ support on admission, and fewer comorbidities. CONCLUSIONS: Almost half of all patients with COVID-19 admitted to critical care developed persistent critical illness, with high resource use in critical care and beyond. However, persistent critical illness was not associated with significantly worse long-term outcomes compared with patients who were critically ill for shorter periods.

Short- and long-term outcomes of intensive care patients with acute kidney disease.

BACKGROUND: Acute kidney disease (AKD) is a proposed definition for acute kidney injury (AKI) lasting 7 days or longer. Little has been reported regarding characteristics of patients with AKD and their short- and long-term outcomes. We describe the epidemiology and risk factors for AKD and outcomes following AKD. METHODS: This retrospective observational cohort study identified patients aged 16 or older admitted to the Glasgow Royal Infirmary and Queen Elizabeth University Hospital intensive care units (ICUs) in Scotland between 1st July 2015 and 30th June 2018. Baseline serum creatinine and subsequent values were used to identify patients with de-novo kidney injury (DNKI). Patients with recovery prior to day 7 were classified as AKI; recovery at day 7 or beyond was classified as AKD. Outcomes were in-hospital and long-term mortality, and proportion of major adverse kidney events (MAKEs). Multivariable logistic regression was used to identify risk factors for AKD. A Cox proportional hazards model was used to identify factors associated with long-term outcomes. FINDINGS: Of the 5,334 patients admitted to ICU who were assessed for DNKI, 1,620 (30·4%) suffered DNKI and of these, 403 (24·9%) met AKD criteria; 984 (60·7%) were male and the median age was 60·0 (IQR=48·0-72·0). Male sex, sepsis and lower baseline estimated glomerular filtration rate (eGFR) were associated with development of AKD. In-ICU (16·1%vs6·2%) and in-hospital (26·1%vs11·6%) mortality rates were significantly higher in AKD patients than AKI patients. Long-term survival was not different for AKD patients (HR=1·16; p-value=0·261) but AKD was associated with subsequent MAKEs (OR=1·25). INTERPRETATION: One in four ICU patients with DNKI met AKD criteria. These patients had an increased risk of short-term mortality and long-term MAKEs. Whilst the trend for long-term survival was lower, this was not significantly different from shorter-term AKI patients. Patients with AKD during their ICU stay should be identified to initiate interventions to reduce risk of future MAKEs. FUNDING: No funding was associated with this study.

Long-term outcomes following severe COVID-19 infection: a propensity matched cohort study.

BACKGROUND: There are limited data describing the long-term outcomes of severe COVID-19. We aimed to evaluate the long-term psychosocial and physical consequences of severe COVID-19 for patients. METHODS: We conducted a multicentre observational cohort study; between 3 and 7 months posthospital discharge, patients who had been admitted to critical care due to severe COVID-19 were invited to an established recovery service. Standardised questionnaires concerning emotional, physical and social recovery, including information on employment, were completed by patients. Using propensity score matching, we explored outcomes between patients admitted to critical care with and without COVID-19, using data from the same recovery programme. RESULTS: Between July 2020 and December 2020, 93 patients who had been admitted to critical with COVID-19 participated. Emotional dysfunction was common: 46.2% of patients had symptoms of anxiety and 34.4% symptoms of depression. At follow-up 53.7% of previously employed patients had returned to employment; there was a significant difference in return to employment across the socio-economic gradient, with lower numbers of patients from the most deprived areas returning to employment (p=0.03). 91 (97.8%) COVID-19 patients were matched with 91 non-COVID-19 patients. There were no significant differences in any measured outcomes between the two cohorts. INTERPRETATION: Emotional and social problems are common in survivors of severe COVID-19 infection. Coordinated rehabilitation is required to ensure patients make an optimal recovery.

Neuropathic agents in the management of pruritus in burn injuries: a systematic review and meta-analysis.

OBJECTIVES: Pruritus is a common and often distressing complication after a burn injury. The purpose of this review is to explore the efficacy of drugs classically used to treat neuropathic pain in the management of pruritus after burn injury. METHODS: A systematic literature search of medical databases was conducted to find studies investigating drugs listed in the National Institute for Health and Care Excellence (NICE) guideline (CG173, "neuropathic pain in adults") for the management of pruritus after burn injury in patients of any age. Controlled studies were stratified by the drug class studied and their risk of bias before conducting meta-analysis. A narrative review of case series or observational studies was presented. Severity of pruritus at any time point, with all quantitative and qualitative measures, was included. RESULTS: Fifteen studies were included in the final analysis, 10 investigated the use of gabapentinoids, 4 studied doxepin, and 1 local anesthetic agents. Meta-analysis of three randomized controlled trials (RCTs) demonstrated that the use of gabapentinoids was associated with an improvement in mean VAS (Visual Analog Scale) 0-10 scores of 2.96 (95% confidence interval (95% CI) 1.20 to 4.73, p<0.001) when compared with placebo or antihistamine. A meta-analysis of four RCTs investigating topical doxepin showed an improvement in mean VAS scores of 1.82 (95% CI 0.55 to 3.09, p<0.001). However, when excluding two studies found to be at high risk of bias, no such improvement was found (-0.32, 95% CI -1.64 to -0.99, p=0.83). CONCLUSION: This study suggests that gabapentinoids are beneficial in the management of burn-related pruritus. There is a lack of evidence to suggest that doxepin is an effective treatment. Topical local anesthetic agents may be safe and beneficial, but studies are scarce. LEVEL OF EVIDENCE: Systematic review, level II.

Postoperative C-reactive protein concentrations to predict infective complications following gastrectomy for cancer.

BACKGROUND AND OBJECTIVES: Gastrectomy for gastric cancer is associated with significant infective postoperative complications. C-reactive protein (CRP) is a useful biomarker in the early detection of infective complications following major abdominal surgery. This single-centre retrospective study aimed to determine the relationship between postoperative CRP levels and development of postoperative infective complications after gastrectomy. METHODS: Daily postoperative CRP levels were analyzed to determine a CRP threshold associated with infective complications. ROC curve analysis was used to determine which postoperative day (POD) gave the optimal cutoff. Multivariate analysis was performed to determine significant factors associated with complications. RESULTS: One hundred and forty-four patients were included. A total of 61 patients (42%) had at least one infective complication. A CRP level of 220 mg/L was associated with the highest AUC (0.765) with a sensitivity of 70% and specificity of 76% (positive predictive value, 67%; negative predictive value, 78%). More patients with a CRP > 220 mg/L on POD 3 developed infective complications (67% vs. 21%, p < 0.001). CONCLUSIONS: A CRP of more than 220 mg/L on POD 3 may be useful to alert clinicians to the increased risk of a postoperative infective complication or enable earlier safe discharge from critical care for those with a lower value.