Deferoxamine in the management of COVID-19 adult patients admitted to ICU: a prospective observational cohort study.

COVID-19 infection is associated with high mortality, and despite extensive studying the scientific society is still working to find a definitive treatment. Some experts postulated a beneficial role of Deferoxamine. Aim: The aim of this study was to compare the outcomes of COVID-19 adult patients admitted to the ICU who received deferoxamine to those who received standard of care. Methods: Prospective observational cohort study, in the ICU of a tertiary referral hospital in Saudi Arabia to compare all-cause hospital mortality between COVID-19 patients who received deferoxamine and standard of care. Results: A total of 205 patients were enrolled, with an average age of 50.1±14.3, 150 patients received standard of care only, and 55 patients received deferoxamine additionally. Hospital mortality was lower in deferoxamine group (25.5 vs. 40.7%, 95% CI=1.3-29.2%; P=0.045). Clinical status score upon discharge was lower in deferoxamine group (3.6±4.3 vs. 6.2±4, 95% CI: 1.4-3.9; P<0.001), as was the difference between discharge score and admission score (indicating clinical improvement). More patients admitted with mechanical ventilation were successfully extubated in the deferoxamine group (61.5 vs. 14.3%, 95% CI: 15-73%; P=0.001), with a higher median ventilator-free days. There were no differences between groups in adverse events. Deferoxamine group was associated with hospital mortality [odds ratio=0.46 (95% CI: 0.22-0.95); P=0.04]. Conclusions: Deferoxamine may have mortality and clinical improvement benefits in COVID-19 adults admitted to ICU. Further powered and controlled studies are required.

A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.

BACKGROUND: COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace. OBJECTIVE: We aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR). METHODS: A federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners' pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers' secure environments, and to support federated cohort discovery queries and meta-analysis. RESULTS: A total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom. CONCLUSIONS: CO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.

"Ventilator-free days" composite outcome in patients with SARS-CoV-2 infection treated with tocilizumab: A retrospective competing risk analysis.

BACKGROUND: SARS-CoV-2 infection demonstrates a wide range of severity, with more severe cases presenting with a cytokine storm with elevated serum interleukin-6; hence, the interleukin-6 receptor antibody tocilizumab was used for the management of severe cases. OBJECTIVE: To explore the effect of tocilizumab on ventilator-free day composite outcomes among critically ill patients with SARS-CoV-2 infection. METHODS: This retrospective propensity score-matching study compared mechanically ventilated patients who received tocilizumab to a control group. RESULTS: Twenty-nine patients in the intervention group were compared to 29 controls. The matched groups were similar. The ventilator-free days composite outcome was higher in the intervention group (sub-distribution hazard ratio 2.7, 95% confidence interval [CI]: 1.2-6.3; p = 0.02), the mortality rate in the intensive care unit was not different (37.9% vs 62%, p = 0.1), and actual ventilator-free days were significantly longer in the tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio for death in the tocilizumab group (HR 0.49, 95% CI: 0.25-0.97; p = 0.04). Positive cultures were not significantly different among the groups (55.2% vs 34.5% in the tocilizumab and control groups, respectively; p = 0.1). CONCLUSIONS: Tocilizumab may improve the composite outcome of ventilator-free days at day 28 among mechanically ventilated patients with SARS-CoV-2 infection. It is associated with significantly longer actual ventilator-free days, insignificantly lower mortality, and higher superinfection.

A National Network of Safe Havens: Scottish Perspective.

For over a decade, Scotland has implemented and operationalized a system of Safe Havens, which provides secure analytics platforms for researchers to access linked, deidentified electronic health records (EHRs) while managing the risk of unauthorized reidentification. In this paper, a perspective is provided on the state-of-the-art Scottish Safe Haven network, including its evolution, to define the key activities required to scale the Scottish Safe Haven network's capability to facilitate research and health care improvement initiatives. A set of processes related to EHR data and their delivery in Scotland have been discussed. An interview with each Safe Haven was conducted to understand their services in detail, as well as their commonalities. The results show how Safe Havens in Scotland have protected privacy while facilitating the reuse of the EHR data. This study provides a common definition of a Safe Haven and promotes a consistent understanding among the Scottish Safe Haven network and the clinical and academic research community. We conclude by identifying areas where efficiencies across the network can be made to meet the needs of population-level studies at scale.

External Validation of 4C ISARIC Mortality Score in Critically ill COVID-19 Patients from Saudi Arabia.

Background: ISARIC mortality score is a risk stratification tool that helps predict the in-hospital mortality of COVID-19 patients. However, this tool was developed and validated in a British population, and thus, the external validation of this tool in local populations is important. Objectives: External validation of the ISARIC mortality score in COVID-19 patients from a large Saudi Arabian intensive care unit (ICU). Methods: This is a retrospective study that included all adult patients with COVID-19 admitted to the ICU of King Saud Medical City, Riyadh, Saudi Arabia, from March 2020 to June 2021. Patients who were pregnant or had pulmonary tuberculosis/human immunodeficiency virus were excluded along with patients with missing variables. Data were collected to calculate the ISARIC mortality score and then fitting receiver operator characteristic curve against patients' outcome. Results: A total of 1493 critically ill COVID-19 patients were included. The mortality was 38%, the area under the curve of the score was 0.81 (95% confidence interval [CI]: 0.79-0.83, P < 0.001) and the cutoff value correctly classified 72.7% of the cohort. The cutoff value of >9 had sensitivity of 70.5% (95% CI: 66.6-74.3); specificity, 73.97% (95% CI: 71-76.8); positive predictive value, 62.4% (95% CI: 59.5-65.2) and negative predictive value, 80.2% (95% CI: 78.2-82.4). Conclusion: The ISARIC score was found to have excellent predictive ability for mortality in critically ill COVID-19 patients in our Saudi Arabian cohort. A cutoff score of >9 was the optimal criterion.

Effect of Tocilizumab on "Ventilator Free Days" Composite Outcome in SARS-CoV-2 Patients: A Retrospective Competing Risk Analysis.

Background: SARS-CoV-2 infection demonstrates a wide range of severity. More severe cases demonstrate a cytokine storm with elevated serum interleukin-6, hence IL-6 receptor antibody tocilizumab was tried for the management of severe cases. Aims: Effect of tocilizumab on ventilator-free days among critically ill SARS-CoV-2 patients. Method: Retrospective propensity score matching study, comparing mechanically ventilated patients who received tocilizumab to a control group. Results: 29 patients in the intervention group were compared to 29 controls. Matched groups were similar. Ventilator-free days were more numerous in the intervention group (SHR 2.7, 95% CI: 1.2 - 6.3; p = 0.02), ICU mortality rate was not different (37.9% versus 62%, p = 0.1), actual ventilator-free periods were significantly longer in tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio of death in tocilizumab group (HR 0.49, 95% CI: 0.25 - 0.97; p = 0.04). There was no difference in positive cultures among groups (55.2% in tocilizumab group versus 34.5% in the control; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator-free days at day 28 among mechanically ventilated SARS-CoV-2 patients; it is associated with significantly longer actual ventilator-free periods, and insignificantly lower mortality and higher superinfection.

Desiderata for the development of next-generation electronic health record phenotype libraries.

BACKGROUND: High-quality phenotype definitions are desirable to enable the extraction of patient cohorts from large electronic health record repositories and are characterized by properties such as portability, reproducibility, and validity. Phenotype libraries, where definitions are stored, have the potential to contribute significantly to the quality of the definitions they host. In this work, we present a set of desiderata for the design of a next-generation phenotype library that is able to ensure the quality of hosted definitions by combining the functionality currently offered by disparate tooling. METHODS: A group of researchers examined work to date on phenotype models, implementation, and validation, as well as contemporary phenotype libraries developed as a part of their own phenomics communities. Existing phenotype frameworks were also examined. This work was translated and refined by all the authors into a set of best practices. RESULTS: We present 14 library desiderata that promote high-quality phenotype definitions, in the areas of modelling, logging, validation, and sharing and warehousing. CONCLUSIONS: There are a number of choices to be made when constructing phenotype libraries. Our considerations distil the best practices in the field and include pointers towards their further development to support portable, reproducible, and clinically valid phenotype design. The provision of high-quality phenotype definitions enables electronic health record data to be more effectively used in medical domains.

Delayed intensive care unit admission from the emergency department: impact on patient outcomes. A retrospective study. / Retardo na transferência do pronto-socorro para a unidade de terapia intensiva: impacto nos desfechos do paciente. Um estudo retrospectivo.

OBJECTIVE: To study the impact of delayed admission by more than 4 hours on the outcomes of critically ill patients. METHODS: This was a retrospective observational study in which adult patients admitted directly from the emergency department to the intensive care unit were divided into two groups: Timely Admission if they were admitted within 4 hours and Delayed Admission if admission was delayed for more than 4 hours. Intensive care unit length of stay and hospital/intensive care unit mortality were compared between the groups. Propensity score matching was performed to correct for imbalances. Logistic regression analysis was used to explore delayed admission as an independent risk factor for intensive care unit mortality. RESULTS: During the study period, 1,887 patients were admitted directly from the emergency department to the intensive care unit, with 42% being delayed admissions. Delayed patients had significantly longer intensive care unit lengths of stay and higher intensive care unit and hospital mortality. These results were persistent after propensity score matching of the groups. Delayed admission was an independent risk factor for intensive care unit mortality (OR = 2.6; 95%CI 1.9 - 3.5; p < 0.001). The association of delay and intensive care unit mortality emerged after a delay of 2 hours and was highest after a delay of 4 hours. CONCLUSION: Delayed admission to the intensive care unit from the emergency department is an independent risk factor for intensive care unit mortality, with the strongest association being after a delay of 4 hours.

OBJETIVO: Estudar o impacto do retardo na admissão à unidade de terapia intensiva em mais do que 4 horas nos desfechos de pacientes críticos. MÉTODOS: Este foi um estudo observacional retrospectivo, no qual pacientes adultos admitidos diretamente do pronto-socorro para a unidade de terapia intensiva foram divididos em dois grupos: Tempo Adequado, se admitidos dentro de 4 horas, e Admissão Retardada, nos casos em que a admissão demorou mais do que 4 horas para ocorrer. Compararam-se, entre os grupos, o tempo de permanência na unidade de terapia intensiva e a taxa de mortalidade na unidade de terapia intensiva e no hospital. Foi realizado pareamento por escore de propensão para correção de desequilíbrios. Utilizou-se uma análise de regressão logística para explorar retardo da admissão como fator independente de risco para mortalidade na unidade de terapia intensiva. RESULTADOS: Durante o período do estudo, 1.887 pacientes foram admitidos diretamente do pronto-socorro para a unidade de terapia intensiva, sendo que 42% dessas admissões foram retardadas. Os pacientes com retardo tiveram permanências na unidade de terapia intensiva significantemente mais longas e maior mortalidade na unidade de terapia intensiva e no hospital. Esses resultados persistiram após pareamento dos grupos por escore de propensão. O retardo da admissão foi fator independente de risco para mortalidade na unidade de terapia intensiva (RC = 2,6; IC95% 1,9 - 3,5; p < 0,001). A associação de retardo e mortalidade na unidade de terapia intensiva surgiu após período de retardo de 2 horas e foi mais alta após período de retardo de 4 horas. CONCLUSÃO: O retardo da admissão do pronto-socorro para a unidade de terapia intensiva é fator de risco independente para mortalidade na unidade de terapia intensiva, sendo a associação mais forte após retardo de 4 horas.

Retardo na transferência do pronto-socorro para a unidade de terapia intensiva: impacto nos desfechos do paciente. Um estudo retrospectivo / Delayed intensive care unit admission from the emergency department: impact on patient outcomes. A retrospective study

RESUMO Objetivo: Estudar o impacto do retardo na admissão à unidade de terapia intensiva em mais do que 4 horas nos desfechos de pacientes críticos. Métodos: Este foi um estudo observacional retrospectivo, no qual pacientes adultos admitidos diretamente do pronto-socorro para a unidade de terapia intensiva foram divididos em dois grupos: Tempo Adequado, se admitidos dentro de 4 horas, e Admissão Retardada, nos casos em que a admissão demorou mais do que 4 horas para ocorrer. Compararam-se, entre os grupos, o tempo de permanência na unidade de terapia intensiva e a taxa de mortalidade na unidade de terapia intensiva e no hospital. Foi realizado pareamento por escore de propensão para correção de desequilíbrios. Utilizou-se uma análise de regressão logística para explorar retardo da admissão como fator independente de risco para mortalidade na unidade de terapia intensiva. Resultados: Durante o período do estudo, 1.887 pacientes foram admitidos diretamente do pronto-socorro para a unidade de terapia intensiva, sendo que 42% dessas admissões foram retardadas. Os pacientes com retardo tiveram permanências na unidade de terapia intensiva significantemente mais longas e maior mortalidade na unidade de terapia intensiva e no hospital. Esses resultados persistiram após pareamento dos grupos por escore de propensão. O retardo da admissão foi fator independente de risco para mortalidade na unidade de terapia intensiva (RC = 2,6; IC95% 1,9 - 3,5; p < 0,001). A associação de retardo e mortalidade na unidade de terapia intensiva surgiu após período de retardo de 2 horas e foi mais alta após período de retardo de 4 horas. Conclusão: O retardo da admissão do pronto-socorro para a unidade de terapia intensiva é fator de risco independente para mortalidade na unidade de terapia intensiva, sendo a associação mais forte após retardo de 4 horas.

Abstract Objective: To study the impact of delayed admission by more than 4 hours on the outcomes of critically ill patients. Methods: This was a retrospective observational study in which adult patients admitted directly from the emergency department to the intensive care unit were divided into two groups: Timely Admission if they were admitted within 4 hours and Delayed Admission if admission was delayed for more than 4 hours. Intensive care unit length of stay and hospital/intensive care unit mortality were compared between the groups. Propensity score matching was performed to correct for imbalances. Logistic regression analysis was used to explore delayed admission as an independent risk factor for intensive care unit mortality. Results: During the study period, 1,887 patients were admitted directly from the emergency department to the intensive care unit, with 42% being delayed admissions. Delayed patients had significantly longer intensive care unit lengths of stay and higher intensive care unit and hospital mortality. These results were persistent after propensity score matching of the groups. Delayed admission was an independent risk factor for intensive care unit mortality (OR = 2.6; 95%CI 1.9 - 3.5; p < 0.001). The association of delay and intensive care unit mortality emerged after a delay of 2 hours and was highest after a delay of 4 hours. Conclusion: Delayed admission to the intensive care unit from the emergency department is an independent risk factor for intensive care unit mortality, with the strongest association being after a delay of 4 hours.

Impact on Efficacy and Safety of Hydrocortisone in Sepsis and Septic Shock - A Systematic Literature Review and Meta-analysis.

BACKGROUND: Sepsis and septic shock are major causes of morbidity and mortality worldwide, associated with a high economic and social burden on healthcare systems and communities, yet with few definite treatment modalities. The efficacy of steroids in the management of sepsis or septic shock remains a controversy and subject of investigation due to their theoretical beneficial effects. METHODS: This was a systematic literature review and meta-analysis on randomized controlled trials of hydrocortisone usage in sepsis or septic shock as of 2000, following the GRADE methodology, considering a primary outcome of 28 day all-cause mortality. RESULTS: Ten randomized control trials were included in the review, 9 of which reported 28 day mortality either as a primary or secondary outcome. Relative risk of dying at 28 days was 0.93 in favor of hydrocortisone (95% CI: 0.86-1.01; P = 0.056). Other secondary outcomes of the review were similarly statistically insignificant. The quality of evidence was graded as very low to low. CONCLUSION: Hydrocortisone, when used in sepsis or septic shock, in critically ill adult patients showed a statistically insignificant trend towards decreasing 28 day all-cause mortality. This warrants consideration of clinical significance for each patient individually.

New Optic Nerve Sonography Quality Criteria in the Diagnostic Evaluation of Traumatic Brain Injury.

BACKGROUND: New sonographic quality criteria to optimize optic nerve sheath diameter (ONSD) measurements were suggested. The latter were correlated to elevated intracranial pressure (ICP) in traumatic brain injury (TBI). AIM: We investigated whether ONSD measurements were correlated to simultaneous ICP measurements in severe TBI. METHODS: Forty patients with severe TBI (Marshall Scale ≥II and GCS ≤8) participated in the study. All patients had an intraparenchymal ICP catheter inserted, while ONSD was measured bilaterally, upon admission and over the next 48 hours, based on the new sonographic criteria. A total of 400 ONSD measurements were performed, while mean ONSD values of both eyes were used in the analysis. RESULTS: ONSD measurements were strongly correlated to ICP values (r=0.74, p < 0.0001). Receiver operator curve (ROC) analysis revealed that the ONSD cutoff value for predicting elevated ICP was 6.4 mm when using the mean of both eyes (AUC = 0.88, 95% CI = 0.80 to 0.95; sensitivity = 85.3%, specificity = 82.6%). Linear regression analysis nested models revealed that sex (p=0.006) and height (p=0.04) were significant predictors of ONSD values. CONCLUSION: When applying the new sonographic quality criteria, ONSD is strongly correlated to ICP in severe TBI. Whether to use such criteria to monitor ONSD as a proxy for ICP trend in TBI remains to be further explored.

Scrutinizing human MHC polymorphism: Supertype analysis using Poisson-Boltzmann electrostatics and clustering.

Peptide-binding MHC proteins are thought the most variable across the human population; the extreme MHC polymorphism observed is functionally important and results from constrained divergent evolution. MHCs have vital functions in immunology and homeostasis: cell surface MHC class I molecules report cell status to CD8+ T cells, NKT cells and NK cells, thus playing key roles in pathogen defence, as well as mediating smell recognition, mate choice, Adverse Drug Reactions, and transplantation rejection. MHC peptide specificity falls into several supertypes exhibiting commonality of binding. It seems likely that other supertypes exist relevant to other functions. Since comprehensive experimental characterization is intractable, structure-based bioinformatics is the only viable solution. We modelled functional MHC proteins by homology and used calculated Poisson-Boltzmann electrostatics projected from the top surface of the MHC as multi-dimensional descriptors, analysing them using state-of-the-art dimensionality reduction techniques and clustering algorithms. We were able to recover the 3 MHC loci as separate clusters and identify clear sub-groups within them, vindicating unequivocally our choice of both data representation and clustering strategy. We expect this approach to make a profound contribution to the study of MHC polymorphism and its functional consequences, and, by extension, other burgeoning structural systems, such as GPCRs.

Not All Acute Abdomen Cases in Early Pregnancy Are Ectopic; Expect the Unexpected: Renal Angiomyolipoma Causing Massive Retroperitoneal Haemorrhage.

Retroperitoneal haemorrhage (or retroperitoneal haematoma) refers to an accumulation of blood found in the retroperitoneal space. It is a rare clinical entity with variable aetiology including anticoagulation, ruptured aortic aneurysm, acute pancreatitis, malignancy, and bleeding from renal aneurysm. Diagnosis of retroperitoneal bleed is sometimes missed or delayed as presentation is often nonspecific. Multislice CT and arteriography are important for diagnosis. There is no consensus about the best management plan for patients with retroperitoneal haematoma. Stable patients can be managed with fluid resuscitation, correction of coagulopathy if any, and blood transfusion. Endovascular options involving selective intra-arterial embolisation or stent-grafts are clearly getting more and more popularity. Open repair is usually reserved for cases when there is failure of conservative or endovascular measures to control the bleeding or expertise is unavailable and in cases where the patient is unstable. Mortality of patients with retroperitoneal haematoma remains high if appropriate and timely measures are not taken. Haemorrhage from a benign renal tumour is a rarer entity which is described in this case report which emphasizes that physicians should have a wide index of suspicion when dealing with patients presenting with significant groin, flank, abdominal, or back pain, or haemodynamic instability of unclear cause. Our patient presented with features of acute abdomen and, being pregnant, was thought of having a ruptured ectopic pregnancy.

Intra-Pleural Colistin Methanesulfonate Therapy for Pleural Infection caused by Carbapenem-Resistant Acinetobacter Baumannii: A Successful Case Report.

Infections caused by carbapenem-resistant, Gram-negative bacteria are an increasing clinical challenge, since the antimicrobial treatment options are often limited to colistin methanesulfonate. No data are available regarding the pharmacokinetics of colistin in pleural fluid. We report the case of a 92-year old man with ventilator-associated pneumonia and pleurisy caused by Acinetobacter baumannii and Escherichia coli, which were both multidrug-resistant. After an unsuccessful treatment with intravenous colistin methanesulfonate and imipen-em-cilastatin, the addition of intra-pleural colistin methanesulfonate to the intravenous treatment led to a prompt clinical, radiological and microbiological resolution. This is the first report of a successful use of intra-pleural colistin in the literature. The intra-pleural colistin therapy should be considered in selected cases of pleurisy caused by multi-resistant Gram-negative bacteria.

Comparison by meta-analysis of percutaneous coronary intervention versus coronary artery bypass grafting in patients with a mean age of ≥70 years.

A paucity of published data evaluating the outcomes of older patients (age ≥70 years) undergoing revascularization for unprotected left main coronary artery disease is available. We performed aggregate data meta-analyses of the clinical outcomes (all-cause mortality, nonfatal myocardial infarction, stroke, repeat revascularization, and major adverse cardiac and cerebrovascular events at 30 days and 12 and 22 months) in studies comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with a mean age of ≥70 years and unprotected left main coronary artery disease. A comprehensive, time-unlimited literature search to January 31, 2013 identified 10 studies with a total of 2,386 patients (PCI, n = 909; CABG, n = 1,477). Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the random-effects model. The patients in the PCI group were more likely than those in the CABG group to present with acute coronary syndrome (59.6% vs 44.8%, p <0.001). PCI was associated with a shorter hospital stay (4.2 ± 0.8 vs 8.3 ± 0.01 days, p <0.001). No significant differences were found between PCI and CABG for all cause-mortality, nonfatal myocardial infarction, and major adverse cardiac and cerebrovascular events at 30 days and 12 and 22 months. However, PCI was associated with lower rates of stroke at 30 days (OR 0.14, 95% CI 0.02 to 0.76) and 12 months (OR 0.14, 95% CI 0.03 to 0.60) and higher rates of repeat revascularization at 22 months (OR 4.34, 95% CI 2.69 to 7.01). These findings were consistent with the findings from a subgroup analysis of patients aged ≥75 years. In conclusion, older patients (age ≥70 years) with unprotected left main coronary artery disease had comparable rates of all-cause mortality, nonfatal myocardial infarction, and major adverse cardiac and cerebrovascular events after PCI or CABG. The patients undergoing PCI had a shorter hospital stay and lower rates of early stroke; however, they experienced higher repeat revascularization rates at longer term follow-up.