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1.
Dtsch Med Wochenschr ; 147(8): 485-491, 2022 04.
Article in German | MEDLINE | ID: covidwho-1805706

ABSTRACT

Hundreds of thousands of individuals who experience lasting sequelae after sepsis and infections in Germany do not receive optimal care. In this White Paper we present measures for improvement, which were developed by a multidisciplinary expect panel as part of the SEPFROK project. Improved care rests on four pillars: 1. cross-sectoral assessment of sequelae and a structured discharge and transition management, 2. interdisciplinary rehabilitation and aftercare with structural support, 3. strengthening the specific health literacy of patients and families, and 4. increased research into causes, prevention and treatment of sequelae. To achieve this, appropriate cross-sectoral care structures and legal frameworks must be created.


Subject(s)
Aftercare , Sepsis , Germany , Humans , Patient Discharge , Sepsis/diagnosis , Sepsis/therapy
2.
J Med Internet Res ; 24(4): e35058, 2022 04 18.
Article in English | MEDLINE | ID: covidwho-1793153

ABSTRACT

BACKGROUND: Improving interprofessional communication and collaboration is necessary to facilitate the early identification and treatment of patients with sepsis. Preparing undergraduate medical and nursing students for the knowledge and skills required to assess, escalate, and manage patients with sepsis is crucial for their entry into clinical practice. However, the COVID-19 pandemic and social distancing measures have created the need for interactive distance learning to support collaborative learning. OBJECTIVE: This study aimed to evaluate the effect of sepsis interprofessional education on medical and nursing students' sepsis knowledge, team communication skills, and skill use in clinical practice. METHODS: A mixed methods design using a 1-group pretest-posttest design and focus group discussions was used. This study involved 415 undergraduate medical and nursing students from a university in Singapore. After a baseline evaluation of the participants' sepsis knowledge and team communication skills, they underwent didactic e-learning followed by virtual telesimulation on early recognition and management of sepsis and team communication strategies. The participants' sepsis knowledge and team communication skills were evaluated immediately and 2 months after the telesimulation. In total, 4 focus group discussions were conducted using a purposive sample of 18 medical and nursing students to explore their transfer of learning to clinical practice. RESULTS: Compared with the baseline scores, both the medical and nursing students demonstrated a significant improvement in sepsis knowledge (P<.001) and team communication skills (P<.001) in immediate posttest scores. At the 2-month follow-up, the nursing students continued to have statistically significantly higher sepsis knowledge (P<.001) and communication scores (P<.001) than the pretest scores, whereas the medical students had no significant changes in test scores between the 2-month follow-up and pretest time points (P=.99). A total of three themes emerged from the qualitative findings: greater understanding of each other's roles, application of mental models in clinical practice, and theory-practice gaps. The sepsis interprofessional education-particularly the use of virtual telesimulation-fostered participants' understanding and appreciation of each other's interprofessional roles when caring for patients with sepsis. Despite noting some incongruities with the real-world clinical practice and not encountering many sepsis scenarios in clinical settings, participants shared the application of mental models using interprofessional communication strategies and the patient assessment framework in their daily clinical practice. CONCLUSIONS: Although the study did not show long-term knowledge retention, the use of virtual telesimulation played a critical role in facilitating the application of mental models for learning transfer and therefore could serve as a promising education modality for sepsis training. For a greater clinical effect, future studies could complement virtual telesimulation with a mannequin-based simulation and provide more evidence on the long-term retention of sepsis knowledge and clinical skills performance.


Subject(s)
COVID-19 , Sepsis , Students, Nursing , Humans , Interprofessional Education , Interprofessional Relations , Pandemics , Patient Care Team , Sepsis/diagnosis , Sepsis/therapy
3.
Pan Afr Med J ; 40: 204, 2021.
Article in English | MEDLINE | ID: covidwho-1643891

ABSTRACT

Sepsis is common and represents a major public health burden with significant associated morbidity and mortality. However, despite substantial advances in sepsis recognition and management in well-resourced health systems, there remains a distinct lack of research into sepsis in Africa. The lack of evidence affects all levels of healthcare delivery from individual patient management to strategic planning at health-system level. This is particular pertinent as African countries experience some of the highest global burden of sepsis. The 2017 World Health Assembly resolution on sepsis and the creation of the Africa Sepsis Alliance provided an opportunity for change. However, progress so far has been frustratingly slow. The recurrent Ebola virus disease outbreaks and the COVID-19 pandemic on the African continent further reinforce the need for urgent healthcare system strengthening. We recommend that African countries develop national action plans for sepsis which should address the needs of all critically ill patients.


Subject(s)
COVID-19 , Sepsis , Africa/epidemiology , Humans , Pandemics , SARS-CoV-2 , Sepsis/diagnosis , Sepsis/epidemiology , Sepsis/therapy
4.
J Hosp Infect ; 122: 84-95, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1620835

ABSTRACT

BACKGROUND: Sepsis is an important global healthcare problem that is a key challenge faced by healthcare professionals face worldwide. One key effort aimed at reducing the global burden of sepsis is educating healthcare professionals about early identification and management of sepsis. AIM: To provide a comprehensive evaluation of sepsis education among healthcare professionals and students. METHODS: Six databases (PubMed, CINAHL, Embase, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were searched. We included studies that described and evaluated any form of education or training on sepsis delivered to healthcare professionals and students. Study outcomes were summarized according to the adapted Kirkpatrick model of training evaluation. RESULTS: Thirty-two studies were included in the review. The learning contents were reported to be in accordance with the Surviving Sepsis Campaign guidelines. Seven studies included the topic of interprofessional teamwork and communication in their sepsis education content. Most educational programmes were effective and reported positive effects on immediate knowledge outcomes. Interventions that were delivered through an active learning approach such as simulation and game-based learning generally produced greater gains than didactic teaching. Improvements in patient care processes and patient outcomes were associated with the concomitant existence or implementation of a hospital sepsis care bundle. CONCLUSION: Incorporating active learning strategies into sepsis education interventions has the potential to improve learners' long-term outcomes. In addition, sepsis education and a protocol-based sepsis care bundle act in synergy to augment greater improvements in care processes and patient benefits.


Subject(s)
Health Personnel , Sepsis , Clinical Competence , Delivery of Health Care , Health Personnel/education , Humans , Sepsis/diagnosis , Sepsis/therapy , Students
5.
BMJ Open Qual ; 11(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1613016

ABSTRACT

INTRODUCTION: Sepsis is a common cause of emergency department (ED) presentation and hospital admission, accounting for a disproportionate number of deaths each year relative to its incidence. Sepsis outcomes have improved with increased recognition and treatment standards promoted by the Surviving Sepsis Campaign. Due to delay in recognition and other barriers, sepsis bundle compliance remains low nationally. We hypothesised that a targeted education intervention regarding use of an electronic health record (EHR) tool for identification and management of sepsis would lead to increased EHR tool utilisation and increased sepsis bundle compliance. METHODS: We created a multidisciplinary quality improvement team to provide training and feedback on EHR tool utilisation within our ED. A prospective evaluation of the rate of EHR tool utilisation was monitored from June through December 2020. Simultaneously, we conducted two retrospective cohort studies comparing overall sepsis bundle compliance for patients when EHR tool was used versus not used. The first cohort was all patients with intention-to-treat for any sepsis severity. The second cohort of patients included adult patients with time of recognition of sepsis in the ED admitted with a diagnosis of severe sepsis or septic shock. RESULTS: EHR tool utilisation increased from 23.3% baseline prior to intervention to 87.2% during the study. In the intention-to-treat cohort, there was a statistically significant difference in compliance between EHR tool utilisation versus no utilisation in overall bundle compliance (p<0.001) and for several individual components: initial lactate (p=0.009), repeat lactate (p=0.001), timely antibiotics (p=0.031), blood cultures before antibiotics (p=0.001), initial fluid bolus (p<0.001) and fluid reassessment (p<0.001). In the severe sepsis and septic shock cohort, EHR tool use increased from 71.2% pre-intervention to 85.0% post-intervention (p=0.008). CONCLUSION: With training, feedback and EHR optimisation, an EHR tool can be successfully integrated into current workflows and appears to increase sepsis bundle compliance.


Subject(s)
Sepsis , Shock, Septic , Adult , Anti-Bacterial Agents/therapeutic use , Electronic Health Records , Emergency Service, Hospital , Guideline Adherence , Humans , Lactic Acid , Retrospective Studies , Sepsis/diagnosis , Sepsis/therapy , Shock, Septic/drug therapy
6.
Int J Mol Sci ; 22(24)2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1599176

ABSTRACT

To determine whether mitigating the harmful effects of circulating microvesicle-associated inducible nitric oxide (MV-A iNOS) in vivo increases the survival of challenged mice in three different mouse models of sepsis, the ability of anti-MV-A iNOS monoclonal antibodies (mAbs) to rescue challenged mice was assessed using three different mouse models of sepsis. The vivarium of a research laboratory Balb/c mice were challenged with an LD80 dose of either lipopolysaccharide (LPS/endotoxin), TNFα, or MV-A iNOS and then treated at various times after the challenge with saline as control or with an anti-MV-A iNOS mAb as a potential immunotherapeutic to treat sepsis. Each group of mice was checked daily for survivors, and Kaplan-Meier survival curves were constructed. Five different murine anti-MV-A iNOS mAbs from our panel of 24 murine anti-MV-A iNOS mAbs were found to rescue some of the challenged mice. All five murine mAbs were used to genetically engineer humanized anti-MV-A iNOS mAbs by inserting the murine complementarity-determining regions (CDRs) into a human IgG1,kappa scaffold and expressing the humanized mAbs in CHO cells. Three humanized anti-MV-A iNOS mAbs were effective at rescuing mice from sepsis in three different animal models of sepsis. The effectiveness of the treatment was both time- and dose-dependent. Humanized anti-MV-A iNOS rHJ mAb could rescue up to 80% of the challenged animals if administered early and at a high dose. Our conclusions are that MV-A iNOS is a novel therapeutic target to treat sepsis; anti-MV-A iNOS mAbs can mitigate the harmful effects of MV-A iNOS; the neutralizing mAb's efficacy is both time- and dose-dependent; and a specifically targeted immunotherapeutic for MV-A iNOS could potentially save tens of thousands of lives annually and could result in improved antibiotic stewardship.


Subject(s)
Cell-Derived Microparticles/metabolism , Nitric Oxide Synthase Type II/metabolism , Sepsis/therapy , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Monoclonal, Humanized/pharmacology , Cell-Derived Microparticles/immunology , Disease Models, Animal , Humans , Lipopolysaccharides/pharmacology , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/immunology , Tumor Necrosis Factor-alpha/pharmacology
7.
Trials ; 22(1): 828, 2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1528691

ABSTRACT

BACKGROUND: It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the Stepped-wedge Cluster Randomized Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality. METHODS AND DESIGN: This study is designed as a stepped-wedge cluster randomized trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2 months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). During the study period, some of the hospital wards were allocated to manage patients with COVID-19. The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects: hospitals and COVID-19 ward status in addition to the intervention. Results will be expressed as relative risk with a 95% confidence interval. CONCLUSION: The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcome analysis will facilitate unbiased analyses of these important clinical data. TRIAL REGISTRATION: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019.


Subject(s)
COVID-19 , Sepsis , Electronics , Hospitals , Humans , SARS-CoV-2 , Sepsis/diagnosis , Sepsis/therapy
8.
Front Immunol ; 12: 738697, 2021.
Article in English | MEDLINE | ID: covidwho-1477824

ABSTRACT

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.


Subject(s)
COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , Cytokine Release Syndrome/therapy , Mesenchymal Stem Cell Transplantation/methods , Cytokine Release Syndrome/pathology , Humans , Inflammation/therapy , Mesenchymal Stem Cells/immunology , SARS-CoV-2 , Sepsis/therapy
9.
Crit Care Med ; 49(11): 1974-1982, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1475880
11.
Semin Respir Crit Care Med ; 42(5): 639-640, 2021 10.
Article in English | MEDLINE | ID: covidwho-1447393
12.
Curr Opin Crit Care ; 27(6): 582-586, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1440674

ABSTRACT

PURPOSE OF REVIEW: Sepsis and septic shock are life-threatening diseases with high mortality. Although efforts have made to improve the survivals, the outcomes are still frustrating. Blood purification was thought to be a promising adjunctive therapy to regulate the excessive cytokine storm or to reduce the endotoxin activity caused by sepsis. Critically ill COVID-19 characterized with the similar disease to sepsis may also benefit from blood purification. RECENT FINDINGS: The recent studies mainly focused on hemadsorption materials. The results of the clinical trials showed a tendency in decrease of cytokine levels and endotoxin activity and improvement in haemodynamics. However, the results were controversial. More evidence about blood purification in sepsis and COVID-19 are needed from currently ongoing trials and future well designed trials. SUMMARY: The blood purification therapy demonstrated the tendency in decrease of cytokines and endotoxin activity in different degree according to the current studies. However, the effect on mortality and haemodynamics is still in controversy. Further well designed, large sample sized studies should focus on the timing of initiating blood purification, the appropriate indications and the optimal type of blood purification membrane or cartridge to provide more evidence for clinical practice.


Subject(s)
COVID-19 , Sepsis , Shock, Septic , Critical Illness , Humans , SARS-CoV-2 , Sepsis/therapy , Shock, Septic/therapy
13.
Int J Mol Sci ; 22(4)2021 Feb 23.
Article in English | MEDLINE | ID: covidwho-1389391

ABSTRACT

Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.


Subject(s)
Cotton Fiber , Endotoxins/blood , Endotoxins/isolation & purification , Hemoperfusion/methods , Immobilization/methods , Polymyxin B/chemistry , Sepsis/therapy , Shock, Septic/therapy , Adsorption , Animals , COVID-19/therapy , Endotoxemia/blood , Endotoxemia/therapy , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/therapy , Immobilization/instrumentation , Sepsis/blood , Shock, Septic/blood
14.
Semin Dial ; 34(6): 457-471, 2021 11.
Article in English | MEDLINE | ID: covidwho-1376444

ABSTRACT

Continuous renal replacement therapy (CRRT) in sepsis does have a role in removing excessive fluid, and also role in removal of mediators although not proven today, and to allow fluid space in order to feed. In these conditions, continuous renal replacement therapy can improve morbidity but never mortality so far. Regarding sepsis, timing has become a more important issue after decades and is currently more discussed than dosing. Rationale of blood purification has evolved a lot in the last years regarding sepsis with the discovery of many types of sorbent allowing ideas from science fiction to become reality in 2021. Undoubtedly, COVID-19 has reactivated the interest of blood purification in sepsis but also in COVID-19. Burn is even more dependent about removal of excessive fluid as compared to sepsis. Regarding cardiac failure, ultrafiltration can improve the quality of life and morbidity when diuretics are becoming inefficient but can never improve mortality. Regarding brain injury, CRRTs have several advantages as compared to intermittent hemodialysis. In liver failure, there have been no randomized controlled trials to examine whether single-pass albumin dialysis offers advantages over standard supportive care, and there is always the cost of albumin.


Subject(s)
Acute Kidney Injury , Burns , COVID-19 , Continuous Renal Replacement Therapy , Heart Failure , Liver Failure , Sepsis , Acute Kidney Injury/therapy , Heart Failure/therapy , Humans , Quality of Life , Renal Dialysis , SARS-CoV-2 , Sepsis/therapy
16.
Blood ; 138(25): 2702-2713, 2021 12 23.
Article in English | MEDLINE | ID: covidwho-1365304

ABSTRACT

Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.


Subject(s)
Extracellular Traps/genetics , Gene Deletion , Intracellular Signaling Peptides and Proteins/genetics , Multiple Organ Failure/genetics , Phosphate-Binding Proteins/genetics , Sepsis/genetics , Acetaldehyde Dehydrogenase Inhibitors/therapeutic use , Adoptive Transfer , Aged , Animals , Cells, Cultured , Disulfiram/therapeutic use , Female , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Male , Mice, Inbred C57BL , Middle Aged , Multiple Organ Failure/pathology , Multiple Organ Failure/therapy , Phosphate-Binding Proteins/antagonists & inhibitors , Sepsis/pathology , Sepsis/therapy
18.
Crit Care Med ; 49(7): 1192-1193, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1327407
19.
Crit Care Nurs Clin North Am ; 33(3): 263-274, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1300065

ABSTRACT

Sepsis is recognized as a major health care problem worldwide. In the United States, mortality from severe sepsis and septic shock remains a serious health problem; yet, the early recognition of sepsis by nurses reduces can reduce mortality, morbidity, and long-term consequences of sepsis for patients. Improving the knowledge of nurses to first recognize the early signs of sepsis and then how to apply the most up-to-date evidence-based treatments can improve outcomes. Enhanced monitoring includes the use of computerized early warning systems to alert nurses of worrisome clinical patterns and promote the early recognition of sepsis.


Subject(s)
Nursing Care , Sepsis , Shock, Septic , Humans , Resuscitation , Sepsis/diagnosis , Sepsis/therapy , Shock, Septic/diagnosis , Shock, Septic/therapy , United States
20.
Rev. Assoc. Med. Bras. (1992) ; 67(supl.1): 26-28, 2021. graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-1309987

ABSTRACT

SUMMARY COVID-19 infection can progress to severe respiratory infection and have high mortality rates. Several pathophysiological factors are observed in fatal cases, with mortality related to multiple organ failure, in addition to the evolution with high levels of serum ferritin, D-dimer, and C-reactive protein. These severe cases often meet the criteria for macrophage activation syndrome with changes in the host's inflammatory response and an inadequate resolution phase. In the present study, the bundle for COVID-19 sepsis is proposed, including early recognition; protection, handwashing and isolation measures; oxygen therapy; early invasive mechanical ventilation; treatment aimed at modifying the clinical course. This strategy may be useful in the control of children with severe COVID-19 cases, as already demonstrated with the implementation of bundles in sepsis and other etiologies.


Subject(s)
Humans , Child , Sepsis/therapy , COVID-19 , Respiration, Artificial , Treatment Outcome , SARS-CoV-2
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