Background: An estimated 11 million deaths are associated with sepsis worldwide. The epidemiology of sepsis-associated deaths in Germany is insufficiently understood, as sepsis deaths cannot be identified in the German mono-causal causes of death statistics. Aim: We aim to analyze the epidemiology and characteristics of sepsis-associated hospital deaths as well as to describe regional disparities. Materials and methods: Retrospective cohort study based on the 2016 German-wide diagnosis related groups (DRG) statistics. Sepsis-associated hospital deaths were identified by explicit and implicit sepsis ICD-10-GM codes. Deaths were described based on clinical characteristics and place of residence by official municipality key. The proportion of sepsis-associated hospital deaths among all deaths was calculated based on the national population statistics. Results: In 2016, there were 58,689 hospital deaths associated with explicitly coded sepsis (14.1% of all hospital deaths). Sepsis mortality was 73 per 100,000 inhabitants and varied 1.8-fold between federal states and 7.9-fold between districts. Of the national deaths, 6.4% were sepsis-associated hospital deaths. This proportion was highest in the 40-64 years age group (9.6%) and higher in males compared to females (7.7% vs. 5.2%). Compared to this, the proportion of deaths associated with implicitly coded sepsis was 47.2% among all hospital deaths and 21.6% among all national deaths. Discussion: Although the direct cause of death cannot be assessed based on our data, the high proportion of sepsis-associated deaths calls for further research and epidemiological surveillance, e.g., by cohort studies or based on multi-causal death statistics in Germany. Weniger anzeigen

Background: Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock. Methods: This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. Results: Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61-0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44-0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64-1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. Conclusion: Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock. Weniger anzeigen

A biomarker describes a measurable indicator of a patient’s clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, „Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?“ We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood-brain barrier (BBB) breakdown, brain injury, and short and long-term mortality. For sepsis, a range of biomarkers is identified, including fluid phase pattern recognition molecules (PRMs), complement system, cytokines, chemokines, damage-associated molecular patterns (DAMPs), non-coding RNAs, miRNAs, cell membrane receptors, cell proteins, metabolites, and soluble receptors. We also provide an overview of immune response biomarkers that can help identify or differentiate between systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and sepsis-associated encephalopathy. However, significant work is needed to identify the optimal combinations of biomarkers that can augment diagnosis, treatment, and good patient outcomes. Keywords: Biomarker, Sepsis, Sepsis-associated encephalopathy, Septic shock, Systemic inflammatory response Weniger anzeigen

Background: Devastating cases of sepsis in previously healthy patients have received widespread attention and helped catalyze state and national mandates to improve sepsis detection and care. It is unclear, however, what proportion of patients hospitalized with sepsis were previously healthy and how their outcomes compare to patients with comorbidities. Research question: Among adults hospitalized with community-onset sepsis, how many are previously healthy and how do their outcomes compare to those with comorbidities? Study design and methods: We retrospectively identified all adults with community-onset sepsis hospitalized in 373 U.S. hospitals from 2009-2015 using clinical indicators of presumed infection and organ dysfunction (CDC’s Adult Sepsis Event criteria). Comorbidities were identified using ICD-9-CM codes. We applied generalized linear mixed models to measure the associations between the presence or absence of comorbidities and short-term mortality (in-hospital death or discharge to hospice), adjusting for severity-of-illness on admission. Results: Of 6,715,286 hospitalized patients, 337,983 (5.0%) had community-onset sepsis. Most sepsis patients (329,052; 97.4%) had at least one comorbidity; only 2.6% were previously healthy. Patients with sepsis who were previously healthy were younger than those with comorbidities (mean 58.0 ± 19.8 vs 67.0 ± 16.5 years), less likely to require ICU care on admission (37.9% vs 50.5%), and more likely to be discharged home (57.9% vs 45.6%) rather than to subacute facilities (16.3% vs 30.8%) but had higher short-term mortality rates (22.8% vs 20.8%, p<.001 for all). The association between previously healthy status and higher short-term mortality persisted after risk-adjustment (adjusted OR 1.99 [95% CI 1.87-2.13])). Interpretation: The vast majority of patients hospitalized with community-onset sepsis have pre-existing comorbidities. However, previously healthy patients may be more likely to die when they present to the hospital with sepsis compared to patients with comorbidities. These findings underscore the importance of early sepsis recognition and treatment for all patients. Keywords: comorbidity, epidemiology, mortality, sepsis Weniger anzeigen

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 summarised 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 programs 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 protocol-based sepsis care bundle act in synergy to augment greater improvements in care processes and patient benefits. Keywords: COVID-19, Care bundle, Interprofessional education, Medical education, Sepsis, Systematic review Weniger anzeigen

Background: Epidemiologic studies are needed for monitoring population-level trends in sepsis. This study examines sepsis-causing microorganisms from 2006 to 2014 in the United States using data from the Nationwide Inpatient Sample database. Methods: 7 860 686 adults hospitalized with sepsis were identified using a validated ICD-9 coding approach. Associated microorganisms were identified by ICD-9 code and classified by major groups (Gram-positive, Gram-negative, fungi, anaerobes) and specific species for analysis of their incidence and mortality. Results: The rate of sepsis incidence has increased for all four major categories of pathogens, while the mortality rate decreased. In 2014, Gram-negative pathogens had a higher incidence than Gram-positives. Anaerobes increased the fastest with an average annual increase of 20.17% (p < 0.001). Fungi had the highest mortality (19.28%) and the slowest annual decrease of mortality (-2.31%, p = 0.006) in 2013, while anaerobic sepsis had the highest hazard of mortality (adjusted HR 1.60, 95% CI 1.53-1.66). Conclusions: Gram-negative pathogens have replaced Gram-positives as the leading cause of sepsis in the United States in 2014 during the study period (2006-2014). The incidence of anaerobic sepsis has an annual increase of 20%, while the mortality of fungal sepsis has not decreased at the same rate as other microorganisms. These findings should inform the diagnosis and management of septic patients, as well as the implementation of public health programs. Weniger anzeigen

Background: There are concerns regarding post-acute sequelae of COVID-19, but it is unclear whether COVID-19 poses a significant downstream mortality risk. The objective was to determine the relationship between COVID-19 infection and 12-month mortality after recovery from the initial episode of COVID-19 in adult patients. Methods: An analysis of electronic health records (EHR) was performed for a cohort of 13,638 patients, including COVID-19 positive and a comparison group of COVID-19 negative patients, who were followed for 12 months post COVID-19 episode at one health system. Both COVID-19 positive patients and COVID-19 negative patients were PCR validated. COVID-19 positive patients were classified as severe if they were hospitalized within the first 30 days of the date of their initial positive test. The 12-month risk of mortality was assessed in unadjusted Cox regressions and those adjusted for age, sex, race and comorbidities. Separate subgroup analyses were conducted for (a) patients aged 65 and older and (b) those <65 years. Results: Of the 13,638 patients included in this cohort, 178 had severe COVID-19, 246 had mild/moderate COVID-19, and 13,214 were COVID-19 negative. In the cohort, 2,686 died in the 12-month period. The 12-month adjusted all-cause mortality risk was significantly higher for patients with severe COVID-19 compared to both COVID-19 negative patients (HR 2.50; 95% CI 2.02, 3.09) and mild COVID-19 patients (HR 1.87; 95% CI 1.28, 2.74). The vast majority of deaths (79.5%) were for causes other than respiratory or cardiovascular conditions. Among patients aged <65 years, the pattern was similar but the mortality risk for patients with severe COVID-19 was increased compared to both COVID-19 negative patients (HR 3.33; 95% CI 2.35, 4.73) and mild COVID-19 patients (HR 2.83; 95% CI 1.59, 5.04). Patients aged 65 and older with severe COVID-19 were also at increased 12-month mortality risk compared to COVID-19 negative patients (HR 2.17; 95% CI 1.66, 2.84) but not mild COVID-19 patients (HR 1.41; 95% CI 0.84, 2.34). Discussion: Patients with a COVID-19 hospitalization were at significantly increased risk for future mortality. In a time when nearly all COVID-19 hospitalizations are preventable this study points to an important and under-investigated sequela of COVID-19 and the corresponding need for prevention. Weniger anzeigen

The emergence of the SARS-CoV-2 virus in December 2019 and the subsequent coronavirus disease 2019 (COVID-19) pandemic has presented the world with the most serious health threat in living memory. The resultant pandemic has caused millions of deaths and unprecedented social and economic disruption. The response to the pandemic has also been unprecedented; countries have closed their borders, some have instituted draconian but effective public health measures, and the global scientific community has come together to produce robust research evidence and novel vaccines in record time. Mass vaccination programs are now underway, and while it is too early to know clearly their effectiveness in ending the pandemic, we can hope that this marks the beginning of the end. Weniger anzeigen

Purpose: The Mid-German Sepsis Cohort (MSC) aims to investigate mid-term and long-term functional disabilities in sepsis survivors from intensive care unit (ICU) discharge until 1 year after. Secondary, post-acute mortality and morbidity, health-related quality of life and healthcare utilisation will be investigated. Participants: The MSC comprises adult (aged ≥18 years) patients who were treated for (severe) sepsis or septic shock on ICU. The participants were recruited between 15 April 2016 and 30 November 2018 from five German centres. Three thousand two hundred and ten patients with sepsis were identified, of which 1968 survived their ICU stay and were eligible for enrolment in the follow-up cohort. Informed consent for follow-up assessment was provided by 907 patients (46.1% of eligible patients). Findings to date: The recruitment of the participants for follow-up assessments and the baseline data collection is completed. Incidence of sepsis was 116.7 patients per 1000 ICU patients. In this cohort profile, we provide an overview of the demographics and the clinical characteristics of both the overall sepsis cohort and the ICU survivors who provided informed consent for follow-up assessment (907 out of 1968 ICU survivors (46.1%)). Future plans: The follow-ups are conducted 3, 6 and 12 months after ICU discharge. Another yearly follow-up up to 5 years after ICU discharge is pursued. Several cooperation and satellite projects were initiated. This prospective cohort offers a unique resource for research on long-term sequelae of sepsis survivors. Trial registration number: German Clinical Trials Registry (DRKS00010050). Weniger anzeigen

Background: Single studies support the presence of several post-COVID-19 symptoms; however, no meta-analysis differentiating hospitalized and non-hospitalized patients has been published to date. This meta-analysis analyses the prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized patients recovered from COVID-19 . Methods: MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were searched up to March 15, 2021. Peer-reviewed studies or preprints reporting data on post-COVID-19 symptoms collected by personal, telephonic or electronic interview were included. Methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. We used a random-effects models for meta-analytical pooled prevalence of each post-COVID-19 symptom, and I² statistics for heterogeneity. Data synthesis was categorized at 30, 60, and ≥90 days after . Results: From 15,577 studies identified, 29 peer-reviewed studies and 4 preprints met inclusion criteria. The sample included 15,244 hospitalized and 9011 non-hospitalized patients. The methodological quality of most studies was fair. The results showed that 63.2, 71.9 and 45.9% of the sample exhibited ≥one post-COVID-19 symptom at 30, 60, or ≥90days after onset/hospitalization. Fatigue and dyspnea were the most prevalent symptoms with a pooled prevalence ranging from 35 to 60% depending on the follow-up. Other post-COVID-19 symptoms included cough (20-25%), anosmia (10-20%), ageusia (15-20%) or joint pain (15-20%). Time trend analysis revealed a decreased prevalence 30days after with an increase after 60days . Conclusion: This meta-analysis shows that post-COVID-19 symptoms are present in more than 60% of patients infected by SARS-CoV‑2. Fatigue and dyspnea were the most prevalent post-COVID-19 symptoms, particularly 60 and ≥90 days after. Weniger anzeigen