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Purpose To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates. Methods Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes. Results Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame). Conclusions Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance., Author(s): C. Fleischmann-Struzek [sup.1], L. Mellhammar [sup.2], N. Rose [sup.1], A. Cassini [sup.3], K. E. Rudd [sup.4], P. Schlattmann [sup.5], B. Allegranzi [sup.3], K. Reinhart [sup.6] [sup.7] [sup.8] Author Affiliations: [...]

Purpose Sepsis contributes considerably to global morbidity and mortality, while reasons for its increasing incidence remain unclear. We assessed risk adjusted secular trends in sepsis and infection epidemiology in Germany. Methods Retrospective cohort study using nationwide German hospital discharge data. We assessed incidence, outcomes and trends of hospital-treated sepsis and infections between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As sensitivity analysis, results were compared with sepsis cases identified by implicit sepsis coding (combined infection and organ dysfunction codes). Results Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at least one infection code. There were 320 198 patients that had explicit sepsis codes including 136 542 patients with severe sepsis and septic shock; 183 656 patients were coded as sepsis without organ dysfunction. For patients with explicitly coded sepsis (including severe sepsis), or with severe sepsis alone, mortality rates over the period 2010-2015 decreased from 26.6 to 23.5%, and from 47.8 to 41.7%, respectively. Conclusions Sepsis and infection remain significant causes of hospital admission and death in Germany. Sepsis-related mortality is higher and has declined to a lesser degree than in other high-income countries. Although infection rates steadily increased, the observed annual increase of sepsis cases seems to result, to a considerable degree, from improved coding of sepsis., Author(s): C. Fleischmann-Struzek [sup.1], A. Mikolajetz [sup.2], D. Schwarzkopf [sup.1], J. Cohen [sup.3], C. S. Hartog [sup.4] [sup.5], M. Pletz [sup.6], P. Gastmeier [sup.7] [sup.8], K. Reinhart [sup.1] [sup.2] [sup.9] [...]

Purpose: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care., Methods: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015-2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information., Results: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9-85.7% depending on sepsis definition), but low sensitivity (26.8-38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29-71.7%, of ICD-diagnosis: 10.7-58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09)., Conclusion: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care., (© 2023. The Author(s).)

Purpose: Sepsis suspicion by Emergency Medical Services (EMS) is associated with improved patient outcomes. This study assessed sepsis incidence and recognition by EMS and analyzed which of the screening tools recommended by the Surviving Sepsis Campaign best facilitates sepsis prediction., Methods: Retrospective cohort study of claims data from health insurances (n = 221,429 EMS cases), and paramedics' and emergency physicians' EMS documentation (n = 110,419); analyzed outcomes were: sepsis incidence and case fatality compared to stroke and myocardial infarction, the extent of documentation for screening-relevant variables and sepsis suspicion, tools' intersections for screening positive in identical EMS cases and their predictive ability for an inpatient sepsis diagnosis., Results: Incidence of sepsis (1.6%) was similar to myocardial infarction (2.6%) and stroke (2.7%); however, 30-day case fatality rate was almost threefold higher (31.7% vs. 13.4%; 11.8%). Complete vital sign documentation was achieved in 8.2% of all cases. Paramedics never, emergency physicians rarely (0.1%) documented a sepsis suspicion, respectively septic shock. NEWS2 had the highest sensitivity (73.1%; Specificity:81.6%) compared to qSOFA (23.1%; Sp:96.6%), SIRS (28.2%; Sp:94.3%) and MEWS (48.7%; Sp:88.1%). Depending on the tool, 3.7% to 19.4% of all cases screened positive; only 0.8% in all tools simultaneously., Conclusion: Incidence and mortality underline the need for better sepsis awareness, documentation of vital signs and use of screening tools. Guidelines may omit MEWS and SIRS as recommendations for prehospital providers since they were inferior in all accuracy measures. Though no tool performed ideally, NEWS2 qualifies as the best tool to predict the highest proportion of septic patients and to rule out cases that are likely non-septic., (© 2024. The Author(s).)

Background: Sepsis is associated with about 20% of deaths worldwide. It often presents with non-specific initial symptoms, making its emergency treatment an interdisciplinary and cross-sectoral challenge. Three in four sepsis survivors suffers from new cognitive, psychological, or physical sequelae for which specific treatment concepts are scarce. The AVENIR project aims to improve the understanding of patient pathways, and subjective care experiences and needs along the entire healthcare pathway before, with and after sepsis. Based on this, concrete recommendations for the organization of care and patient information materials will be developed with close patient participation., Methods: Mixed-methods study including (1) analysis of anonymized nationwide health claims data from Germany, (2) linkage of health claims data with patient care reports (PCR) of emergency medical services from study regions in two federal states within Germany, and (3) qualitative exploration of the patient, relative, and care provider perspective on sepsis care. In (1), we analyze inpatient and outpatient health care utilization until 30 days pre-sepsis; clinical sepsis care including intra- and inter-hospital transfers; and rehabilitation, inpatient and outpatient aftercare of sepsis survivors as well as costs for health care utilization until 24 months post-sepsis. We attempt to identify survivor classes with similar health care utilization by Latent Class Analyses. In (2), PCR are linked with health claims data to establish a comprehensive database outlining care pathways for sepsis patients from pre-hospital to follow-up. We investigate e.g., whether correct initial assessment is associated with acute (e.g., same-day lethality) and long-term (e.g., new need for care, long-term mortality) outcomes of patients. We compare the performance of sepsis-specific screening tools such as qSOFA, NEWS-2 or PRESEP in the pre-clinical setting. In (3), semi-structured interviews as well as synchronous and asynchronous online focus groups are conducted and analyzed using qualitative content analyses techniques., Discussion: The results of the AVENIR study will contribute to a deeper understanding of sepsis care pathways in Germany. They may serve as a base for improvements and innovations in sepsis care, that in the long-term can contribute to reduce the personal, medical, and societal burden of sepsis and its sepsis sequelae., Trial Registration: Registered at German Clinical Trial Register (ID: DRKS00031302, date of registration: 5th May 2023)., (© 2024. The Author(s).)

Background: Sepsis is one of the most frequent causes of death worldwide, but the recording of population-based epidemiology is challenging, which is why reliable data on sepsis incidence and mortality are only available in a few, mostly highly-resourced countries., Objective: The aim of this narrative review is to provide an overview of sepsis epidemiology worldwide and in Germany based on current literature, to identify challenges in this research area, and to give an outlook on future developments., Materials and Methods: Selective literature review. PubMed and Google Scholar were searched for current literature. The results were processed narratively., Results: Based on modeling studies or meta-analyses of prospective studies, global annual sepsis incidence was found to be 276-678/100,000 persons. Case fatality ranged from 22.5 to 26.7%. However, current data sources have several limitations, as administrative data of selected individual countries-mostly with high income-were used as their basis. In these administrative data, sepsis is captured with limited validity. Prospective studies using clinical data often have limited comparability or lack population reference., Conclusion: There is a lack of reliable data sources and definitions to monitor the epidemiology of sepsis and collect reliable global estimates. Increased policy efforts and new scientific approaches are needed to improve our understanding of sepsis epidemiology, identify vulnerable populations, and develop and target effective interventions., (© 2023. The Author(s).)

Background: Sepsis is a medical emergency with potentially life-threatening consequences. Patients play a crucial role in preventing and recognizing sepsis at an early stage. The understanding of risk groups' sepsis knowledge and their ability to use this knowledge to recognize sepsis as an emergency is incomplete., Methods: We conducted a cross-sectional survey in Germany and included a sample of 740 persons stratified by age (< 60 years,  ≥ 60 years), specific chronic diseases (e.g. diabetes, chronic diseases, cancer), and region (Berlin/Brandenburg vs. other federal states of Germany). Standardized questionnaires were administered by a market research institute through online, telephone, or face-to-face methods. We assessed sepsis knowledge through a series of questions and the ability to recognize sepsis as an emergency through five case vignettes. To identify predictors of sepsis knowledge and the ability to recognize sepsis as a medical emergency, we conducted multiple linear regressions., Results: Of the 36 items on sepsis knowledge, participants answered less than 50 per cent correctly (mean 44.1%; standard deviation (SD) 20.1). Most patients knew that sepsis is a defensive host response to infection (75.9%), but only 30.8% knew that vaccination can prevent infections that lead to sepsis. Across the five vignettes, participants identified sepsis as an emergency in only 1.33 of all cases on average (SD = 1.27). Sepsis knowledge was higher among participants who were older, female, and more highly educated and who reported more extensive health information seeking behaviour. The ability to recognize sepsis as an emergency was higher among younger participants, participants without chronic diseases, and participants with higher health literacy, but it was not significantly associated with sepsis knowledge., Conclusions: Risk groups showed low levels of knowledge regarding the preventive importance of vaccination and a low ability to recognize sepsis as a medical emergency. Higher levels of sepsis knowledge alone were not sufficient to improve the ability to identify sepsis as a medical emergency. It is crucial to develop effective educational strategies-especially for persons with lower education levels and infrequent health information seeking behaviour-that not only transfer but also facilitate the choice of appropriate actions, such as seeking timely emergency care., Trial Registration: DRKS00024561. Registered 9 March 2021., (© 2023. The Author(s).)

Background: Hospital-acquired infections are a common source of sepsis. Hospital onset of sepsis was found to be associated with higher acute mortality and hospital costs, yet its impact on long-term patient-relevant outcomes and costs is unknown., Objective: We aimed to assess the association between sepsis origin and acute and long-term outcomes based on a nationwide population-based cohort of sepsis patients in Germany., Methods: This retrospective cohort study used nationwide health claims data from 23 million health insurance beneficiaries. Sepsis patients with hospital-acquired infections (HAI) were identified by ICD-10-codes in a cohort of adult patients with hospital-treated sepsis between 2013 and 2014. Cases without these ICD-10-codes were considered as sepsis cases with community-acquired infection (CAI) and were matched with HAI sepsis patients by propensity score matching. Outcomes included in-hospital/12-month mortality and costs, as well as readmissions and nursing care dependency until 12 months postsepsis., Results: We matched 33,110 HAI sepsis patients with 28,614 CAI sepsis patients and 22,234 HAI sepsis hospital survivors with 19,364 CAI sepsis hospital survivors. HAI sepsis patients had a higher hospital mortality than CAI sepsis patients (32.8% vs. 25.4%, RR 1.3, p < .001). Similarly, 12-months postacute mortality was higher (37.2% vs. 30.1%, RR=1.2, p < .001). Hospital and 12-month health care costs were 178% and 22% higher in HAI patients than in CAI patients, respectively. Twelve months postsepsis, HAI sepsis survivors were more often newly dependent on nursing care (33.4% vs. 24.0%, RR=1.4, p < .001) and experienced 5% more hospital readmissions (mean number of readmissions: 2.1 vs. 2.0, p < .001)., Conclusions: HAI sepsis patients face an increased risk of adverse outcomes both during the acute sepsis episode and in the long-term. Measures to prevent HAI and its progression into sepsis may be an opportunity to mitigate the burden of long-term impairments and costs of sepsis, e.g., by early detection of HAI progressing into sepsis, particularly in normal wards; adequate sepsis management and adherence to sepsis bundles in hospital-acquired sepsis; and an improved infection prevention and control., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Importance: Despite the large health burden, reliable data on sepsis epidemiology are lacking; studies using International Statistical Classification of Diseases and Related Health Problems (ICD)-coded hospital discharge diagnosis for sepsis identification suffer from limited sensitivity. Also, ICD data do not allow investigation of underlying pathogens and antimicrobial resistance., Objectives: To generate reliable epidemiological estimates by linking data from a population-based database to a reference standard of clinical medical record review., Design, Setting, and Participants: This was a retrospective, observational cohort study using a population-based administrative database including all acute care hospitals of the Scania region in Sweden in 2019 and 2020 to identify hospital-treated sepsis cases by ICD codes. From this database, clinical medical records were also selected for review within 6 strata defined by ICD discharge diagnosis (both with and without sepsis diagnosis). Data were analyzed from April to October 2022., Main Outcomes and Measures: Hospital and population incidences of sepsis, case fatality, antimicrobial resistance, and temporal dynamics due to COVID-19 were assessed, as well as validity of ICD-10 case identification methods compared with the reference standard of clinical medical record review., Results: Out of 295 531 hospitalizations in 2019 in the Scania region of Sweden, 997 patient medical records were reviewed, among which 457 had sepsis according to clinical criteria. Of the patients with clinical sepsis, 232 (51%) were female, and 357 (78%) had at least 1 comorbidity. The median (IQR) age of the cohort was 76 (67-85) years. The incidence of sepsis in hospitalized patients according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in 2019 was 4.1% (95% CI, 3.6-4.5) by medical record review. This corresponds to an annual incidence rate of 747 (95% CI, 663-832) patients with sepsis per 100 000 population. No significant increase in sepsis during the COVID-19 pandemic nor a decrease in sepsis incidence when excluding COVID-19 sepsis was observed. Few sepsis cases caused by pathogens with antimicrobial resistance were found. The validity of ICD-10-based case identification in administrative data was low., Conclusions and Relevance: In this cohort study of sepsis epidemiology, sepsis was a considerable burden to public health in Sweden. Supplying administrative data with information from clinical medical records can help to generate reliable data on sepsis epidemiology.

Purpose: Return to a normal state of living is a key patient-relevant outcome for sepsis survivors. The Reintegration to Normal Living Index (RNLI) assesses self-perceived participation in patients with chronic disease, but its psychometric properties have been analyzed neither for patients after sepsis nor in a German patient cohort. This study aims to analyze the psychometric properties of the German version of the RNLI in sepsis survivors., Methods: In a prospective multicenter survey study, 287 sepsis survivors were interviewed 6 and 12 months after hospital discharge. Multiple-group categorical confirmatory factor analyses with three competing models were used to explore the factor structure of the RNLI. Concurrent validity was evaluated in relation to the EQ-5D-3L and the Barthel Index of Activities of Daily Living (ADL)., Results: Regarding structural validity, all models showed an acceptable model fit. Because of high correlation between the latent variables in the two-factor models (up to r = 0.969) and for reason of parsimony, we opted for the common factor model to analyze the concurrent validity. Our analyses showed moderate positive correlations between RNLI score and ADL score (r ≥ 0.630), EQ-5D-3L visual analogue scale (r ≥ 0.656) and EQ-5D-3L utility score (r ≥ 0.548). The reliability assessed by McDonald's Omega was 0.94., Conclusion: We found convincing evidence for good reliability, structural and concurrent validity of the RNLI in German sepsis survivors. We propose to use the RNLI in addition to generic health-related quality of life measures to assess the reintegration to normal living after sepsis., (© 2023. The Author(s).)

Background: Long-term impairments after sepsis can impede the return to work in survivors. We aimed to describe rates of return to work 6 and 12 months postsepsis., Methods: This retrospective, population-based cohort study was based on health claims data of the German AOK health insurance of 23.0 million beneficiaries. We included 12-months survivors after hospital-treated sepsis in 2013/2014, who were ≤60 years at the time of the admission and were working in the year presepsis. We assessed the prevalence of return to work (RTW), persistent inability to work and early retirement., Results: Among 7,370 working age sepsis survivors, 69.2% returned to work at 6 months postsepsis, while 22.8% were on sick leave and 8.0% retired early. At 12 months postsepsis, the RTW rate increased to 76.9%, whereas 9.8% were still on sick leave and 13.3% retired early. Survivors who returned to work had a mean of 70 (SD 93) sick leave days in the 12 months presepsis (median 28 days, IQR 108 days)., Conclusion: One out of four working age sepsis survivors does not resume work in the year postsepsis. Specific rehabilitation and targeted aftercare may be opportunities to reduce barriers to RTW after sepsis., (Copyright © 2023 Fleischmann-Struzek, Ditscheid, Rose, Spoden, Wedekind, Schlattmann, Günster, Reinhart, Hartog and Freytag.)

Background: We aimed to examine urban-rural disparities in sepsis case fatality rates among patients with community-acquired sepsis in Germany., Methods: Retrospective cohort study using de-identified data of the nationwide statutory health insurance AOK, covering approx. 30% of the German population. We compared in-hospital- and 12-month case fatality between rural and urban sepsis patients. We calculated odds ratios (OR) with 95% confidence intervals and the estimated adjusted odds ratio (OR adj ) using logistic regression models to account for potential differences in the distribution of age, comorbidities, and sepsis characteristics between rural and urban citizens., Results: We identified 118,893 hospitalized patients with community-acquired sepsis in 2013-2014 with direct hospital admittance. Sepsis patients from rural areas had lower in-hospital case fatality rates compared to their urban counterparts (23.7% vs. 25.5%, p < 0.001, Odds Ratio (OR) = 0.91 (95% CI 0.88, 0.94), OR adj = 0.89 (95% CI 0.86, 0.92)). Similar differences were observable for 12-month case fatalities (45.8% rural vs. 47.0% urban 12-month case fatality, p < 0.001, OR = 0.95 (95% CI 0.93, 0.98), OR adj = 0.92 (95% CI 0.89, 0.94)). Survival benefits were also observable in rural patients with severe community-acquired sepsis or patients admitted as emergencies. Rural patients of <40 years had half the odds of dying in hospital compared to urban patients in this age bracket (OR adj = 0.49 (95% CI 0.23, 0.75), p = 0.002)., Conclusion: Rural residence is associated with short- and long-term survival benefits in patients with community-acquired sepsis. Further research on patient, community, and health-care system factors is needed to understand the causative mechanisms of these disparities.

Background: Sepsis survivors often suffer from new morbidities. Current rehabilitation therapies are not tailored to their specific needs. The perspective of sepsis survivors and their caregivers on rehabilitation and aftercare is insufficiently understood. We aimed to assess how sepsis survivors in Germany rated the suitability, extent and satisfaction with rehabilitation therapies that they underwent in the year following the acute sepsis episode., Methods: Prospective mixed-methods, multicenter study among a cohort of adult ICU-treated sepsis survivors and their caregivers. Interviews were conducted 6 and 12 months after ICU discharge by telephone and comprised closed as well as open-ended questions. Primary outcomes were the utilization and patient satisfaction with inpatient and outpatient rehabilitation and post-sepsis aftercare in general. Open-ended questions were analyzed according to the principles of content analysis., Results: Foun hundred interviews were performed with 287 patients and/or relatives. At 6 months after sepsis, 85.0% of survivors had applied for and 70.0% had undergone rehabilitation. Among these, 97% received physical therapy, but only a minority reported therapies for specific ailments including pain, weaning from mechanical ventilation, cognitive deficits of fatigue. Survivors were moderately satisfied with the suitability, extent, and overall results of received therapies and perceived deficits in the timeliness, accessibility, and specificity of therapies as well as deficits in the structural support frameworks and patient education., Conclusion: From the perspective of survivors who undergo rehabilitation, therapies should already begin in hospital, be more appropriate for their specific ailments and include better patient and caregiver education. The general aftercare and structural support framework should be improved., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Born, Matthäus-Krämer, Bichmann, Boltz, Esch, Heydt, Sell, Streich, Scherag, Reinhart, Hartog and Fleischmann-Struzek.)

Rationale: Sepsis often leads to long-term functional deficits and increased mortality in survivors. Postacute rehabilitation can decrease long-term sepsis mortality, but its impact on nursing care dependency, health care use, and costs is insufficiently understood. Objectives: To assess the short-term (7-12 months postdischarge) and long-term (13-36 months postdischarge) effect of inpatient rehabilitation within 6 months after hospitalization on mortality, nursing care dependency, health care use, and costs. Methods: An observational cohort study used health claims data from the health insurer AOK (Allgemeine Ortskrankenkasse). Among 23.0 million AOK beneficiaries, adult beneficiaries hospitalized with sepsis in 2013-2014 were identified by explicit codes from the International Classification of Diseases, Tenth Revision. The study included patients who were nonemployed presepsis, for whom rehabilitation is reimbursed by the AOK and thus included in the dataset, and who survived at least 6 months postdischarge. The effect of rehabilitation was estimated by statistical comparisons of patients with rehabilitation (treatment group) and those without (reference group). Possible differential effects were investigated for the subgroup of ICU-treated sepsis survivors. The study used inverse probability of treatment weighting based on propensity scores to adjust for differences in relevant covariates. Costs for rehabilitation in the 6 months postsepsis were not included in the cost analysis. Results: Among 41,918 6-month sepsis survivors, 17.2% ( n  = 7,224) received rehabilitation. There was no significant difference in short-term survival between survivors with and without rehabilitation. Long-term survival rates were significantly higher in the rehabilitation group (90.4% vs. 88.7%; odds ratio [OR] = 1.2; 95% confidence interval [95% CI] = 1.1-1.3; P  = 0.003). Survivors with rehabilitation had a higher mean number of hospital readmissions (7-12 months after sepsis: 0.82 vs. 0.76; P  = 0.014) and were more frequently dependent on nursing care (7-12 months after sepsis: 47.8% vs. 42.3%; OR = 1.2; 95% CI = 1.2-1.3; P  < 0.001; 13-36 months after sepsis: 52.5% vs. 47.5%; OR = 1.2; 95% CI = 1.1-1.3; P  < 0.001) compared with those without rehabilitation, whereas total health care costs at 7-36 months after sepsis did not differ between groups. ICU-treated sepsis patients with rehabilitation had higher short- and long-term survival rates (short-term: 93.5% vs. 90.9%; OR = 1.5; 95% CI = 1.2-1.7; P  < 0.001; long-term: 89.1% vs. 86.3%; OR = 1.3; 95% CI = 1.1-1.5; P  < 0.001) than ICU-treated sepsis patients without rehabilitation. Conclusions: Rehabilitation within the first 6 months after ICU- and non-ICU-treated sepsis is associated with increased long-term survival within 3 years after sepsis without added total health care costs. Future work should aim to confirm and explain these exploratory findings.

Background: Methods for assessing long-term outcome quality of acute care for sepsis are lacking. We investigated a method for measuring long-term outcome quality based on health claims data in Germany., Materials and Methods: Analyses were based on data of the largest German health insurer, covering 32% of the population. Cases (aged 15 years and older) with ICD-10-codes for severe sepsis or septic shock according to sepsis-1-definitions hospitalized in 2014 were included. Short-term outcome was assessed by 90-day mortality; long-term outcome was assessed by a composite endpoint defined by 1-year mortality or increased dependency on chronic care. Risk factors were identified by logistic regressions with backward selection. Hierarchical generalized linear models were used to correct for clustering of cases in hospitals. Predictive validity of the models was assessed by internal validation using bootstrap-sampling. Risk-standardized mortality rates (RSMR) were calculated with and without reliability adjustment and their univariate and bivariate distributions were described., Results: Among 35,552 included patients, 53.2% died within 90 days after admission; 39.8% of 90-day survivors died within the first year or had an increased dependency on chronic care. Both risk-models showed a sufficient predictive validity regarding discrimination [ AUC = 0.748 (95% CI: 0.742; 0.752) for 90-day mortality; AUC = 0.675 (95% CI: 0.665; 0.685) for the 1-year composite outcome, respectively], calibration (Brier Score of 0.203 and 0.220; calibration slope of 1.094 and 0.978), and explained variance ( R 2 = 0.242 and R 2 = 0.111). Because of a small case-volume per hospital, applying reliability adjustment to the RSMR led to a great decrease in variability across hospitals [from median (1st quartile, 3rd quartile) 54.2% (44.3%, 65.5%) to 53.2% (50.7%, 55.9%) for 90-day mortality; from 39.2% (27.8%, 51.1%) to 39.9% (39.5%, 40.4%) for the 1-year composite endpoint]. There was no substantial correlation between the two endpoints at hospital level (observed rates: ρ = 0, p = 0.99; RSMR: ρ = 0.017, p = 0.56; reliability-adjusted RSMR: ρ = 0.067; p = 0.026)., Conclusion: Quality assurance and epidemiological surveillance of sepsis care should include indicators of long-term mortality and morbidity. Claims-based risk-adjustment models for quality indicators of acute sepsis care showed satisfactory predictive validity. To increase reliability of measurement, data sources should cover the full population and hospitals need to improve ICD-10-coding of sepsis., Competing Interests: CF-S was funded by grants from the German Federal Ministry of Education and Research, outside the submitted work and the German Innovations Fund of the Federal Joint Committee in Germany (G-BA), inside and outside the submitted work. DS leads the coordinating bureau of the German Quality Network sepsis–a quality initiative to improve hospital care for sepsis–and was partly funded via this project from 2015 to 2022. KR was shareholder with less of 0.5% of InflaRx NV a Jena/Germany based Biotech Company that evaluates an immunmodulatory approach for the adjunctive treatment of COVID-19. PS was funded by grants from the German Federal Ministry of Education and Research, outside the submitted work and the German Innovations Fund of the Federal Joint Committee in Germany (G-BA) outside the submitted work. AS was funded by grants from the German Federal Ministry of Education and Research, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wedekind, Fleischmann-Struzek, Rose, Spoden, Günster, Schlattmann, Scherag, Reinhart and Schwarzkopf.)

Sepsis is associated with 11 million global deaths annually. Although serious consequences of sepsis can generally be avoided with prevention and early detection, research has not yet addressed the efficacy of evidence-based health information formats for different risk groups. This study examines whether two evidence-based health information formats—text based and graphical—differ in how well they foster informed choice and risk and health literacy and in how well they support different sepsis risk groups. Based on a systematic literature review, two one-page educative formats on sepsis prevention and early detection were designed—one text based and one graphical. A sample of 500 German participants was randomly shown one of the two formats; they were then assessed on whether they made informed choices and on their risk and health literacy. For both formats, >70% of participants made informed choices for sepsis prevention and >75% for early detection. Compared with the graphical format, the text-based format was associated with higher degrees of informed choice (p = 0.012, OR = 1.818) and risk and health literacy (p = 0.032, OR = 1.710). Both formats can foster informed choices and risk and health literacy on sepsis prevention and early detection, but the text-based format appears to be more effective.

Background: Sequelae of COVID-19 can be severe and longlasting. We compared frequencies of fatigue, depression and cognitive dysfunction in survivors of SARS-CoV-2-infection and sepsis., Methods: We performed a prospective cohort study of 355 symptomatic post-COVID patients who visited our out-patient clinic for post-COVID-19 care. We compared them with 272 symptomatic patients from the Mid-German Sepsis Cohort, which investigates the long-term courses of sepsis survivors. Possible predictors for frequent clinical findings (fatigue, signs of depression, cognitive dysfunction) in post-COVID were investigated with multivariable logistic regression., Results: Median age of the post-COVID patients was 51 years (range 17-86), 60.0% were female, and 31.8% required hospitalization during acute COVID-19. In the post-COVID patients (median follow-up time: 163 days) and the post-sepsis patients (180 days), fatigue was found in 93.2% and 67.8%, signs of depression were found in 81.3% and 10.9%, and cognitive dysfunction was found in 23.5% and 21.3%, respectively. In post-COVID, we did not observe an association between fatigue or depression and the severity of acute COVID-19. In contrast, cognitive dysfunction was associated with hospitalization (out-patient versus in-patient) and more frequent in post-COVID patients treated on an ICU compared to the MSC patients., Conclusion: In post-COVID patients, fatigue and signs of depression are more common than in sepsis survivors, independent from the acute SARS-CoV-2-infection. In contrast, cognitive dysfunction is associated with hospitalization. Despite the differences in frequencies, owing to the similarity of post-COVID and post-sepsis sequelae, this knowledge may help in implementing follow-up approaches after SARS-CoV-2 infection., (© 2022. The Author(s).)

Sepsis survival is associated with adverse outcomes. Knowledge about risk factors for adverse outcomes is lacking. We performed a population-based cohort study of 116,507 survivors of hospital-treated sepsis identified in health claims data of a German health insurance provider. We determined the development and risk factors for long-term adverse events: new dependency on chronic care, chronic dialysis, long-term respiratory support, and 12-month mortality. At-risk patients were defined by absence of these conditions prior to sepsis. Risk factors were identified using simple and multivariable logistic regression analyses. In the first year post-sepsis, 48.9% (56,957) of survivors had one or more adverse outcome, including new dependency on chronic care (31.9%), dialysis (2.8%) or respiratory support (1.6%), and death (30.7%). While pre-existing comorbidities adversely affected all studied outcomes (>4 comorbidities: OR 3.2 for chronic care, OR 4.9 for dialysis, OR 2.7 for respiratory support, OR 4.7 for 12-month mortality), increased age increased the odds for chronic care dependency and 12-month mortality, but not for dialysis or respiratory support. Hospital-acquired and multi-resistant infections were associated with increased risk of chronic care dependency, dialysis, and 12-month mortality. Multi-resistant infections also increased the odds of respiratory support. Urinary or respiratory infections or organ dysfunction increased the odds of new dialysis or respiratory support, respectively. Central nervous system infection and organ dysfunction had the highest OR for chronic care dependency among all infections and organ dysfunctions. Our results imply that patient- and infection-related factors have a differential impact on adverse life changing outcomes after sepsis. There is an urgent need for targeted interventions to reduce the risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spoden, Hartog, Schlattmann, Freytag, Ostermann, Wedekind, Storch, Reinhart, Günster and Fleischmann-Struzek.)

Sepsis is the life-threatening organ dysfunction caused by a dysregulated host response to infection. With an estimated 48.9 million patients being affected by sepsis every year, sepsis is one of the most common diseases worldwide. Approximately 20% of global deaths are considered as sepsis-related. In Germany, a study based on nationwide hospital discharge data of almost all German hospitals found a sepsis incidence of 158 per 100,000 inhabitants. Estimates based on clinical patient data from other industrialized countries were 780/100,000 (Sweden) and 517/100,000 (USA). However, the comparability of incidence rates is limited due to the different data sources and sepsis case identification strategies used. In all, 41.7% of sepsis patients died in hospital, and 17.9% of intensive care unit patients are affected by sepsis. Case identification of sepsis in health claims data has a low sensitivity; therefore, it is likely that sepsis incidence is underestimated using these data, as many sepsis cases are not coded as such. For the purpose of epidemiological surveillance, health claims data should be complemented by other data sources such as registries or electronic health records., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Sepsis is one of the leading causes of preventable deaths in hospitals. This study presents the evaluation of a quality collaborative, which aimed to decrease sepsis-related hospital mortality., Methods: The German Quality Network Sepsis (GQNS) offers quality reporting based on claims data, peer reviews, and support for establishing continuous quality management and staff education. This study evaluates the effects of participating in the GQNS during the intervention period (April 2016-June 2018) in comparison to a retrospective baseline (January 2014-March 2016). The primary outcome was all-cause risk-adjusted hospital mortality among cases with sepsis. Sepsis was identified by International Classification of Diseases (ICD) codes in claims data. A controlled time series analysis was conducted to analyze changes from the baseline to the intervention period comparing GQNS hospitals with the population of all German hospitals assessed via the national diagnosis-related groups (DRGs)-statistics. Tests were conducted using piecewise hierarchical models. Implementation processes and barriers were assessed by surveys of local leaders of quality improvement teams., Results: Seventy-four hospitals participated, of which 17 were university hospitals and 18 were tertiary care facilities. Observed mortality was 43.5% during baseline period and 42.7% during intervention period. Interrupted time-series analyses did not show effects on course or level of risk-adjusted mortality of cases with sepsis compared to the national DRG-statistics after the beginning of the intervention period ( p = 0.632 and p = 0.512, respectively). There was no significant mortality decrease in the subgroups of patients with septic shock or ventilation >24 h or predefined subgroups of hospitals. A standardized survey among 49 local quality improvement leaders in autumn of 2018 revealed that most hospitals did not succeed in implementing a continuous quality management program or relevant measures to improve early recognition and treatment of sepsis. Barriers perceived most commonly were lack of time (77.6%), staff shortage (59.2%), and lack of participation of relevant departments (38.8%)., Conclusion: As long as hospital-wide sepsis quality improvement efforts will not become a high priority for the hospital leadership by assuring adequate resources and involvement of all pertinent stakeholders, voluntary initiatives to improve the quality of sepsis care will remain prone to failure., Competing Interests: DS and HR were funded in part by grants from the German Federal Ministry of Education and Research during and outside the submitted work and by annual fees paid by hospitals to participate in the GQNS. CF-S was funded by grants from the German Federal Ministry of Education and Research and the German Innovations Fund of the Federal Joint Committee in Germany (G-BA), outside the submitted work. MGr reports grants from German Federal Ministry of Education and Research, outside the submitted work. MP reports grants by the Federal Ministry of Education and Research, outside the submitted work. DT-R reports grants from German Federal Ministry of Education and Research, outside the submitted work. KR was shareholder with less of 0.5% of InflaRx NV a Jena/Germany based Biotech Company that evaluates a immunmodulatory approach for the adjunctive treatment of COVID-19. MGl was employed by KH Labor GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schwarzkopf, Rüddel, Brinkmann, Fleischmann-Struzek, Friedrich, Glas, Gogoll, Gründling, Meybohm, Pletz, Schreiber, Thomas-Rüddel and Reinhart.)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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., (© 2021. The Author(s).)

Background: To date, cost-effectiveness of influenza and pneumococcal vaccinations was assumed in several health economic modelling studies, but confirmation by real-world data is sparse. The aim of this study is to assess the effects on health care utilisation and costs in the elderly using real-world data on both, outpatient and inpatient care., Methods: Retrospective community-based cohort study with 138,877 individuals aged ≥ 60 years, insured in a large health insurance fund in Thuringia (Germany). We assessed health care utilisation and costs due to influenza- or pneumococcal-associated diseases, respiratory infections, and sepsis in 2015 and 2016. Individuals were classified into four groups according to their vaccination status from 2008 to 2016 (none, both, or either only influenza or pneumococcal vaccination). Inverse probability weighting based on 236 pre-treatment covariates was used to adjust for potential indication and healthy vaccinee bias., Results: Influenza vaccination appeared as cost-saving in 2016, with lower disease-related health care costs of - €178.87 [95% CI - €240.03;- €117.17] per individual (2015: - €50.02 [95% CI - €115.48;€15.44]). Cost-savings mainly resulted from hospital inpatient care, whereas higher costs occurred for outpatient care. Overall cost savings of pneumococcal vaccination were not statistically significant in both years, but disease-related outpatient care costs were lower in pneumococci-vaccinated individuals in 2015 [- €9.43; 95% CI - €17.56;- €1.30] and 2016 [- €12.93; 95% CI - €25.37;- €0.48]. Although we used complex adjustment, residual bias cannot be completely ruled out., Conclusion: Influenza and pneumococcal vaccination in the elderly can be cost-saving in selective seasons and health care divisions. As cost effects vary, interpretation of findings is partly challenging., (© 2021. The Author(s).)

Objective: Coronavirus disease 2019 is a heterogeneous disease most frequently causing respiratory tract infection, which can induce respiratory failure and multiple organ dysfunction syndrome in its severe forms. The prevalence of coronavirus disease 2019-related sepsis is still unclear; we aimed to describe this in a systematic review., Data Sources: MEDLINE (PubMed), Cochrane, and Google Scholar databases were searched based on a prespecified protocol (International Prospective Register for Systematic Reviews: CRD42020202018)., Study Selection: Studies reporting on patients with confirmed coronavirus disease 2019 diagnosed with sepsis according to sepsis-3 or according to the presence of infection-related organ dysfunctions necessitating organ support/replacement were included in the analysis. The primary end point was prevalence of coronavirus disease 2019-related sepsis among adults hospitalized in the ICU and the general ward. Among secondary end points were the need for ICU admission among patients initially hospitalized in the general ward and the prevalence of new onset of organ dysfunction in the ICU. Outcomes were expressed as proportions with respective 95% CI., Data Extraction: Two reviewers independently screened and reviewed existing literature and assessed study quality with the Newcastle-Ottawa Scale and the Methodological index for nonrandomized studies., Data Synthesis: Of 3,825 articles, 151 were analyzed, only five of which directly reported sepsis prevalence. Noting the high heterogeneity observed, coronavirus disease 2019-related sepsis prevalence was 77.9% (95% CI, 75.9-79.8; I2 = 91%; 57 studies) in the ICU, and 33.3% (95% CI, 30.3-36.4; I2 = 99%; 86 studies) in the general ward. ICU admission was required for 17.7% (95% CI, 12.9-23.6; I2 = 100%) of ward patients. Acute respiratory distress syndrome was the most common organ dysfunction in the ICU (87.5%; 95% CI, 83.3-90.7; I2 = 98%)., Conclusions: The majority of coronavirus disease 2019 patients hospitalized in the ICU meet Sepsis-3 criteria and present infection-associated organ dysfunction. The medical and scientific community should be aware and systematically report viral sepsis for prognostic and treatment implications., Competing Interests: Dr. Karakike received funding from the Horizon 2020 Marie Skłodowska-Curie Grant European Sepsis Academy (grant 676129). Dr. Netea’s institution received funding from Roche; he received funding form an ERC Advanced Grant (833247), a Spinoza grant of the Netherlands Organization for Scientific Research, TTxD, GSK, and ViiV HealthCare; he disclosed he is on the scientific Advisory Board at Trained Therapeutic and Discovery; received independent educational grants from AbbVie, Abbott CH, Astellas Pharma Europe, AxisShield, bioMérieux, InflaRx GmbH, the Medicines Company, and XBiotech. Dr. Reinhart disclosed that he was the President of the Global Sepsis Alliance and that he is a shareholder of InflaRx NV, a Jena/Germany-based Biotech Company that evaluates an immune-modulatory approach for the adjunctive treatment of coronavirus disease 2019. Dr. Giamarellos-Bourboulis’ institution received funding from the Framework 7 Program, HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon 2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis); he received funding from AbbVie, United States; Abbott CH; Angelini; Astellas Pharma; AxisShield; bioMérieux; Biotest; Brahms GmbH; InflaRx GmbH; MSD Greece; XBiotech; and The Medicines Company; independent educational grants from AbbVie, Abbott CH, Astellas Pharma Europe, AxisShield, bioMérieux, InflaRx GmbH, the Medicines Company, and XBiotech. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Importance: Sepsis survivorship is associated with postsepsis morbidity, but epidemiological data from population-based cohorts are lacking., Objective: To quantify the frequency and co-occurrence of new diagnoses consistent with postsepsis morbidity and mortality as well as new nursing care dependency and total health care costs after sepsis., Design, Setting, and Participants: This retrospective cohort study based on nationwide health claims data included a population-based cohort of 23.0 million beneficiaries of a large German health insurance provider. Patients aged 15 years and older with incident hospital-treated sepsis in 2013 to 2014 were included. Data were analyzed from January 2009 to December 2017., Exposures: Sepsis, identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) hospital discharge codes., Main Outcomes and Measures: New medical, psychological, and cognitive diagnoses; long-term mortality; dependency on nursing care; and overall health care costs in survivors at 1 to 12, 13 to 24, and 25 to 36 months after hospital discharge., Results: Among 23.0 million eligible individuals, we identified 159 684 patients hospitalized with sepsis in 2013 to 2014. The mean (SD) age was 73.8 (12.8) years, and 75 809 (47.5%; 95% CI, 47.2%-47.7%) were female patients. In-hospital mortality was 27.0% (43 177 patients; 95% CI, 26.8%-27.3%). Among 116 507 hospital survivors, 86 578 (74.3%; 95% CI, 74.1%-74.6%) had a new diagnosis in the first year post sepsis; 28 405 (24.4%; 95% CI, 24.1%-24.6%) had diagnoses co-occurring in medical, psychological, or cognitive domains; and 23 572 of 74 878 survivors (31.5%; 95% CI, 31.1%-31.8%) without prior nursing care dependency were newly dependent on nursing care. In total, 35 765 survivors (30.7%; 95% CI, 30.4%-31.0%) died within the first year. In the second and third year, 53 089 (65.8%; 95% CI, 65.4%-66.1%) and 40 959 (59.4%; 95% CI, 59.0%-59.8%) had new diagnoses, respectively. Health care costs for sepsis hospital survivors for 3 years post sepsis totaled a mean of €29 088/patient ($32 868/patient) (SD, €44 195 [$49 938]). New postsepsis morbidity (>1 new diagnosis) was more common in survivors of severe sepsis (75.6% [95% CI, 75.1%-76.0%]) than nonsevere sepsis (73.7% [95% CI, 73.4%-74.0%]; P < .001) and more common in survivors treated in the intensive care unit (78.3% [95% CI, 77.8%-78.7%]) than in those not treated in the intensive care unit (72.8% [95% CI, 72.5%-73.1%]; P < .001). Postsepsis morbidity was 68.5% (95% CI, 67.5%-69.5%) among survivors without prior morbidity and 56.1% (95% CI, 54.2%-57.9%) in survivors younger than 40 years., Conclusions and Relevance: In this study, new medical, psychological, and cognitive diagnoses consistent with postsepsis morbidity were common after sepsis, including among patients with less severe sepsis, no prior diagnoses, and younger age. This calls for more efforts to elucidate the underlying mechanisms, define optimal screening for common new diagnoses, and test interventions to prevent and treat postsepsis morbidity.

Objective: Sepsis is responsible for a massive burden of disease, with a global estimate of 48.9 million cases resulting in approximately 11 million deaths annually. Survivors of sepsis may also experience long-term impairments that can persist for years after hospital discharge. These cognitive, physical and/or psychosocial deficits may contribute to a lower health related quality of life and represent a significant ongoing burden to the individual, the community and the health care system. We aim to systematically review the available evidence on long-term functional and quality of life outcomes after sepsis in children and adults. Data Sources: Medline, EMBASE, and CINAHL will be searched for eligible studies. Study Selection: Studies of adult and pediatric survivors of sepsis who had required admission to intensive care will be included. A minimum 6 month prospective follow up will be required. Accepted outcomes will be any validated measure of health-related quality of life (HRQoL) or functional deficits, using the Post-Intensive Care Syndrome (PICS) framework of cognitive, physical or psychosocial outcomes. Data Extraction: Data extraction will include information related to study characteristics, population characteristics, clinical criteria and outcomes. Data Synthesis: Studies meeting the inclusion criteria will be presented descriptively separated for pediatric and adult age groups. Meta-analysis will be attempted if sufficient primary data from several studies applying the same tests and outcomes are available. The primary outcome is HRQoL after sepsis; secondary outcomes include the functional status at follow-up. Conclusions: This systematic review will define the long-term impact of sepsis survivorship. The data will contribute to informing patient, clinician and stakeholder decisions and guide further research and resource management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simpson, Long, Fleischmann-Struzek, Minogue, Venkatesh, Hammond, Tian and Schlapbach.)

Background: Sepsis is a substantial health care burden. Data on regional variation in sepsis incidence in Germany and any possible associations with regional socioeconomic deprivation and health care capacity is lacking., Methods: Ecological study based on the nationwide hospital Diagnosis-related Groups (DRG) statistics data of 2016. We identified sepsis by ICD-10-codes and calculated crude and age-standardized incidence proportions in the 401 administrative German districts. Associations between socioeconomic and health care capacity indicators and crude and age-adjusted sepsis incidence were investigated by simple and multiple negative binomial (NB) regressions., Results: In 2016, sepsis incidence was 178 per 100,000 inhabitants and varied 10-fold between districts. We found that the rate of students leaving school without certificate was significantly associated with crude and age-standardized explicit sepsis incidence in the simple and multiple NB regressions. While we observed no evidence for an association to the capacity of hospital beds and general practitioners, the distance to the nearest pharmacy was associated with crude- and age-standardized sepsis incidence. In the multiple regression analyses, an increase of the mean distance + 1000 m was associated with an expected increase by 21.6 [95% CI, 10.1, 33.0] (p < 0.001), and 11.1 [95% CI, 1.0, 21.2]/100,000 population (p = .026) after adjusting for age differences between districts., Conclusions: Residence in districts with lower socioeconomic status (e.g., less education) and further distance to pharmacies are both associated with an increased sepsis incidence. This warrants further research with individual-level patient data to better model and understand such dependencies and to ultimately design public health interventions to address the burden of sepsis in Germany., (© 2021. The Author(s).)

Objectives: Worldwide, more than half of all sepsis cases occur in pediatric and adolescent patients, particularly in neonates. Previous population-based studies in these age groups often were limited to either neonatal or pediatric patients admitted to ICUs. We aimed to investigate the overall and age-specific incidence and case fatality of sepsis in children in Germany, a high-income country with a total population of 82 million., Design: Retrospective observational study based on the German Diagnosis-related Groups statistics of the years 2010-2016., Setting: All acute care hospitals in Germany except for prison and psychiatric hospitals., Patients: Pediatric patients less than or equal to 19 years with International Classification of Diseases, 10th Revision-coded sepsis, neonates with International Classification of Diseases, 10th Revision-coded neonatal sepsis., Interventions: None., Measurements and Main Results: We analyzed pediatric sepsis incidence in patients aged birth to less than or equal to 19 years old, case fatality, and underlying comorbidities, and neonatal sepsis incidence and case fatality within the neonatal period. We identified 14,635 pediatric sepsis cases among 15.4 million pediatric hospitalizations between 2010 and 2016 (= 0.1% of pediatric hospitalizations). The incidence of pediatric sepsis was 14 cases per 100,000 children between 0 and 19 years. Case fatality was 16.6% and decreased from 17.8% (2010) to 15.0% (2016). A total of 11.5% of hospital deaths in the age group 0-19 years were associated with pediatric sepsis. Sepsis incidence and case fatality were highest in children less than 1 year old and declined in older children and adolescents. Admissions with pediatric sepsis were more common in children with preexisting comorbidities compared with those without (0.52% vs 0.03% of pediatric admissions). In neonates, the incidence of neonatal sepsis was 1,006 cases per 100,000 live births. Case fatality was 3.9%. While 17.7% of very low birth weight infants had neonatal sepsis, only 2.1% of low birth weight and 0.6% of normal birth weight neonates were affected, respectively., Conclusions: Sepsis is also in Germany a common and frequently fatal condition in pediatric patients, particularly among neonates and children with comorbidities., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Influenza and pneumococcal vaccinations are recommended in the elderly to reduce life-threatening complications like sepsis. Protection may be reduced with increasing age. We aimed to assess the effectiveness of both vaccines in the elderly by performing a retrospective cohort study of 138,877 individuals aged ≥60 y in Germany, who were insured in a large statutory health insurance (AOK PLUS). We used longitudinal claims data to classify individuals according to vaccination status 2008-2014, and assessed vaccine effectiveness (VE) in 2015 and 2016. Inverse probability weighting based on generalized propensity scores was used to adjust for systematic between-group differences. Influenza vaccination was associated with a reduction of hospital treatment in laboratory-confirmed influenza in 2015 (VE = 41.32 [95%CI 0.85, 65.26]), but had no significant impact on the overall influenza incidence. Complications of influenza (pneumonia and sepsis) were reduced in 2016. We found a rise in influenza-like illness and acute respiratory infections in both years and an increased 90-d mortality after hospital-treated pneumonia in vaccinees in 2015. Pneumococcal vaccination was effective in preventing hospital-treated pneumonia within the first and second year after vaccination (VE = 52.45 [13.31, 73.92] and 46.04 [5.46, 69.21], respectively), but had no impact on sepsis incidence or pneumonia mortality. Influenza and pneumococcal vaccination can prevent severe complications from influenza and hospital-treated pneumonia in the elderly, respectively. Vaccine effects differ between years and seasons and are partly difficult to interpret. Despite extensive efforts to adjust for between-group differences, residual bias cannot be ruled out, possibly explaining signals like increased ILI or pneumonia mortality.

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)., Competing Interests: Competing interests: CSH declares funding from the German Federal Joint Committee Innovations-Funds and the European Society of Intensive Care Medicine. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There have not yet been any prospective registry studies in Germany with active investigation of the long-term survival of patients with sepsis., Methods: The Jena Sepsis Registry (JSR) included all patients with a diagnosis of sepsis in the four intensive care units of Jena University Hospital from January 2011 to December 2015. Long-term survival 6-48 months after diagnosis was documented by asking the treating general practitioners. The survival times were studied with Kaplan-Meier estimators. Cox regressions were calculated to show associations between possible predictors and survival time., Results: 1975 patients with sepsis or septic shock were included. The mean time of observation was 730 days. For 96.4% of the queries to the general practitioners, information on long-term survival was available. Mortality in the intensive care unit was 34% (95% confidence interval [32; 37]), and in-hospital mortality was 45% [42; 47]. The overall mortality six months after diagnosis was 59% [57; 62], the overall mortality 48 months after diagnosis was 74% [72; 78]. Predictors of shorter survival were age, nosocomial origin of sepsis, diabetes, cerebrovascular disease, duration of stay in the intensive care unit, and renal replacement therapy., Conclusion: The nearly 75% mortality four years after diagnosis indicates that changes are needed both in the acute treatment of patients with sepsis and in their multi-sector long-term care. The applicability of these findings may be limited by their having been obtained in a single center.

Introduction: Sepsis is a major cause of preventable deaths in hospitals. This study aims to investigate if sepsis incidence and quality of care can be assessed using inpatient administrative health data (IAHD)., Methods and Analysis: Design: Retrospective observational validation study using routine data to assess the diagnostic accuracy of sepsis coding in IAHD regarding sepsis diagnosis based on medical record review., Procedure: A stratified sample of 10 000 patients with an age ≥15 years treated in between 2015 and 2017 in 10 German hospitals is investigated. All available information of medical records is screened by trained physicians to identify true sepsis cases ('gold standard') both according to current ('sepsis-1') definitions and new ('sepsis-3') definitions. Data from medical records are linked to IAHD on patient level using a pseudonym., Analyses: Proportions of cases with sepsis according to sepsis-1 and sepsis-3 definitions are calculated and compared with estimates from coding of sepsis in IAHD. Predictive accuracy (sensitivity, specificity) of different coding abstraction strategies regarding the gold standard is estimated. Predictive accuracy of mortality risk factors obtained from IAHD regarding the respective risk factors obtained from medical records is calculated. An IAHD-based risk model for hospital mortality is compared with a record-based risk model regarding model-fit and predicted risk of death. Analyses adjust for sampling weights. The obtained estimates of sensitivity and specificity for sepsis coding in IAHD are used to estimate adjusted incidence proportions of sepsis based on German national IAHD., Ethics and Dissemination: The study has been approved by the ethics commission of the Jena University Hospital (No. 2018-1065-Daten). The results of the study will be discussed in an expert panel to write a memorandum on improving the utility of IAHD for epidemiological surveillance and quality management of sepsis care., Trial Registration Number: DRKS00017775; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Sepsis is recognized as a global public health problem, but the proportion due to hospital-acquired infections remains unclear. We aimed to summarize the epidemiological evidence related to the burden of hospital-acquired (HA) and ICU-acquired (ICU-A) sepsis., Methods: We searched MEDLINE, Embase and the Global Index Medicus from 01/2000 to 03/2018. We included studies conducted hospital-wide or in intensive care units (ICUs), including neonatal units (NICUs), with data on the incidence/prevalence of HA and ICU-A sepsis and the proportion of community and hospital/ICU origin. We did random-effects meta-analyses to obtain pooled estimates; inter-study heterogeneity and risk of bias were assessed., Results: Of the 13,239 studies identified, 51 met the inclusion criteria; 22 were from low- and middle-income countries. Twenty-eight studies were conducted in ICUs, 13 in NICUs, and ten hospital-wide. The proportion of HA sepsis among all hospital-treated sepsis cases was 23.6% (95% CI 17-31.8%, range 16-36.4%). In the ICU, 24.4% (95% CI 16.7-34.2%, range 10.3-42.5%) of cases of sepsis with organ dysfunction were acquired during ICU stay and 48.7% (95% CI 38.3-59.3%, range 18.7-69.4%) had a hospital origin. The pooled hospital incidence of HA sepsis with organ dysfunction per 1000 patients was 9.3 (95% CI 7.3-11.9, range 2-20.6)). In the ICU, the pooled incidence of HA sepsis with organ dysfunction per 1000 patients was 56.5 (95% CI 35-90.2, range 9.2-254.4) and it was particularly high in NICUs. Mortality of ICU patients with HA sepsis with organ dysfunction was 52.3% (95% CI 43.4-61.1%, range 30.1-64.6%). There was a significant inter-study heterogeneity. Risk of bias was low to moderate in ICU-based studies and moderate to high in hospital-wide and NICU studies., Conclusion: HA sepsis is of major public health importance, and the burden is particularly high in ICUs. There is an urgent need to improve the implementation of global and local infection prevention and management strategies to reduce its high burden among hospitalized patients.

The number of patients who survive sepsis is growing. However, two of three sepsis survivors suffer from new physical or mental sequelae. Cognitive deficits, depression or limitations of the activities of daily living can seriously impair quality of life and working ability. Sepsis sequelae cover a range of lesions; current rehabilitation therapies appear unsuited because they are focused on only one organ system. An interdisciplinary approach is necessary to evaluate and treat sepsis sequelae. Survivors and their relatives should be informed about sepsis and possible sequelae as early as possible. Further studies are needed to improve the understanding of pathomechanisms and effectivity of treatment interventions for sepsis sequelae., Competing Interests: Christiane Hartog gibt Förderungen durch das Bundesministerium für Bildung und Forschung (BMBF), den Innovationsfonds des Gemeinsamen Bundesausschusses (G-BA) und die European Society of Intensive Care Medicine an. Carolin Fleischmann-Struzek erhält Förderungen durch das BMBF und den Innovationsfonds des G-BA und gibt eine Beratertätigkeit bei der WHO an. Björn Weiss gibt Honorare für Beratertätigkeiten bzw. Vorträge von Orion Pharma Ltd. bzw. Dr. F. Köhler Chemie an. Konrad Reinhart erhält Förderung durch das BMBF, den Innovationsfonds des G-BA und die Stiftung Charité. Claudia Denke und Ulf Bodechtel geben an, dass keine Interessenkonflikte vorliegen., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017., Methods: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates., Findings: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia., Interpretation: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa., Funding: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access Article under the CC BY 4.0 licence. Published by Elsevier Ltd.. All rights reserved.)

Background: Germany has more intensive care unit (ICU) beds per capita than the USA, but the utilization of these resources at the end of life is unknown., Methods: Retrospective observational study using nationwide German hospital discharge data (DRG statistics; DRG, diag- nosis-related groups) from 2007 to 2015. We investigated hospital deaths and use of intensive care services during terminal hospitalizations. Population-based incidences were standardized to the age and sex distribution of the German population., Results: Standardized hospital admission rates increased by 0.8% annually (from 201.9 to 214.6 per 1000 population), while hospital admissions involving ICU care increased by 3.0% annually (from 6.5 to 8.2 per 1000 population). Among all deaths in the German population, the proportion of hospital deaths with ICU care increased by 2.3% annually (from 9.8% to 11.8%). Among all hospital deaths, the proportion involving ICU care increased by 2.8% annually from 20.6% (2007) to 25.6% (2015). In patients aged 65 and older, the use of intensive care services during terminal hospitalizations increased 3 times faster than hospital deaths., Conclusion: Use of intensive care services during terminal hospitalizations increased across all age groups, particularly the elderly. The increased need for end-of-life care in the ICU calls for improvements in educational, policy, and reimbursement strategies. It is unclear whether ICU care was appropriate and compliant with patient preferences.

Background: Sepsis is a life-threatening medical emergency requiring early diagnosis and urgent treatment. Knowledge is crucial, especially in major risk groups such as the elderly. We therefore assessed sophisticated knowledge about sepsis in the German elderly population., Methods: A telephone survey was carried out with a representative sample of 701 Germans from 16 federal states and a separate cohort of 700 participants from Thuringia, all aged ≥ 60 years. Sepsis knowledge was assessed via a 10-item questionnaire. Sociodemographic data and health information sources were assessed to identify determinants of sepsis knowledge., Results: Of the participants, 88.6% had heard the term "sepsis" before; however, 50% of these failed to define sepsis correctly. Even if the knowledge of symptoms was moderately good, most participants could not correctly identify causes of sepsis and underestimated its incidence. Only a minority was aware that immunization may prevent sepsis. Regressions revealed that being younger, better educated and living in rural areas predicted higher levels of sepsis knowledge. Pharmacists were a relevant source of sepsis information., Conclusions: Despite overall awareness of sepsis, the understanding of its risk factors, symptoms and prevention is low in the elderly, with important implications for emergency and intensive care. We suggest further educational measures to improve early sepsis recognition and prevention through vaccination.

Introduction: Administrative data are used to generate estimates of sepsis epidemiology and can serve as source for quality indicators. Aim was to compare estimates on sepsis incidence and mortality based on different ICD-code abstraction strategies and to assess their validity for sepsis case identification based on a patient sample not pre-selected for presence of sepsis codes., Materials and Methods: We used the national DRG-statistics for assessment of population-level sepsis incidence and mortality. Cases were identified by three previously published International Statistical Classification of Diseases (ICD) coding strategies for sepsis based on primary and secondary discharge diagnoses (clinical sepsis codes (R-codes), explicit coding (all sepsis codes) and implicit coding (combined infection and organ dysfunction codes)). For the validation study, a stratified sample of 1120 adult patients admitted to a German academic medical center between 2007-2013 was selected. Administrative diagnoses were compared to a gold standard of clinical sepsis diagnoses based on manual chart review., Results: In the validation study, 151/937 patients had sepsis. Explicit coding strategies performed better regarding sensitivity compared to R-codes, but had lower PPV. The implicit approach was the most sensitive for severe sepsis; however, it yielded a considerable number of false positives. R-codes and explicit strategies underestimate sepsis incidence by up to 3.5-fold. Between 2007-2013, national sepsis incidence ranged between 231-1006/100,000 person-years depending on the coding strategy., Conclusions: In the sample of a large tertiary care hospital, ICD-coding strategies for sepsis differ in their accuracy. Estimates using R-codes are likely to underestimate the true sepsis incidence, whereas implicit coding overestimates sepsis cases. Further multi-center evaluation is needed to gain better understanding on the validity of sepsis coding in Germany., Competing Interests: The authors have declared that no competing interests exist. The above funding does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Influenza and pneumococcal vaccination can prevent disease and potentially life-threatening complications like sepsis. Elderly people have an increased risk of severe disease and therefore constitute a major target group for vaccination. To increase vaccination coverage, targeted interventions are needed that take theory-based specific determinants of vaccination behaviour into account. Moreover, message and campaign design should consider specific age-related characteristics (e.g., information processing, media use). The aim of this study is (i) to identify the specific informational and interventional needs of this risk group, (ii) to design and implement a targeted intervention aiming to decrease vaccine hesitancy, increase vaccine uptake and decrease the health and economic burden due to the respective diseases, and (iii) to measure the effect of this evidence-informed intervention on various levels., Methods: Prospective, multi-methods intervention study targeting individuals aged ≥60 years in a model region in Germany (federal state of Thuringia, 500,000 inhabitants ≥60 years old). The development of the intervention follows theory-based and evidence-informed principles: Data from a cross-sectional representative study provide insights into specific determinants of the target group's vaccination behaviour. Additionally, media use is analysed to identify adequate communication channels for specific subgroups. In pilot studies, the intervention materials are adapted to the specific cognitive requirements of the target group. For development and implementation of the intervention, an interdisciplinary and trans-sectoral approach is used, including psychology, communication science, design, medical science, epidemiology and various public health players. The intervention will be implemented in autumn and winter 2017/18 and 2018/19 and adjusted in between. Evaluation of the intervention includes: awareness, use and recall of intervention materials, effects on changes in determinants of vaccination behaviour, self-reported vaccine uptake, and vaccination coverage in the intervention area (primary outcomes), as well as disease incidences (secondary outcomes) and the economic burden of influenza, pneumonia, invasive pneumococcal disease and sepsis for the healthcare system (tertiary outcomes)., Discussion: The data will add to the body of evidence on the effectiveness of evidence-informed vaccination campaign development as well as on the clinical and economic effects of pneumococcal and influenza vaccination. The effect of the intervention will teach valuable lessons about the principles of campaign development and evaluation, and can motivate a subsequent nationwide intervention., Trial Registration: DRKS00012653 . Registered 24.11.2017. Retrospectively registered.

Background: Sepsis is a major cause of preventable deaths in hospitals. Feasible and valid methods for comparing quality of sepsis care between hospitals are needed. The aim of this study was to develop a risk-adjustment model suitable for comparing sepsis-related mortality between German hospitals., Methods: We developed a risk-model using national German claims data. Since these data are available with a time-lag of 1.5 years only, the stability of the model across time was investigated. The model was derived from inpatient cases with severe sepsis or septic shock treated in 2013 using logistic regression with backward selection and generalized estimating equations to correct for clustering. It was validated among cases treated in 2015. Finally, the model development was repeated in 2015. To investigate secular changes, the risk-adjusted trajectory of mortality across the years 2010-2015 was analyzed., Results: The 2013 deviation sample consisted of 113,750 cases; the 2015 validation sample consisted of 134,851 cases. The model developed in 2013 showed good validity regarding discrimination (AUC = 0.74), calibration (observed mortality in 1st and 10th risk-decile: 11%-78%), and fit (R2 = 0.16). Validity remained stable when the model was applied to 2015 (AUC = 0.74, 1st and 10th risk-decile: 10%-77%, R2 = 0.17). There was no indication of overfitting of the model. The final model developed in year 2015 contained 40 risk-factors. Between 2010 and 2015 hospital mortality in sepsis decreased from 48% to 42%. Adjusted for risk-factors the trajectory of decrease was still significant., Conclusions: The risk-model shows good predictive validity and stability across time. The model is suitable to be used as an external algorithm for comparing risk-adjusted sepsis mortality among German hospitals or regions based on administrative claims data, but secular changes need to be taken into account when interpreting risk-adjusted mortality.