Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed. Weniger anzeigen

Importance: It is unclear whether antimicrobial timing for sepsis has changed outside of performance incentive initiatives. Objective: To examine temporal trends and variation in time-to-antibiotics for sepsis in the US Department of Veterans Affairs (VA) health care system. Design, setting, and participants: This observational cohort study included 130 VA hospitals from 2013 to 2018. Participants included all patients admitted to the hospital via the emergency department with sepsis from 2013 to 2018, using a definition adapted from the Centers for Disease Control and Prevention Adult Sepsis Event definition, which requires evidence of suspected infection, acute organ dysfunction, and systemic antimicrobial therapy within 12 hours of presentation. Data were analyzed from October 6, 2020, to July 1, 2021. Exposures: Time from presentation to antibiotic administration. Main outcomes and measures: The main outcome was differences in time-to-antibiotics across study periods, hospitals, and patient subgroups defined by presenting temperature and blood pressure. Temporal trends in time-to-antibiotics were measured overall and by subgroups. Hospital-level variation in time-to-antibiotics was quantified after adjusting for differences in patient characteristics using multilevel linear regression models. Results: A total of 111 385 hospitalizations for sepsis were identified, including 107 547 men (96.6%) men and 3838 women (3.4%) with a median (interquartile range [IQR]) age of 68 (62-77) years. A total of 7574 patients (6.8%) died in the hospital, and 13 855 patients (12.4%) died within 30 days. Median (IQR) time-to-antibiotics was 3.9 (2.4-6.5) hours but differed by presenting characteristics. Unadjusted median (IQR) time-to-antibiotics decreased over time, from 4.5 (2.7-7.1) hours during 2013 to 2014 to 3.5 (2.2-5.9) hours during 2017 to 2018 (P < .001). In multilevel models adjusted for patient characteristics, median time-to-antibiotics declined by 9.0 (95% CI, 8.8-9.2) minutes per calendar year. Temporal trends in time-to-antibiotics were similar across patient subgroups, but hospitals with faster baseline time-to-antibiotics had less change over time, with hospitals in the slowest tertile decreasing time-to-antibiotics by 16.6 minutes (23.1%) per year, while hospitals in the fastest tertile decreased time-to-antibiotics by 7.2 minutes (13.1%) per year. In the most recent years (2017-2018), median time-to-antibiotics ranged from 3.1 to 6.7 hours across hospitals (after adjustment for patient characteristics), 6.8% of variation in time-to-antibiotics was explained at the hospital level, and odds of receiving antibiotics within 3 hours increased by 65% (95% CI, 56%-77%) for the median patient if moving to a hospital with faster time-to-antibiotics. Conclusions and relevance: This cohort study across nationwide VA hospitals found that time-to-antibiotics for sepsis has declined over time. However, there remains significant variability in time-to-antibiotics not explained by patient characteristics, suggesting potential unwarranted practice variation in sepsis treatment. Efforts to further accelerate time-to-antibiotics must be weighed against risks of overtreatment. Weniger anzeigen

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. Keywords: Ecological study, Incidence, Medical services, Sepsis, Socioeconomic factors Weniger anzeigen

Objectives: Sepsis is a life-threatening medical emergency. There is a paucity of information on whether quality improvement approaches reduce the in-hospital sepsis caseload or save lives and decrease the healthcare system and society’s cost at the provincial/national levels. This study aimed to assess the outcomes and economic impact of a province-wide quality improvement initiative in Canada. Design: Retrospective population-based study with interrupted time series and return on investment analyses. Setting: The sepsis cases and deaths averted over time for British Columbia were calculated and compared with the rest of Canada (excluding Quebec and three territories). Patients: Aggregate data were obtained from the Canadian Institute for Health Information on risk-adjusted in-hospital sepsis rates and sepsis mortality in acute care sites across Canada. Interventions: In 2012, the British Columbia Sepsis Network was formed to reduce sepsis occurrence and mortality through education, knowledge translation, and quality improvement. Measurements and main results: A return on investment analysis compared the financial investment for the British Columbia Sepsis Network with the savings from averted sepsis occurrence and mortality. An estimated 981 sepsis cases and 172 deaths were averted in the post-British Columbia Sepsis Network period (2014-2018). The total cost, including the development and implementation of British Columbia Sepsis Network, was $449,962. Net savings due to cases averted after program costs were considered were $50.6 million in 2018. This translates into a return of $112.5 for every dollar invested. Conclusions: British Columbia Sepsis Network appears to have averted a greater number of sepsis cases and deaths in British Columbia than the national average and yielded a positive return on investment. Our findings strengthen the policy argument for targeted quality improvement initiatives for sepsis care and provide a model of care for other provinces in Canada and elsewhere globally. Weniger anzeigen

Purpose: Sepsis remains amongst the most common causes of death worldwide. It has been described as a disease of the elderly, but contemporary data on risk factors and mortality is lacking. Materials and methods: Multi-center longitudinal cohort study using non-public, state of California data from January 1, 2008 to September 31, 2015. Patients with sepsis, severe sepsis, and septic shock were identified using ICD-9-CM diagnosis and procedure codes with age subgroups of 18-44, 45-64, 65-74, 75-84, and >85 years old. Descriptive statistics and a single direct logistic regression model were used to present data on incidence and mortality and to identify independent factors associated with mortality. Results: Of 30,282,159 total inpatient encounters, 20,358,569 met inclusion criteria and 1,566,306 met sepsis criteria. Conditions associated with mortality included metastatic cancer, age, liver disease, residing in a care facility, and a gastrointestinal source of infection as well as fungal infection. Mortality in the >85-year-old subgroup with septic shock was 45.7%, lower than previously reported. Conclusion: Age remains an important sepsis risk factor, but other conditions correlated more closely with sepsis-associated death. Patients over 85 years of age suffering from septic shock may have a better chance of survival than previously thought. Weniger anzeigen

In critically ill patients with sepsis, there is a grave lack of effective treatment options to address the illness-defining inappropriate host response. Currently, treatment is limited to source control and supportive care, albeit with imminent approval of immune modulating drugs for COVID-19-associated lung failure the potential of host-directed strategies appears on the horizon. We suggest expanding the concept of sepsis by incorporating infectious stress within the general stress response of the cell to define sepsis as an illness state characterized by allostatic overload and failing adaptive responses along with biotic (pathogen) and abiotic (e.g., malnutrition) environmental stress factors. This would allow conceptualizing the failing organismic responses to pathogens in sepsis with an ancient response pattern depending on the energy state of cells and organs towards other environmental stressors in general. Hence, the present review aims to decipher the heuristic value of a biological definition of sepsis as a failing stress response. These considerations may motivate a better understanding of the processes underlying „host defense failure“ on the organismic, organ, cell and molecular levels. Keywords: Allostatic overload, Energy metabolism, Host stress response, Resistance, Sepsis, Tolerance Weniger anzeigen

Objectives: The aim of this study was to identify prehospital and early hospital risk factors associated with 30-day mortality in patients with blood culture-confirmed community-acquired bloodstream infection (CA-BSI) in Sweden. Methods: A retrospective case-control study of 1624 patients with CA-BSI (2015-2016), 195 non-survivors satisfying the inclusion criteria were matched 1:1 with 195 survivors for age, gender and microorganism. All forms of contact with a healthcare provider for symptoms of infection within 7 days prior CA-BSI episode were registered. Logistic regression was used to analyse risk factors for 30-day all-cause mortality. Results: Of the 390 patients, 61% (115 non-survivors and 121 survivors) sought prehospital contact. The median time from first prehospital contact till hospital admission was 13 hours (6-52) for non-survivors and 7 hours (3-24) for survivors (p<0.01). Several risk factors for 30-day all-cause mortality were identified: prehospital delay OR=1.26 (95% CI: 1.07 to 1.47), p<0.01; severity of illness (Sequential Organ Failure Assessment score) OR=1.60 (95% CI: 1.40 to 1.83), p<0.01; comorbidity score (updated Charlson Index) OR=1.13 (95% CI: 1.05 to 1.22), p<0.01 and inadequate empirical antimicrobial therapy OR=3.92 (95% CI: 1.64 to 9.33), p24 hours from first contact remained an important risk factor for 30-day all-cause mortality due to CA-BSI OR=6.17 (95% CI: 2.19 to 17.38), p<0.01. Conclusion: Prehospital delay and inappropriate empirical antibiotic therapy were found to be important risk factors for 30-day all-cause mortality associated with CA-BSI. Increased awareness and earlier detection of BSI in prehospital and early hospital care is critical for rapid initiation of adequate management and antibiotic treatment. Weniger anzeigen

Importance: In October 2015, the Centers for Medicare & Medicaid Services began requiring US hospitals to report adherence to the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1). Objective: To evaluate the association of SEP-1 implementation with sepsis treatment patterns and outcomes in diverse hospitals. Design, setting, and participants: This retrospective cohort study with interrupted time-series analysis and logistic regression models was conducted among adults admitted to 114 hospitals from October 2013 to December 2017 with suspected sepsis (blood culture orders, ≥2 systemic inflammatory response syndrome criteria, and acute organ dysfunction) within 24 hours of hospital arrival. Data analysis was conducted from September 2020 to September 2021. Exposures: SEP-1 implementation in the fourth quarter (Q4) of 2015. Main outcomes and measures: The primary outcome was quarterly rates of risk-adjusted short-term mortality (in-hospital death or discharge to hospice). Secondary outcomes included lactate testing and administration of anti-methicillin-resistant Staphylococcus aureus (MRSA) or antipseudomonal β-lactam antibiotics within 24 hours of hospital arrival. Generalized estimating equations with robust sandwich variances were used to fit logistic regression models to assess for changes in level or trends in these outcomes, adjusting for baseline characteristics and severity of illness. Results: The cohort included 117 510 patients (median [IQR] age, 67 years [55-78] years; 60 530 [51.5%] men and 56 980 [48.5%] women) with suspected sepsis. Lactate testing rates increased from 55.1% (95% CI, 53.9%-56.2%) in Q4 of 2013 to 76.7% (95% CI, 75.4%-78.0%) in Q4 of 2017, with a significant level change following SEP-1 implementation (odds ratio [OR], 1.34; 95% CI, 1.04-1.74). There were increases in use of anti-MRSA antibiotics (19.8% [95% CI, 18.9%-20.7%] in Q4 of 2013 to 26.3% [95% CI, 24.9%-27.7%] in Q4 of 2017) and antipseudomonal antibiotics (27.7% [95% CI, 26.7%-28.8%] in Q4 of 2013 to 40.5% [95% CI, 38.9%-42.0%] in Q4 of 2017), but these trends preceded SEP-1 and did not change with SEP-1 implementation. Unadjusted short-term mortality rates were similar in the pre-SEP-1 period (Q4 of 2013 through Q3 of 2015) vs the post-SEP-1 period (Q1 of 2016 through Q4 of 2017) (20.3% [95% CI, 20.0%-20.6%] vs 20.4% [95% CI, 20.1%-20.7%]), and SEP-1 implementation was not associated with changes in level (OR, 0.94; 95% CI, 0.68-1.29) or trend (OR, 1.00; 95% CI, 0.97-1.04) for risk-adjusted short-term mortality rates. Conclusions and relevance: In this cohort study, SEP-1 implementation was associated with an immediate increase in lactate testing rates, no change in already-increasing rates of broad-spectrum antibiotic use, and no change in short-term mortality rates for patients with suspected sepsis. Other approaches to decrease sepsis mortality may be warranted. Weniger anzeigen

Purpose: There is limited knowledge on how the source of infection impacts the host response to sepsis. We aimed to compare the host response in sepsis patients with a single, known source at admission (< 24 h) to the intensive care unit. Methods: From the molecular diagnosis and risk stratification of sepsis (MARS) prospective cohort, we measured 16 plasma host response biomarkers reflective of key host response pathways in 621 sepsis patients. In a subgroup (n = 335), blood leukocyte transcriptomes were compared between the sources. Differences in clinical patient profiles and survival were compared in the whole sepsis cohort (n = 2019). Results: The plasma biomarker cohort was categorized into sepsis originating from the respiratory tract (n = 334, 53.8%), abdomen (n = 159, 25.6%), urinary tract (n = 44, 7.1%), cardiovascular (n = 41, 6.6%), central nervous system (CNS) (n = 18, 2.9%), or skin (n = 25, 4%). This analysis revealed stronger inflammatory and cytokine responses, loss of vascular integrity and coagulation activation in abdominal sepsis relative to respiratory. Endothelial cell activation was prominent in urinary, cardiovascular and skin infections, while CNS infection was associated with the least host response aberrations. The leukocyte transcriptional response showed the largest overlap between abdominal and pulmonary infections (76% in common); notable differences between the sources were detected regarding hemostasis, cytokine signaling, innate and adaptive immune, and metabolic transcriptional pathways. After adjustment for confounders, the source of infection remained an independent contributor to 30-day mortality (unadjusted p = 0.001, adjusted p = 0.028). Conclusion: Sepsis heterogeneity is partly explained by source-specific host response dysregulations and should be considered when selecting patients for trials testing immune modulatory drugs. Weniger anzeigen

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. Weniger anzeigen