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Background Existing sepsis quality improvement initiatives focus on recognition and treatment of sepsis upon hospital admission. Yet many patients are evaluated in the clinic within 1 day of sepsis hospitalization. Objectives To determine the circumstances of clinic visits that precede sepsis hospitalization, including illness severity, whether patients are referred to the hospital, and time lapse and change in illness severity between clinic and hospital evaluation. Methods In a retrospective cohort study at a tertiary academic medical center, data from electronic medical records were collected for all adult patients evaluated in an outpatient clinic within 1 day of sepsis hospitalization in 2017. Results Of 1450 patients hospitalized with sepsis, 118 had an established outpatient provider and a clinic visit within 1 day of admission and thus were included. During the clinic visit, 47 patients (39.8%) had a quick Sequential Organ Failure Assessment (qSOFA) score ≥1, and 59 (50.0%) had vital sign abnormalities. Most (74, 62.7%) were sent directly to the emergency department or hospital. Upon emergency department/hospital presentation, 62 patients (52.5%) had a worsening qSOFA score and/ or vital signs and 27 (22.9%) had worsening of multiple parameters. Median time lapse from clinic to emergency department/hospital evaluation was 3.2 hours. Conclusions One in 10 patients hospitalized for sepsis had been evaluated in a clinic within 1 day of admission. At that clinic visit, most patients had an elevated qSOFA score or abnormal vital signs and a majority were sent directly to the emergency department/hospital. Half experienced clinical deterioration between the clinic visit and arrival in the emergency department/hospital.

Background As more individuals survive sepsis, there is an urgent need to understand its effects on patient-reported outcomes. Research Question What is the effect of sepsis on self-rated health, and what role, if any, does functional disability play in mediating this effect? Study Design and Methods We conducted a survey- and administrative claims-based retrospective cohort study using the US Health and Retirement Study, a nationally representative cohort-based survey of older adults in the United States, from 2000 through 2016. We matched Medicare beneficiaries hospitalized with sepsis in 2000 to 2008 to nonhospitalized individuals. Self-rated health and functional disability were tracked biannually for 8 years. Differences in self-rated health between the cohorts were measured using mixed models with and without controlling for changes in functional disability. Results Seven hundred fifty-eight individuals with sepsis were matched 1:1 to 758 nonhospitalized individuals, all aged 65 years and older. Among survivors, sepsis was associated with worse self-rated health in years 2 and 4 (adjusted absolute difference in self-rated health on a 5-point scale in year 2: −0.24 [95% CI, −0.38 to −0.10] and year 4: −0.17 [95% CI, −0.33 to −0.02]) but not in years 6 or 8. After accounting for changes in functional status, the association between sepsis and self-rated health was still present but reduced in year 2 (adjusted absolute difference in self-rated health, −0.18 [95% CI, −0.31 to −0.05]) and was not present in years 4, 6, or 8. Interpretation Self-rated health worsened initially after sepsis but returned to the level of that of nonhospitalized control subjects by year 6. Mitigating sepsis-related functional disability may play a key role in improving self-rated health after sepsis.

Background Acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are associated with high in-hospital mortality. However, in cohorts of ARDS patients from the 1990s, patients more commonly died from sepsis or multi-organ failure rather than refractory hypoxemia. Given increased attention to lung-protective ventilation and sepsis treatment in the past 25 years, we hypothesized that causes of death may be different among contemporary cohorts. These differences may provide clinicians with insight into targets for future therapeutic interventions. Methods We identified adult patients hospitalized at a single tertiary care center (2016–2017) with AHRF, defined as PaO2/FiO2 ≤ 300 while receiving invasive mechanical ventilation for > 12 h, who died during hospitalization. ARDS was adjudicated by multiple physicians using the Berlin definition. Separate abstractors blinded to ARDS status collected data on organ dysfunction and withdrawal of life support using a standardized tool. The primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. Results We identified 385 decedents with AHRF, of whom 127 (33%) had ARDS. The most common primary causes of death were sepsis (26%), pulmonary dysfunction (22%), and neurologic dysfunction (19%). Multi-organ failure was present in 70% at time of death, most commonly due to sepsis (50% of all patients), and 70% were on significant respiratory support at the time of death. Only 2% of patients had insupportable oxygenation or ventilation. Eighty-five percent died following withdrawal of life support. Patients with ARDS more often had pulmonary dysfunction as the primary cause of death (28% vs 19%; p = 0.04) and were also more likely to die while requiring significant respiratory support (82% vs 64%; p

Background\ud Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.\ud Methods\ud We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.\ud Results\ud The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.\ud Conclusion\ud The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

Key Points Question How has timing of antibiotics for sepsis changed over time in US Department of Veterans Affairs Hospitals? Findings In this cohort of 111 385 veterans hospitalized with sepsis from 2013 to 2018, median time to antibiotics declined by 9 minutes per year. However, there was significant variation in time to antibiotics across hospitals, even after adjustment for patient characteristics. Meaning These findings suggest that there is potential for performance improvement for sepsis hospitalizations, but efforts to further accelerate time-to-antibiotics must be weighed against the risks of overtreatment., This cohort study examines temporal trends and variations in time-to-antibiotics for sepsis in the US Department of Veterans Affairs health care system., 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

ImportanceChildren commonly experience physical, cognitive, or emotional sequelae after sepsis. However, little is known about the development or progression of medical conditions after pediatric sepsis.ObjectiveTo quantify the development and progression of 4 common conditions in the 6 months after sepsis and to assess whether they differed after hospitalization for sepsis vs nonsepsis among critically ill children.Design, Setting, and ParticipantsThis cohort study of 101 511 children (ExposuresIntensive care unit hospitalization for sepsis vs all-cause intensive care unit hospitalizations, excluding sepsis.Main Outcomes and MeasuresPrimary outcomes were the development of 4 target conditions (chronic respiratory failure, seizure disorder, supplemental nutritional dependence, and chronic kidney disease) within 6 months of hospital discharge. Secondary outcomes were the progression of the 4 target conditions among children with the condition before hospitalization. Outcomes were identified via diagnostic and procedural codes, durable medical equipment codes, and prescription medications. Differences in the development and the progression of conditions between pediatric patients with sepsis and pediatric patients with nonsepsis who survived intensive care unit hospitalization were assessed using logistic regression with matching weights.ResultsA total of 5150 survivors of pediatric sepsis and 96 361 survivors of nonsepsis intensive care unit hospitalizations were identified; 2593 (50.3%) were female. The median age was 9.5 years (IQR, 3-15 years) in the sepsis cohort and 7 years (IQR, 2-13 years) in the nonsepsis cohort. Of the 5150 sepsis survivors, 670 (13.0%) developed a new target condition, and 385 of 1834 (21.0%) with a preexisting target condition had disease progression. A total of 998 of the 5150 survivors (19.4%) had development and/or progression of at least 1 condition. New conditions were more common among sepsis vs nonsepsis hospitalizations (new chronic respiratory failure: 4.6% vs 1.9%; odds ratio [OR], 2.54 [95% CI, 2.19-2.94]; new supplemental nutritional dependence: 7.9% vs 2.7%; OR, 3.17 [95% CI, 2.80-3.59]; and new chronic kidney disease: 1.1% vs 0.6%; OR, 1.65 [95% CI, 1.25-2.19]). New seizure disorder was less common (4.6% vs 6.0%; OR, 0.77 [95% CI, 0.66-0.89]). Progressive supplemental nutritional dependence was more common (1.5% vs 0.5%; OR, 2.95 [95% CI, 1.60-5.42]), progressive epilepsy was less common (33.7% vs 40.6%; OR, 0.74 [95% CI, 0.65-0.86]), and progressive respiratory failure (4.4% vs 3.3%; OR, 1.35 [95% CI, 0.89-2.04]) and progressive chronic kidney disease (7.9% vs 9.2%; OR, 0.84 [95% CI, 0.18-3.91]) were similar among survivors of sepsis vs nonsepsis admitted to an intensive care unit.Conclusions and RelevanceIn this national cohort of critically ill children who survived sepsis, 1 in 5 developed or had progression of a condition of interest after sepsis hospitalization, suggesting survivors of pediatric sepsis may benefit from structured follow-up to identify and treat new or worsening medical comorbid conditions.

Rationale: Sepsis commonly results in elevated serum troponin levels and increased risk for postsepsis cardiovascular complications; however, the association between troponin levels during sepsis and cardiovascular complications after sepsis is unclear. Objectives: To evaluate the association between serum troponin levels during sepsis and 1 year after sepsis cardiovascular events. Methods: We analyzed adults aged ⩾40 years without preexisting cardiovascular disease within 5 years, admitted with sepsis across 21 hospitals from 2011 to 2017. Peak serum troponin I levels during sepsis were grouped as normal (⩽0.04 ng/ml) or tertiles of abnormal (>0.04 to ⩽0.09 ng/ml, >0.09 to ⩽0.42 ng/ml, or >0.42 ng/ml). Multivariable adjusted cause-specific Cox proportional hazards models with death as a competing risk were used to assess associations between peak troponin I levels and a composite cardiovascular outcome (atherosclerotic cardiovascular disease, atrial fibrillation, and heart failure) in the year following sepsis. Models were adjusted for presepsis and intrasepsis factors considered potential confounders. Measurements and Main Results: Among 14,046 eligible adults with troponin I measured, 2,012 (14.3%) experienced the composite cardiovascular outcome, including 832 (10.9%) patients with normal troponin levels, as compared with 370 (17.3%), 376 (17.6%), and 434 (20.3%) patients within each sequential abnormal troponin tertile, respectively (P 0.42) = 1.77; 95% CI, 1.56–2.00). Conclusions: Among patients without preexisting cardiovascular disease, troponin elevation during sepsis identified patients at increased risk for postsepsis cardiovascular complications. Strategies to mitigate cardiovascular complications among this high-risk subset of patients are warranted.

OBJECTIVE Cancer and its treatment are known to be important risk factors for sepsis, contributing to an estimated 12% of U.S. sepsis admissions in the 1990s. However, cancer treatment has evolved markedly over the past 2 decades. We sought to examine how cancer-related sepsis differs from non-cancer-related sepsis. DESIGN Observational cohort. SETTING National Readmissions Database (2013-2014), containing all-payer claims for 49% of U.S. POPULATION PATIENTS A total of 1,104,363 sepsis hospitalizations. INTERVENTIONS We identified sepsis hospitalizations in the U.S. National Readmissions Database using explicit codes for severe sepsis, septic shock, or Dombrovskiy criteria (concomitant codes for infection and organ dysfunction). We classified hospitalizations as cancer-related versus non-cancer-related sepsis based on the presence of secondary diagnosis codes for malignancy. We compared characteristics (site of infection and organ dysfunction) and outcomes (in-hospital mortality and 30-d readmissions) of cancer-related versus non-cancer-related sepsis hospitalizations. We also completed subgroup analyses by age, cancer types, and specific cancer diagnoses. MEASUREMENTS AND MAIN RESULTS There were 27,481,517 hospitalizations in National Readmissions Database 2013-2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related. In-hospital mortality in cancer-related sepsis was 27.9% versus 19.5% in non-cancer-related sepsis. The median count of organ dysfunctions was indistinguishable, but the rate of specific organ dysfunctions differed by small amounts (e.g., hematologic dysfunction 20.1% in cancer-related sepsis vs 16.6% in non-cancer-related sepsis; p < 0.001). Cancer-related sepsis was associated with an adjusted absolute increase in in-hospital mortality ranging from 2.2% to 15.2% compared with non-cancer-related sepsis. The mortality difference was greatest in younger adults and waned with age. Patients (23.2%) discharged from cancer-related sepsis were rehospitalized within 30 days, compared with 20.1% in non-cancer-related sepsis (p < 0.001). CONCLUSIONS In this cohort of over 1 million U.S. sepsis hospitalizations, more than one in five were cancer related. The difference in mortality varies substantially across age spectrum and is greatest in younger adults. Readmissions were more common after cancer-related sepsis.

Background To study patient physiology throughout a period of acute hospitalization, we sought to create accessible, standardized nationwide data at the level of the individual patient-facility-day. This methodology paper summarizes the development, organization, and characteristics of the Veterans Affairs Patient Database 2014–2017 (VAPD 2014–2017). The VAPD 2014–2017 contains acute hospitalizations from all parts of the nationwide VA healthcare system with daily physiology including clinical data (labs, vitals, medications, risk scores, etc.), intensive care unit (ICU) indicators, facility, patient, and hospitalization characteristics. Methods The VA data structure and database organization represents a complex multi-hospital system. We define a single-site hospitalization as one or more consecutive stays with an acute treating specialty at a single facility. The VAPD 2014–2017 is structured at the patient-facility-day level, where every patient-day in a hospital is a row with separate identification variables for facility, patient, and hospitalization. The VAPD 2014–2017 includes daily laboratory, vital signs, and inpatient medication. Such data were validated and verified through lab value range and comparison with patient charts. Sepsis, risk scores, and organ dysfunction definitions were standardized and calculated. Results We identified 565,242 single-site hospitalizations (SSHs) in 2014; 558,060 SSHs in 2015; 553,961 SSHs in 2016; and 550,236 SSHs in 2017 at 141 VA hospitals. The average length of stay was four days for all study years. In-hospital mortality decreased from 2014 to 2017 (1.7 to 1.4%), 30-day readmission rates increased from 15.3% in 2014 to 15.6% in 2017; 30-day mortality also decreased from 4.4% in 2014 to 4.1% in 2017. From 2014 to 2017, there were 107,512 (4.8%) of SSHs that met the Center for Disease Control and Prevention’s Electronic Health Record-based retrospective definition of sepsis. Conclusion The VAPD 2014–2017 represents a large, standardized collection of granular data from a heterogeneous nationwide healthcare system. It is also a direct resource for studying the evolution of inpatient physiology during both acute and critical illness. Electronic supplementary material The online version of this article (10.1186/s12874-019-0740-x) contains supplementary material, which is available to authorized users.

OBJECTIVE: Severe sepsis is a significant cause of healthcare use and morbidity among pediatric patients, but little is known about readmission diagnoses. We sought to determine the most common readmission diagnoses after pediatric severe sepsis, the extent to which post-sepsis readmissions may be potentially preventable, and whether patterns of readmission diagnoses differ compared to readmissions after other common acute medical hospitalizations. DESIGN: Observational Cohort Study SETTING: National Readmission Database (2013-2014), including all-payer hospitalizations from 22 states. PATIENTS: 4528 pediatric severe hospitalizations, matched by age, gender, comorbidities, and length of stay to 4528 pediatric hospitalizations for other common acute medical conditions. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: We compared rates of 30-day all-cause, diagnosis-specific, and potentially preventable hospital readmissions using McNemar’s chi-square tests for paired data. Among 5841 eligible pediatric severe sepsis hospitalizations with live discharge, 4528 (77.5%) were matched 1:1 to 4528 pediatric hospitalizations for other acute medical conditions. Of 4528 matched sepsis hospitalizations, 851 (18.8% (95% CI 16.0, 18.2)) were re-hospitalized within 30 days, compared to 775 (17.1% (95% CI 17.1, 20.0)) of matched hospitalizations for other causes (p=0.02). The most common readmission diagnoses were chemotherapy, device complication, and sepsis, all of which were several-fold higher after sepsis versus after matched non-sepsis hospitalization. Only 11.5% of readmissions were for ambulatory care sensitive conditions compared to 23% of rehospitalizations after common acute medical conditions. CONCLUSION: More than 1 in 6 children surviving severe sepsis were re-hospitalized within 30 days, most commonly for maintenance chemotherapy, medical device complications, or recurrent sepsis. Only a small proportion of readmissions were for ambulatory care sensitive conditions.

Sepsis is a leading cause of death and disability whose heterogeneity is often cited as a key impediment to translational progress.To test the hypothesis that there are consequential and significant differences in sepsis outcomes that result from differences in a patient's clinical course leading up to sepsis hospitalization.We conducted an observational cohort study of U.S. Health and Retirement Study (HRS) participants in Medicare (1998-2012) and U.S. Department of Veterans Affairs beneficiaries (2009). Using latent profile analysis, we identified patient subtypes based on trajectory of presepsis healthcare facility use. Subtypes were identified in the derivation cohort (1,512 sepsis hospitalizations among earlier HRS participants), then validated them in two additional cohorts (1,992 sepsis hospitalizations among later HRS participants; 32,525 sepsis hospitalizations among U.S. Department of Veterans Affairs beneficiaries). We measured the association between presepsis path and 90-day mortality using chi-square tests and multivariable logistic regression.We identified three subtypes: low use of inpatient healthcare facilities, comprising 84% of the derivation cohort; rising use, 12%; and high use, 4%. The shape and distribution of presepsis trajectories were similar in all three cohorts. In the derivation cohort, 90-day mortality differed by presepsis trajectory as follows: 38% (low use), 63% (rising use), and 48% (high use) (P 0.001). This association persisted in the validation cohorts (P 0.001 for each). The rising use class remained an independent predictor of mortality after adjustment for potential confounders, including detailed physiologic data.In national cohorts of patients with sepsis, we have shown that several distinct paths into sepsis exist. These paths, identified by trajectories of presepsis healthcare use, are predictive of 90-day mortality.

IMPORTANCE: Some experts have cautioned that national and health system emphasis on rapid administration of antimicrobials for sepsis may increase overall antimicrobial use even among patients without sepsis. OBJECTIVE: To assess whether temporal changes in antimicrobial timing for sepsis are associated with increasing antimicrobial use, days of therapy, or broadness of antimicrobial coverage among all hospitalized patients at risk for sepsis. DESIGN, SETTING, AND PARTICIPANTS: This is an observational cohort study of hospitalized patients at 152 hospitals in 2 health care systems during 2013 to 2018, admitted via the emergency department with 2 or more systemic inflammatory response syndrome (SIRS) criteria. Data analysis was performed from June 10, 2021, to March 22, 2022. EXPOSURES: Hospital-level temporal trends in time to first antimicrobial administration. OUTCOMES: Antimicrobial outcomes included antimicrobial use, days of therapy, and broadness of antibacterial coverage. Clinical outcomes included in-hospital mortality, 30-day mortality, length of hospitalization, and new multidrug-resistant (MDR) organism culture positivity. RESULTS: Among 1 559 523 patients admitted to the hospital via the emergency department with 2 or more SIRS criteria (1 269 998 male patients [81.4%]; median [IQR] age, 67 [59-77] years), 273 255 (17.5%) met objective criteria for sepsis. In multivariable models adjusted for patient characteristics, the adjusted median (IQR) time to first antimicrobial administration to patients with sepsis decreased by 37 minutes, from 4.7 (4.1-5.3) hours in 2013 to 3.9 (3.6-4.4) hours in 2018, although the slope of decrease varied across hospitals. During the same period, antimicrobial use within 48 hours, days of antimicrobial therapy, and receipt of broad-spectrum coverage decreased among the broader cohort of patients with SIRS. In-hospital mortality, 30-day mortality, length of hospitalization, new MDR culture positivity, and new MDR blood culture positivity decreased over the study period among both patients with sepsis and those with SIRS. When examining hospital-specific trends, decreases in antimicrobial use, days of therapy, and broadness of antibacterial coverage for patients with SIRS did not differ by hospital antimicrobial timing trend for sepsis. Overall, there was no evidence that accelerating antimicrobial timing for sepsis was associated with increasing antimicrobial use or impaired antimicrobial stewardship. CONCLUSIONS AND RELEVANCE: In this multihospital cohort study, the time to first antimicrobial for sepsis decreased over time, but this trend was not associated with increasing antimicrobial use, days of therapy, or broadness of antimicrobial coverage among the broader population at-risk for sepsis, which suggests that shortening the time to antibiotics for sepsis is feasible without leading to indiscriminate antimicrobial use.

Rationale: In 2013, the New York State Department of Health (NYSDOH) began a mandatory state-wide initiative to improve early recognition and treatment of severe sepsis and septic shock. Objectives: This study examines protocol initiation, 3-hour and 6-hour sepsis bundle completion, and risk-adjusted hospital mortality among adult patients with severe sepsis and septic shock. Methods: Cohort analysis included all patients from all 185 hospitals in New York State reported to the NYSDOH from April 1, 2014, to June 30, 2016. A total of 113,380 cases were submitted to NYSDOH, of which 91,357 hospitalizations from 183 hospitals met study inclusion criteria. NYSDOH required all hospitals to submit and follow evidence-informed protocols (including elements of 3-h and 6-h sepsis bundles: lactate measurement, early blood cultures and antibiotic administration, fluids, and vasopressors) for early identification and treatment of severe sepsis or septic shock. Measurements and Main Results: Compliance with elements of the sepsis bundles and risk-adjusted mortality were studied. Of 91,357 patients, 74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour bundle compliance increased from 53.4% to 64.7% during the study period (P

PurposeTo quantify the frequency and co-occurrence of new diagnoses consistent with post-sepsis morbidity, mortality, new nursing care dependency, and total healthcare costs after sepsis.MethodsPopulation-based cohort study using healthcare claims data from 23 million beneficiaries of a German health insurance provider. We included adult patients with incident hospital-treated sepsis identified by ICD-10 codes in 2013-2014. New medical, psychological and cognitive diagnoses associated with post-sepsis morbidity; mortality; dependency on nursing care; and total health care costs in survivors were assessed to 3 years after hospital discharge.ResultsAmong 116,507 sepsis patients who survived hospitalization for sepsis, 74.3% had a new medical, psychological or cognitive diagnosis in the first year after discharge. 20.6% and 3.8% had new diagnoses in two and three domains, respectively. 31.5% were newly dependent on nursing care, and 30.7% died within the first year. In the second and third year, 65.8% and 59.4% of survivors had new diagnoses, respectively. Healthcare costs totaled an average 36,585 Euro/patient in three years, including index hospitalization costs. Occurrence of new diagnoses in predefined subgroups was: 73.7% (survivors of non-severe sepsis), 75.6% (severe sepsis), 78.3% (ICU-treated sepsis), 72.8% (non-ICU treated sepsis) and 68.5% (survivors without prior diagnoses).ConclusionsNew medical, psychological and cognitive diagnoses consistent with post-sepsis morbidity are 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 post-sepsis morbidity.Trial RegistrationDRKS00016340Take home messageThis large population-based cohort of over 100,000 survivors of hospital-treated sepsis found high rates and a broad spectrum of new diagnoses consistent with post-sepsis morbidity, frequent new nursing care dependency, and high long-term mortality 1-3 years post sepsis. Post-sepsis morbidity was not limited to the oldest survivors or those with the most severe illness, but also affected younger survivors and those without pre-existing diagnoses.

Objectives To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. Design The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. Methods Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. Results The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? Conclusions Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.

Rationale: In 2017, the U.S. Centers for Disease Control and Prevention (CDC) developed a new surveillance definition of sepsis, the adult sepsis event (ASE), to better track sepsis epidemiology. The ASE requires evidence of acute organ dysfunction and defines baseline organ function pragmatically as the best in-hospital value. This approach may undercount sepsis if new organ dysfunction does not resolve by discharge. Objectives: To understand how sepsis identification and outcomes differ when using the best laboratory values during hospitalization versus methods that use historical lookbacks to define baseline organ function. Methods: We identified all patients hospitalized at 138 Veterans Affairs hospitals (2013–2018) admitted via the emergency department with two or more systemic inflammatory response criteria, were treated with antibiotics within 48 hours (i.e., had potential infection), and completed 4+ days of antibiotics (i.e., had suspected infection). We considered the following three approaches to defining baseline renal, hematologic, and liver function: the best values during hospitalization (as in the Centers for Disease Control and Prevention’s ASE), the best values during hospitalization plus the prior 90 days (3-mo baseline), and the best values during hospitalization plus the prior 180 days (6-mo baseline). We determined how many patients met the criteria for sepsis by each approach, and then compared characteristics and outcomes of sepsis hospitalizations between the three approaches. Results: Among 608,128 hospitalizations with potential infection, 72.1%, 68.5%, and 58.4% had creatinine, platelet, and total bilirubin measured, respectively, in the prior 3 months. A total of 86.0%, 82.6%, and 74.8%, respectively, had these labs in the prior 6 months. Using the hospital baseline, 100,568 hospitalizations met criteria for community-acquired sepsis. By contrast, 111,983 and 117,435 met criteria for sepsis using the 3- and 6-month baselines, for a relative increase of 11% and 17%, respectively. Patient characteristics were similar across the three approaches. In-hospital mortality was 7.2%, 7.0%, and 6.8% for sepsis hospitalizations identified using the hospital, 3-month baseline, and 6-month baseline. The 30-day mortality was 12.5%, 12.7%, and 12.5%, respectively. Conclusions: Among veterans hospitalized with potential infection, the majority had laboratory values in the prior 6 months. Using 3- and 6-month lookbacks to define baseline organ function resulted in an 11% and 17% relative increase, respectively, in the number of sepsis hospitalizations identified.

OBJECTIVE: To evaluate the physical and psychosocial domains of health-related quality of life (HRQL) among children during the first year following community-acquired septic shock, and explore factors associated with poor physical and psychosocial HRQL outcomes. DESIGN: Secondary analysis of the Life after Pediatric Sepsis Evaluation (LAPSE). SETTING: Twelve academic PICUs in the United States. PATIENTS: Children ≥1 month and

This cohort study examined the number and type of outpatient health visits before and after hospitalization for pediatric severe sepsis.

OBJECTIVES Severe sepsis is a significant cause of healthcare utilization and morbidity among pediatric patients. However, little is known about how commonly survivors acquire new medical devices during pediatric severe sepsis hospitalization. We sought to determine the rate of new device acquisition (specifically, tracheostomy placement, gastrostomy tube placement, vascular access devices, ostomy procedures, and amputation) among children surviving hospitalizations with severe sepsis. For contextualization, we compare this to rates of new device acquisition among three comparison cohorts: 1) survivors of all-cause pediatric hospitalizations; 2) matched survivors of nonsepsis infection hospitalizations; and 3) matched survivors of all-cause nonsepsis hospitalization with similar organ dysfunction. DESIGN Observational cohort study. SETTING Nationwide Readmission Database (2016), including all-payer hospitalizations from 27 states. PATIENTS Eighteen-thousand two-hundred ten pediatric severe sepsis hospitalizations; 532,738 all-cause pediatric hospitalizations; 16,173 age- and sex-matched nonsepsis infection hospitalizations; 15,025 organ dysfunction matched all-cause nonsepsis hospitalizations; and all with live discharge. MEASUREMENTS AND MAIN RESULTS Among 18,210 pediatric severe sepsis hospitalizations, 1,024 (5.6%) underwent device placement. Specifically, 3.5% had new gastrostomy, 3.1% new tracheostomy, 0.6% new vascular access devices, 0.4% new ostomy procedures, and 0.1% amputations. One-hundred forty hospitalizations (0.8%) included two or more new devices. After applying the Nationwide Readmissions Database sampling weights, there were 55,624 pediatric severe sepsis hospitalizations and 1,585,194 all-cause nonsepsis hospitalizations with live discharge in 2016. Compared to all-cause pediatric hospitalizations, severe sepsis hospitalizations were eight-fold more likely to involve new device acquisition (6.4% vs 0.8%; p < 0.001). New device acquisition was also higher in severe sepsis hospitalizations compared with matched nonsepsis infection hospitalizations (5.1% vs 1.2%; p < 0.01) and matched all-cause hospitalizations with similar organ dysfunction (4.7% vs 2.8%; p < 0.001). CONCLUSIONS In this nationwide, all-payer cohort of U.S. pediatric severe sepsis hospitalizations, one in 20 children surviving severe sepsis experienced new device acquisition. The procedure rate was nearly eight-fold higher than all-cause, nonsepsis pediatric hospitalizations, and four-fold higher than matched nonsepsis infection hospitalizations.

As more individuals survive sepsis, there is an urgent need to understand its effects on patient-reported outcomes.What is the effect of sepsis on self-rated health, and what role, if any, does functional disability play in mediating this effect?We conducted a survey- and administrative claims-based retrospective cohort study using the US Health and Retirement Study, a nationally representative cohort-based survey of older adults in the United States, from 2000 through 2016. We matched Medicare beneficiaries hospitalized with sepsis in 2000 to 2008 to nonhospitalized individuals. Self-rated health and functional disability were tracked biannually for 8 years. Differences in self-rated health between the cohorts were measured using mixed models with and without controlling for changes in functional disability.Seven hundred fifty-eight individuals with sepsis were matched 1:1 to 758 nonhospitalized individuals, all aged 65 years and older. Among survivors, sepsis was associated with worse self-rated health in years 2 and 4 (adjusted absolute difference in self-rated health on a 5-point scale in year 2: -0.24 [95% CI, -0.38 to -0.10] and year 4: -0.17 [95% CI, -0.33 to -0.02]) but not in years 6 or 8. After accounting for changes in functional status, the association between sepsis and self-rated health was still present but reduced in year 2 (adjusted absolute difference in self-rated health, -0.18 [95% CI, -0.31 to -0.05]) and was not present in years 4, 6, or 8.Self-rated health worsened initially after sepsis but returned to the level of that of nonhospitalized control subjects by year 6. Mitigating sepsis-related functional disability may play a key role in improving self-rated health after sepsis.

Sepsis has long been established as an important cause of morbidity and mortality. Efforts to reduce this burden have focused on improved recognition and early treatment, as there have been no new targeted therapies for sepsis. Sepsis-3 was published in 2016 and produced an updated definition of sepsis as life-threatening organ dysfunction due to a dysregulated host response to infection, better aligned with our current pathophysiological understanding of the syndrome. Sepsis-3 also put forth data-driven clinical criteria (sequential organ failure assessment [SOFA] and quick-SOFA [qSOFA]) which consistently identify patients at highest risk for adverse outcomes. Numerous studies have now evaluated the performance of SOFA and qSOFA compared to prior definitions (utilizing systemic inflammatory response syndrome [SIRS]), and SOFA and qSOFA consistently outperform SIRS in predicting adverse outcomes such as in-hospital mortality. Sepsis-3 allows for improved recognition of high-risk sepsis patients compared with prior definitions. However, as Sepsis-3 requires organ dysfunction to already be present, it does not identify patients prior to clinical deterioration. Therefore, sepsis remains a clinical diagnosis, requiring clinical judgment to identify infection and a dysregulated host response. As such, the diagnosis remains subjective in clinical practice, and recognition is imperfect.

An estimated 14 million patients survive sepsis hospitalization each year. However, survivors commonly experience new functional disability, cognitive impairment, and a high rate of further medical setbacks, including hospital readmission and late death. One in 5 older survivors has a potentially preventable hospital admission with in 90 days, most commonly for infection. Treatment should focus on preventing the common sequelae of critical illness during the initial hospitalization, tailoring medical care to minimize the risk for common and potentially preventable causes of hospital readmission, and promoting functional recovery.

The overarching goals of early sepsis management include early recognition, appropriate antibiotic therapy and source control, maintenance of hemodynamic stability, and supportive care of organ dysfunction. Despite increasing awareness of the global burden of sepsis, and general agreement on the goals of management, there is ongoing controversy regarding the implementation of specific treatment strategies to optimize patient outcomes. This article will address five current points of controversy in the management of sepsis and septic shock. These include optimal timing of antibiotics in patients with potential sepsis, the role of glucocorticoids in septic shock, vitamin C as a novel therapy for sepsis, the ideal intravenous fluid for resuscitation, and the optimal balance of fluid resuscitation and vasopressor administration in septic shock. For each of these topics, we review relevant literature, discuss areas of controversy, and present our current approach to management.

OBJECTIVES To quantify healthcare utilization in the week preceding sepsis hospitalization to identify potential opportunities to improve the recognition and treatment of sepsis prior to admission. DESIGN Retrospective study. SETTING Two large integrated healthcare delivery systems in the United States. PARTICIPANTS Hospitalized sepsis patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We quantified clinician-based encounters in each of the 7 days preceding sepsis admission, as well as on the day of admission, and categorized them as: hospitalization, subacute nursing facility, emergency department, urgent care, primary care, and specialty care. We identified the proportion of encounters with diagnoses for acute infection based on 28 single-level Clinical Classification Software categories. We also quantified the use of antibiotics over the same interval and used linear regression to evaluate time trends. We included a total of 14,658 Kaiser Permanente Northern California sepsis hospitalizations and 31,369 Veterans Health Administration sepsis hospitalizations. Over 40% of patients in both cohorts required intensive care. A total of 7,747 Kaiser Permanente Northern California patients (52.9%) and 14,280 Veterans Health Administration patients (45.5%) were seen by a clinician in the week before sepsis. Prior to sepsis, utilization of subacute nursing facilities remained steady, whereas hospital utilization declined. Primary care, specialty care, and emergency department visits increased, particularly at admission day. Among those with a presepsis encounter, 2,648 Kaiser Permanente Northern California patients (34.2%) and 3,858 Veterans Health Administration patients (27.0%) had at least one acute infection diagnosis. An increasing percentage of outpatient encounters also had infectious diagnoses (3.3%/d; 95% CI, 1.5%-5.1%; p < 0.01), particularly in primary and specialty care settings. Prior to sepsis hospitalization, the use of antibiotics also increased steadily (2.1%/d; 95% CI, 1.1%-3.1%; p < 0.01). CONCLUSIONS Over 45% of sepsis patients had clinician-based encounters in the week prior to hospitalization with an increasing frequency of diagnoses for acute infection and antibiotic use in the outpatient setting. These presepsis encounters offer several potential opportunities to improve the recognition, risk stratification, and treatment prior to sepsis hospitalization.

Purpose We sought to measure inpatient healthcare utilization among U.S. Veteran Affairs beneficiaries surviving sepsis hospitalization, and to examine how post-sepsis utilization varies by select patient characteristics. Materials and methods Retrospective cohort study of 26,561 Veterans who survived sepsis hospitalization in 2009. Using difference-in-differences analysis, we compared changes in healthcare utilization in one year before and one year after sepsis hospitalization by Veteran age, illness severity, and recent nursing facility use. Results Median days in a healthcare facility increased from 5 to 10. Veterans with recent nursing facility use spent a median 65 days (or 86% of days alive) in a healthcare facility in the year after sepsis. Older age, greater illness severity, and recent nursing home use were each associated with spending more days, and a greater proportion of days alive, in a healthcare facility during the year after sepsis. However, none of these characteristics was associated with a greater rise in utilization after sepsis. Conclusions Veterans surviving sepsis experience high rates of post-sepsis mortality and significant increases in healthcare facility use. Recent nursing facility use is strongly predictive of greater post-sepsis healthcare utilization.

Purpose Sepsis survivors have a higher risk of rehospitalisation and of long-term mortality. We assessed the rate, diagnosis, and independent predictors for rehospitalisation in adult sepsis survivors. Methods We searched for non-randomized studies and randomized clinical trials in MEDLINE, Cochrane Library, Web of Science, and EMBASE (OVID interface, 1992–October 2019). The search strategy used controlled vocabulary terms and text words for sepsis and hospital readmission, limited to humans, and English language. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms. Results The literature search identified 12,544 records. Among 56 studies (36 full and 20 conference abstracts) that met our inclusion criteria, all were non-randomised studies. Studies most often report 30-day rehospitalisation rate (mean 21.4%, 95% confidence interval [CI] 17.6–25.4%; N = 36 studies reporting 6,729,617 patients). The mean (95%CI) rehospitalisation rates increased from 9.3% (8.3–10.3%) by 7 days to 39.0% (22.0–59.4%) by 365 days. Infection was the most common rehospitalisation diagnosis. Risk factors that increased the rehospitalisation risk in sepsis survivors were generic characteristics such as older age, male, comorbidities, non-elective admissions, hospitalisation prior to index sepsis admission, and sepsis characteristics such as infection and illness severity, with hospital characteristics showing inconsistent associations. The overall certainty of evidence was moderate for rehospitalisation rates and low for risk factors. Conclusions Rehospitalisation events are common in sepsis survivors, with one in five rehospitalisation events occurring within 30 days of hospital discharge following an index sepsis admission. The generic and sepsis-specific characteristics at index sepsis admission are commonly reported risk factors for rehospitalisation. Registration PROSPERO CRD 42016039257, registered on 14-06-2016. Electronic supplementary material The online version of this article (10.1007/s00134-019-05908-3) contains supplementary material, which is available to authorized users.

This study uses National Readmissions Database data to characterize incidence of and mortality due to maternal sepsis within 42 days of delivery hospitalization discharge in the United States between 2013 and 2016.

An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment, physical disability, and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. To address this unmet need, the International Sepsis Forum convened a Colloquium in February 2018 on "Understanding and Enhancing Sepsis Survivorship". The goals were to identify (1) gaps and limitations of current research, (2) shorter-term priorities, and (3) longer-term priorities for understanding and enhancing sepsis survivorship. Twenty-six experts from eight countries participated. The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on post-sepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment into cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This Perspective reviews Colloquium discussions, the identified priorities, and current initiatives to address them. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Although the devastating consequences of sepsis are well-known (1), the diagnosis of this clinical syndrome has proven to be highly challenging (2). Until recently, sepsis was defined by two or more systemic inflammatory response syndrome (SIRS) criteria in the presence of infection (3). However, af

Background In observational studies of the general population, higher body mass index (BMI) has been associated with increased incidence of and mortality from bloodstream infection (BSI) and sepsis. On the other hand, higher BMI has been observed to be apparently protective among patients with infection and sepsis. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI. Methods and findings We used a population-based cohort in Norway followed from 1995 to 2017 (the Trøndelag Health Study [HUNT]), and carried out linear and nonlinear Mendelian randomization analyses. Among 55,908 participants, the mean age at enrollment was 48.3 years, 26,324 (47.1%) were men, and mean BMI was 26.3 kg/m2. During a median 21 years of follow-up, 2,547 (4.6%) participants experienced a BSI, and 451 (0.8%) died from BSI. Compared with a genetically predicted BMI of 25 kg/m2, a genetically predicted BMI of 30 kg/m2 was associated with a hazard ratio for BSI incidence of 1.78 (95% CI: 1.40 to 2.27; p < 0.001) and for BSI mortality of 2.56 (95% CI: 1.31 to 4.99; p = 0.006) in the general population, and a hazard ratio for BSI mortality of 2.34 (95% CI: 1.11 to 4.94; p = 0.025) in an inverse-probability-weighted analysis of patients with BSI. Limitations of this study include a risk of pleiotropic effects that may affect causal inference, and that only participants of European ancestry were considered. Conclusions Supportive of a causal relationship, genetically predicted BMI was positively associated with BSI incidence and mortality in this cohort. Our findings contradict the “obesity paradox,” where previous traditional epidemiological studies have found increased BMI to be apparently protective in terms of mortality for patients with BSI or sepsis., Tormod Rogne and colleagues investigate whether body mass index influences risk of mortality from bloodstream infection., Author summary Why was this study done? It is well-recognized that overweight and obesity are associated with increased risk of bloodstream infection (BSI) and sepsis, but it is not fully understood whether this is due to body weight in itself or factors related to body weight (such as exercise or smoking habits). While a large number of studies have observed that BSI or sepsis patients who are overweight or obese have a reduced risk of dying from those diseases, there is reason to suspect that these findings are biased. We wanted to evaluate whether genetically predicted body mass index (BMI)—which is independent of lifestyle factors—was associated with risk of developing and dying from a BSI. What did the researchers do and find? We used clinical and genetic information from the Trøndelag Health Study in Norway on 55,908 participants representative of the adult Norwegian population. Similar to what has been found in non-genetic studies, we found that increased genetically predicted BMI was associated with an increased risk of developing a BSI. Contrary to many observational studies, we found that among BSI patients, being overweight or obese was associated with an increased risk of death from bloodstream infection. What do these findings mean? The findings of many previous observational studies of an apparently protective effect of overweight or obesity among patients with BSI or sepsis may be affected by other factors, such as accompanying characteristics of overweight or obese individuals, or by who ends up participating in the studies. In this cohort, higher genetically predicted BMI was associated with an increased risk of developing and dying from a BSI, also among BSI patients, and our findings support the worldwide initiative to reduce the prevalence of overweight and obesity.

Introduction Over the past decade, there has been an increase in the proportion of patients admitted to the cardiac intensive care unit (CICU) with non-cardiac comorbidities and admission diagnoses. However, organ system dysfunction and causes of death in CICU patients remains poorly characterized. Given the increasing proportion of admissions to the CICU for non-cardiac diagnoses, we hypothesized that there would be a substantial proportion of non-cardiac organ dysfunction and death due to non-cardiac causes. Methods We identified adult patients admitted to a CICU at a large tertiary care center (2015-2019) who died during the hospitalization. Principal hospitalization diagnosis, demographics, organ system dysfunctions, cause of death, and withdrawal of life support were abstracted via a standardized tool used in prior studies. The primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. Results We identified 258 decedents admitted to the CICU. Most patients (76%) had cardiac dysfunction, defined as cardiogenic shock or sustained ventricular arrhythmia. However, only 11% of patients had cardiac dysfunction alone, 89% experienced non-cardiac organ dysfunction, and 24% died without cardiac dysfunction. Multi-organ failure and sepsis were present in 70% and 54% of patients, respectively. The most common primary causes of death were cardiac (58%), pulmonary (15%), and neurologic dysfunction (11%). The majority of patients (76%) died after withdrawal of life-sustaining interventions. Conclusions In this contemporary cohort of CICU decedents, 3 of 4 patients had cardiogenic shock or sustained ventricular arrhythmias. However, non-cardiac organ dysfunction occurred in the vast majority, and nearly half had a non-cardiac primary cause of death. The high frequency of multi-organ failure and non-cardiac causes of death underscores the importance of broad cardiac and non-cardiac critical care training among physicians practicing in the CICU.

Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

Background Many randomized controlled trials (RCTs) employ mortality at a given time as a primary outcome. There are at least three common ways to measure 90-day mortality: first, all-location mortality, that is, all-cause mortality within 90 days of randomization at any location. Second, ARDSnet mortality is death in a healthcare facility of greater intensity than the patient was in prior to the hospitalization during which they were randomized. Finally, in-hospital mortality is death prior to discharge from the primary hospitalization of randomization. Data comparing the impact of these different measurements on sample size are lacking. We evaluated the extent to which event rates vary by mortality definition. Methods This was a retrospective cohort study of 30,691 patients hospitalized at Veterans Affairs (VA) hospitals for sepsis during 2009. 12,727 (41.5%) received care in an ICU setting. For each patient, we measured event rates for three different 90-day mortality outcomes: all-location mortality, ARDSnet mortality, and in-hospital mortality. We also calculated sample sizes necessary to power an example RCT given those event rates. Results At 90 days, all-location mortality was 26.4% (95% CI 25.9–26.9%), ARDSnet mortality was 19.2% (95% CI 18.8–19.7%), and in-hospital mortality was 13.4% (95% CI 13.0–13.8%) (p < 0.01 all comparisons). These respective event rates result in different required sample sizes to achieve a 20% relative reduction in mortality with 80% power and a 5% false positive rate. Such a trial of VA sepsis patients would require 2080 patients for all-location mortality, 3080 for ARDSnet mortality, and 4796 for in-hospital mortality. Among sepsis patients mechanically ventilated in an ICU, 2438 experienced all-location mortality (46.2% [95% CI 44.8–47.5%]), 2181 experienced ARDSnet mortality (41.3% [95% CI 40.0–42.6%]), and 1894 experienced in-hospital mortality (36.0% [95% CI 34.7–37.3%]). Conclusions Event rates vary substantially in sepsis patients based on the chosen 90-day mortality definition. This could have important implications for RCT design trade-offs. Electronic supplementary material The online version of this article (10.1186/s13063-018-2570-2) contains supplementary material, which is available to authorized users.