Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

https://jamanetwork.com/journals/jama/articlepdf/2492881/jsc160002.pdf

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.

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KDIGO clinical practice guidelines for acute kidney injury.

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Absence of long-range severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission from a highly infectious patient with undiagnosed coronavirus disease 2019 (COVID-19) in a positive-pressure room.

Rationale: Ventilator-associated event (VAE) surveillance provides an objective means to measure and compare complications that develop during mechanical ventilation by identifying patients with su...

/pdf/incidence-characteristics-and-outcomes-of-ventilator-qyoj8plu2s.pdf

Incidence, Characteristics, and Outcomes of Ventilator-Associated Events during the COVID-19 Pandemic.

420 www.ccmjournal.org March 2020 • Volume 48 • Number 3 Sepsis is a major cause of morbidity and mortality, yet precisely how much it costs the U.S. healthcare system has not been well characterized. The most recent national estimate from the Health Care Utilization Project (HCUP) was $23.7 billion for hospitalizations with codes for septicemia in 2013 (1). Although this report identified septicemia as the most expensive condition treated in U.S. hospitals, this cost is a significant underestimate of the true costs associated with sepsis given that: 1) many patients have sepsis, severe sepsis, or septic shock without septicemia, 2) sepsis survivors often require skilled nursing care after hospitalization, adding substantial additional costs, and 3) not every hospitalization with septicemia gets coded for septicemia (2). The 2013 HCUP analysis also found that 62% of the costs from septicemia hospitalizations were paid for by Medicare, even though Medicare patients only accounted for 46% of total inpatient costs nationally (1). This likely reflects the higher frequency of sepsis in elderly patients and their more complicated courses compared with younger patients (3). Importantly, the Medicare population has grown much faster than the overall U.S. population in recent years as the “baby boomer” generation has reached Medicare eligibility. Medicare spending has grown in parallel with the increase in the eligible population, accounting for 20% of national health expenditures in 2017 (4). In light of these trends, understanding the burden and costs associated with sepsis among Medicare beneficiaries is of great interest to clinicians, hospital administrators, public health officials, payers, and policy makers. In this issue of Critical Care Medicine, Buchman et al (5) present detailed statistics on the costs and mortality rates associated with hospitalizations with sepsis diagnoses among Medicare beneficiaries between 2012 and 2018. Their data source includes outcomes and costs following hospitalization, including admissions to skilled nursing facilities. This allows for a more comprehensive assessment of sepsis burden compared to most other epidemiologic studies. The study includes a full range of sepsis codes, including the codes for septicemia and the sepsis-specific codes for sepsis, severe sepsis, and septic shock introduced in 2002. The primary findings were as follows. First, the number of inpatient Medicare Part A/B hospitalizations with a sepsis diagnosis code rose from just over 800,000 in 2012 to over 1.1 million in 2018, a rate that outpaced the growth in the Medicare population. Second, the total costs of inpatient admissions with sepsis codes rose from $17.8 to $22.4 billion, whereas the total cost of skilled nursing facility care in the 90 days following sepsis-coded hospitalizations rose from $3.9 to $5.6 billion. Third, when combining care from total inpatient admissions and subsequent skilled nursing facility care among Medicare Part A, B, and Medicare Advantage patients, the total costs rose from $27.6 to $41.5 billion. Finally, 6-month sepsis-associated mortality rates declined over the study period but remained extraordinarily high: approximately 60% for patients with codes for septic shock, 36.4% for severe sepsis, and 30.9% for unspecified sepsis. The numbers presented are eye-popping, yet they still potentially underestimate sepsis burden and costs given the limitations of administrative data for characterizing sepsis epidemiology. Prior work has demonstrated that explicit sepsis codes generally have good positive predictive value (particularly the codes for severe sepsis and septic shock), but they have low sensitivity and tend to be preferentially applied to patients with more severe disease (6). This means that the true burden and costs of sepsis may actually be higher than reported. A potential bias toward applying sepsis codes to the sickest subset of patients may also explain why mortality rates in this study were so much higher than the 90-day mortality rates reported in recent randomized controlled trials of septic shock (generally 20–30%) (7). *See also p. 276.

The Eye-Popping Costs Associated With Sepsis Diagnoses Among Medicare Beneficiaries.

Abstract Background Ceftazidime–avibactam (CAV) was US FDA-approved for complicated intra-abdominal/urinary tract infections in 2015, and for hospital-acquired/ventilator-associated pneumonia in 2018. However, little is known about its real-world use. Methods Encounters of inpatients receiving CAV at academic hospitals in the VizientTM Clinical Resource Manager were identified (CAV encounters). CAV administered for ≤2 consecutive days during an encounter or any duration of CAV within 2 days of admission (excluding acute care hospital transfers) was considered empiric therapy. Targeted therapy was defined as ≥4 consecutive days or death within 2 days of therapy; empiric and targeted therapy cohorts were mutually inclusive. CAV-encounter characteristics, use patterns and Infectious Disease (ID) consultation were examined. Quarterly hospital uptake of CAV and % change in CAV encounter prevalence (using Poisson regression) were calculated. Results From January 2015 to December 2017, 20,590 CAV doses occurred in 2,128 encounters among 1,652 patients. Mean duration of therapy was 8 ± 7.9 days (range 1–86); overall mortality was 24%. The number of hospitals prescribing CAV increased from 5 to 92/168 and quarterly prevalence of CAV encounters increased from 5/10,000 hospitalizations in 2015q1 to 9.8 in 2017q4 (% change=2.1[0.7–3.6] %/quarter; (P = 0.004). Therapy was empiric in 904 (42%) encounters and targeted in 1,472 (69%); 63% of empiric CAV was initiated within 2 days of admission. CAV was initiated in the ICU in 862 (40.5%) encounters. Infection site was coded as respiratory in 34%, urinary in 26% and abdominal in 16% of encounters. Within 31 hospitals reporting consultant specialty, 29% of targeted therapy occurred without ID consultation. For targeted therapy encounters, CAV monotherapy occurred in 841 (57%) and combination therapy in 631 (43%) encounters, which most often included aminoglycosides, colistin or tigecycline. Mortality was 22% in the monotherapy and 25% in the combination therapy group (P = 0.08). Conclusion CAV use across US academic medical centers has increased modestly over 3 years. More than 40% of CAV prescriptions appear to be empiric and targeted therapy often occurs without ID consultation at academic centers. Disclosures All authors: No reported disclosures.

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Michael Klompas

Papers

Absence of long-range severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission from a highly infectious patient with undiagnosed coronavirus disease 2019 (COVID-19) in a positive-pressure room.

Incidence, Characteristics, and Outcomes of Ventilator-Associated Events during the COVID-19 Pandemic.

The Eye-Popping Costs Associated With Sepsis Diagnoses Among Medicare Beneficiaries.

2398. Utilization Practices of Ceftazidime–Avibactam at Academic Medical Centers in the United States

Medical Mistrust in the Context of Ebola