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.

/pdf/kdigo-clinical-practice-guidelines-for-acute-kidney-injury-27tybolw7l.pdf

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

Commentary on : Zhang TT, Tang SS, Fu LJ. The effectiveness of different concentrations of chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. J Clin Nurs 2014;23:1461–75.[OpenUrl][1][CrossRef][2][PubMed][3]



Intubation and mechanical ventilation increase patients’ risk for pneumonia. The endotracheal tube facilitates microbial colonisation of the oropharynx and passage of oral secretions from the oropharynx to the lungs. Routine oral …

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https://ebn.bmj.com/content/ebnurs/early/2014/09/17/eb-2014-101944.full.pdf

Review: does chlorhexidine prevent ventilator-associated pneumonia?

Electronic Health Record (EHR) data are increasingly being used to monitor population health on account of their timeliness, granularity, and large sample sizes. While EHR data are often sufficient to estimate disease prevalence and trends for large geographic areas, the same accuracy and precision may not carry over for smaller areas that are sparsely represented by non-random samples.We developed small-area estimation models using a combination of EHR data drawn from MDPHnet, an EHR-based public health surveillance network in Massachusetts, the American Community Survey, and state hospitalization data. We estimated municipality-specific prevalence rates of asthma, diabetes, hypertension, obesity, and smoking in each of the 351 municipalities in Massachusetts in 2016. Models were compared against Behavioral Risk Factor Surveillance System (BRFSS) state and small area estimates for 2016.Integrating progressively more variables into prediction models generally reduced mean absolute error (MAE) relative to municipality-level BRFSS small area estimates: asthma (2.24% MAE crude, 1.02% MAE modeled), diabetes (3.13% MAE crude, 3.48% MAE modeled), hypertension (2.60% MAE crude, 1.48% MAE modeled), obesity (4.92% MAE crude, 4.07% MAE modeled), and smoking (5.33% MAE crude, 2.99% MAE modeled). Correlation between modeled estimates and BRFSS estimates for the 13 municipalities in Massachusetts covered by BRFSS's 500 Cities ranged from 81.9% (obesity) to 96.7% (diabetes).Small-area estimation using EHR data is feasible and generates estimates comparable to BRFSS state and small-area estimates. Integrating EHR data with survey data can provide timely and accurate disease monitoring tools for areas with sparse data coverage. 

/pdf/small-area-estimation-for-public-health-surveillance-using-2qalqhig.pdf

Small-area estimation for public health surveillance using electronic health record data: reducing the impact of underrepresentation

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) demonstrated successfully in multiple studies (up to 12 mg/kg/day), however there is sparse literature demonstrating the effects of dosing on clinical outcomes such as clinical cure rate, safety, and mortality. Methods: A single-center, retrospective, observational study of patients with positive VRE cultures and concurrent daptomycin was conducted at a Veterans Affairs Medical Center from September 1, 2003 to December 31, 2015. Multivariate regression models were used to estimate the association between weight-based dosing (total body weight) and mortality, ICU admission, hospital readmission, reinfection, length of stay, and ICU length of stay. Results: 135 patients received daptomycin over the study period, of which 77 patients met inclusion criteria. Study population demographics included: 95% male; mean age 65.5 (SD±9.3) years, BMI 27, Charlson comorbidity 6; E. faecium 61.1%. Microbiologic failure 18.2%. Average dose 6 mg/kg (±1.3mg/kg) and duration 18 (±15) days. Observed 30-day and 90-day mortalities were 25.9% and 35.1%. Average dose in survivors was 6.1 mg/kg vs. 5.7 mg/kg in the non-survivors. In a logistic regression model the odds of 90-day mortality was lower in patients with higher dosing regimens versus those with lower dosages (OR 0.67; 95% CI 0.449–0.999, p<0.05). When dosing was increased by 1 unit (mg/kg), a 33% reduction in likelihood to experience 90-day mortality was noted. Thirty day mortality (p=0.39), length of stay (p=0.16), ICU admission (p=0.74), and ICU length of stay (p=0.62) were not significantly different. Conclusions: Increased daptomycin dosing exhibited a significant impact on 90-day mortality in VRE infections. This study highlights the need for careful selection of appropriate doses when treating VRE. Further studies on dosing impact are needed.

717: ultrashort-course antibiotics for suspected vap with minimal and stable ventilator settings

Automated chronic disease surveillance and visualization using electronic health record data

Abstract Timely and accurate data on the epidemiology of sepsis is essential to inform public policy, clinical practice, and research priorities. Recent studies have illuminated several ongoing questions about sepsis epidemiology, including the incidence and outcomes of sepsis in non-Western countries and in specialized populations such as surgical patients, patients with cancer, and the elderly. There have also been new insights into the limitations of current surveillance methods using administrative data and increasing experience tracking sepsis incidence and outcomes using “big data” approaches that take advantage of detailed electronic health record data. The COVID-19 pandemic, however, has fundamentally changed the landscape of sepsis epidemiology. It has increased sepsis rates, helped highlight ongoing controversies about how to define sepsis, and intensified debate about the possible unintended consequences of overly rigid sepsis care bundles. Despite these controversies, there is a growing consensus that severe COVID-19 causing organ dysfunction is appropriate to label as sepsis, even though it is treated very differently from bacterial sepsis, and that surveillance strategies need to be modified to reliably identify these cases to fully capture and delineate the current burden of sepsis. This review will summarize recent insights into the epidemiology of sepsis and highlight several urgent questions and priorities catalyzed by COVID-19.

Michael Klompas

Papers

Review: does chlorhexidine prevent ventilator-associated pneumonia?

Small-area estimation for public health surveillance using electronic health record data: reducing the impact of underrepresentation

717: ultrashort-course antibiotics for suspected vap with minimal and stable ventilator settings

Automated chronic disease surveillance and visualization using electronic health record data

Update on Sepsis Epidemiology in the Era of COVID-19