The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness.

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.

Surviving Sepsis Campaign: Research Priorities for Sepsis and Septic Shock.

OBJECTIVE: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. DESIGN: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. METHODS: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (Supplemental Table 1, Supplemental Digital Content 2, http://links.lww.com/CCM/D636) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. RESULTS: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: 1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; 2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; 3) should rapid diagnostic tests be implemented in clinical practice?; 4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; 5) what are the predictors of sepsis long-term morbidity and mortality?; and 6) what information identifies organ dysfunction? CONCLUSIONS: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Adherence to long-acting inhaled therapies among patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Long-acting inhaled medications are an important component of the treatment of patients with chronic obstructive pulmonary disease (COPD), yet few studies have examined the determinants of medication adherence among this patient population. OBJECTIVE: We sought to identify factors associated with adherence to long-acting beta-agonists (LABA) and inhaled corticosteroids (ICS) among patients with COPD. METHODS: We performed secondary analysis of baseline data collected in a randomized trial of 376 Veterans with spirometrically confirmed COPD. We used electronic pharmacy records to assess adherence, defined as a medication possession ratio of ≥0.80. We investigated the following exposures: patient characteristics, disease severity, medication regimen complexity, health behaviors, confidence in self-management, and perceptions of provider skill. We performed multivariable logistic regression, clustered by provider, to estimate associations. RESULTS: Of the 167 patients prescribed LABA, 54% (n = 90) were adherent to therapy while only 40% (n = 74) of 184 the patients prescribed ICS were adherent. Higher adherence to LABA and ICS was associated with patient perception of their provider as being an "expert" in diagnosing and managing lung disease [For LABA: OR = 21.70 (95% CI 6.79, 69.37); For ICS OR = 7.93 (95% CI 1.71, 36.67)]. Factors associated with adherence to LABA, but not ICS, included: age, education, race, COPD severity, smoking status, and confidence in self-management. CONCLUSIONS: Adherence to long-acting inhaled medications among patients with COPD is poor, and determinants of adherence likely differ by medication class. Patient perception of clinician expertise in lung disease was the factor most highly associated with adherence to long-acting therapies.

Do windy areas have more wind turbines: An empirical analysis of wind installed capacity in Native tribal nations.

The decarbonization of the electricity sector is leading to a substantial increase in the demand for wind energy. Will tribal nations, which account for 7.8% of utility-scale wind capacity, benefit from this policy shift? To examine why tribal nations vary in translating wind energy potential into wind installed capacity, we have constructed an original dataset of the potential as well as the location of wind turbines across tribal nations. Our statistical analysis of 286 tribal nations suggests that wind energy potential is not associated with wind installed capacity. Instead, casino square footage, a proxy for tribal nation's administrative capacity and business acumen, is associated with wind installed capacity. Political orientation plays a role as well: tribal nations are more likely to have wind installed capacity when they value tribal sovereignty. While tribes suffering from natural disasters do not install more wind turbines, those receiving federal grants for wind energy projects, and located in states that already have a substantial number of wind turbines, are more apt to have wind turbines. Surprisingly, tribes located in states with renewable portfolio standards do not show an association with installed wind turbines capacity.

The Evolution of the National Special Pathogen System of Care.

Infectious disease outbreaks and pandemics have repeatedly threatened public health and have severely strained healthcare delivery systems throughout the past century. Pathogens causing respiratory illness, such as influenza viruses and coronaviruses, as well as the highly communicable viral hemorrhagic fevers, pose a large threat to the healthcare delivery system in the United States and worldwide. Through the Hospital Preparedness Program, within the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, a nationwide Regional Ebola Treatment Network (RETN) was developed, building upon a state- and jurisdiction-based tiered hospital approach. This network, spearheaded by the National Emerging Special Pathogens Training and Education Center, developed a conceptual framework and plan for the evolution of the RETN into the National Special Pathogen System of Care (NSPS). Building the NSPS strategy involved reviewing the literature and the initial framework used in forming the RETN and conducting an extensive stakeholder engagement process to identify gaps and develop solutions. From this, the NSPS strategy and implementation plan were formed. The resulting NSPS strategy is an ambitious but critical effort that will have impacts on the mitigation efforts of special pathogen threats for years to come.

Development and Validation of a Machine Learning Model to Estimate Bacterial Sepsis Among Immunocompromised Recipients of Stem Cell Transplant.

Importance: Sepsis disproportionately affects recipients of allogeneic hematopoietic cell transplant (allo-HCT), and timely detection is crucial. However, the atypical presentation of sepsis within this population makes detection challenging, and existing clinical sepsis tools have limited prognostic value among this high-risk population. Objective: To develop a full risk factor (demographic, transplant, clinical, and laboratory factors) and clinical factor-specific automated bacterial sepsis decision support tool for recipients of allo-HCT with potential bloodstream infections (PBIs). Design, Setting, and Participants: This prognostic study used data from adult recipients of allo-HCT transplanted at the Fred Hutchinson Cancer Research Center, Seattle, Washington, between June 2010 and June 2019 randomly divided into 70% modeling and 30% validation data sets. Tools were developed using the area under the curve (AUC) optimized SuperLearner, and their performance was compared with existing clinical sepsis tools: National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), and Systemic Inflammatory Response Syndrome (SIRS), using the validation data set. Data were analyzed between January and October of 2020. Main Outcomes and Measures: The primary outcome was high-sepsis risk bacteremia (culture confirmed gram-negative species, Staphylococcus aureus, or Streptococcus spp bacteremia), and the secondary outcomes were 10- and 28-day mortality. Tool discrimination and calibration were examined using accuracy metrics and expected vs observed probabilities. Results: Between June 2010 and June 2019, 1943 recipients of allo-HCT received their first transplant, and 1594 recipients (median [interquartile range] age at transplant, 54 [43-63] years; 911 [57.2%] men; 1242 individuals [77.9%] identifying as White) experienced at least 1 PBI. Of 8131 observed PBIs, 238 (2.9%) were high-sepsis risk bacteremia. Compared with high-sepsis risk bacteremia, the full decision support tool had the highest AUC (0.85; 95% CI, 0.81-0.89), followed by the clinical factor-specific tool (0.72; 95% CI, 0.66-0.78). SIRS had the highest AUC of existing tools (0.64; 95% CI, 0.57-0.71). The full decision support tool had the highest AUCs for PBIs identified in inpatient (0.82; 95% CI, 0.76-0.89) and outpatient (0.82; 95% CI, 0.75-0.89) settings and for 10-day (0.85; 95% CI, 0.79-0.91) and 28-day (0.80; 95% CI, 0.75-0.84) mortality. Conclusions and Relevance: These findings suggest that compared with existing tools and the clinical factor-specific tool, the full decision support tool had superior prognostic accuracy for the primary (high-sepsis risk bacteremia) and secondary (short-term mortality) outcomes in inpatient and outpatient settings. If used at the time of culture collection, the full decision support tool may inform more timely sepsis detection among recipients of allo-HCT.

Triage of Scarce Critical Care Resources in COVID-19 An Implementation Guide for Regional Allocation: An Expert Panel Report of the Task Force for Mass Critical Care and the American College of Chest Physicians.

Public health emergencies have the potential to place enormous strain on health systems. The current pandemic of the novel 2019 coronavirus disease has required hospitals in numerous countries to expand their surge capacity to meet the needs of patients with critical illness. When even surge capacity is exceeded, however, principles of critical care triage may be needed as a means to allocate scarce resources, such as mechanical ventilators or key medications. The goal of a triage system is to direct limited resources towards patients most likely to benefit from them. Implementing a triage system requires careful coordination between clinicians, health systems, local and regional governments, and the public, with a goal of transparency to maintain trust. We discuss the principles of tertiary triage and methods for implementing such a system, emphasizing that these systems should serve only as a last resort. Even under triage, we must uphold our obligation to care for all patients as best possible under difficult circumstances.

The effects of smoking cessation on the risk of chronic obstructive pulmonary disease exacerbations.

BACKGROUND: Smoking cessation has been demonstrated to reduce the rate of loss of lung function and mortality among patients with mild to moderate chronic obstructive pulmonary disease (COPD). There is a paucity of evidence about the effects of smoking cessation on the risk of COPD exacerbations. OBJECTIVE: We sought to examine whether smoking status and the duration of abstinence from tobacco smoke is associated with a decreased risk of COPD exacerbations. DESIGN: We assessed current smoking status and duration of smoking abstinence by self-report. Our primary outcome was either an inpatient or outpatient COPD exacerbation. We used Cox regression to estimate the risk of COPD exacerbation associated with smoking status and duration of smoking cessation. PARTICIPANTS: We performed a cohort study of 23,971 veterans who were current and past smokers and had been seen in one of seven Department of Veterans Affairs (VA) primary care clinics throughout the US. MEASUREMENTS AND MAIN RESULTS: In comparison to current smokers, ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socio-economic status (adjusted HR 0.78, 95% CI 0.75-0.87). The magnitude of the reduced risk was dependent on the duration of smoking abstinence (adjusted HR: quit < 1 year, 1.04; 95% CI 0.87-1.26; 1-5 years 0.93, 95% CI 0.79-1.08; 5-10 years 0.84, 95% CI 0.70-1.00; > or = 10 years 0.65, 95% CI 0.58-0.74; linear trend <0.001). CONCLUSIONS: Smoking cessation is associated with a reduced risk of COPD exacerbations, and the described reduction is dependent upon the duration of abstinence.

Characterising variation in composition and activation criteria of rapid response and cardiac arrest teams: a survey of Medicare participating hospitals in five American states.

OBJECTIVES: To characterise the variation in composition, leadership, and activation criteria of rapid response and cardiac arrest teams in five north-eastern states of the USA. DESIGN: Cross-sectional study consisting of a voluntary 46-question survey of acute care hospitals in north-eastern USA. SETTING: Acute care hospitals in New York, New Jersey, Rhode Island, Vermont, and Pennsylvania. PARTICIPANTS: Surveys were completed by any member of the rapid response team (RRT) with a working knowledge of team composition and function. Participants were all Medicare-participating acute care hospitals, including teaching and community hospitals as well as hospitals from rural, urban and suburban areas. RESULTS: Out of 378 hospitals, contacts were identified for 303, and 107 surveys were completed. All but two hospitals had an RRT, 70% of which changed members daily. The most common activation criteria were clinical concern (95%), single vital sign abnormalities (77%) and early warning score (59%). Eighty one per cent of hospitals had a dedicated cardiac arrest team.RRT composition varied widely, with respiratory therapists, critical care nurses, physicians and nurse managers being the most likely to attend (89%, 78%, 64% and 51%, respectively). Consistent presence of critical care physicians was uncommon and both cardiac arrest teams and teams were frequently led by trainee physicians, often without senior supervision. CONCLUSIONS: As the largest study to date in the USA, we have demonstrated wide heterogeneity, rapid team turnover and a lack of senior supervision of RRT and cardiac arrest teams. These factors likely contribute to the mixed results seen in studies of RRTs.

Rapid Response and Cardiac Arrest Teams: A Descriptive Analysis of 103 American Hospitals.

Despite improvements in the management of in-hospital cardiac arrest over the past decade, in-hospital cardiac arrest continues to be associated with poor prognosis. This has led to the development of rapid response systems, hospital-wide efforts to improve patient outcomes by centering on prompt identification of decompensating patients, expert clinical management, and continuous quality improvement of processes of care. The rapid response system may include cardiac arrest teams, which are centered on identification and treatment of patients with in-hospital cardiac arrest. However, few evidence-based guidelines exist to guide the formation of such teams, and the degree of their variation across the United States has not been well described. DESIGN: Descriptive cross-sectional, internet-based survey. SETTING: Cohort of preidentified clinicians involved in their hospital's adult rapid response system across the United States. SUBJECTS: Clinicians who had been identified by study team members using personal and professional contacts over a 7-month period from June 2018 to December 2018. INTERVENTIONS: An 80-item survey was developed by the investigators. It sought information on the afferent (identification and notification of providers) and efferent (response of providers to patient) limbs of the rapid response system, as well as management of patients post in-hospital cardiac arrest. MEASUREMENTS AND MAIN RESULTS: One-hundred fourteen surveys were distributed. Of these, 109 (96%) were completed. Six were duplicates and were excluded, leaving a total of 103 surveys from 103 hospitals in 30 states. Seventy-six percent of hospitals were academic, 30% were large hospitals (> 750 inpatient beds), and 58% had large ICUs (> 50 ICU beds). We found wide variation in the structure and function in both the afferent and efferent limbs of the rapid response system. The majority of hospitals had a rapid response team and a cardiac arrest team. Most rapid response teams contained a provider, a critical care nurse, and a respiratory therapist. In hospitals with training programs in internal medicine, anesthesia, emergency medicine, or critical care, 45% of rapid response teams and 75% of cardiac arrest teams were led by trainees, with inconsistent attending presence. Targeted temperature management and coronary catheterization were widely used post in-hospital cardiac arrest, but indications varied considerably. CONCLUSIONS: We have demonstrated substantial variation in the structure and function of rapid response systems as well as in management of patients during and after in-hospital cardiac arrest.

The association between alcohol consumption and risk of COPD exacerbation in a veteran population.

BACKGROUND: Alcohol has been associated with COPD-related mortality but has not yet been demonstrated to be an independent risk factor for COPD exacerbation. Our objective was to evaluate the association between alcohol consumption and the subsequent risk of COPD exacerbation. METHODS: A prospective cohort study of general medicine outpatients seen at one of seven Veterans Affairs (VA) medical centers who returned health screening questionnaires. Three screening questionnaires, AUDIT-C (0 to 12 points), CAGE (0 to 4 points), and a single item about the frequency of drinking six or more drinks on an occasion (binge drinking), were used to classify alcohol consumption. The main outcome, COPD exacerbation, was based on primary VA discharge diagnosis (International Classification of Diseases, Ninth Revision) or outpatient diagnosis of COPD accompanied by prescriptions for either antibiotics or prednisone within 2 days. RESULTS: Among the 30,503 patients followed up for a median of 3.35 years, those patients with AUDIT-C scores > or = 6, CAGE scores > or = 2, or who reported binge drinking at least weekly were at an increased risk of COPD exacerbation in age-adjusted analysis. Adjusted hazard ratios were 1.4 (95% confidence interval [CI], 1.1 to 1.7) for AUDIT-C score > or = 6, 1.4 (95% CI, 1.3 to 1.5) for CAGE score > or = 2, and 1.6 (95% CI, 1.2 to 2.2) for those who reported binge drinking daily or almost daily. However, with adjustment for measures of tobacco use, the association between alcohol consumption and increased risk of COPD exacerbation was no longer evident. CONCLUSIONS: Alcohol consumption, whether quantified by AUDIT-C, CAGE score, or binge drinking, was not associated with an increased risk of COPD exacerbation independent of tobacco use.

Surviving sepsis campaign: research priorities for sepsis and septic shock.

OBJECTIVE: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. DESIGN: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. METHODS: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. RESULTS: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction? CONCLUSIONS: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Risk factors for group B streptococcal genitourinary tract colonization in pregnant women.

OBJECTIVE: To identify risk factors for group B streptococcus (GBS) colonization in pregnancy, hypothesizing that health care workers may have increased risk. METHODS: Population-based, case-control study comparing 40,459 cases of GBS colonization, identified from Washington State birth certificate data linked to hospital discharge data for live births between 1997 and 2002, with 84,268 controls matched by year of delivery by multivariable logistic regression. RESULTS: After adjustment for confounders, the following characteristics were independently associated with increased maternal GBS colonization: health care occupation (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.07-1.38), black race (OR 1.54, 95% CI 1.36-1.74), overweight (OR 1.07, 95% CI 1.01-1.12), obesity (OR 1.20, 95% CI 1.13-1.28), severe obesity (OR 1.45, 95% CI 1.28-1.63), median income greater than lowest quintile (OR 1.29, 95% CI 1.20-1.39 for fifth versus first quintile), some high school education (OR 1.21, 95% CI 1.05-1.40), high school graduate (OR 1.35, 95% CI 1.16-1.56), and adequate prenatal care (OR 1.14, 95% CI 1.06-1.24). Hispanic women (OR 0.88, 95% CI 0.80-0.96) and smokers (OR for 1-10 cigarettes per day 0.90, 95% CI 0.83-0.97) had a decreased odds of colonization. CONCLUSION: Health care workers, black women, and women with high body mass index may be at greater risk of GBS colonization in pregnancy. However, any increases in risk are modest and the association between a health care occupation and GBS colonization needs to be investigated further.