Sepsis-Associated Acute Kidney Disease and Long-term Kidney Outcomes

Rationale & Objective: Sepsis-associated acute kidney injury often leads to acute kidney disease (AKD), predisposing patients to long-term complications such as chronic kidney disease (CKD), kidney failure with replacement therapy (KFRT), or mortality. Risk stratification of patients with AKD represents an opportunity to assist with prognostication of long-term kidney complications. Study Design: Single-center retrospective cohort. Setting & Participants: 6,290 critically ill patients admitted to the intensive care unit with severe sepsis or septic shock. Patients were separated into cohorts based on incident acute kidney injury or not, and survivors identified who were alive and free of KFRT up to 90 days. Predictors: AKD stage (0A, 0C, or ≥1) using the last serum creatinine concentration available by discharge or up to 90 days postdischarge. Outcome: Time to development of incident CKD, progression of CKD, KFRT, or death. Analytical Approach: Multivariable Cox proportional hazards models. Results: Patients surviving kidney injury associated with sepsis often fail to return to baseline kidney function by discharge: 577/1,231 (46.9%) with stage 0C or 1 or greater AKD. AKD stage was significantly associated with the composite primary outcome. Stages 0C AKD and 1 or greater AKD were significantly and progressively associated with the primary outcome when compared with stage 0A AKD (adjusted HR [aHR], 1.74; 95% CI, 1.32-2.29, and aHR, 3.25; 95% CI, 2.52-4.20, respectively). Additionally, stage 1 or greater AKD conferred higher risk above stage 0C AKD (aHR, 1.87; 95% CI, 1.44-2.43). CKD incidence or progression and KFRT, more so than mortality, occurred with greater frequency in higher stages of AKD. Limitations: Retrospective design, single center, exclusion of patients with KFRT within 90 days of discharge, potential ascertainment bias, and inability to subclassify above AKD stage 1. Conclusions: Risk stratification using recommended AKD stages at hospital discharge or shortly thereafter associates with the development of long-term kidney outcomes following sepsis-associated acute kidney injury

PHarmacist Avoidance or Reductions in Medical Costs in CRITically Ill Adults: PHARM-CRIT Study

OBJECTIVES: To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions. DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019. SETTING: Community hospitals and academic medical centers in the United States. PARTICIPANTS: ICU clinical pharmacists. INTERVENTIONS: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance. MEASUREMENTS AND MAIN RESULTS: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established sections was adverse drug event prevention (5,777 interventions;$5,822,539 CA), resource utilization (12,630 interventions; $4,491,318), individualization of patient care (29,284 interventions;$9,680,036 cost avoidance), prophylaxis (1,639 interventions; $1,414,465 cost avoidance), hands-on care (1,828 interventions;$1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; $656,110 cost avoidance). Mean cost avoidance was$418 per intervention, $845 per patient day, and$7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is $1,784,302. The potential monetary cost avoidance to pharmacist salary ratio was between$3.3:1 and $9.6:1. CONCLUSIONS: Pharmacist involvement in the care of critically ill patients results in significant avoidance of healthcare costs, particularly in the areas of individualization of patient care, adverse drug event prevention, and resource utilization. The potential monetary cost avoidance to pharmacist salary ratio employing an ICU clinical pharmacist is between$3.3:1 and $9.6:1

Frequency and Types of Healthcare Encounters in the Week Preceding a Sepsis Hospitalization: A Systematic Review

OBJECTIVES: Early recognition and treatment are critical to improving sepsis outcomes. We sought to identify the frequency and types of encounters that patients have with the healthcare system in the week prior to a sepsis hospitalization. DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and the Cochrane Library. STUDY SELECTION: Observational cohort studies of patients hospitalized with sepsis or septic shock that were assessed for an outpatient or emergency department encounter with the healthcare system in the week prior to hospital admission. DATA EXTRACTION: The primary outcome was the proportion of patients with a healthcare encounter in the time period assessed (up to 1 week) prior to a hospitalization with sepsis. DATA SYNTHESIS: Six retrospective observational studies encompassing 6,785,728 sepsis admissions were included for evaluation, ranging from a 263-patient single-center cohort to a large database evaluating 6,731,827 sepsis admissions. The average (unweighted) proportion of patients having an encounter with the healthcare system in the week prior to a sepsis hospitalization was 32.7% and ranged from 10.3% to 52.9%. These encounters commonly involved presentation or potential symptoms of infectious diseases, antibiotic prescriptions, and appeared to increase in frequency closer to a sepsis hospitalization admission. No consistent factors were identified that distinguished a healthcare encounter as more or less likely to precede a sepsis hospitalization in the subsequent week. CONCLUSIONS: Patients that present to the hospital with sepsis are frequently evaluated in the healthcare system in the week prior to admission. Further research is necessary to understand if these encounters offer earlier opportunities for intervention to prevent the transition from infection to sepsis, whether they merely reflect the comorbidities of sepsis patients with a high baseline rate of healthcare encounters, or the declining trajectory of a patient\u27s overall health in response to infection

Serum Renin and Major Adverse Kidney Events in Critically Ill Patients: A Multicenter Prospective Study

BACKGROUND: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. METHODS: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. RESULTS: Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. CONCLUSIONS: In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality

Efficacy and Safety of Vancomycin Loading Doses in Critically Ill Patients with Methicillin-Resistant \u3ci\u3eStaphylococcus aureus\u3c/i\u3e Infection

Background: While vancomycin loading doses may facilitate earlier pharmacokinetic–pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults. Methods: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent. Results: There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences. Conclusion: Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection

Vancomycin Dosing Practices among Critical Care Pharmacists: A Survey of Society of Critical Care Medicine Pharmacists

Introduction: Critically ill patients and their pharmacokinetics present complexities often not considered by consensus guidelines from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Prior surveys have suggested discordance between certain guideline recommendations and reported infectious disease pharmacist practice. Vancomycin dosing practices, including institutional considerations, have not previously been well described in the critically ill patient population. Objectives: To evaluate critical care pharmacists\u27 self-reported vancomycin practices in comparison to the 2009 guideline recommendations and other best practices identified by the study investigators. Methods: An online survey developed by the Research and Scholarship Committee of the Clinical Pharmacy and Pharmacology (CPP) Section of the Society of Critical Care Medicine (SCCM) was sent to pharmacist members of the SCCM CPP Section practicing in adult intensive care units in the spring of 2017. This survey queried pharmacists\u27 self-reported practices regarding vancomycin dosing and monitoring in critically ill adults. Results: Three-hundred and sixty-four responses were received for an estimated response rate of 26%. Critical care pharmacists self-reported largely following the 2009 vancomycin dosing and monitoring guidelines. The largest deviations in guideline recommendation compliance involve consistent use of a loading dose, dosing weight in obese patients, and quality improvement efforts related to systematically monitoring vancomycin-associated nephrotoxicity. Variation exists regarding pharmacist protocols and other practices of vancomycin use in critically ill patients. Conclusion: Among critical care pharmacists, reported vancomycin practices are largely consistent with the 2009 guideline recommendations. Variations in vancomycin dosing and monitoring protocols are identified, and rationale for guideline non-adherence with loading doses elucidated

PHarmacist Avoidance or Reductions in Medical Costs in Patients Presenting the EMergency Department: PHARM-EM Study

Objectives: To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. Design: A multicenter, prospective, observational study was performed between August 2018 and January 2019. Setting: Community and academic hospitals in the United States. Participants: Emergency medicine clinical pharmacists. Interventions: Recommendations classified into one of 38 intervention categories associated with cost avoidance. Measurements and Main Results: Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions;$2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122;$1,787,170), prophylaxis (24; $22,804), hands-on care (3,533;$2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was$538.61 per intervention, $875.60 per patient, and$8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between$1.4:1 and $10.6:1. Conclusions: Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between$1.4:1 and $10.6:1

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure