The evolution of post-intensive care syndrome

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Discrete Optimization for Interpretable Study Populations and Randomization Inference in an Observational Study of Severe Sepsis Mortality

Motivated by an observational study of the effect of hospital ward versus intensive care unit admission on severe sepsis mortality, we develop methods to address two common problems in observational studies: (1) when there is a lack of covariate overlap between the treated and control groups, how to define an interpretable study population wherein inference can be conducted without extrapolating with respect to important variables; and (2) how to use randomization inference to form confidence intervals for the average treatment effect with binary outcomes. Our solution to problem (1) incorporates existing suggestions in the literature while yielding a study population that is easily understood in terms of the covariates themselves, and can be solved using an efficient branch-and-bound algorithm. We address problem (2) by solving a linear integer program to utilize the worst case variance of the average treatment effect among values for unobserved potential outcomes that are compatible with the null hypothesis. Our analysis finds no evidence for a difference between the sixty day mortality rates if all individuals were admitted to the ICU and if all patients were admitted to the hospital ward among less severely ill patients and among patients with cryptic septic shock. We implement our methodology in R, providing scripts in the supplementary material

Acute respiratory distress syndrome as a precursor to post-intensive care syndrome

More than 6 million patients are cared for in an intensive care unit annually in the United States, and millions more internationally. Acute respiratory failure (ARF) is a common indication for intensive care unit admission, one that afflicts more than half of critically ill patients. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening form of ARF. With advances in care over the last 50 years, the majority of ARF and ARDS patients survive. The survivorship literature is largely one that describes functional impairments and reduced quality of life after critical illness. In this review article, we put forth the concept that ARDS is a precursor to post-intensive care syndrome, defined as new or worsening impairments in cognition, mental health, and/or physical health after critical illness. This "precursor" paradigm is suggested as a means to a better end for patients with ARDS, by detailing care provisions and strategies to optimize short-term and long-term outcomes

Randomization Inference and Sensitivity Analysis for Composite Null Hypotheses With Binary Outcomes in Matched Observational Studies

We present methods for conducting hypothesis testing and sensitivity analyses for composite null hypotheses in matched observational studies when outcomes are binary. Causal estimands discussed include the causal risk difference, causal risk ratio, and the effect ratio. We show that inference under the assumption of no unmeasured confounding can be performed by solving an integer linear program, while inference allowing for unmeasured confounding of a given strength requires solving an integer quadratic program. Through simulation studies and data examples, we demonstrate that our formulation allows these problems to be solved in an expedient manner even for large datasets and for large strata. We further exhibit that through our formulation, one can assess the impact of various assumptions about the potential outcomes on the performed inference. R scripts are provided that implement our methods. Supplementary materials for this article are available online. Keywords: Causal inference; Causal risk; Effect ratio; Integer programming; Sensitivity analysi

Temporal Trends in Incidence, Sepsis-Related Mortality, and Hospital-Based Acute Care After Sepsis.

OBJECTIVES: A growing number of patients survive sepsis hospitalizations each year and are at high risk for readmission. However, little is known about temporal trends in hospital-based acute care (emergency department treat-and-release visits and hospital readmission) after sepsis. Our primary objective was to measure temporal trends in sepsis survivorship and hospital-based acute care use in sepsis survivors. In addition, because readmissions after pneumonia are subject to penalty under the national readmission reduction program, we examined whether readmission rates declined after sepsis hospitalizations related to pneumonia. DESIGN AND SETTING: Retrospective, observational cohort study conducted within an academic healthcare system from 2010 to 2015. PATIENTS: We used three validated, claims-based approaches to identify 17,256 sepsis or severe sepsis hospitalizations to examine trends in hospital-based acute care after sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 2010 to 2015, sepsis as a proportion of medical and surgical admissions increased from 3.9% to 9.4%, whereas in-hospital mortality rate for sepsis hospitalizations declined from 24.1% to 14.8%. As a result, the proportion of medical and surgical discharges at-risk for hospital readmission after sepsis increased from 2.7% to 7.8%. Over 6 years, 30-day hospital readmission rates declined modestly, from 26.4% in 2010 to 23.1% in 2015, driven largely by a decline in readmission rates among survivors of nonsevere sepsis, and nonpneumonia sepsis specifically, as the readmission rate of severe sepsis survivors was stable. The modest decline in 30-day readmission rates was offset by an increase in emergency department treat-and-release visits, from 2.8% in 2010 to a peak of 5.4% in 2014. CONCLUSIONS: Owing to increasing incidence and declining mortality, the number of sepsis survivors at risk for hospital readmission rose significantly between 2010 and 2015. The 30-day hospital readmission rates for sepsis declined modestly but were offset by a rise in emergency department treat-and-release visits

Hypoxia alters posterior cingulate cortex metabolism during a memory task: a 1H fMRS study

Environmental hypoxia (fraction of inspired oxygen (F(I)O(2)) ~ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required. To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (F(I)O(2) = 0.209) and after two hours of poikilocapnic hypoxia (F(I)O(2) = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia. Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046). We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF

Return to employment following critical illness and its association with psychosocial outcomes: a systematic review and meta-analysis

Background: Patients who survive critical illness have well-defined physical, cognitive, emotional, and familial problems. However, the impact of these problems on survivors’ ability to return to work and other financial outcomes are less clear. Objective: To determine the financial and employment consequences of an intensive care stay, we performed a systematic review and meta-analysis. Data Source We searched MEDLINE, Embase, and CINAHL (1970-2018). All study designs except narrative reviews, case reports, case control studies, and editorials were included. Included studies assessed financial outcomes in patients admitted to critical care, and their caregivers. Data Extraction: Two reviewers independently applied eligibility criteria, assessed quality and extracted data. The primary outcome reported was return to employment among those previously employed. We also examined financial stress and the impact financial outcomes had on quality of life and psychosocial health. Data Synthesis: From 5765 eligible abstracts, 51 studies were included, which provided data on 858 caregivers/family members and 7267 patients. Forty-two papers reported on patient outcomes and 11 papers on caregiver/family members. Two papers included data from both patients and caregivers/family members. Return to employment was the most commonly reported financial outcome for critical care survivors. The pooled estimate for return to employment—among those who were employed prior to critical illness—was 33% (95% CI: 21%-48%), 55% (95% CI: 45%-64%) and 56% (95% CI: 45%-66%) at 3, 6, and 12 months, respectively. Across the studies included in this review, there was a positive association with psychosocial health if patients returned to employment. This included improved health related quality of life and fewer depressive symptoms. With caregivers/family members, six studies reported changes to employment such as reduced hours and lost earnings. Conclusions: Following critical illness, many patients who were previously employed do not return to work, even one year later. This new job loss is associated with worse health related quality of life amongst survivors and worse psychological function amongst survivors and caregivers/family members. More interventional research is required to understand how best to support employability after critical illness