Postseptic Cognitive Impairment and Expression of APOE in Peripheral Blood: The Cognition After SepsiS (CASS) Observational Pilot Study.

BACKGROUND: Cognitive impairment after sepsis is an important clinical problem. Determinants of postseptic cognitive impairment are not well understood. We thus undertook a systems biology approach to exploring a possible role for apolipoprotein E (APOE) in postseptic cognitive impairment. DESIGN: Prospective, observational cohort. SETTING: Intermountain Medical Center, a tertiary referral center in Utah. PATIENTS/PARTICIPANTS: Patients with sepsis admitted to study intensive care units. INTERVENTIONS: None. METHODS: We obtained peripheral blood for deep sequencing of RNA and followed up survivors at 6 months with a battery of cognitive instruments. We defined cognitive impairment based on the 6-month Hayling test of executive function. In our primary analysis, we employed weighted network analysis. Secondarily, we compared variation in gene expression between patients with normal versus impaired cognition. MEASUREMENTS AND MAIN RESULTS: We enrolled 40 patients, of whom 34 were follow-up eligible and 31 (91%) completed follow-up; 1 patient's RNA sample was degraded-the final analytic cohort was 30 patients. Mean Hayling test score was 5.8 (standard deviation 1.1), which represented 20% with impaired executive function. The network module containing APOE was dominated by low-expression genes, with no association on primary analysis (P = .8). Secondary analyses suggested several potential lines of future investigation, including oxidative stress. CONCLUSIONS: In this prospective pilot cohort, executive dysfunction affected 1 in 5 survivors of sepsis. The APOE gene was sparsely transcribed in peripheral leukocytes and not associated with cognitive impairment. Future lines of research are suggested.

Impact of Critical Illness on Resource Utilization: A Comparison of Use in the Year Before and After ICU Admission.

OBJECTIVES: Increasingly, patients admitted to an ICU survive to hospital discharge; many with ongoing medical needs. The full impact of an ICU admission on an individual's resource utilization and survivorship trajectory in the United States is not clear. We sought to compare healthcare utilization among ICU survivors in each year surrounding an ICU admission. DESIGN: Retrospective cohort of patients admitted to an ICU during one calendar year (2012) in a multipayer healthcare system. We assessed mortality, hospital readmissions (categorized by ambulatory care sensitive conditions and emergency department), and outpatient visits. We compared the proportion of patients with visits during the pre-ICU year versus the post-ICU year. PATIENTS: People admitted to an Intermountain healthcare ICU for greater than 48 hours in the year 2012 INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: Among 4,074 ICU survivors, 45% had increased resource utilization. Readmission rates at 30-day, 90-day, and 1-year were 15%, 26%, and 43%. The proportion of patients with a hospital admission increased significantly in the post-ICU period (43% vs 29%; p < 0.001). Of patients with a readmission in the post-ICU period, 24% were ambulatory care sensitive condition. Patients with increased utilization differed by socioeconomic status, insurance type, and severity of illness. Sixteen percent of patients had either an emergency department or inpatient admission, but no outpatient visits during the post-ICU period. CONCLUSIONS: An ICU admission is associated with increased resource utilization including hospital readmissions, with many due to an ambulatory care sensitive condition. Lower socioeconomic status and higher severity of illness are associated with increased resource utilization. After an ICU visit patients seem to use hospital resources over outpatient resources. Interventions to improve and coordinate care after ICU discharge are needed.

Effects of sprint interval training on cardiorespiratory fitness while in a hyperbaric oxygen environment.

Objectives: Hyperbaric oxygen (HBO2) exposure may enhance cardiorespiratory fitness. Exercise training and HBO2 exposure stimulate mitochondrial biogenesis, increase capillary density, and induce adaptive antioxidant mechanisms. We hypothesized that an exercise regimen of sprint interval training (SIT) while breathing HBO2 would lead to a greater improvement in exercise performance compared to the same training breathing ambient air. Methods: Healthy long-term intermediate-altitude residents, ages 20-39 years, with normal spirometry and cardiorespiratory fitness were randomized to two groups: one performing six sessions of a SIT regimen over two weeks in a hyperbaric chamber (1.4 ATA [141.9 kPa], FiO2=1.0); the other performing under ambient pressure conditions (0.85 ATA [86.1 kPa], FiO2=0.21). Training effect was evaluated by comparing incremental cycle ergometry cardiopulmonary exercise testing before and after the training regimen. The primary outcome measure was peak oxygen consumption (V̇O2), while secondary outcomes included additional exercise parameters. The effect of study group on exercise parameters was assessed using two-factor repeated measures ANOVA. Results: Of 58 participants randomized, 49 completed the training program and all cardiopulmonary exercise tests (n=23 HBO2, n=26 ambient). Both groups experienced an increase in peak V̇O2: 8.1% HBO2 and 7.1% ambient; the differences were not significant (p=0.50). Secondary parameters of peak work rate and peak V̇E experienced a significantly higher change in the HBO2 group compared to the ambient group (p=0.05 and p=0.03, respectively). Conclusion: Cardiorespiratory fitness improved after a two-week SIT regimen, but improvement in peak V̇O2 was not significantly different between ambient and HBO2 groups.

Randomized Feasibility Trial of a Low Tidal Volume-Airway Pressure Release Ventilation Protocol Compared With Traditional Airway Pressure Release Ventilation and Volume Control Ventilation Protocols.

OBJECTIVES: Low tidal volume (= tidal volume ≤ 6 mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable and can exceed tidal volume breaths of low tidal volume-volume control. We evaluate the application of a low tidal volume-compatible airway pressure release ventilation protocol that manages release volumes on both clinical and feasibility endpoints. DESIGN: We designed a prospective randomized trial in patients with acute hypoxemic respiratory failure. We randomized patients to low tidal volume-volume control, low tidal volume-airway pressure release ventilation, and traditional airway pressure release ventilation with a planned enrollment of 246 patients. The study was stopped early because of low enrollment and inability to consistently achieve tidal volumes less than 6.5 mL/kg in the low tidal volume-airway pressure release ventilation arm. Although the primary clinical study endpoint was PaO2/FIO2 on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms. SETTING: Four Intermountain Healthcare tertiary ICUs. PATIENTS: Adult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation. INTERVENTIONS: Low tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation. MEASUREMENTS AND MAIN RESULTS: We observed wide variability and higher tidal (release for airway pressure release ventilation) volumes in both airway pressure release ventilation (8.6 mL/kg; 95% CI, 7.8-9.6) and low tidal volume-airway pressure release ventilation (8.0; 95% CI, 7.3-8.9) than volume control (6.8; 95% CI, 6.2-7.5; p = 0.005) with no difference between airway pressure release ventilation and low tidal volume-airway pressure release ventilation (p = 0.58). Recognizing the limitations of small sample size, we observed no difference in 52 patients in day 3 PaO2/ FIO2 (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax. CONCLUSIONS: Airway pressure release ventilation resulted in release volumes often exceeding 12 mL/kg despite a protocol designed to target low tidal volume ventilation. Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway pressure release ventilation is not feasible at this time in the absence of an explicit, generalizable, and reproducible low tidal volume-airway pressure release ventilation protocol.

Acute Physiologic Stress and Subsequent Anxiety Among Family Members of ICU Patients.

OBJECTIVES: The ICU is a complex and stressful environment and is associated with significant psychologic morbidity for patients and their families. We sought to determine whether salivary cortisol, a physiologic measure of acute stress, was associated with subsequent psychologic distress among family members of ICU patients. DESIGN: This is a prospective, observational study of family members of adult ICU patients. SETTING: Adult medical and surgical ICU in a tertiary care center. SUBJECTS: Family members of ICU patients. INTERVENTIONS: Participants provided five salivary cortisol samples over 24 hours at the time of the patient ICU admission. The primary measure of cortisol was the area under the curve from ground; the secondary measure was the cortisol awakening response. Outcomes were obtained during a 3-month follow-up telephone call. The primary outcome was anxiety, measured by the Hospital Anxiety and Depression Scale-Anxiety. Secondary outcomes included depression and posttraumatic stress disorder. MEASUREMENTS AND MAIN RESULTS: Among 100 participants, 92 completed follow-up. Twenty-nine participants (32%) reported symptoms of anxiety at 3 months, 15 participants (16%) reported depression symptoms, and 14 participants (15%) reported posttraumatic stress symptoms. In our primary analysis, cortisol level as measured by area under the curve from ground was not significantly associated with anxiety (odds ratio, 0.94; p = 0.70). In our secondary analysis, however, cortisol awakening response was significantly associated with anxiety (odds ratio, 1.08; p = 0.02). CONCLUSIONS: Roughly one third of family members experience anxiety after an ICU admission for their loved one, and many family members also experience depression and posttraumatic stress. Cortisol awakening response is associated with anxiety in family members of ICU patients 3 months following the ICU admission. Physiologic measurements of stress among ICU family members may help identify individuals at particular risk of adverse psychologic outcomes.

Association of hospice utilization and publicly reported outcomes following hospitalization for pneumonia or heart failure: a retrospective cohort study.

BACKGROUND: The Center for Medicare and Medicaid Services (CMS) and the Hospital Quality Alliance began collecting and reporting United States hospital performance in the treatment of pneumonia and heart failure in 2008. Whether the utilization of hospice might affect CMS-reported mortality and readmission rates is not known. METHODS: Hospice utilization (mean days on hospice per decedent) for 2012 from the Dartmouth Atlas (a project of the Dartmouth Institute that reports a variety of public health and policy-related statistics) was merged with hospital-level 30-day mortality and readmission rates for pneumonia and heart failure from CMS. The association between hospice use and outcomes was analyzed with multivariate quantile regression controlling for quality of care metrics, acute care bed availability, regional variability and other measures. RESULTS: 2196 hospitals reported data to both CMS and the Dartmouth Atlas in 2012. Higher rates of hospice utilization were associated with lower rates of 30-day mortality and readmission for pneumonia but not for heart failure. Higher quality of care was associated with lower rates of mortality for both pneumonia and heart failure. Greater acute care bed availability was associated with increased readmission rates for both conditions (p < 0.05 for all). CONCLUSIONS: Higher rates of hospice utilization were associated with lower rates of 30-day mortality and readmission for pneumonia as reported by CMS. While causality is not established, it is possible that hospice referrals might directly affect CMS outcome metrics. Further clarification of the relationship between hospice referral patterns and publicly reported CMS outcomes appears warranted.

Understanding patient outcomes after acute respiratory distress syndrome: identifying subtypes of physical, cognitive and mental health outcomes.

PURPOSE: With improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding survivors' posthospitalisation outcomes is increasingly important. However, little is known regarding associations among physical, cognitive and mental health outcomes. Identification of outcome subtypes may advance understanding of post-ARDS morbidities. METHODS: We analysed baseline variables and 6-month health status for participants in the ARDS Network Long-Term Outcomes Study. After division into derivation and validation datasets, we used weighted network analysis to identify subtypes from predictors and outcomes in the derivation dataset. We then used recursive partitioning to develop a subtype classification rule and assessed adequacy of the classification rule using a kappa statistic with the validation dataset. RESULTS: Among 645 ARDS survivors, 430 were in the derivation and 215 in the validation datasets. Physical and mental health status, but not cognitive status, were closely associated. Four distinct subtypes were apparent (percentages in the derivation cohort): (1) mildly impaired physical and mental health (22% of patients), (2) moderately impaired physical and mental health (39%), (3) severely impaired physical health with moderately impaired mental health (15%) and (4) severely impaired physical and mental health (24%). The classification rule had high agreement (kappa=0.89 in validation dataset). Female Latino smokers had the poorest status, while male, non-Latino non-smokers had the best status. CONCLUSIONS: We identified four post-ARDS outcome subtypes that were predicted by sex, ethnicity, pre-ARDS smoking status and other baseline factors. These subtypes may help develop tailored rehabilitation strategies, including investigation of combined physical and mental health interventions, and distinct interventions to improve cognitive outcomes.

Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy.

OBJECTIVES: Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate, < 80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock. DESIGN: Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013. SETTING: One large academic referral hospital and two community hospitals. PATIENTS: Adult patients with septic shock requiring vasopressors. INTERVENTION: None. MEASUREMENTS: Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score. RESULTS: We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p < 0.001). Relatively bradycardic patients were older (65 vs 60 yr; p < 0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p < 0.001). CONCLUSIONS: Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.

Application of a simplified definition of diastolic function in severe sepsis and septic shock.

BACKGROUND: Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. METHODS: In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. RESULTS: We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. CONCLUSIONS: A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

Association of left ventricular longitudinal strain with central venous oxygen saturation and serum lactate in patients with early severe sepsis and septic shock.

INTRODUCTION: In septic shock, assessment of cardiac function often relies on invasive central venous oxygen saturation (ScvO2). Ventricular strain is a non-invasive method of assessing ventricular wall deformation and may be a sensitive marker of heart function. We hypothesized that it may have a relationship with ScvO2 and lactate. METHODS: We prospectively performed transthoracic echocardiography in patients with severe sepsis or septic shock and measured (1) left ventricular longitudinal strain from a four-chamber view and (2) ScvO2. We excluded patients for whom image quality was inadequate or for whom ScvO2 values were unobtainable. We determined the association between strain and ScvO2 with logistic and linear regression, using covariates of mean arterial pressure, central venous pressure, and vasopressor dose. We determined the association between strain and lactate. We considered strain greater than -17% as abnormal and strain greater than -10% as severely abnormal. RESULTS: We studied 89 patients, 68 of whom had interpretable images. Of these patients, 42 had measurable ScvO2. Sixty percent of patients had abnormal strain, and 16% had severely abnormal strain. Strain is associated with low ScvO2 (linear coefficient -1.05, p =0.006; odds ratio 1.23 for ScvO2 <60%, p =0.016). Patients with severely abnormal strain had significantly lower ScvO2 (56.1% vs. 67.5%, p <0.01) and higher lactate (2.7 vs. 1.9 mmol/dl, p =0.04) than those who did not. Strain was significantly different between patients, based on a threshold ScvO2 of 60% (-13.7% vs. -17.2%, p =0.01) but not at 70% (-15.0% vs. -18.2%, p =0.08). CONCLUSIONS: Left ventricular strain is associated with low ScvO2 and hyperlactatemia. It may be a non-invasive surrogate for adequacy of oxygen delivery during early severe sepsis or septic shock.

Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: a randomized trial.

Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment. Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled. Conclusions from our study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS. This trial was registered at www.clinicaltrials.gov as #NCT02295475.

Prevalence, Characteristics, and Outcomes of Emergency Department Discharge Among Patients With Sepsis.

Importance: Sepsis guidelines and research have focused on patients with sepsis who are admitted to the hospital, but the scope and implications of sepsis that is managed in an outpatient setting are largely unknown. Objective: To identify the prevalence, risk factors, practice variation, and outcomes for discharge to outpatient management of sepsis among patients presenting to the emergency department (ED). Design, Setting, and Participants: This cohort study was conducted at the EDs of 4 Utah hospitals, and data extraction and analysis were performed from 2017 to 2021. Participants were adult ED patients who presented to a participating ED from July 1, 2013, to December 31, 2016, and met sepsis criteria before departing the ED alive and not receiving hospice care. Exposures: Patient demographic and clinical characteristics, health system parameters, and ED attending physician. Main Outcomes and Measures: Information on ED disposition was obtained from electronic medical records, and 30-day mortality data were acquired from Utah state death records and the US Social Security Death Index. Factors associated with ED discharge rather than hospital admission were identified using penalized logistic regression. Variation in ED discharge rates between physicians was estimated after adjustment for potential confounders using generalized linear mixed models. Inverse probability of treatment weighting was used in the primary analysis to assess the noninferiority of outpatient management for 30-day mortality (noninferiority margin of 1.5%) while adjusting for multiple potential confounders. Results: Among 12 333 ED patients with sepsis (median [IQR] age, 62 [47-76] years; 7017 women [56.9%]) who were analyzed in the study, 1985 (16.1%) were discharged from the ED. After penalized regression, factors associated with ED discharge included age (adjusted odds ratio [aOR], 0.90 per 10-y increase; 95% CI, 0.87-0.93), arrival to ED by ambulance (aOR, 0.61; 95% CI, 0.52-0.71), organ failure severity (aOR, 0.58 per 1-point increase in the Sequential Organ Failure Assessment score; 95% CI, 0.54-0.60), and urinary tract (aOR, 4.56 [95% CI, 3.91-5.31] vs pneumonia), intra-abdominal (aOR, 0.51 [95% CI, 0.39-0.65] vs pneumonia), skin (aOR, 1.40 [95% CI, 1.14-1.72] vs pneumonia) or other source of infection (aOR, 1.67 [95% CI, 1.40-1.97] vs pneumonia). Among 89 ED attending physicians, adjusted ED discharge probability varied significantly (likelihood ratio test, P < .001), ranging from 8% to 40% for an average patient. The unadjusted 30-day mortality was lower in discharged patients than admitted patients (0.9% vs 8.3%; P < .001), and their adjusted 30-day mortality was noninferior (propensity-adjusted odds ratio, 0.21 [95% CI, 0.09-0.48]; adjusted risk difference, 5.8% [95% CI, 5.1%-6.5%]; P < .001). Alternative confounder adjustment strategies yielded odds ratios that ranged from 0.21 to 0.42. Conclusions and Relevance: In this cohort study, discharge to outpatient treatment of patients who met sepsis criteria in the ED was more common than previously recognized and varied substantially between ED physicians, but it was not associated with higher mortality compared with hospital admission. Systematic, evidence-based strategies to optimize the triage of ED patients with sepsis are needed.

Right Ventricular Dysfunction in Early Sepsis and Septic Shock.

BACKGROUND: Sepsis is a frequently lethal state, commonly associated with left ventricular (LV) dysfunction. Right ventricular (RV) dysfunction in sepsis is less well understood. RESEARCH QUESTION: In septic patients, how common is RV dysfunction, and is it associated with worse outcomes? STUDY DESIGN AND METHODS: We measured echocardiographic parameters on critically ill patients with severe sepsis or septic shock within the first 24 hours of ICU admission. We defined RV dysfunction as fractional area change (FAC) less than 35% or tricuspid annulus systolic plane excursion (TAPSE) less than 1.6 cm. We defined LV systolic dysfunction as ejection fraction (EF) less than 45% or longitudinal strain greater than -19%. Using logistic regression, we assessed the relationship between 28-day mortality and presence of RV dysfunction and LV systolic dysfunction, controlling for receipt of vasopressors, receipt of fluid, mechanical ventilation, and the acute physiology and chronic health evaluation (APACHE II) score. RESULTS: We studied 393 patients. RV and LV dysfunction were common (48% and 63%, respectively). Mean echocardiographic values were: RV end-diastolic area, 22.4 ± 7.0 cm2; RV end-systolic area, 14.2 ± 6.0 cm2; RV FAC, 38 ± 11%; TAPSE, 1.8 ± .06 cm; RV longitudinal strain, -15.3 ± 6.5%; LV EF, 60% ± 14%; LV longitudinal strain, -16.5% ± 6.0%. Patients with RV dysfunction had higher 28-day mortality (31% vs 16%, P = .001). In our multivariable regression model, RV dysfunction was associated with increased mortality (OR, 3.4; CI, 1.7-6.8; P = .001), and LV systolic dysfunction was not (OR, 0.63; CI, 0.3 -1.2; P = .32) INTERPRETATION: Right ventricular dysfunction is present in nearly half of studied septic patients and is associated with over threefold higher 28-day mortality.

Post-discharge thrombosis and bleeding in medical patients: A novel risk score derived from ubiquitous biomarkers.

BACKGROUND: Some hospitalized medical patients experience venous thromboembolism (VTE) following discharge. Prophylaxis extended beyond hospital discharge (extended duration thromboprophylaxis [EDT]) may reduce this risk. However, EDT is costly and can cause bleeding, so selecting appropriate patients is essential. We formerly reported the performance of a mortality risk prediction score (Intermountain Risk Score [IMRS]) that was minimally predictive of 90-day hospital-associated venous thromboembolism (HA-VTE) and major bleeding (HA-MB). We used the components of the IMRS to calculate de novo risk scores to predict 90-day HA-VTE (HA-VTE IMRS) and major bleeding (HA-MB IMRS). METHODS: From 45 669 medical patients we randomly assigned 30 445 to derive the HA-VTE IMRS and the HA-MB IMRS. Backward stepwise regression and bootstrapping identified predictor covariates from the blood count and basic chemistry. These candidate variables were split into quintiles, and the referent quintile was that with the lowest event rate for HA-VTE and HA-MB; respectively. A clinically relevant rate of HA-VTE and HA-MB was used to inform outcome rates. Performance was assessed in the derivation set of 15 224 patients. RESULTS: The HA-VTE IMRS and HA-MB IMRS area under the receiver operating curve (AUC) in the derivation set were 0.646, and 0.691, respectively. In the validation set, the HA-VTE IMRS and HA-MB IMRS AUCs were 0.60 and 0.643. CONCLUSIONS: Risk scores derived from components of routine labs ubiquitous in clinical care identify patients that are at risk for 90-day postdischarge HA-VTE and major bleeding. This may identify a subset of patients with high HA-VTE risk and low HA-MB risk who may benefit from EDT.

Predicting postdischarge hospital-associated venous thromboembolism among medical patients using a validated mortality risk score derived from common biomarkers.

BACKGROUND: Discharged medical patients are at risk for venous thromboembolism (VTE). It is difficult to identify which discharged patients would benefit from extended duration thromboprophylaxis. The Intermountain Risk Score is a prediction score derived from discrete components of the complete blood cell count and basic metabolic panel and is highly predictive of 1-year mortality. We sought to ascertain if the Intermountain Risk Score might also be predictive of 90-day postdischarge hospital-associated VTE (HA-VTE). METHODS: We applied the Intermountain Risk Score to 60 064 medical patients who survived 90 days after discharge and report predictiveness for HA-VTE. Area under the receiver operating curve analyses were performed. We then assessed whether the Intermountain Risk Score improved prediction of 2 existing VTE risk assessment models. RESULTS: The Intermountain Risk Score poorly predicted HA-VTE (area under the curve = 0.58; 95% confidence interval [CI], 0.56-0.60). Each clinical risk assessment model was superior to the Intermountain Risk Score (UTAH area under the curve, 0.63; Kucher area under the curve, 0.62; Intermountain Risk Score area under the curve, 0.58; P < .001 for each comparison). Adding the Intermountain Risk Score to these scores did not substantially improve the performance of either risk assessment model (UTAH + Intermountain Risk Score, 0.65; Kucher + Intermountain Risk Score, 0.64). CONCLUSION: The Intermountain Risk Score demonstrated poor predictiveness for HA-VTE when compared to existing risk assessment models. Adding the Intermountain Risk Score to existing risk assessment models did not improve upon either risk assessment model alone to justify the added complexity.

Comparative evaluation of the clinical laboratory-based Intermountain risk score with the Charlson and Elixhauser comorbidity indices for mortality prediction.

BACKGROUND: The Charlson and Elixhauser comorbidity indices are mortality predictors often used in clinical, administrative, and research applications. The Intermountain Mortality Risk Scores (IMRS) are validated mortality predictors that use all factors from the complete blood count and basic metabolic profile. How IMRS, Charlson, and Elixhauser relate to each other is unknown. METHODS: All inpatient admissions except obstetric patients at Intermountain Healthcare's 21 adult care hospitals from 2010-2014 (N = 197,680) were examined in a observational cohort study. The most recent admission was a patient's index encounter. Follow-up to 2018 used hospital death records, Utah death certificates, and the Social Security death master file. Three Charlson versions, 8 Elixhauser versions, and 3 IMRS formulations were evaluated in Cox regression and the one of each that was most predictive was used in dual risk score mortality analyses (in-hospital, 30-day, 1-year, and 5-year mortality). RESULTS: Indices with the strongest mortality associations and selected for dual score study were the age-adjusted Charlson, the van Walraven version of the acute Elixhauser, and the 1-year IMRS. For in-hospital mortality, Charlson (c = 0.719; HR = 4.75, 95% CI = 4.45, 5.07), Elixhauser (c = 0.783; HR = 5.79, CI = 5.41, 6.19), and IMRS (c = 0.821; HR = 17.95, CI = 15.90, 20.26) were significant predictors (p<0.001) in univariate analyses. Dual score analysis of Charlson (HR = 1.79, CI = 1.66, 1.92) with IMRS (HR = 13.10, CI = 11.53, 14.87) and of Elixhauser (HR = 3.00, CI = 2.80, 3.21) with IMRS (HR = 11.42, CI = 10.09, 12.92) found significance for both scores in each model. Results were similar for 30-day, 1-year, and 5-year mortality. CONCLUSIONS: IMRS provided the strongest ability to predict mortality, adding to and attenuating the predictive ability of the Charlson and Elixhauser indices whose mortality associations remained statistically significant. IMRS uses common, standardized, objective laboratory data and should be further evaluated for integration into mortality risk evaluations.

Depression and Change in Caregiver Burden Among Family Members of Intensive Care Unit Survivors.

BACKGROUND: Family members of patients in intensive care units may experience psychological distress and substantial caregiver burden. OBJECTIVE: To evaluate whether change in caregiver burden from intensive care unit admission to 3-month follow-up is associated with caregiver depression at 3 months. METHODS: Caregiver burden was assessed at enrollment and 3 months later, and caregiver depression was assessed at 3 months. Depression was measured with the Hospital Anxiety and Depression Score. The primary analysis was the association between depression at 3 months and change in caregiver burden, controlling for a history of caregiver depression. RESULTS: One hundred one participants were enrolled; 65 participants had a surviving loved one and completed 3-month follow-up. At 3-month follow-up, 12% of participants met criteria for depression. Increased caregiver burden over time was significantly associated with depression at follow-up (Fisher exact test, P = .004), although this association was not significant after controlling for self-reported history of depression at baseline (Cochran-Mantel-Haenszel test, P = .23). CONCLUSIONS: Family members are increasingly recognized as a vulnerable population susceptible to negative psychological outcomes after a loved one's admission to the intensive care unit. In this small sample, no significant association was found between change in caregiver burden and depression at 3 months after controlling for baseline depression.

Unanticipated critical findings on echocardiography in septic patients.

BACKGROUND: Echocardiography is increasingly performed among septic patients as a routine part of evaluation and management in the intensive care unit (ICU). The rate of unanticipated critical findings (e.g., severe left or right ventricular dysfunction or pericardial tamponade) on such echocardiograms is unknown. We evaluated a retrospective cohort of septic ICU patients in whom transthoracic echocardiography was performed as a routine part of sepsis management. In addition to identifying critical findings, we defined whether each critical finding was anticipated, and whether the clinical team responded to the critical finding. The primary outcome was rate of unanticipated critical findings, which we hypothesized would occur in fewer than 5% of patients. We also performed an exploratory analysis of the association between unanticipated critical finding and mortality, controlling for severity of illness. RESULTS: We studied 393 patients. Unanticipated critical findings were identified in 5% (95% CI 3-7%) of patients (n = 20). Among the 20 patients with unanticipated critical findings, a response to the unanticipated critical finding was identified in 12 (60%) patients. An unanticipated critical finding was not significantly associated with 28-day mortality when controlling for admission APACHE II (p = 0.27). CONCLUSIONS: Unanticipated critical findings on echocardiograms in septic ICU patients are uncommon. The potential therapeutic relevance of echocardiography to sepsis is more likely related to hemodynamic management than to traditional cardiac diagnoses. Research studies that employ blinded echocardiograms in septic patients may anticipate unblinding for critical findings approximately 1 in every 20 echocardiograms.