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Septic shock is a common deadly disease often associated with cardiovascular dysfunction. Left ventricular longitudinal strain (LV LS) has been proposed as a sensitive marker to measure cardiovascular function; however, it is not available universally in standard clinical echocardiograms. We sought to derive a predictive model for LV LS, using machine learning techniques with the hope that we may uncover surrogates for LV LS. We found that left ventricular ejection fraction, tricuspid annular plane systolic excursion, sepsis source, height, mitral valve Tei index, LV systolic dimension, aortic valve ejection time, and peak acceleration rate were all predictive of LV LS in this initial exploratory model. Future modeling work may uncover combinations of these variables which may be powerful surrogates for LV LS and cardiovascular function.

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.

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.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).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.Patient demographic and clinical characteristics, health system parameters, and ED attending physician.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.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.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.

Sepsis is a frequently lethal state, commonly associated with left ventricular (LV) dysfunction. Right ventricular (RV) dysfunction in sepsis is less well understood.In septic patients, how common is RV dysfunction, and is it associated with worse outcomes?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.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 cm

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.

We aimed to describe elderly engagement in recreational activities, their injury patterns, preinjury risks and outcomes.A 16-year retrospective trauma registry review. All trauma patients ≥65 years admitted after injury sustained during sport were evaluated, and compared to a non-sport cohort of elderly trauma patients.During the study period, 9697 admissions age ≥65 were identified. 526 (5%) were sport-related. Compared to the non-sport group, the sport cohort was younger, had fewer medical comorbidities, and was more severely injured. The common sport mechanisms were skiing, offroad vehicle use and bicycling, and common sport injuries involved lower extremity, chest, and head. Sport patients were more often discharged home than non-sport patients (73% vs 36%, p 0.001). There was no difference in ICU or hospital LOS between groups. The hospital mortality rate was 3% in sport and 5% in non-sport patients (p = 0.06).Over time, the number of elderly sport-related trauma patients increased. Our data suggest that being active may improve outcomes after trauma in older adults.

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 an 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.

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.

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.

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.

Practice guidelines recommend against intensive insulin therapy in patients who are critically ill based on trials that had high rates of severe hypoglycemia. Intermountain Healthcare uses a computerized IV insulin protocol that allows choice of blood glucose (BG) targets (80-110 vs 90-140 mg/dL) and has low rates of severe hypoglycemia. We sought to study the effects of BG target on mortality in adult patients in cardiac ICUs that have very low rates of severe hypoglycemia.Critically ill patients receiving IV insulin were treated with either of two BG targets (80-110 vs 90-140 mg/dL). We created a propensity score for BG target using factors thought to have influenced clinicians' choice, and then we performed a propensity score-adjusted regression analysis for 30-day mortality.There were 1,809 patients who met inclusion criteria. Baseline patient characteristics were similar. Median glucose was lower in the 80-110 mg/dL group (104 vs 122 mg/dL, P .001). Severe hypoglycemia occurred at very low rates in both groups (1.16% vs 0.35%, P = .051). Unadjusted 30-day mortality was lower in the 80-110 mg/dL group (4.3% vs 9.2%, P .001). This remained after propensity score-adjusted regression (OR, 0.65; 95% CI, 0.43-0.98; P = .04).Tight glucose control can be achieved with low rates of severe hypoglycemia and is associated with decreased 30-day mortality in a cohort of largely patients in cardiac ICUs. Although such findings should not be used to guide clinical practice at present, the use of tight glucose control should be reexamined using a protocol that has low rates of severe hypoglycemia.

Background Guidelines suggest anticoagulation of patients with high pretest probability of pulmonary embolism (PE) while awaiting diagnostic test results (preemptive anticoagulation). Data relevant to the practice of preemptive anticoagulation are not available. Methods We reviewed 3,500 consecutive patients who underwent CT pulmonary angiography (CTPA) at two EDs. We classified the pretest probability for PE using the revised Geneva Score (RGS) as low (RGS 0-3), intermediate (RGS 4-10), or high (RGS 11-18). We classified patients with a high pretest probability of PE as receiving preemptive anticoagulation if therapeutic anticoagulation was given before CTPA completion. Patients with a high bleeding risk and those receiving treatment for DVT before CTPA were excluded from the preemptive anticoagulation analysis. We compared the time elapsed between ED registration and CTPA completion for patients with a low, intermediate, and high pretest probability for PE. Results We excluded three of 3,500 patients because CTPA preceded ED registration. Of the remaining 3,497 patients, 167 (4.8%) had a high pretest probability for PE. After excluding 29 patients for high bleeding risk and 21 patients who were treated for DVT prior to CTPA, only two of 117 patients (1.7%) with a high pretest probability for PE received preemptive anticoagulation. Furthermore, 37 of the remaining 115 patients (32%) with a high pretest probability for PE had a preexisting indication for anticoagulation but did not receive preemptive anticoagulation. The time from ED registration to CTPA completion did not differ based on the pretest probability of PE. Conclusions Physicians rarely use preemptive anticoagulation in patients with a high pretest probability for PE. Clinicians do not expedite CTPA examinations for patients with a high pretest probability for PE.

Cardiopulmonary exercise testing (CPET) plays an important role in clinical medicine and research. Repeatability of CPET parameters has not been well characterized, but is important to assess variability and determine if there have been meaningful changes in a given CPET parameter.We recruited 45 healthy subjects and performed two symptom-limited CPET within 30 d using a cycle ergometer. Differences in relevant CPET parameters between CPET-1 and CPET-2 were assessed using a paired t-test. Coefficient of variation (CoV) and Bland-Altman plots are reported. Factors that may be associated with variability were analyzed (sex, age, time of day, fitness level). The coefficient of repeatability was calculated for peak oxygen consumption (V˙O2) and V˙O2 at lactate threshold (LT) to establish a 95% threshold for meaningful change.There were no significant differences between tests in the parameters reported. Specifically, we found overall low CoV in peak V˙O2 (4.9%), V˙O2@LT (10.4%), peak O2 pulse (4.6%), peak minute ventilation (V˙E; 7.4%), V˙E/V˙CO2@LT (4.0%), and V˙E/V˙O2@LT (4.8%). The CoV for peak respiratory exchange ratio@LT was significantly affected by diurnal factors; age, sex, and fitness level did not affect variability. The 95% threshold for meaningful change was 0.540 L·min in peak V˙O2 and 0.520 L·min in V˙O2@LT.Repeatability of CPET parameters is generally higher than previously reported. There were no significant differences in variability related to sex, age, and fitness level; diurnal factors had a limited effect. The threshold for meaningful change in peak V˙O2 and for V˙O2@LT should be considered when gauging a response to therapies or training.

Supplemental Digital Content is available in the text., 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.

We present the final design, environmental testing, and launch history of MiniCarb, a 6U CubeSat developed through a partnership between NASA Goddard Space Flight Center and Lawrence Livermore National Laboratory. MiniCarb’s science payload, developed at Goddard, was an occultation-viewing, passive laser heterodyne radiometer for observing methane, carbon dioxide, and water vapor in Earth’s atmosphere at ∼1.6 µm s−1. MiniCarb’s satellite, developed at Livermore, implemented their CubeSat Next Generation Bus plug-and-play architecture to produce a modular platform that could be tailored to a range of science payloads. Following the launch on 5 December 2019, MiniCarb traveled to the International Space Station and was set into orbit on 1 February 2020 via Northrop Grumman’s Cygnus capsule which deployed MiniCarb with tipoff rotation of about 20° s−1 (significantly higher than the typical rate of 3° s−1 from prior CubeSats), from which the attitude control system was unable to recover resulting in a loss of power. In spite of this early failure, MiniCarb had many successes including rigorous environmental testing, successful deployment of its solar panels, and a successful test of the radio and communication through the Iridium network. This prior work and enticing cost (approximately $2 M for the satellite and $250 K for the payload) makes MiniCarb an ideal candidate for a low-cost and rapid rebuild as a single orbiter or constellation to globally observe key greenhouse gases.

Objective To determine whether heart rate variability (HRV; a physiological measure of acute stress) is associated with persistent psychological distress among family members of adult intensive care unit (ICU) patients. Methods This prospective study investigated family members of patients admitted to a study ICU. Participants’ variability in heart rate tracings were measured by low frequency (LF)/high frequency (HF) ratio and detrended fluctuation analysis (DFA). Questionnaires were completed 3 months after enrollment to ascertain outcome rates of anxiety, depression, and post-traumatic stress disorder (PTSD). Results Ninety-nine participants were enrolled (median LF/HF ratio, 0.92 [interquartile range, 0.64–1.38]). Of 92 participants who completed the 3-month follow-up, 29 (32%) had persistent anxiety. Logistic regression showed that LF/HF ratio (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.43, 1.53) was not associated with 3-month outcomes. In an exploratory analysis, DFA α (OR 0.93, 95% CI 0.87, 0.99), α1 (OR 0.97, 95% CI 0.94, 0.99), and α2 (OR 0.94, 95% CI 0.88, 0.99) scaling components were associated with PTSD development. Conclusion Almost one-third of family members experienced anxiety at three months after enrollment. HRV, measured by LF/HF ratio, was not a predictor of psychologic distress, however, exploratory analyses indicated that DFA may be associated with PTSD outcomes.

Computer clinical decision support (CDS) systems are uncommon in the pediatric intensive care unit (PICU), despite evidence suggesting they improve outcomes in adult ICUs. We reasoned that a bedside CDS protocol for intravenous insulin titration, eProtocol-insulin, would be feasible and safe in critically ill children.We retrospectively reviewed data from non-diabetic children admitted to the PICU with blood glucose (BG) ≥140 mg/dL who were managed with intravenous insulin by either unaided clinician titration or eProtocol-insulin. Primary outcomes were BG measurements in target range (80-110 mg/dL) and severe hypoglycemia (BG ≤40 mg/dL); secondary outcomes were 60-day mortality and PICU length of stay. We assessed bedside nurse satisfaction with the eProtocol-insulin protocol by using a 5-point Likert scale and measured clinician compliance with eProtocol-insulin recommendations.Over 5 years, 69 children were titrated with eProtocol-insulin versus 104 by unaided clinicians. eProtocol-insulin achieved target range more frequently than clinician titration (41% vs. 32%, P 0.001). Severe hypoglycemia was uncommon in both groups (4.3% of patients in eProtocol-insulin, 8.7% in clinician titration, P = 0.37). There were no differences in mean time to BG target or median BG between the groups. Mortality was 23% in both groups. Clinician compliance with eProtocol-insulin recommendations was 89%. Nurses believed that eProtocol-insulin was easy to understand and safer than clinician titration.eProtocol-insulin is safe for titration of intravenous insulin in critically ill children. Clinical research protocols and quality improvement initiatives aimed at optimizing BG control should utilize detailed computer protocols that enable replicable clinician decisions.

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.Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013.One large academic referral hospital and two community hospitals.Adult patients with septic shock requiring vasopressors.None.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.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 (p0.001). Relatively bradycardic patients were older (65 vs 60 yr; p0.001) 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 (p0.001).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.

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.

We present the design of a portable version of our miniaturized laser heterodyne radiometer (mini-LHR) that simultaneously measures methane (CH4) and carbon dioxide (CO2) in the atmospheric column. The mini-LHR fits on a backpack frame, operates autonomously, and requires no infrastructure because it is powered by batteries charged by a folding 30 W solar panel. Similar to our earlier instruments, the mini-LHR is a passive laser heterodyne radiometer that operates by collecting sunlight that has undergone absorption by CH4 and CO2. Within the mini-LHR, sunlight is mixed with light from a distributive feedback (DFB) laser centered at approximately 1.64 μm where both gases have absorption features. The laser scans across these absorption features roughly every minute and the resulting beat signal is collected in the radio frequency (RF). Scans are averaged into half hour and hour data products and analyzed using the Planetary Spectrum Generator (PSG) retrieval to extract column mole fractions. Instrument performance is demonstrated through two deployments at significantly different sites in interior Alaska and Hawaii. The resolving power (λ/∆λ) is greater than 500,000 at 1.64 μm with precisions of better than 20 ppb and 1 ppm for CH4 and CO2, respectively. Because mini-LHR instruments are portable and can be co-located, they can be used to characterize bias between larger, stationary, column observing instruments. In addition, mini-LHRs can be deployed quickly to respond to transient events such as methane leaks or can be used for field studies targeting geographical regions.

Background Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. Results In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > − 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5–67.0) years and admission APACHE II score of 21.0 (16.0–32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p −5). Conclusions In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM.

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.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.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).Cardiorespiratory fitness improved after a two-week SIT regimen, but improvement in peak V̇O2 was not significantly different between ambient and HBO2 groups.

Spirometry is necessary for the optimal management of patients with respiratory disease. The quality of spirometry performed in the primary care setting has been inconsistent.We aimed to evaluate spirometer accuracy, determine the clinical significance of inaccurate spirometers, and assess the quality of spirograms obtained in primary care offices.We tested 17 spirometers used in primary care offices with a waveform generator; accuracy and precision were assessed using American Thoracic Society criteria. The clinical significance of inaccurate instruments was determined by applying the FEVOnly 1 of 17 spirometers met accuracy criteria, with mean errors for FVC, FEVMost spirometers tested were not accurate. The magnitude of the errors resulted in significant changes in the categorization of patients with obstruction. Acceptable-quality tests were produced for only 60% of patients. Our results raise concerns regarding the utility of spirometry obtained in primary care offices without greater attention to quality assurance and training.

IntroductionAs short-term mortality declines for critically ill patients, a growing number of survivors face long-term physical, cognitive and/or mental health impairments. After hospital discharge, many critical illness survivors require an in-depth plan to address their healthcare needs. Early after hospital discharge, numerous survivors experience inadequate care or a mismatch between their healthcare needs and what is provided. Many patients are readmitted to the hospital, have substantial healthcare resource use and experience long-lasting morbidity. The objective of this study is to investigate the gap in healthcare needs occurring immediately after hospital discharge and its association with hospital readmissions or death for survivors of acute respiratory failure (ARF).Methods and analysisIn this multicentre prospective cohort study, we will enrol 200 survivors of ARF in the intensive care unit (ICU) who are discharged directly home from their acute care hospital stay. Unmet healthcare needs, the primary exposure of interest, will be evaluated as soon as possible within 1 to 4 weeks after hospital discharge, via a standardised telephone assessment. The primary outcome, death or hospital readmission, will be measured at 3 months after discharge. Secondary outcomes (eg, quality of life, cognitive impairment, depression, anxiety and post-traumatic stress disorder) will be measured as part of 3-month and 6-month telephone-based follow-up assessments. Descriptive statistics will be reported for the exposure and outcome variables along with a propensity score analysis, using inverse probability weighting for the primary exposure, to evaluate the relationship between the primary exposure and outcome.Ethics and disseminationThe study received ethics approval from Vanderbilt University Medical Center Institutional Review Board (IRB) and the University of Utah IRB (for the Veterans Affairs site). These results will inform both clinical practice and future interventional trials in the field. We plan to disseminate the results in peer-reviewed journals, and via national and international conferences.Trial registration detailsClinicalTrials.gov (NCT03738774). Registered before enrollment of the first patient.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a devastating complication that occurs in about 3% of survivors of acute pulmonary embolism (PE) [1]. Genetic risk factors may differentiate patients with acute PE who develop CTEPH from those who do not develop CTEPH. The Factor V Leiden (FVL) and Prothrombin G20210A (PT) variants are the most common genetic risk factors for venous thromboembolism (VTE) [2, 3]. In European CTEPH patients, the frequencies of these variants are not increased compared to either patients with non-CTEPH pulmonary hypertension or healthy controls [4–7]. While this data suggests that genetic risk factors for CTEPH and PE may be distinct [8], no studies have directly compared the frequencies of these variants in patients with CTEPH and patients with acute PE who did not develop CTEPH. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Dodson reports grants from Actelion Pharmaceuticals (via the Entelligence Young Investigator Program), grants from Intermountain Research and Medical Foundation, during the conduct of the study. Conflict of interest: Dr. Sumner has nothing to disclose. Conflict of interest: Dr. Carlsen has nothing to disclose. Conflict of interest: Dr. Cirulis has nothing to disclose. Conflict of interest: Dr. Wilson has nothing to disclose. Conflict of interest: Dr. Gadre has nothing to disclose. Conflict of interest: Dr. Fernandes reports personal fees from Bayer, personal fees from Bristol-Meyers-Squibb, outside the submitted work. Conflict of interest: Dr. Brown has nothing to disclose. Conflict of interest: Dr. Best has nothing to disclose. Conflict of interest: Dr. Elliott reports other from United Therapeutics, other from Lung Rx LLC, grants from Arena Pharmaceuticals, grants from Respira Therapeutics, grants from Lung Biotechnology PBC, outside the submitted work.

In addition to hyperglycemia, hypoglycemia, and glycemic variability, reduced time in targeted blood glucose range (TIR) is associated with increased risk of death in critically ill patients. This relation between TIR and mortality may be confounded by diabetic status and antecedent glycemic control.This study retrospectively analyzed critically ill patients managed with the same IV insulin protocol at multiple centers. The percentage of TIR between 70 and 139 mg/dL was calculated. Patients with diabetic ketoacidosis, patients who had 10 blood glucose readings, and patients with repeat admissions were excluded. The highest recorded glycosylated hemoglobin value in the preceding 3 months or up to 1 month following admission were used as a surrogate for the patient's preexisting glucose control. Stratified regression analyses were performed for 30-day mortality, with covariates of age, sex, TIR ≥ 80%, Acute Physiology Score, and Charlson Comorbidity Index.A total of 9,028 patients, 53.2% of whom had diabetes, were studied. Median TIR was 84.1% for nondiabetic patients and 64.5% for patients with diabetes. Mortality was lower in those with TIR 80% compared with those with TIR ≤ 80% (12.4% vs 19.2%; P .001). TIR 80% was independently associated with reduced mortality in nondiabetic patients (OR, 0.52; P .001), patients with diabetes (OR, 0.69; P = .001), and patients with well-controlled disease (OR, 0.50; P .001) but not in patients with poorly controlled disease (OR, 0.86; P = .40).TIR was independently associated with mortality in critically ill patients, particularly those with good antecedent glucose control.