During critical illness, impaired endothelial vascular reactivity predicts prolonged acute brain dysfunction, but relationships between endothelial activation, blood-brain barrier/neurological ...injury, and acute brain dysfunction, including delirium, remain unexamined. We tested the hypothesis that elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury are associated with delirium duration during critical illness.
Prospective cohort study.
Medical and surgical ICUs in an academic medical center.
Adults in acute respiratory failure and/or shock.
None.
We enrolled subjects within 72 hours of organ failure diagnosis in the ICU. We measured plasma concentrations of plasminogen activator inhibitor-1, E-selectin, and angiopoietin-2 as markers of endothelial activation and S100B as a marker of blood-brain barrier/neurological injury in blood collected at enrollment. We assessed patients for delirium and coma twice daily after enrollment using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Among 134 patients with a median (interquartile) age of 57 years (46-66 yr) and Acute Physiology and Chronic Health Evaluation II of 26 (19-31), delirium occurred in 94 patients (70%) with a median duration of 2 days (0-4 d). Higher plasminogen activator inhibitor-1 (p = 0.002), E-selectin (p = 0.02), and S100B (p < 0.001) concentrations were associated with fewer delirium/coma-free days after adjusting for age, Charlson comorbidity index, modified Sequential Organ Failure Assessment score, and severe sepsis. Similarly, higher plasminogen activator inhibitor-1 (p = 0.007) and S100B (p = 0.01) concentrations were associated with longer delirium duration in survivors. Adjusting for S100B did not alter plasminogen activator inhibitor-1 and E-selectin associations with delirium, suggesting that these associations were not mediated by blood-brain barrier/neurological injury.
Elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury during critical illness are associated with prolonged delirium after biomarker measurement. Future research is needed to determine whether these processes have pathophysiologic roles in delirium and whether therapies targeted at the endothelium or blood-brain barrier can prevent and/or treat delirium during critical illness.
To characterize survivors' employment status after critical illness and to determine if duration of delirium during hospitalization and residual cognitive function are each independently associated ...with decreased employment.
Prospective cohort investigation with baseline and in-hospital clinical data and follow-up at 3 and 12 months.
Medical and surgical ICUs at two tertiary-care hospitals.
Previously employed patients from the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors study who survived a critical illness due to respiratory failure or shock were evaluated for global cognition and employment status at 3- and 12-month follow-up.
We used multivariable logistic regression to evaluate independent associations between employment at both 3 and 12 months and global cognitive function at the same time point, and delirium during the hospital stay. At 3-month follow-up, 113 of the total survival cohort of 448 (25%) were identified as being employed at study enrollment. Of these, 94 survived to 12-month follow-up. At 3- and 12-month follow-up, 62% and 49% had a decrease in employment, 57% and 49% of whom, respectively, were newly unemployed. After adjustment for physical health status, depressive symptoms, marital status, level of education, and severity of illness, we did not find significant predictors of employment status at 3 months, but better cognition at 12 months was marginally associated with lower odds of employment reduction at 12 months (odds ratio, 0.49; p = 0.07).
Reduction in employment after critical illness was present in the majority of our ICU survivors, approximately half of which was new unemployment. Cognitive function at 12 months was a predictor of subsequent employment status. Further research is needed into the potential relationship between the impact of critical illness on cognitive function and employment status.
We examined population-based surveillance data from the Tennessee Emerging Infections Program to determine whether neighborhood socioeconomic status was associated with influenza hospitalization ...rates. Hospitalization data collected during October 2007-April 2014 were geocoded (N = 1,743) and linked to neighborhood socioeconomic data. We calculated age-standardized annual incidence rates, relative index of inequality, and concentration curves for socioeconomic variables. Influenza hospitalizations increased with increased percentages of persons who lived in poverty, had female-headed households, lived in crowded households, and lived in population-dense areas. Influenza hospitalizations decreased with increased percentages of persons who were college educated, were employed, and had health insurance. Higher incidence of influenza hospitalization was also associated with lower neighborhood socioeconomic status when data were stratified by race.
Delirium's pathophysiology is poorly understood. We sought to determine if plasma biomarkers of inflammation, coagulation, endothelial activation, and blood brain barrier (BBB) injury were associated ...with emergency department (ED) delirium duration.
We enrolled hospitalized patients who were 65 years or older from the ED. Plasma biomarkers of inflammation (interleukin-6 IL-6, IL-8, soluble tumor necrosis factor receptor I sTNFRI), coagulation (Protein C), endothelial activation (plasminogen activating inhibitor-1 PAI-1), and BBB injury (S100B) at were measured using blood obtained at enrollment. The dependent variable was ED delirium duration which was determined by the Brief Confusion Assessment Method assessed in the ED and hospitalization. Proportional odds logistic regression analyses were performed adjusted for relevant confounders and allowing for interaction by baseline dementia status.
A total of 156 patients were enrolled. IL-6 (POR = 1.59, 95%CI: 1.09-2.32) and PAI-1 (POR = 2.96, 95%CI: 1.48 to 6.85) were independently associated with more prominent ED delirium duration in subjects without dementia only. No significant associations between IL-8, Protein C, sTNRFI, and S100B and ED delirium duration were observed.
Plasma Biomarkers of systemic inflammation and endothelial activation are associated with ED delirium duration in older ED patients without dementia.
Antipsychotics are used to treat delirium in the intensive care unit (ICU) despite unproven efficacy. We hypothesized that atypical antipsychotic treatment in the ICU is a risk factor for ...antipsychotic prescription at discharge, a practice that might increase risk since long-term use is associated with increased mortality.
After excluding patients on antipsychotics prior to admission, we examined antipsychotic use in a prospective cohort of ICU patients with acute respiratory failure and/or shock. We collected data on medication use from medical records and assessed patients for delirium using the Confusion Assessment Method for the ICU. Using multivariable logistic regression, we analyzed whether age, delirium duration, atypical antipsychotic use, and discharge disposition (each selected a priori) were independent risk factors for discharge on an antipsychotic. We also examined admission Acute Physiology and Chronic Health Evaluation (APACHE) II score, haloperidol use, and days of benzodiazepine use in post hoc analyses.
After excluding 18 patients due to prior antipsychotic use and three who withdrew, we included 500 patients. Among 208 (42%) treated with an antipsychotic, median (interquartile range) age was 59 (49-69) years and APACHE II score was 26 (22-32), characteristics that were similar among antipsychotic nonusers. Antipsychotic users were more likely than nonusers to have had delirium (93% vs. 61%, p < 0.001). Of the 208 antipsychotic users, 172 survived to hospital discharge, and 42 (24%) of these were prescribed an antipsychotic at discharge. Treatment with an atypical antipsychotic was the only independent risk factor for antipsychotic prescription at discharge (odds ratio 17.6, 95% confidence interval 4.9 to 63.3; p < 0.001). Neither age, delirium duration, nor discharge disposition were risk factors (p = 0.11, 0.38, and 0.12, respectively) in the primary regression model, and post hoc analyses found APACHE II (p = 0.07), haloperidol use (p = 0.16), and days of benzodiazepine use (p = 0.31) were also not risk factors for discharge on an antipsychotic.
In this study, antipsychotics were used to treat nearly half of all antipsychotic-naïve ICU patients and were prescribed at discharge to 24% of antipsychotic-treated patients. Treatment with an atypical antipsychotic greatly increased the odds of discharge with an antipsychotic prescription, a practice that should be examined carefully during medication reconciliation since these drugs carry "black box warnings" regarding long-term use.
The incidence and risk factors of post-traumatic stress disorder (PTSD) related to the intensive care unit (ICU) experience have not been reported in a mixed veteran and civilian cohort.
To describe ...the incidence and risk factors for ICU-related PTSD in veterans and civilians.
This is a prospective, observational, multicenter cohort enrolling adult survivors of critical illness after respiratory failure and/or shock from three Veterans Affairs and one civilian hospital. After classifying those with/without preexisting PTSD (i.e., PTSD before hospitalization), we then assessed all subjects for ICU-related PTSD at 3 and 12 months post hospitalization.
Of 255 survivors, 181 and 160 subjects were assessed for ICU-related PTSD at 3- and 12-month follow-up, respectively. A high probability of ICU-related PTSD was found in up to 10% of patients at either follow-up time point, whether assessed by PTSD Checklist Event-Specific Version (score ≥ 50) or item mapping using the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). In the multivariable regression, preexisting PTSD was independently associated with ICU-related PTSD at both 3 and 12 months (P < 0.001), as was preexisting depression (P < 0.03), but veteran status was not a consistent independent risk factor for ICU-related PTSD (3-month P = 0.01, 12-month P = 0.48).
This study found around 1 in 10 ICU survivors experienced ICU-related PTSD (i.e., PTSD anchored to their critical illness) in the year after hospitalization. Preexisting PTSD and depression were strongly associated with ICU-related PTSD.
Abstract Purpose To quantify the prevalence of prescribed opioid analgesics among pregnant women enrolled in Tennessee Medicaid from 1995 to 2009. Methods Retrospective cohort study of 277,555 ...pregnancies identified from birth and fetal death certificates, and linked to previously validated, computerized pharmacy records. Poisson regression was used to estimate trends over time, rate ratios, and 95% confidence intervals (CI). Results During the study period, 29% of pregnant women filled a prescription for an opioid analgesic. From 1995 to 2009, any pregnancy-related use increased 1.90-fold (95% CI, 1.83–1.98), first trimester use increased 2.27-fold (95% CI, 2.14–2.41), and second or third trimester use increased 2.02-fold (95% CI, 1.93–2.12), after adjusting for maternal characteristics. Any pregnancy-related, first trimester, and second or third trimester use were each more likely among mothers who were at least 21 years old, white, non-Hispanic, prima gravid, resided in nonurban areas, enrolled in Medicaid owing to disability, and who had less than a high school education. Conclusions Opioid analgesic use by Tennessee Medicaid-insured pregnant women increased nearly 2-fold from 1995 to 2009. Additional study is warranted to understand the implications of this increased use.
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