Objectives: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. Design: Observational study. Setting: Three Indianapolis hospitals. Patients: Three-hundred twenty-one critically ill delirious patients. Interventions: None. Measurements and Main Results: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100β lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100β levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality. Conclusions: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.

Background/Objective: Delirium in the intensive care units (ICU) is prevalent with both delirium duration and delirium severity associated with adverse outcomes. We designed a pragmatic trial to test the efficacy of a pharmacological management of delirium (PMD) bundle in improving delirium/coma free days and reducing delirium severity among ICU patients. Design: A randomized pragmatic clinical trial. Setting: Medical, surgical, and progressive ICUs of three tertiary care hospitals. Participants: 351 critically ill patients. Intervention: A multi-component PMD bundle consisting of reducing the exposure to 20 definite anticholinergic medications and benzodiazepines, and prescribing low-dose haloperidol. Measurements: The primary outcomes were delirium/coma free days measured through Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU) and delirium severity measured through Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7. Secondary outcomes were in-hospital and post-hospital discharge 30-day mortality, ICU and hospital lengths of stay, and delirium-related hospital complications. Results: We randomized 351 critically ill delirious patients [mean age=59.3 years (SD 16.9); 52% female, 42% African-Americans] to receive the PMD bundle or usual care. There were no significant differences in median delirium/coma free days at day 8 [PMD: 4 (IQR 2–7) days versus usual care 5 (1–7), p=0.888] or at day 30 [26 (IQR 19–29) days versus 26 (14–29), p=0.991]. There were no significant differences for decrease in delirium severity at day 8, but at hospital discharge, the intervention group showed a greater reduction in delirium severity [PMD: mean decrease in CAM-ICU-7 score=3.2 (SD 3.3) versus usual care: mean decrease=2.5 (SD 3.2); p=0.046]. No differences were observed between groups for ICU and hospital lengths of stay, mortality and delirium-related hospital complications. Similar results were observed when analyses were limited to patients ≥ 65 and ≥ 75 years. Conclusion and Relevance: Implementing the PMD Bundle in the ICU did not reduce delirium duration or severity among critically ill patients. Trial Registration: clinicaltrials.gov Identifier:

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Objectives: To determine delirium occurrence rate, duration, and severity in patients admitted to the ICU with coronavirus disease 2019. Design: Retrospective data extraction study from March 1, 2020, to June 7, 2020. Delirium outcomes were assessed for up to the first 14 days in ICU. Setting: Two large, academic centers serving the state of Indiana. Patients: Consecutive patients admitted to the ICU with positive severe acute respiratory syndrome coronavirus 2 nasopharyngeal swab polymerase chain reaction test from March 1, 2020, to June 7, 2020, were included. Individuals younger than 18 years of age, without any delirium assessments, or without discharge disposition were excluded. Measurements and Main Results: Primary outcomes were delirium rates and duration, and the secondary outcome was delirium severity. Two-hundred sixty-eight consecutive patients were included in the analysis with a mean age of 58.4 years (sd, 15.6 yr), 40.3% were female, 44.4% African American, 20.7% Hispanic, and a median Acute Physiology and Chronic Health Evaluation II score of 18 (interquartile range, 13–25). Delirium without coma occurred in 29.1% of patients, delirium prior to coma in 27.9%, and delirium after coma in 23.1%. The first Confusion Assessment Method for the ICU assessment was positive for delirium in 61.9%. Hypoactive delirium was the most common subtype (87.4%). By day 14, the median number of delirium/coma-free were 5 days (interquartile range, 4–11 d), and median Confusion Assessment Method for the ICU-7 score was 6.5 (interquartile range, 5–7) indicating severe delirium. Benzodiazepines were ordered for 78.4% of patients in the cohort. Mechanical ventilation was associated with greater odds of developing delirium (odds ratio, 5.0; 95% CI, 1.1–22.2; p = 0.033) even after adjusting for sedative medications. There were no between-group differences in mortality. Conclusions: Delirium without coma occurred in 29.1% of patients admitted to the ICU. Delirium persisted for a median of 5 days and was severe. Mechanical ventilation was significantly associated with odds of delirium even after adjustment for sedatives. Clinical attention to manage delirium duration and severity, and deeper understanding of the virus’ neurologic effects is needed for patients with coronavirus disease 2019.

Introduction Psychosexual counseling may enhance sexual performance outcomes in men with erectile dysfunction (ED) treated with a phosphodiesterase type 5 (PDE5) inhibitor. Aim To determine the potential long-term effects of cognitive behavioral therapy (CBT) on Pakistani men with ED who had undergone treatment with a PDE5 inhibitor (PDE5i). Methods In a 15–18-month follow-up, we reassessed a subsample of 20 men who had been treated with either PDE5is (monotherapy group) or CBT + PDE5i (combined group) on 2 dimensions: sexual functioning and mental health functioning. Main Outcome Measure International Index of Erectile Function was used to assess sexual function, and 2 Mental Health Inventory subscales were used to assess anxiety and depression. A brief semi-structured interview assessed men’s current sexual status and evaluation of their CBT experience. Results Men in the combined group continued to show improvement on erectile function and several other sexual parameters, whereas men in the monotherapy group showed either no further improvement or a decrement in sexual response parameters. The results did not appear to be related to changes in relationship satisfaction or mental health indices. Clinical Implications Adjunctive CBT shows long-term benefits in men with ED treated with a PDE5i. Strength & Limitations Effect sizes were strong, overcoming the small sample size, but attrition may affect the generalizability of the findings. Conclusion In the first long-term follow-up study of its kind, CBT proved an effective and supportive adjunctive treatment for Pakistani men with ED taking a PDE5i, with benefits extending long after the end of treatment.