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Item Biomarkers of human cardiopulmonary response after short-term exposures to medical laser generated particulate matter from simulated procedures: a pilot study(Wolters Kluwer, 2016-09) Lopez, Ramon; Farber, Mark O.; Wong, Vincent; Lacey, Steven E.; Environmental Health Science, School of Public HealthObjective We conducted an exposure chamber study in humans using a simulated clinical procedure lasing porcine tissue to demonstrate evidence of effects of exposure to laser generated particulate matter (LGPM). Methods We measured pre- and post-exposure changes in exhaled nitric oxide (eNO), spirometry, heart rate variability (HRV), and blood markers of inflammation in five volunteers. Results Change in pre- and post-exposure measurements of eNO and spirometry were unremarkable. Neutrophil and lymphocyte counts increased and fibrinogen levels decreased in four of the five subjects. Measures of HRV showed decreases in the standard deviation of normal between beat intervals and sequential five-minute intervals. Conclusion These data represent the first evidence of human physiologic response to LGPM exposure. Further exploration of coagulation effects and HRV are warranted.Item The CAM-ICU-7 Delirium Severity Scale: A Novel Delirium Severity Instrument for Use in the Intensive Care Unit(Wolters Kluwer, 2017-05) Khan, Babar A.; Perkins, Anthony J.; Gao, Sujuan; Hui, Siu L.; Campbell, Noll L.; Farber, Mark O.; Chlan, Linda L.; Boustani, Malaz A.; Medicine, School of MedicineOBJECTIVES: Delirium severity is independently associated with longer hospital stays, nursing home placement, and death in patients outside the ICU. Delirium severity in the ICU is not routinely measured because the available instruments are difficult to complete in critically ill patients. We designed our study to assess the reliability and validity of a new ICU delirium severity tool, the Confusion Assessment Method for the ICU-7 delirium severity scale. DESIGN: Observational cohort study. SETTING: Medical, surgical, and progressive ICUs of three academic hospitals. PATIENTS: Five hundred eighteen adult (≥ 18 yr) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received the Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale, and Delirium Rating Scale-Revised-98 assessments. A 7-point scale (0-7) was derived from responses to the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale items. Confusion Assessment Method for the ICU-7 showed high internal consistency (Cronbach's α = 0.85) and good correlation with Delirium Rating Scale-Revised-98 scores (correlation coefficient = 0.64). Known-groups validity was supported by the separation of mechanically ventilated and nonventilated assessments. Median Confusion Assessment Method for the ICU-7 scores demonstrated good predictive validity with higher odds (odds ratio = 1.47; 95% CI = 1.30-1.66) of in-hospital mortality and lower odds (odds ratio = 0.8; 95% CI = 0.72-0.9) of being discharged home after adjusting for age, race, gender, severity of illness, and chronic comorbidities. Higher Confusion Assessment Method for the ICU-7 scores were also associated with increased length of ICU stay (p = 0.001). CONCLUSIONS: Our results suggest that Confusion Assessment Method for the ICU-7 is a valid and reliable delirium severity measure among ICU patients. Further research comparing it to other delirium severity measures, its use in delirium efficacy trials, and real-life implementation is needed to determine its role in research and clinical practice.Item Clinical Decision Support System and Incidence of Delirium in Cognitively Impaired Older Adults Transferred to Intensive Care(American Association of Critical-Care Nurses, 2013) Khan, Babar A.; Calvo-Ayala, Enrique; Campbell, Noll; Perkins, Anthony; Ionescu, Ruxandra; Tricker, Jason; Campbell, Tiffany; Zawahiri, Mohammed; Buckley, John D.; Farber, Mark O.; Boustani, Malaz A.; Medicine, School of MedicineBackground: Elderly patients with cognitive impairment are at increased risk of developing delirium, especially in the intensive care unit. Objective: To evaluate the efficacy of a computer-based clinical decision support system that recommends consulting a geriatrician and discontinuing use of urinary catheters, physical restraints, and unnecessary anticholinergic drugs in reducing the incidence of delirium. Methods: Data for a subgroup of patients enrolled in a large clinical trial who were transferred to the intensive care units of a tertiary-care, urban public hospital in Indianapolis were analyzed. Data were collected on frequency of orders for consultation with a geriatrician; discontinuation of urinary catheterization, physical restraints, or anticholinergic drugs; and the incidence of delirium. Results: The sample consisted of 60 adults with cognitive impairment. Mean age was 74.6 years; 45% were African American, and 52% were women. No differences were detected between the intervention and the control groups in orders for consultation with a geriatrician (33% vs 40%; P = .79) or for discontinuation of urinary catheters (72% vs 76%; P = .99), physical restraints (12% vs 0%; P=.47), or anticholinergic drugs (67% vs 36%; P=.37). The 2 groups did not differ in the incidence of delirium (27% vs 29%; P = .85). Conclusion: Use of a computer-based clinical decision support system may not be effective in changing prescribing patterns or in decreasing the incidence of delirium.Item Delirium Incidence, Duration and Severity in Critically Ill Patients with COVID-19(2020-06-01) Khan, Sikandar H.; Lindroth, Heidi; Perkins, Anthony J.; Jamil, Yasser; Wang, Sophia; Roberts, Scott; Farber, Mark O.; Rahman, Omar; Gao, Sujuan; Marcantonio, Edward R.; Boustani, Malaz; Machado, Roberto; Khan, Babar A.; Medicine, School of MedicineBackground: Delirium incidence, duration and severity in patients admitted to the intensive care unit (ICU) due to COVID-19 is not known. Methods: We conducted an observational study at two large urban academic Level 1 trauma centers. Consecutive patients admitted to the ICU with a positive SARS-CoV-2 nasopharyngeal swab polymerase chain reaction test from March 1st, 2020 to April 27, 2020, were included. Individuals younger than 18 years of age, without any documented delirium assessments (CAM-ICU), or without a discharge disposition were excluded. The primary outcomes were delirium rates and delirium duration and the secondary outcome was delirium severity. Outcomes were assessed for up to the first 14 days of ICU stay. Results: Of 243 consecutive patients with confirmed COVID-19 admitted to the ICU, 144 met eligibility criteria and were included in the analysis. Delirium occurred in 73.6% (106/144) and delirium or coma occurred in 76.4% (110/144). Sixty-three percent of patients were positive for delirium on the first CAM-ICU assessment. The median duration of delirium and coma was 7 days (IQR: 3-10), and the median delirium duration was 5 days (IQR: 2-7). The median CAM-ICU-7 score was 6 (IQR: 4-7) representing severe delirium. Mechanical ventilation was associated with greater odds of developing delirium (OR: 42.1, 95%CI: 13.0-137.1). Mortality was 26.4% in patients with delirium compared to 15.8% in patients without delirium. Conclusions: 73.6% of patients admitted to the ICU with COVID-19 experience delirium that persists for approximately 1 week. Invasive mechanical ventilation is significantly associated with odds of delirium. Clinical attention to prevent and manage delirium and reduce delirium duration and severity is urgently needed for patients with COVID-19.Item Deprescribing in the Pharmacologic Management of Delirium (de-PMD): A Randomized Trial in the Intensive Care Unit(Wiley, 2019-04) Campbell, Noll L.; Perkins, Anthony J.; Khan, Babar A.; Gao, Sujuan; Farber, Mark O.; Khan, Sikandar; Wang, Sophia; Boustani, Malaz A.; Medicine, School of MedicineOBJECTIVE: Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. DESIGN: Multi-site randomized clinical trial SETTING: ICU’s of three large hospitals PARTICIPANTS: Two hundred adults aged ≥ 18 years admitted to an ICU with delirium according to the Richmond Agitation Severity Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. MEASUREMENTS: Primary outcomes were delirium duration measured by the CAM-ICU, and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. RESULTS: Participants had a mean age of 61.8 (standard deviation: 14.3) years, 59% female, and 52% African American with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (p=0.219) or benzodiazepines (p=0.566), the median total anticholinergic score (p=0.282), or the median total benzodiazepine dose in lorazepam equivalents (p=0.501). Neither median delirium/coma-free days (p=0.361) nor median change in delirium severity scores (p=0.582 for DRS-R-98; p=0.333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. CONCLUSIONS: When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes.Item Effectiveness of implementing a wake up and breathe program on sedation and delirium in the ICU(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-12) Khan, Babar A.; Fadel, William F.; Tricker, Jason L.; Carlos, W. Graham; Farber, Mark O.; Hui, Siu L.; Campbell, Noll L.; Ely, E. Wesley; Boustani, Malaz A.; Department of Medicine, IU School of MedicineOBJECTIVES: Mechanically ventilated critically ill patients receive significant amounts of sedatives and analgesics that increase their risk of developing coma and delirium. We evaluated the impact of a "Wake-up and Breathe Protocol" at our local ICU on sedation and delirium. DESIGN: A pre/post implementation study design. SETTING: A 22-bed mixed surgical and medical ICU. PATIENTS: Seven hundred two consecutive mechanically ventilated ICU patients from June 2010 to January 2013. INTERVENTIONS: Implementation of daily paired spontaneous awakening trials (daily sedation vacation plus spontaneous breathing trials) as a quality improvement project. MEASUREMENTS AND MAIN RESULTS: After implementation of our program, there was an increase in the mean Richmond Agitation Sedation Scale scores on weekdays of 0.88 (p < 0.0001) and an increase in the mean Richmond Agitation Sedation Scale scores on weekends of 1.21 (p < 0.0001). After adjusting for age, race, gender, severity of illness, primary diagnosis, and ICU, the incidence and prevalence of delirium did not change post implementation of the protocol (incidence: 23% pre vs 19.6% post; p = 0.40; prevalence: 66.7% pre vs 55.3% post; p = 0.06). The combined prevalence of delirium/coma decreased from 90.8% pre protocol implementation to 85% postimplementation (odds ratio, 0.505; 95% CI, 0.299-0.853; p = 0.01). CONCLUSIONS: Implementing a "Wake Up and Breathe Program" resulted in reduced sedation among critically ill mechanically ventilated patients but did not change the incidence or prevalence of delirium.Item Interventions to improve the physical function of ICU survivors: a systematic review(American College of Chest Physicians, 2013-11) Calvo-Ayala, Enrique; Khan, Babar A.; Farber, Mark O.; Ely, E. Wesley; Boustani, Malaz A.; Medicine, School of MedicineBACKGROUND: ICU admissions are ever increasing across the United States. Following critical illness, physical functioning (PF) may be impaired for up to 5 years. We performed a systematic review of randomized controlled trials evaluating the efficacy of interventions targeting PF among ICU survivors. The objective of this study was to identify effective interventions that improve long-term PF in ICU survivors. METHODS: MEDLINE, Excerpta Medica Database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Physiotherapy Evidence-Based Database (PEDro) were searched between 1990 and 2012. Two reviewers independently evaluated studies for eligibility, critically appraised the included studies, and extracted data into standardized evidence tables. RESULTS: Fourteen studies met the inclusion criteria. Interventions included exercise/physical therapy (PT), parenteral nutrition, nurse-led follow-up, spontaneous awakening trials, absence of sedation during mechanical ventilation, and early tracheotomy. Nine studies failed to demonstrate efficacy on PF of the ICU survivors. However, early physical exercise and PT-based interventions had a positive effect on long-term PF. CONCLUSIONS: The only effective intervention to improve long-term PF in critically ill patients is exercise/PT; its benefit may be greater if started earlier. Further research in this area comparing different interventions and timing is needed.Item Mortality Rates in a Diverse Cohort of Mechanically Ventilated Patients With Novel Coronavirus in the Urban Midwest(Wolters Kluwer, 2020-08) Twigg, Homer L. III; Khan, Sikandar H.; Perkins, Anthony J.; Roberts, Scott; Sears, Catherine R.; Rahman, Omar; Smith, Joseph P.; Kapoor, Rajat; Farber, Mark O.; Ellender, Timothy; Carlos, Graham; Gilroy, Grant; Buckley, John; Bosslet, Gabriel; Machado, Roberto; Gao, Sujuan; Khan, Babar A.; Medicine, School of MedicineObjectives: Differences in mortality rates previously reported in critically ill patients with coronavirus disease 2019 have increased the need for additional data on mortality and risk factors for death. We conducted this study to describe length of stay, mortality, and risk factors associated with in-hospital mortality in mechanically ventilated patients with coronavirus disease 2019. Design: Observational study. Setting: Two urban, academic referral hospitals in Indianapolis, Indiana. Patients or Subjects: Participants were critically ill patients 18 years old and older, admitted with coronavirus disease 2019 between March 1, 2020, and April 27, 2020. Interventions: None. Measurements and Main Results: Outcomes included in-hospital mortality, duration of mechanical ventilation, and length of stay. A total of 242 patients were included with mean age of 59.6 years (sd, 15.5 yr), 41.7% female and 45% African American. Mortality in the overall cohort was 19.8% and 20.5% in the mechanically ventilated subset. Patients who died were older compared with those that survived (deceased: mean age, 72.8 yr [sd, 10.6 yr] vs patients discharged alive: 54.3 yr [sd, 14.8 yr]; p < 0.001 vs still hospitalized: 59.5 yr [sd, 14.4 yr]; p < 0.001) and had more comorbidities compared with those that survived (deceased: 2 [0.5–3] vs survived: 1 [interquartile range, 0–1]; p = 0.001 vs still hospitalized: 1 [interquartile range, 0–2]; p = 0.015). Older age and end-stage renal disease were associated with increased hazard of in-hospital mortality: age 65–74 years (hazard ratio, 3.1 yr; 95% CI, 1.2–7.9 yr), age 75+ (hazard ratio, 4.1 yr; 95% CI, 1.6–10.5 yr), and end-stage renal disease (hazard ratio, 5.9 yr; 95% CI, 1.3–26.9 yr). The overall median duration of mechanical ventilation was 9.3 days (interquartile range, 5.7–13.7 d), and median ICU length of stay in those that died was 8.7 days (interquartile range, 4.0–14.9 d), compared with 9.2 days (interquartile range, 4.0–14.0 d) in those discharged alive, and 12.7 days (interquartile range, 7.2–20.3 d) in those still remaining hospitalized. Conclusions: We found mortality rates in mechanically ventilated patients with coronavirus disease 2019 to be lower than some previously reported with longer lengths of stay.Item Pharmacological Management of Delirium in the Intensive Care Unit: A Randomized Pragmatic Clinical Trial(Wiley, 2019-05) Khan, Babar A.; Perkins, Anthony J.; Campbell, Noll L.; Gao, Sujuan; Farber, Mark O.; Wang, Sophia; Khan, Sikandar H.; Zarzaur, Ben L.; Boustani, Malaz A.; Biostatistics, School of Public HealthBACKGROUND/OBJECTIVE: Delirium in the intensive care units (ICUs) 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: A total of 351 critically ill patients. INTERVENTION: A multicomponent 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 the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU), and delirium severity, measured through Delirium Rating Scale-Revised-98 and the CAM-ICU-7. Secondary outcomes were in-hospital and posthospital 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 years]; 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 vs usual care = 4 [interquartile range {IQR} = 2-7] days vs 5 [IQR = 1-7] days; P = .888) or at day 30 (PMD vs usual care = 26 [IQR 19-29] days vs 26 [IQR, 14-29] days; P = .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 (mean decrease in CAM-ICU-7 score for PMD vs usual care = 3.2 [SD = 3.3] vs 2.5 [SD = 3.2]; P = .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 years or older and 75 years or older. 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: NCT00842608. J Am Geriatr Soc 67:1057-1065, 2019.Item Relationship between African-American Race and Delirium in the Intensive Care Unit(Wolters Kluwer, 2016-09) Khan, Babar A.; Perkins, Anthony; Hui, Siu L.; Gao, Sujuan; Campbell, Noll L.; Farber, Mark O.; Boustani, Malaz A.; Medicine, School of MedicineObjective Delirium is a highly prevalent syndrome of acute brain dysfunction among critically ill patients that has been linked to multiple risk factors such as age, pre-existing cognitive impairment, and use of sedatives; but to date the relationship between race and delirium is unclear. We conducted this study to identify whether African-American race is a risk factor for developing ICU delirium. Design A prospective cohort study. Setting Medical and Surgical ICUs of a university affiliated, safety-net hospital in Indianapolis, Indiana. Patients 2087 consecutive admissions with 1008 African-Americans admitted to the ICU services from May 2009 to August 2012. Interventions None Measurements and Main Results Incident delirium defined as first positive Confusion Assessment Method for the ICU (CAM-ICU) result after an initial negative CAM-ICU; and prevalent delirium defined as positive CAM-ICU on first CAM-ICU assessment. The overall incident delirium rate in African-Americans was 8.7% compared to 10.4% in Caucasians (P: 0.26). The prevalent delirium rate was 14% in both African-Americans and Caucasians (P: 0.95). Significant age and race interactions were detected for incident delirium (P: 0.02), but not for prevalent delirium (P: 0.3). The hazard ratio for incident delirium for African-Americans in the 18–49 years age group compared to Caucasians of similar age was 0.4 (0.1– 0.9). The hazard and odds ratios for incident and prevalent delirium in other groups were not different. Conclusions African-American race does not confer any additional risk for developing incident or prevalent delirium in the ICU. Instead younger African-Americans tend to have lower rates of incident delirium compared to similar age Caucasians.