Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes. METHODS: This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete. FINDINGS: Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo. INTERPRETATION: In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults. FUNDING: National Institutes of Health and the US Department of Veterans Affairs.

Collaborative Care for Injured Older Adults: The Trauma Medical Home Randomized Clinical Trial.

Importance: Older adults with recent injuries can have impaired long-term biopsychosocial function and may benefit from interventions adapted to their needs. Objective: To determine if a collaborative care intervention, Trauma Medical Home (TMH), improved the biopsychosocial function of older patients in the year after injury. Design, Setting, and Participants: This was a single-blinded, randomized clinical trial conducted at 4 level I trauma centers in Indianapolis, Indiana, and Madison, Wisconsin. Between October 2017 and October 2021, patients aged 50 years and older with an Injury Severity Score (ISS) of 9 or greater and without traumatic brain or spinal cord injury were enrolled. Exclusions were significant brain injury or a spinal cord injury with a persistent neurologic deficit at the time of enrollment, extensive burns, pregnancy, incarceration, neurodegenerative disease, visual or auditory impairment that would preclude study participation, a life expectancy of less than 1 year, significant alcohol or drug use history, and acute stroke during admission. Of 10 276 patients screened, 430 were randomized and 299 completed 12-month follow-up. Data were analyzed from March to July 2023. Intervention: Intervention patients received 6 months of TMH delivered by a nurse care coordinator guided by an interdisciplinary team (trauma surgeon, pulmonary critical care and geriatrician physicians, nurses, and psychologist) in partnership with primary care. The care coordinator used standard protocols to monitor and treat biopsychosocial symptoms. Main Outcomes and Measures: Primary outcomes were Medical Outcome Study Short Form-36 (SF-36) score and Short Physical Performance Battery (SPPB) score at 12 months. Secondary outcomes were Patient Health Questionnaire-9 (PHQ-9) score, the Generalized Anxiety Disorder scale-7 (GAD-7) score, and health care utilization. Results: A total of 429 participants (228 [53.1%] female; mean [SD] age, 69.3 [10.8] years; mean [SD] ISS, 12.3 [4.6]) completed baseline assessments and were randomized. Follow-up was 76% (n = 324) at 6 months and 70% (n = 299) at 12 months. There were no differences between the TMH and usual care groups at 12 months in SF-36 Physical Component Summary score (mean [SD], 40.42 [12.82] vs 39.18 [12.43]), SF-36 Mental Component Summary score (mean [SD], 53.92 [10.02] vs 53.21 [10.82]), or SPPB score (mean [SD], 8.00 [3.60] vs 8.28 [3.88]). Secondary outcomes were also no different. Planned subgroup analysis revealed patients with baseline symptoms of anxiety or depression (high GAD-7 and PHQ-9 scores) experienced improvement in the Mental Component Summary score when randomized to the TMH intervention. Conclusions and Relevance: The TMH intervention did not significantly influence quality of life, depressive and anxiety symptoms, or physical function of older adults with injury at 12 months. Subgroup analysis showed positive impact in patients with a high burden of anxiety and depression symptoms at enrollment. Collaborative care interventions may improve long-term outcomes of select patients, but further research is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03108820.

Identification of predictive patient characteristics for assessing the probability of COVID-19 in-hospital mortality.

As the world emerges from the COVID-19 pandemic, there is an urgent need to understand patient factors that may be used to predict the occurrence of severe cases and patient mortality. Approximately 20% of SARS-CoV-2 infections lead to acute respiratory distress syndrome caused by the harmful actions of inflammatory mediators. Patients with severe COVID-19 are often afflicted with neurologic symptoms, and individuals with pre-existing neurodegenerative disease have an increased risk of severe COVID-19. Although collectively, these observations point to a bidirectional relationship between severe COVID-19 and neurologic disorders, little is known about the underlying mechanisms. Here, we analyzed the electronic health records of 471 patients with severe COVID-19 to identify clinical characteristics most predictive of mortality. Feature discovery was conducted by training a regularized logistic regression classifier that serves as a machine-learning model with an embedded feature selection capability. SHAP analysis using the trained classifier revealed that a small ensemble of readily observable clinical features, including characteristics associated with cognitive impairment, could predict in-hospital mortality with an accuracy greater than 0.85 (expressed as the area under the ROC curve of the classifier). These findings have important implications for the prioritization of clinical measures used to identify patients with COVID-19 (and, potentially, other forms of acute respiratory distress syndrome) having an elevated risk of death.

Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Over 50% of Acute Respiratory Failure (ARF) survivors experience cognitive, physical, and psychological impairments that negatively impact their quality of life (QOL). Objective: To evaluate the efficacy of a post-intensive care unit (ICU) program, the Mobile Critical Care Recovery Program (m-CCRP) consisting of a nurse care coordinator supported by an interdisciplinary team, in improving the QOL of ARF survivors. Design, Setting, and Participants: This randomized clinical trial with concealed outcome assessments among ARF survivors was conducted from March 1, 2017, to April 30, 2022, with a 12-month follow-up. Patients were admitted to the ICU services of 4 Indiana hospitals (1 community, 1 county, 2 academic), affiliated with the Indiana University School of Medicine. Intervention: A 12-month nurse-led collaborative care intervention (m-CCRP) supported by an interdisciplinary group of clinicians (2 intensivists, 1 geriatrician, 1 ICU nurse, and 1 neuropsychologist) was compared with a telephone-based control. The intervention comprised longitudinal symptom monitoring coupled with nurse-delivered care protocols targeting cognition, physical function, personal care, mobility, sleep disturbances, pain, depression, anxiety, agitation or aggression, delusions or hallucinations, stress and physical health, legal and financial needs, and medication adherence. Main Outcomes and Measures: The primary outcome was QOL as measured by the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), with scores on each component ranging from 0-100, and higher scores indicating better health status. Results: In an intention-to-treat analysis among 466 ARF survivors (mean [SD] age, 56.1 [14.4] years; 250 [53.6%] female; 233 assigned to each group), the m-CCRP intervention for 12 months did not significantly improve the QOL compared with the control group (estimated difference in change from baseline between m-CCRP and control group: 1.61 [95% CI, -1.06 to 4.29] for SF-36 PCS; -2.50 [95% CI, -5.29 to 0.30] for SF-36 MCS. Compared with the control group, the rates of hospitalization were higher in the m-CCRP group (117 [50.2%] vs 95 [40.8%]; P = .04), whereas the 12-month mortality rates were not statistically significantly lower (24 [10.3%] vs 38 [16.3%]; P = .05). Conclusions and Relevance: Findings from this randomized clinical trial indicated that a nurse-led 12-month comprehensive interdisciplinary care intervention did not significantly improve the QOL of ARF survivors after ICU hospitalization. These results suggest that further research is needed to identify specific patient groups who could benefit from tailored post-ICU interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03053245.

Risk factors for dementia in older intensive care unit (ICU) survivors.

INTRODUCTION: As the number of older intensive care unit (ICU) survivors grows, there is an urgent need to identify modifiable risk factors for post-ICU dementia. METHODS: We performed a secondary data analysis of 3144 ICU patients ≥ 50 years of age without a history of dementia or severe mental illness who were screened as part of the Pharmacological Management of Delirium (PMD) study. Delirium was assessed using the Confusion Assessment Method for the ICU. Dementia was identified using International Classification of Diseases Ninth and Tenth revision codes for dementia or prescription of anti-dementia medication. RESULTS: Average age (standard deviation) was 65.2 ± 9.5 years; 50.4% were female; and 37.3% were Black. Analyses identified stroke (adjusted hazard ratio [HR] 2.49; 95% confidence interval [CI: 1.52, 4.07], P < 0.001), and depression (adjusted HR 3.03; 95% CI [1.80, 5.10], P < 0.001) as post-ICU risk factors for dementia. DISCUSSION: Future studies will need to examine whether interventions targeting post-ICU stroke and depression can lower dementia incidence in ICU survivors. HIGHLIGHTS: Risk factors for post-intensive care unit (ICU) dementia were distinct from those of Alzheimer's disease. Cardiovascular risk factors were not associated with dementia in older ICU survivors. Post-ICU stroke was associated with a higher risk of dementia in older ICU survivors. Post-ICU depression was associated with a higher risk of dementia in older ICU survivors.

Serum proteomic analysis in esophagectomy patients with postoperative delirium: A case-control study.

BACKGROUND: Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy. OBJECTIVES: Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population. METHODS: We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds1) test. RESULTS: 52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman rs = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs = 0.61, 95%CI = [0.29, 0.81]). CONCLUSIONS: We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.

Corrigendum: Applications and techniques for fast machine learning in science.

[This corrects the article DOI: 10.3389/fdata.2022.787421.].

Delirium and neuropsychological recovery among emergency general surgery survivors (DANE): study protocol for a randomized controlled trial and collaborative care intervention.

BACKGROUND: Delirium is a complex neuropsychiatric syndrome which consists of acute and varying changes in cognition and consciousness. Patients who develop delirium are at increased risk for a constellation of physical, cognitive, and psychological disabilities long after the delirium has ended. Collaborative care models integrating primary and specialty care in order to address patients with complex biopsychosocial needs have been demonstrated to improve outcomes in patients with chronic diseases. The purpose of this study is to evaluate the ability of a collaborative care model on the neuropsychologic recovery of delirium survivors following emergency surgery. METHODS: This protocol describes a multicenter (eight hospitals in three states) randomized controlled trial in which 528 patients who develop delirium following emergency surgery will be randomized to either a collaborative care model or usual care. The efficacy of the collaborative care model on cognitive, physical, and psychological recovery in these delirium survivors will then be evaluated over 18 months. DISCUSSION: This will be among the first randomized clinical trials in postoperative delirium survivors evaluating an intervention designed to mitigate the downstream effects of delirium and improve the neuropsychologic recovery after surgery. We hope that the results of this study will add to and inform strategies to improve postoperative recovery in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov NCT05373017. Registered on May 12, 2022.

Development of a population-level prediction model for intensive care unit (ICU) survivorship and mortality in older adults: A population-based cohort study.

Background and Aims: Given the growing utilization of critical care services by an aging population, development of population-level risk models which predict intensive care unit (ICU) survivorship and mortality may offer advantages for researchers and health systems. Our objective was to develop a risk model for ICU survivorship and mortality among community dwelling older adults. Methods: This was a population-based cohort study of 48,127 patients who were 50 years and older with at least one primary care visit between January 1, 2017, and December 31, 2017. We used electronic health record (EHR) data to identify variables predictive of ICU survivorship. Results: ICU admission and mortality within 2 years after index primary care visit date were used to divide patients into three groups of "alive without ICU admission", "ICU survivors," and "death." Multinomial logistic regression was used to identify EHR predictive variables for the three patient outcomes. Cross-validation by randomly splitting the data into derivation and validation data sets (60:40 split) was used to identify predictor variables and validate model performance using area under the receiver operating characteristics (AUC) curve. In our overall sample, 92.2% of patients were alive without ICU admission, 6.2% were admitted to the ICU at least once and survived, and 1.6% died. Greater deciles of age over 50 years, diagnoses of chronic obstructive pulmonary disorder or chronic heart failure, and laboratory abnormalities in alkaline phosphatase, hematocrit, and albumin contributed highest risk score weights for mortality. Risk scores derived from the model discriminated between patients that died versus remained alive without ICU admission (AUC = 0.858), and between ICU survivors versus alive without ICU admission (AUC = 0.765). Conclusion: Our risk scores provide a feasible and scalable tool for researchers and health systems to identify patient cohorts at increased risk for ICU admission and survivorship. Further studies are needed to prospectively validate the risk scores in other patient populations.

Delirium and Neuropsychological Recovery among Emergency General Surgery Survivors (DANE): study protocol for a randomized controlled trial and collaborative care intervention.

Background: Delirium is a complex neuropsychiatric syndrome which consists of acute and varying changes in cognition and consciousness. Patients who develop delirium are at increased risk for a constellation of physical, cognitive, and psychological disability long after the delirium has ended. Collaborative care models integrating primary and specialty care in order to address patients with complex biopsychosocial needs has been demonstrated to improve outcomes in patients with chronic diseases. The purpose of this study is to evaluate the ability of a collaborative care model on the neuropsychologic recovery of delirium survivors following emergency surgery. Methods: This protocol describes a multicenter (eight hospitals in three states) randomized controlled trial in which 528 patients who develop delirium following emergency surgery will be randomized to either a collaborative care model or usual care. The efficacy of the collaborative care model on cognitive, physical, and psychological recovery in this delirium survivors will then be evaluated over eighteen months. Discussion: This will be among the first randomized clinical trials in postoperative delirium survivors evaluating an intervention designed to mitigate the downstream effects of delirium and improve the neuropsychologic recovery after surgery. We hope that the results of this study will add to and inform strategies to improve postoperative recovery in this patient group. Trial registration: NCT05373017 (clinicaltrials.gov).

Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study.

OBJECTIVE: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU). PATIENTS: 178 ICU patients with delirium, alive and remaining in ICU at one week. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. CONCLUSION: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.

Evaluation of Photocatalytic, Antioxidant, and Antibacterial Efficacy of Almond Oil Capped Zinc Oxide Nanoparticles.

In this study, ZnO nanoparticles (NPs) were synthesized in the presence of almond oil at various molar ratios of zinc acetate and sodium hydroxide, including 0.5:1, 0.75:1, 1:1, 1.25:1, and 1.5:1, to obtain pH values of 11, 10, 9, 8, and 7, respectively. The XRD results revealed that ZnO NPs exhibit a hexagonal structure, with high crystallinity. SEM results showed that dense and large sized ZnO NPs were formed at pH 11, and relatively small (~30-40 nm) NPs were obtained at pH 9. The size distribution can be explained in terms of the presence of OH- ions at different pH levels. However, the larger size of the NPs at pH 7 compared to those at pH 8-11 were due to the coalescence of NPs suitable for antioxidant/antibacterial activities. ZnO NPs demonstrated a high degradation efficiency (~93%) in 90 min, with a high rate constant for Methyl Orange (MO), which is better than the previously reported rate. The larger sized almond oil capped ZnO NPs also showed excellent radical scavenging activity (94%) and are proven to be good carriers to resist Escherichia coli (E. coli) bacteria.

Mortality and Discharge Location of Intensive Care Patients With Alzheimer Disease and Related Dementia.

BACKGROUND: Intensive care unit (ICU) utilization has increased among patients with Alzheimer disease and related dementia (ADRD), although outcomes are poor. OBJECTIVES: To compare ICU discharge location and subsequent mortality between patients with and patients without ADRD enrolled in Medicare Advantage. METHODS: This observational study used Optum's Clinformatics Data Mart Database from years 2016 to 2019 and included adults aged >67 years with continuous Medicare Advantage coverage and a first ICU admission in 2018. Alzheimer disease and related dementia and comorbid conditions were identified from claims. Outcomes included discharge location (home vs other facilities) and mortality (within the same calendar month of discharge and within 12 months after discharge). RESULTS: A total of 145 342 adults met inclusion criteria; 10.5% had ADRD and were likely to be older, female, and have more comorbid conditions. Only 37.6% of patients with ADRD were discharged home versus 68.6% of patients who did not have ADRD (odds ratio [OR], 0.40; 95% CI, 0.38-0.41). Both death in the same month as discharge (19.9% vs 10.3%; OR, 1.54; 95% CI, 1.47-1.62) and death in the 12 months after discharge (50.8% vs 26.2%; OR, 1.95; 95% CI, 1.88-2.02) were twice as common among patients with ADRD. CONCLUSIONS: Patients with ADRD have lower home discharge rates and greater mortality after an ICU stay than patients without ADRD.

Potential of Secondary Metabolites of Diaporthe Species Associated with Terrestrial and Marine Origins.

Diaporthe species produce versatile secondary metabolites (SMs), including terpenoids, fatty acids, polyketides, steroids, and alkaloids. These structurally diverse SMs exhibit a wide range of biological activities, including cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, and phytotoxic activities, which could be exploited in the medical, agricultural, and other modern industries. This review comprehensively covers the production and biological potencies of isolated natural products from the genus Diaporthe associated with terrestrial and marine origins. A total of 275 SMs have been summarized from terrestrial (153; 55%) and marine (110; 41%) origins during the last twelve years, and 12 (4%) compounds are common to both environments. All secondary metabolites are categorized predominantly on the basis of their bioactivities (cytotoxic, antibacterial, antifungal, and miscellaneous activity). Overall, 134 bioactive compounds were isolated from terrestrial (92; 55%) and marine (42; 34%) origins, but about half the compounds did not report any kind of activity. The antiSMASH results suggested that Diaporthe strains are capable of encoding a wide range of SMs and have tremendous biosynthetic potential for new SMs. This study will be useful for future research on drug discovery from terrestrial and marine natural products.

Relationship between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prescribing and delirium in the ICU-A secondary analysis.

BACKGROUND: Studies suggest Angiotensin-Converting Enzyme inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) may slow the decline of memory function in individuals with mild to moderate Alzheimer's disease by regulating migroglial activation and oxidative stress within the brain's reticular activating system. Therefore, we evaluated the relationship between delirium prevalence and being prescribed ACEI and ARB in participants admitted to the intensive care units (ICU). METHODS: A secondary analysis of data from two parallel pragmatic randomized controlled trials was performed. ACEI and ARB exposure was defined as being prescribed an ACEI or an ARB within six months prior to the ICU admission. The primary endpoint was the first positive delirium assessment based on Confusion Assessment Method for the ICU (CAM-ICU) for up to thirty days. RESULTS: A total of 4791 patients admitted to the medical, surgical, and progressive ICU and screened for eligibility for the parent studies between February 2009 and January 2015 from two level 1 trauma and one safety net hospital in a large urban academic health system were included. Delirium rates in the ICU were not significantly different among participants with no exposure to ACEI/ARB (12.6%), or exposure to ACEI (14.4%), ARB (11.8%), or ACEI and ARB in combination (15.4%) in six months prior to the ICU admission. Exposure to ACEI (OR = 0.97[0.77, 1.22]), ARB (OR = 0.70 [0.47, 1.05]), or both (OR = 0.97 [0.33, 2.89]) in six months prior to ICU admission was not significantly associated with odds of delirium during the ICU admission after adjusting for age, gender, race, co-morbidities, and insurance status. CONCLUSIONS: While the impact of ACEI and ARB exposure prior to the ICU admission was not associated with the prevalence of delirium in this study, further research is needed to fully understand the impact of antihypertensive medications on delirium.

Symptom Assessment for Mechanically Ventilated Patients: Principles and Priorities: An Official American Thoracic Society Workshop Report.

Mechanically ventilated patients experience many adverse symptoms, such as anxiety, thirst, and dyspnea. However, these common symptoms are not included in practice guideline recommendations for routine assessment of mechanically ventilated patients. An American Thoracic Society-sponsored workshop with researchers and clinicians with expertise in critical care and symptom management was convened for a discussion of symptom assessment in mechanically ventilated patients. Members included nurses, physicians, a respiratory therapist, a speech-language pathologist, a critical care pharmacist, and a former intensive care unit patient. This report summarizes existing evidence and consensus among workshop participants regarding 1) symptoms that should be considered for routine assessment of adult patients receiving mechanical ventilation; 2) key symptom assessment principles; 3) strategies that support symptom assessment in nonvocal patients; and 4) areas for future clinical practice development and research. Systematic patient-centered assessment of multiple symptoms has great potential to minimize patient distress and improve the patient experience. A culture shift is necessary to promote ongoing holistic symptom assessment with valid and reliable instruments. This report represents our workgroup consensus on symptom assessment for mechanically ventilated patients. Future work should address how holistic, patient-centered symptom assessment can be embedded into clinical practice.

Dislodged Coronary Stents: The Presnaring Technique.

When dislodged stents remain on the coronary wire, the wire can be snared outside of the body (presnaring), and the snare loop advanced over the wire into the body to retrieve the stent. Presnaring may be a valuable technique to retrieve dislodged coronary stents when the stent remains on the coronary wire, as demonstrated in the 2 patients described.

Chemical Investigation of Endophytic Diaporthe unshiuensis YSP3 Reveals New Antibacterial and Cytotoxic Agents.

Chemical investigation of the plant-derived endophytic fungus Diaporthe unshiuensis YSP3 led to the isolation of four new compounds (1-4), including two new xanthones (phomopthane A and B, 1 and 2), one new alternariol methyl ether derivative (3) and one α-pyrone derivative (phomopyrone B, 4), together with eight known compounds (5-12). The structures of new compounds were interpreted on the basis of spectroscopic data and single-crystal X-ray diffraction analysis. All new compounds were assessed for their antimicrobial and cytotoxic potential. Compound 1 showed cytotoxic activity against HeLa and MCF-7 cells with IC50 values of 5.92 µM and 7.50 µM, respectively, while compound 3 has an antibacterial effect on Bacillus subtilis (MIC value 16 µg/mL).

Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19.

Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity. DESIGN: Retrospective, observational cohort study. SETTING: ICUs at two large, urban, academic referral hospitals. PATIENTS: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17-2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02-1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14-1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08-2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04-1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14-2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03-1.79; p = 0.030) and delirium severity the next day (ß = 0.30; se, 0.07; p ≤ 0.01). CONCLUSIONS: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.

Facile green synthesis, analysis, in vitro antidiabetic and antimicrobial activity of ZnO macropores.

Rapid increase in population and development in industry causes many problems such as microbial contaminations and chronic diseases such as diabetes. Materials synthesized at nanoscale are novel antidiabetic and antimicrobial agents. ZnO nanoparticles with macropores characteristics are synthesized by green methods. Turmeric, clove buds and green tea extracts are used as additives. X-ray diffraction results confirmed the hexagonal wurtzite structure of ZnO nanoparticles and crystallinity was quit high in case of green tea extract. Sample synthesized with clove shows relatively higher crystallite size (10.64) which is pertaining to variation in Zn2+ and OH- ions. The nanoparticles are more or less spherical in nature, macropores and clustered together revealed by SEM images. Macroporosity of the sample was further confirmed by nitrogen adsorption-desorption isotherm. The deep absorption band at 605 cm-1 in FTIR spectra attributed the wurtzite-type ZnO. The major dominating sharp peak was detected at 437 cm-1 in Raman spectra which is a feature of the wurtzite hexagonal phase ZnO. UV-Vis spectra showed red shift from wavelength 362 to 375 nm with different plant extracts. Impedance analysis showed a high dielectric constant and low tangent loss in case of green tea extract. ZnO synthesized using green tea exhibited ~ 95% α-glucosidase inhibition activity and 91% α-amylase inhibition activity. Antibacterial results revealed that synthesized ZnO nanoparticles showed activity against Bacillus subtilis and E. coli with inhibition zone 35 mm and 29 mm, respectively.