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.

The Effect of In-Person Primary and Secondary School Instruction on County-Level Severe Acute Respiratory Syndrome Coronavirus 2 Spread in Indiana.

BACKGROUND: Our goal was to determine the county-level effect of in-person primary and secondary school reopening on daily cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Indiana. METHODS: In this county-level, population-based study, we used a panel data regression analysis of the proportion of in-person learning to evaluate an association with community-wide daily new SARS-CoV-2 cases. The study period was 12 July 2020-6 October 2020. We included 73 of 92 (79.3%) Indiana counties in the analysis, accounting for 85.7% of school corporations and 90.6% of student enrollment statewide. The primary exposure was the proportion of students returning to in-person instruction. The primary outcome was the daily new SARS-CoV-2 cases per 100 000 residents at the county level. RESULTS: There is a statistically significant relationship between the proportion of students attending K-12 schools in-person and the county level daily cases of SARS-CoV-2 28 days later. For all ages, the coefficient of interest (ß) is estimated at 3.36 (95% confidence interval, 1.91 to 4.81; P < .001). This coefficient represents the effect of a change in the proportion of students attending in-person on new daily cases 28 days later. For example, a 10 percentage point increase in K-12 students attending school in-person is associated with a daily increase in SARS-CoV-2 cases in the county equal to 0.336 cases/100 000 residents of all ages. CONCLUSIONS: In-person primary and secondary school is associated with a statistically significant but proportionally small increase in the spread of SARS-CoV-2 cases.

Postoperative delirium and its relationship with biomarkers for dementia: a meta-analysis.

OBJECTIVES: This study seeks to identify Alzheimer's and related dementias (ADRD) biomarkers associated with postoperative delirium (POD) via meta-analysis. DESIGN: A comprehensive search was conducted. Studies met the following inclusion criteria: >18 years of age, identified POD with standardized assessment, and biomarker measured in the AT(N)-X (A = amyloid, T = tau, (N)=neurodegeneration, X-Other) framework. Exclusion criteria: focus on prediction of delirium, delirium superimposed on dementia, other neurologic or psychiatric disorders, or terminal delirium. Reviewers extracted and synthesized data for the meta-analysis. SETTING: Meta-analysis. PARTICIPANTS: Patients with POD. MEASUREMENTS: Primary outcome: association between POD and ATN-X biomarkers. Secondary outcomes involved sample heterogeneity. RESULTS: 28 studies were included in this meta-analysis. Studies focused on inflammatory and neuronal injury biomarkers; there were an insufficient number of studies for amyloid and tau biomarker analysis. Two inflammatory biomarkers (IL-6, and CRP) showed a significant relationship with POD (IL-6 n = 10, standardized mean difference (SMD): 0.53, 95% CI: 0.36-0.70; CRP n = 14, SMD: 0.53, 95% CI: 0.33-0.74). Two neuronal injury biomarkers (blood-based S100B and NfL) were positively associated with POD (S100B n = 5, SMD: 0.40, 95% CI: 0.11-0.69; NFL n = 2, SMD: 0.93, 95% CI: 0.28-1.57). Of note, many analyses were impacted by significant study heterogeneity. CONCLUSIONS: This meta-analysis identified an association between certain inflammatory and neuronal injury biomarkers and POD. Future studies will need to corroborate these relationships and include amyloid and tau biomarkers in order to better understand the relationship between POD and ADRD.

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.

Nutritional Assessment of Denture Wearers Using Matched Electronic Dental-Health Record Data.

PURPOSE: To assess the nutritional profile of denture wearers through a retrospective cohort study using nutritional biomarkers from matched electronic dental and health record (EDR-EHR) data. MATERIALS AND METHODS: The case group (denture wearers) included matched EDR-EHR data of patients who received removable partial, complete, and implant-supported prosthodontic treatments between January 1, 2010 and December 31, 2018, study time. The control (nondenture wearers) group did not have recorded denture treatments and included patient records within 1 year of the denture index date (first date of case patients' receiving complete or partial denture) of the matching cases. The qualified patients' EDR were matched with their EHR based on the availability of laboratory reports within 2 years of receiving the dentures (index date). Nutritional biomarkers were selected from laboratory reports for complete blood count, comprehensive and basic metabolic profile, lipid, and thyroid panels. Summary statistics were performed, and general linear mixed effect models were used to evaluate the rate of change over time (slope) of nutritional biomarkers before and after the index date. Likelihood ratio tests were performed to determine the differences between dentures and controls. RESULTS: The final cohort included 10,481 matched EDR-EHR data with 3,519 denture wearers and 6,962 controls that contained laboratory results within the study time. The denture wearers' mean age was 57 ±10 years and the control group was 56 ±10 years with 55% females in both groups. Pre-post analysis among denture wearers revealed decreased serum albumin (p = 0.002), calcium (p = 0.039), creatinine (p < 0.001) during the post-index time. Hemoglobin (Hb) was higher pre-index, and was decreasing during the time period but did not change post-index (p < 0.001). Among denture wearers, completely edentulous patients had a significant decrease in serum albumin, creatinine, blood urea nitrogen (BUN), but increased estimated glomerular filtration rate (eGFR). In partially edentulous patients, total cholesterol decreased (p = 0.018) and TSH (p = 0.004), BUN (p < 0.001) increased post-index. Patients edentulous in either upper or lower arch had decreased BUN and eGFR during post-index. Compared to controls, denture wearers showed decreased serum albumin and protein (p = 0.008), serum calcium (p = 0.001), and controls showed increased Hb (p = 0.035) during post-index. CONCLUSIONS: The study results indicate nutritional biomarker variations among denture wearers suggesting a risk for undernutrition and the potential of using selected nutritional biomarkers to monitor nutritional profile.

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).

A Meta-analysis of Clinical Trials Evaluating the Impact of Bivalirudin-based Anticoagulation for Primary Percutaneous Coronary on Long-Term Mortality.

ABSTRACT: Bivalirudin and heparin are the principal anticoagulants used during primary percutaneous coronary intervention (PCI) for patients experiencing ST-elevation myocardial infarctions. Based on previous meta-analyses, bivalirudin improves 30-day mortality rates compared with heparin, especially when vascular access is predominantly femoral. However, no meta-analysis has yet reported whether this mortality benefit with bivalirudin persists beyond 30 days. Scientific databases and websites were searched to find randomized controlled trials, and risk ratios (RRs) were calculated using random effect models. Data from 4 trials were analyzed. Compared with heparin ± glycoprotein IIb/IIIa inhibitors, bivalirudin decreased all-cause mortality [RR, 0.81; 95% confidence interval (CI), 0.69-0.94; P = 0.008], cardiac mortality (RR, 0.72; 95% CI, 0.60-0.88; P = 0.001), and net adverse clinical events (RR, 0.83; 95% CI, 0.72-0.97; P = 0.016) at 1 year. In conclusion, a bivalirudin-based anticoagulation strategy during primary percutaneous coronary intervention significantly decreases the 1-year risks for all-cause mortality, cardiac mortality, and net adverse clinical events compared with heparin ± glycoprotein IIb/IIIa inhibitor.

Predicting COVID-19-Related Health Care Resource Utilization Across a Statewide Patient Population: Model Development Study.

BACKGROUND: The COVID-19 pandemic has highlighted the inability of health systems to leverage existing system infrastructure in order to rapidly develop and apply broad analytical tools that could inform state- and national-level policymaking, as well as patient care delivery in hospital settings. The COVID-19 pandemic has also led to highlighted systemic disparities in health outcomes and access to care based on race or ethnicity, gender, income-level, and urban-rural divide. Although the United States seems to be recovering from the COVID-19 pandemic owing to widespread vaccination efforts and increased public awareness, there is an urgent need to address the aforementioned challenges. OBJECTIVE: This study aims to inform the feasibility of leveraging broad, statewide datasets for population health-driven decision-making by developing robust analytical models that predict COVID-19-related health care resource utilization across patients served by Indiana's statewide Health Information Exchange. METHODS: We leveraged comprehensive datasets obtained from the Indiana Network for Patient Care to train decision forest-based models that can predict patient-level need of health care resource utilization. To assess these models for potential biases, we tested model performance against subpopulations stratified by age, race or ethnicity, gender, and residence (urban vs rural). RESULTS: For model development, we identified a cohort of 96,026 patients from across 957 zip codes in Indiana, United States. We trained the decision models that predicted health care resource utilization by using approximately 100 of the most impactful features from a total of 1172 features created. Each model and stratified subpopulation under test reported precision scores >70%, accuracy and area under the receiver operating curve scores >80%, and sensitivity scores approximately >90%. We noted statistically significant variations in model performance across stratified subpopulations identified by age, race or ethnicity, gender, and residence (urban vs rural). CONCLUSIONS: This study presents the possibility of developing decision models capable of predicting patient-level health care resource utilization across a broad, statewide region with considerable predictive performance. However, our models present statistically significant variations in performance across stratified subpopulations of interest. Further efforts are necessary to identify root causes of these biases and to rectify them.

Eremophilane Sesquiterpenes and Benzene Derivatives from the Endophyte Microdiplodia sp. WGHS5.

Three new eremophilane sesquiterpenes phomadecalins G-I (1-3) and two new benzene derivatives microdiplzenes A and B (12 and 13), together with nine known eremophilane sesquiterpenes (4-11 and 14) were isolated from an endophytic fungus, Microdiplodia sp. WGHS5. Their structures were elucidated by the interpretation of HR-ESI-MS and NMR data; meanwhile, the absolute configurations of new compounds were determined on the base of ECD calculations. All compounds were evaluated for the antimicrobial activities and antiproliferative effect on human gastric cancer cell lines (BGC-823).

On the influence of demographic structure and industrial growth on environmental quality.

The working-age population is an essential driver of economic growth that facilitates industrial growth, trade, and urbanization, but its impression on environmental quality is under-researched. This study proposes a novel framework to estimate the impact of demographic structure, industrial growth, and urbanization on two indicators of the environment (CO2 & Ecological footprints) in seven South Asian countries (SAARC) over 1985-2016 employing "Stochastic Impact by Regression on Population, Affluence, and Technology (STIRPAT)" framework. The results showed the variables have "cross-sectional dependence" and panel heterogeneity. Similarly, the Pedroni, Kao & Westerlund tests indicated the cointegration relationship between the models' chosen variables. The long-run empirical estimates imply that the linear term of industrial growth is negative. The quadratic term is positive, thus supporting the U-shaped Kuznets phenomenon in the SAARC countries. Similarly, the working-age population (demographic structure), urbanization, and trade are detrimental environmental quality indicators. The causal linkages developed between the variables duly verified the causality between demographic structure, urbanization, and industrial growth with environmental degradation based on ecological footprints and CO2 emissions. These results for SAARC countries offer important policies for theorists, academicians, and practitioners.

Incidence of Venous Thromboembolism in Critically Ill Coronavirus Disease 2019 Patients Receiving Prophylactic Anticoagulation.

OBJECTIVES: One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses. The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation. DESIGN: Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation. SETTING: Tertiary-care center in Indianapolis, IN, United States. PATIENTS: Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 45 patients were included. Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis. Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02). Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). D-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both). Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35). Ultrasound evaluation is recommended if D-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if D-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%). CONCLUSIONS: Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019. There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. D-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.

Biomarkers of Delirium Duration and Delirium Severity in the ICU.

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-100ß 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-100ß 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-100ß 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-100ß 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.

Associations Between Mean Arterial Pressure and Poor ICU Outcomes in Critically Ill Patients With Cirrhosis: Is 65 The Sweet Spot?

OBJECTIVES: Mean arterial pressure is critically important in patients with cirrhosis in the ICU, however, there is limited data to guide therapies and targets. DESIGN: Retrospective observational study. SETTING: Tertiary care ICU. PATIENTS: Two hundred and seventy-three critically ill patients with cirrhosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed a comprehensive time-weighted mean arterial pressure analysis (time-weighted-average-mean arterial pressure and cumulative-time-below various mean arterial pressure-thresholds) during the first 24-hours after ICU admission (median: 25 mean arterial pressure measurements per-patient). Time-weighted-average-mean arterial pressure captures both the severity and duration of hypotension below a mean arterial pressure threshold and cumulative-time-below is the total time spent below a mean arterial pressure threshold. Individual univariable and multivariable logistic regression models were assessed for each time-weighted-average-mean arterial pressure and cumulative-time-below mean arterial pressure threshold (55, 60, 65, 70, and 75 mm Hg) for ICU-mortality. Time-weighted-average-mean arterial pressure: for 1 mm Hg decrease in mean arterial pressure below 75, 70, 65, 60, and 55 mm Hg, the odds for ICU-mortality were 14%, 18%, 26%, 41%, and 74%, respectively (p < 0.01, all thresholds). The association between time-weighted-average-mean arterial pressure and ICU-mortality for each threshold remained significant after adjusting for model for end-stage liver disease-sodium score, mechanical ventilation, vasopressor use, renal replacement therapy, grade 3/4 hepatic encephalopathy, WBC count, and albumin. Cumulative-time-below: odds for ICU-mortality were 4%, 6%, 10%, 12%, and 12% for each-hour spent below 75, 70, 65, 60, and 55 mm Hg, respectively. In the adjusted models, significant associations only remained for mean arterial pressure less than 65 mm Hg (odds ratio, 1.07; 95% CI, 1.00-1.14; p = 0.05) and < 60 mm Hg (odds ratio, 1.10; 95% CI, 1.01-1.18; p = 0.04). CONCLUSIONS: These data suggest that maintaining a mean arterial pressure of greater than 65 mm Hg may be a reasonable target in patients with cirrhosis admitted to the ICU. However, further prospective randomized trials are needed to determine the optimal mean arterial pressure-targets in this patient population.

Society of Critical Care Medicine's International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness.

BACKGROUND: After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when remain unclear. OBJECTIVES: Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for postdischarge impairments. PARTICIPANTS: Thirty-one international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine's Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers. DESIGN: Society of Critical Care Medicine consensus conference on post-intensive care syndrome prediction and assessment, held in Dallas, in May 2019. A systematic search of PubMed and the Cochrane Library was conducted in 2018 and updated in 2019 to complete an original systematic review and to identify pre-existing systematic reviews. MEETING OUTCOMES: We concluded that existing tools are insufficient to reliably predict post-intensive care syndrome. We identified factors before (e.g., frailty, preexisting functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2-4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment test; Hospital Anxiety and Depression Scale; Impact of Event Scale-Revised (post-traumatic stress disorder); 6-minute walk; and/or the EuroQol-5D-5L, a health-related quality of life measure (physical function). CONCLUSIONS: Beginning with an assessment of a patient's pre-ICU functional abilities at ICU admission, clinicians have a care coordination strategy to identify and manage impairments across the continuum. As hospital discharge approaches, clinicians should use brief, standardized assessments and compare these results to patient's pre-ICU functional abilities ("functional reconciliation"). We recommend serial assessments for post-intensive care syndrome-related problems continue within 2-4 weeks of hospital discharge, be prioritized among high-risk patients, using the identified screening tools to prompt referrals for services and/or more detailed assessments.

Critical Care Recovery Center: a model of agile implementation in intensive care unit (ICU) survivors.

BACKGROUND: As many as 70% of intensive care unit (ICU) survivors suffer from long-term physical, cognitive, and psychological impairments known as post-intensive care syndrome (PICS). We describe how the first ICU survivor clinic in the United States, the Critical Care Recovery Center (CCRC), was designed to address PICS using the principles of Agile Implementation (AI). METHODS: The CCRC was designed using an eight-step process known as the AI Science Playbook. Patients who required mechanical ventilation or were delirious ≥48 hours during their ICU stay were enrolled in the CCRC. One hundred twenty subjects who completed baseline HABC-M CG assessments and had demographics collected were included in the analysis to identify baseline characteristics that correlated with higher HABC-M CG scores. A subset of patients and caregivers also participated in focus group interviews to describe their perceptions of PICS. RESULTS: Quantitative analyses showed that the cognitive impairment was a major concern of caregivers. Focus group data also confirmed that caregivers of ICU survivors (n = 8) were more likely to perceive cognitive and mental health symptoms than ICU survivors (n = 10). Caregivers also described a need for ongoing psychoeducation about PICS, particularly cognitive and mental health symptoms, and for ongoing support from other caregivers with similar experiences. CONCLUSIONS: Our study demonstrated how the AI Science Playbook was used to build the first ICU survivor clinic in the United States. Caregivers of ICU survivors continue to struggle with PICS, particularly cognitive impairment, months to years after discharge. Future studies will need to examine whether the CCRC model of care can be adapted to other complex patient populations seen by health-care professionals.

Bioactive-guided structural optimization of 1,2,3-triazole phenylhydrazones as potential fungicides against Fusarium graminearum.

The phytopathogenic fungus Fusarium graminearum is the major causal agent of fusarium head blight (FHB), which is one of the most serious diseases in wheat. Based on our previous work, the 1,2,3-triazole phenylhydrazone scaffold was further optimized at three modification sites to improve its antifungal activity against F. graminearum. The optimization yielded compound 8d was discovered to be a potent fungicidal agent with an EC50 value of 0.28 µg/mL against F. graminearum, which is 3.6 times lower than previously reported. In addition, 8d also exhibited good inhibitory activities against Rhizoctonia solani and Sclerotinia sclerotiorum with EC50 values of 0.86 and 1.66 µg/mL, respectively. In vivo testing demonstrated that 8d could effectively suppress the disease development of FHB at 200 µg/mL with a protection efficacy of 80.6%. Scanning electron micrographs and transmission electron micrographs showed that the external morphology and internal contents of F. graminearum hyphae were abnormal after 24 h of 8d treatment. Therefore, compound 8d was a promising fungicide candidate for further development.

A roadmap to advance delirium research: Recommendations from the NIDUS Scientific Think Tank.

Delirium is an acute disorder of attention and cognition. It occurs across the life span, yet it is particularly common among older adults, and is closely linked with underlying neurocognitive disorders. Evidence is mounting that intervening on delirium may represent an important opportunity for delaying the onset or progression of dementia. To accelerate the current understanding of delirium, the Network for Investigation of Delirium: Unifying Scientists (NIDUS) held a conference "Advancing Delirium Research: A Scientific Think Tank" in June 2019. This White Paper encompasses the major knowledge and research gaps identified at the conference: advancing delirium definition and measurement, understanding delirium pathophysiology, and prevention and treatment of delirium. A roadmap of research priorities is proposed to advance the field in a systematic, interdisciplinary, and coordinated fashion. A call is made for an international consortium and biobank targeted to delirium, as well as a public health campaign to advance the field.

Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives.

OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. CONCLUSIONS: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.

Aging and Postintensive Care Syndrome- Family: A Critical Need for Geriatric Psychiatry.

Postintensive care syndrome-family (PICS-F) describes the psychological symptoms that affect the family members of patients hospitalized in the intensive care unit (ICU) or recently discharged from the ICU. Geriatric psychiatrists should be concerned about PICS-F for several reasons. First, ICU hospitalization in older adults is associated with higher rates of cognitive and physical impairment compared with older adults hospitalized in non-ICU settings or dwelling in the community. This confers a special burden on the caregivers of these older ICU survivors compared with other geriatric populations. Second, as caregivers themselves age, caring for this unique burden can be more challenging compared with other geriatric populations. Third, evidence for models of care centered on patients with multimorbidity and their caregivers is limited. A deeper understanding of how to care for PICS and PICS-F may inform clinical practice for other geriatric populations with multimorbidity and their caregivers. Geriatric psychiatrists may play a key role in delivering coordinated care for PICS-F by facilitating timely diagnosis and interdisciplinary collaboration, advocating for the healthcare needs of family members suffering from PICS-F, and leading efforts within healthcare systems to increase awareness and treatment of PICS-F. This clinical review will appraise the current literature about the impact of critical illness on the family members of ICU survivors and identify crucial gaps in our knowledge about PICS-F among aging patients and caregivers.

Aging and Post-Intensive Care Syndrome: A Critical Need for Geriatric Psychiatry.

Because of the aging of the intensive care unit (ICU) population and an improvement in survival rates after ICU hospitalization, an increasing number of older adults are suffering from long-term impairments because of critical illness, known as post-intensive care syndrome (PICS). This article focuses on PICS-related cognitive, psychological, and physical impairments and the impact of ICU hospitalization on families and caregivers. The authors also describe innovative models of care for PICS and what roles geriatric psychiatrists could play in the future of this rapidly growing population.