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.