Sleep disorder syndromes of post-acute sequelae of SARS-CoV-2 (PASC) / Long Covid.

INTRODUCTION: COVID-19 infection has resulted in a high prevalence of a post-infectious syndrome, known as post-acute sequelae of SARS-CoV-2 (PASC) or "Long COVID". PASC is a heterogeneous disease with a high prevalence of sleep disturbances, varying from an insomnia disorder to excessive daytime sleepiness. METHODS: Patients seen in the Covid Survivorship Program at the Beth Israel Deaconess Medical Center Boston, USA, were screened for sleep disorders as part of a comprehensive multi-system evaluation. Those who screened positive were referred for a comprehensive sleep evaluation in a dedicated COVID-19-Sleep clinic, followed by diagnostic sleep testing and treatment. This report summarizes patients who completed an American Academy of Sleep Medicine (AASM) accredited facility-based diagnostic evaluation. International Classification of Sleep Disorders 3rd Edition-Revised criteria were met for all diagnoses. RESULTS: In 42 patients with PASC, five categories of sleep disorder syndromes were observed following a sleep clinic evaluation, including obstructive sleep apnea, chronic insomnia disorder, primary hypersomnia, REM behavior disorder (RBD), and new onset circadian phase delay. Seven patients met criteria for idiopathic hypersomnia, and two had narcolepsy type 2. RBD patients were infected in three different waves; circadian disturbance patients were all infected in the winter wave of 2020/21, and the primary hypersomnolence group occurred during all waves, predominantly the initial wave of 2020. A peculiar form of insomnia was a persistent loss of sleep regularity. CONCLUSIONS: Specific sleep symptoms/syndromes are reported in this select group of patients with PASC/Long Covid. As new onset sleep complaints are prevalent in PASC, we recommend a complete clinical and investigative sleep evaluation for persistent severe sleep symptoms following COVID-19 infection.

Nirmatrelvir-Ritonavir for Acute COVID-19 in Patients With Cardiovascular Disease and Postacute Sequelae of SARS-CoV-2 Infection.

Background: There is limited evidence of association of nirmatrelvir-ritonavir (NMV-r) and incidence of postacute sequelae of SARS-CoV-2 infection (PASC) in patients with pre-existing cardiovascular disease (CVD). Objectives: The objective of this study was to assess the association of NMV-r in nonhospitalized, vaccinated patients with pre-existing CVD and occurrence of PASC. Methods: We conducted a retrospective cohort study utilizing the TriNetX research network, including vaccinated patients with pre-existing CVD who developed COVID-19 between December 2021 and December 2022. Two cohorts were created based on NMV-r administration within 5 days of diagnosis: NMV-r and non-NMV-r cohort. The main outcome was presence of PASC, assessed between 30 to 90 days and 90 to 180 days after index COVID-19 infection. After propensity score matching, both cohorts were compared using t-test and chi-square test for continuous and categorical variables, respectively. Results: A total of 26,953 patients remained in each cohort after propensity score matching. Broadly defined PASC occurred in 6,925 patients (26%) in the NMV-r cohort vs 8,150 patients (30.6%) in the non-NMV-r cohort (OR: 0.80; 95% CI: 0.76-0.82; P < 0.001) from 30 to 90 days and in 6,692 patients (25.1%) as compared to 8,910 patients (33.5%) (OR: 0.25, 95% CI: 0.23-0.29; P < 0.001) from 90 to 180 days. Similarly, narrowly defined PASC occurred in 5,335 patients (20%) in the NMV-r cohort vs 6,271 patients (23.6%) in the non-NMV-r cohort between 30 and 90 days (OR: 0.81, 95% CI: 0.78-0.84, P < 0.001) and in 5,121 patients (19.2%) as compared to 6,964 patients (26.1%) (OR: 0.67, 95% CI: 0.64-0.70, P < 0.001) between 90 and 180 days. Conclusions: NMV-r in nonhospitalized vaccinated patients with pre-existing CVD with COVID-19 was associated with a reduction in PASC and health care utilization.

Resilience, Survival, and Functional Independence in Older Adults Facing Critical Illness.

BACKGROUND: Older adults surviving critical illness often experience new or worsening functional impairments. Modifiable positive psychological constructs such as resilience may mitigate post-intensive care morbidity. RESEARCH QUESTION: Is pre-ICU resilience associated with: (1) post-ICU survival; (2) the drop in functional independence during the ICU stay; or (3) the trend in predicted independence before vs after the ICU stay? STUDY DESIGN AND METHODS: This retrospective cohort study was performed by using Medicare-linked Health and Retirement Study surveys from 2006 to 2018. Older adults aged ≥ 65 years admitted to an ICU were included. Resilience was calculated prior to ICU admission. The resilience measure was defined from the Simplified Resilience Score, which was previously adapted and validated for the Health and Retirement Study. Resilience was scored by using the Leave-Behind survey normalized to a scale from 0 (lowest resilience) to 12 (highest resilience). Outcomes were survival and probability of functional independence. Survival was modeled by using Gompertz models and independence using joint survival models adjusting for sociodemographic and clinical variables. Average marginal effects were estimated to determine independence probabilities. RESULTS: Across 3,409 patients aged ≥ 65 years old admitted to ICUs, preexisting frailty (30.5%) and cognitive impairment (24.3%) were common. Most patients were previously independent (82.7%). Mechanical ventilation occurred in 14.8% and sepsis in 43.2%. Those in the highest resilience group (vs lowest resilience) had a lower risk of post-ICU mortality (adjusted hazard ratio, 0.81; 95% CI, 0.70-0.94). Higher resilience was associated with greater likelihood of post-ICU functional independence (estimated probability of functional independence 5 years after ICU discharge in highest-to-lowest resilience groups (adjusted hazard ratio [95% CI]): 0.53 (0.33-0.74), 0.47 (0.26-0.68), 0.49 (0.28-0.70), and 0.36 (0.17-0.55); P < .01. Resilience was not associated with a difference in the drop in independence during the ICU stay or a difference in the pre-ICU vs post-ICU trend in predicted independence . INTERPRETATION: ICU survivors with higher resilience had increased rates of survival and functional independence, although the slope of functional decline before vs after the ICU stay did not differ according to resilience group.

Surface chemical heterogeneous distribution in over-lithiated Li1+xCoO2 electrodes.

In commercial Li-ion batteries, the internal short circuits or over-lithiation often cause structural transformation in electrodes and may lead to safety risks. Herein, we investigate the over-discharged mechanism of LiCoO2/graphite pouch cells, especially spatially resolving the morphological, surface phase, and local electronic structure of LiCoO2 electrode. With synchrotron-based X-ray techniques and Raman mapping, together with spectroscopy simulations, we demonstrate that over-lithiation reaction is a surface effect, accompanied by Co reduction and surface structure transformation to Li2CoO2/Co3O4/CoO/Li2O-like phases. This surface chemical distribution variation is relevant to the depth and exposed crystalline planes of LiCoO2 particles, and the distribution of binder/conductive additives. Theoretical calculations confirm that Li2CoO2-phase has lower electronic/ionic conductivity than LiCoO2-phase, further revealing the critical effect of distribution of conductive additives on the surface chemical heterogeneity evolution. Our findings on such surface phenomena are non-trivial and highlight the capability of synchrotron-based X-ray techniques for studying the spatial chemical phase heterogeneity.

Beyond the ICU Rotation: The Importance of Trainee Involvement in Post-Intensive Care Unit Clinics.

Medical learners are vital to the care of critically ill patients in the intensive care unit (ICU). Although these learners are exposed to the challenges and stresses of acute ICU management, they do not typically experience the benefits of following ICU patients and families longitudinally after their ICU rotation. Post-ICU clinics and recovery programs may fill this crucial gap in trainee education. These clinics have emerged as an appealing approach to potentially support patient recovery, enhance provider satisfaction, and provide feedback on vital lessons learned in long-term follow-up to improve the quality of ICU care. Notably, the effect of such a program on trainee education has not been explored. In this article, we propose a framework for medical learner participation in post-ICU follow-up based on the Accreditation Council for Graduate Medical Education milestones and discuss the potential benefits, including: education about post-ICU recovery, including post-intensive care syndrome and post-intensive care syndrome-family; experience in quality improvement to enhance ICU care by understanding long-term outcomes; engagement in reflection; and mitigation of compassion fatigue and burnout.

Six-Month Impairment in Cognition, Mental Health, and Physical Function Following COVID-19-Associated Respiratory Failure.

To determine the prevalence and extent of impairments impacting health-related quality of life among survivors of COVID-19 who required mechanical ventilation, 6 months after hospital discharge. DESIGN: Multicenter, prospective cohort study, enrolling adults 18 years old or older with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received mechanical ventilation for 48 hours or more and survived to hospital discharge. Eligible patients were contacted 6 months after discharge for telephone-based interviews from March 2020 to December 2020. Assessments included: Montreal Cognitive Assessment-Blind, Hospital Anxiety and Depression Scale, Impact of Event Scale-6, EuroQOL 5 domain quality-of-life questionnaire, and components of the Multidimensional Dyspnea Profile. SETTING: Two tertiary academic health systems. PATIENTS: Of 173 eligible survivors, a random sample of 63 were contacted and 60 consented and completed interviews. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age was 57 + 13 years and mean duration of invasive mechanical ventilation was 14 + 8.2 days. Six months post-discharge, 48 patients (80%; 95% CI, 68-88%) met criteria for post-intensive care syndrome (PICS), with one or more domains impaired. Among patients with PICS, 28 (47%; 95% CI, 35-59%) were impaired in at least 2 domains, and 12 (20%; 95% CI, 12-32%) impaired in all three domains. Significant symptoms of post-traumatic stress were present in 20 patients (33%; 95% CI, 23-46%), anxiety in 23 (38%; 95% CI, 27-51%), and depression in 25 (42%; 95% CI, 30-54%). Thirty-three patients (55%; 95% CI, 42-67%) had impairments in physical activity; 25 patients (42%; 95% CI, 30-54%) demonstrated cognitive impairment. CONCLUSIONS: Eighty percent of COVID-19 survivors who required mechanical ventilation demonstrated PICS 6 months after hospital discharge. Patients were commonly impaired in multiple PICS domains as well as coexisting mental health domains.

Characteristics of Post-ICU and Post-COVID Recovery Clinics in 29 U.S. Health Systems.

The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States. DESIGN: Cross-sectional survey. SETTING: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated. PATIENTS: None. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%; physical, 69%; and cognitive, 46%). CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.

Microbotanical residues for the study of early hominin tools.

More than 2 million years ago in East Africa, the earliest hominin stone tools evolved amidst changes in resource base, with pounding technology playing a key role in this adaptive process. Olduvai Gorge (now Oldupai) is a famed locality that remains paramount for the study of human evolution, also yielding some of the oldest battering tools in the world. However, direct evidence of the resources processed with these technologies is lacking entirely. One way to obtain this evidence is through the analysis of surviving residues. Yet, linking residues with past processing activities is not simple. In the case of plant exploitation, this link can only be established by assessing site-based reference collections inclusive of both anthropogenic and natural residues as a necessary first step and comparative starting point. In this paper, we assess microbotanical remains from rock clasts sourced at the same quarry utilized by Oldowan hominins at Oldupai Gorge. We mapped this signal and analysed it quantitatively to classify its spatial distribution objectively, extracting proxies for taxonomic identification and further comparison with freestanding soils. In addition, we used blanks to manufacture pounding tools for blind, controlled replication of plant processing. We discovered that stone blanks are in fact environmental reservoirs in which plant remains are trapped by lithobionts, preserved as hardened accretions. Tool use, on the other hand, creates residue clusters; however, their spatial distribution can be discriminated from purely natural assemblages by the georeferencing of residues and statistical analysis of resulting patterns. To conclude, we provide a protocol for best practice and a workflow that has the advantage of overcoming environmental noise, reducing the risk of false positive, delivering a firm understanding of residues as polygenic mixtures, a reliable use of controls, and most importantly, a stronger link between microbotanical remains and stone tool use.

Predicting hypoglycemia in critically Ill patients using machine learning and electronic health records.

Hypoglycemia is a common occurrence in critically ill patients and is associated with significant mortality and morbidity. We developed a machine learning model to predict hypoglycemia by using a multicenter intensive care unit (ICU) electronic health record dataset. Machine learning algorithms were trained and tested on patient data from the publicly available eICU Collaborative Research Database. Forty-four features including patient demographics, laboratory test results, medications, and vitals sign recordings were considered. The outcome of interest was the occurrence of a hypoglycemic event (blood glucose < 72 mg/dL) during a patient's ICU stay. Machine learning models used data prior to the second hour of the ICU stay to predict hypoglycemic outcome. Data from 61,575 patients who underwent 82,479 admissions at 199 hospitals were considered in the study. The best-performing predictive model was the eXtreme gradient boosting model (XGBoost), which achieved an area under the received operating curve (AUROC) of 0.85, a sensitivity of 0.76, and a specificity of 0.76. The machine learning model developed has strong discrimination and calibration for the prediction of hypoglycemia in ICU patients. Prospective trials of these models are required to evaluate their clinical utility in averting hypoglycemia within critically ill patient populations.

Structure - Functionality of lentil protein-polyphenol conjugates.

Lentil protein isolate (LPI) was conjugated with plant polyphenols (quercetin, rutin, ellagic acid), and the structural and functional characteristics of the conjugates were determined in comparison with the proteins and pure polyphenols. The interaction between polyphenols and protein was achieved by a grafting method at pH 9.0 in the presence of atmospheric oxygen. Surface plasmon resonance measurements showed polyphenols' direct interaction with LPI, with the order of binding strength quercetin > ellagic acid > rutin. The degree of conjugation also followed the same order. Structural analysis of the conjugates was performed using FTIR, intrinsic fluorescence, and surface hydrophobicity. A significant improvement in DPPH radical scavenging and ferric reducing antioxidant power of the conjugates was observed compared to the polyphenols. However, there was a decrease in the surface activity of the conjugates compared to LPI. Such conjugation provides a novel way to combine the advantages of using plant protein and polyphenols in developing a novel food ingredient.

Data-driven curation process for describing the blood glucose management in the intensive care unit.

Analysis of real-world glucose and insulin clinical data recorded in electronic medical records can provide insights into tailored approaches to clinical care, yet presents many analytic challenges. This work makes publicly available a dataset that contains the curated entries of blood glucose readings and administered insulin on a per-patient basis during ICU admissions in the Medical Information Mart for Intensive Care (MIMIC-III) database version 1.4. Also, the present study details the data curation process used to extract and match glucose values to insulin therapy. The curation process includes the creation of glucose-insulin pairing rules according to clinical expert-defined physiologic and pharmacologic parameters. Through this approach, it was possible to align nearly 76% of insulin events to a preceding blood glucose reading for nearly 9,600 critically ill patients. This work has the potential to reveal trends in real-world practice for the management of blood glucose. This data extraction and processing serve as a framework for future studies of glucose and insulin in the intensive care unit.

Transpulmonary pressure measurements and lung mechanics in patients with early ARDS and SARS-CoV-2.

PURPOSE: Acute Respiratory Distress Syndrome (ARDS) secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has demonstrated variable oxygenation and respiratory-system mechanics without investigation of transpulmonary and chest-wall mechanics. This study describes lung, chest wall and respiratory-system mechanics in patients with SARS-CoV-2 and ARDS. METHODS: Data was collected from forty patients with confirmed SARS-CoV-2 and ARDS at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Esophageal balloons were placed to estimate pleural and transpulmonary pressures. Clinical characteristics, respiratory-system, transpulmonary, and chest-wall mechanics were measured over the first week. RESULTS: Patients had moderate-severe ARDS (PaO2/FiO2 123[98-149]) and were critically ill (APACHE IV 108 [94-128] and SOFA 12 [11-13]). PaO2/FiO2 improved over the first week (150 mmHg [122.9-182] to 185 mmHg [138-228] (p = 0.035)). Respiratory system (30-35 ml/cm H2O), lung (40-50 ml/cm H2O) and chest wall (120-150 ml/cm H2O) compliance remained similar over the first week. Elevated basal pleural pressures correlated with BMI. Patients required prolonged mechanical ventilation (14.5 days [9.5-19.0]), with a mortality of 32.5%. CONCLUSIONS: Patients displayed normal chest-wall mechanics, with increased basal pleural pressure. Respiratory system and lung mechanics were similar to known existing ARDS cohorts. The wide range of respiratory system mechanics illustrates the inherent heterogeneity that is consistent with typical ARDS.

Qualitative and quantitative analysis of microplastics and microfiber contamination in effluents of the City of Saskatoon wastewater treatment plant.

In recent years, contamination of the environment with microplastics has received increasing scientific and public attention. Wastewater treatment plants (WWTPs) are considered important emitters of microparticles into aquatic systems. Among these microparticles are microplastics from, e.g., cosmetic products, and microfibers that are released during laundry of textiles made from synthetic fibers. The purpose of this study was to qualitatively and quantitatively characterize microplastic and microfiber contamination in effluents of the City of Saskatoon WWTP, Saskatchewan, Canada. The WWTP discharges directly into the South Saskatchewan River, which is an important water resource of central economic and environmental importance to the Canadian Prairies. To achieve this goal, a reference dataset was developed by determining Raman and Fourier-transform infrared (FTIR) spectra of neat plastic standards. Subsequently, samples were obtained from the final effluent of the Saskatoon WWTP during winter, spring, and summer 2019 by use of fine-meshed plankton nets. Microplastics and microfibers were extracted using Fenton oxidation and filtration, counted, and their identity determined by comparing Raman and FTIR spectra of individual microplastics and microfibers with the previously developed reference dataset. The number concentrations of both microplastics and microfibers were relatively stable across seasons, and fibers accounted for 82% of the total number of synthetic microparticles. Although the average total number concentration of microplastics and microfibers was only 1.76 per liter of effluent, at an average daily discharge of 80 million liters, this would amount to the emission of 141 million particles into the river per day. While the environmental relevance of these findings remains to be demonstrated, these results are an important first step toward understanding the magnitude of microplastic contamination in the Canadian Prairies.