Promoting Students' Mental Health through Design and Implementation of Multi-Activity Pods in Educational Institutions Using the WELL Building Standard

The findings of several research studies conducted with university students that aimed to investigate the quantitative relationship between psychological distress, sleep difficulties, and homesickness have shown a significant interrelation among those factors. All the previous studies demonstrated benefits of napping, meditation, relaxation, and sharing feelings and experiences on students' mental well-being, which could enrich the brain's educational capacity, a matter that is relevant to a student's learning level. This study aimed to encourage on-campus students to alleviate their feelings and relax. This process will help students to recharge their energy, in addition to increasing their alertness and focusing abilities, especially since the COVID-19 pandemic has intensified global stresses. In this study, the authors used a systematic review and literature analysis to understand the relationship between mental stresses and student performance. We then used an evidence-based research opinion poll and presented our work at different academic exhibitions for feedback as an approach for developing an experimental conceptual multi-activity unit that can be used across university campuses. The 'Reviving Pod';was specifically designed for different activities: napping, meditation, and virtual communication. The designed approach utilizes state-of-the-art technologies (embedded sensors, smart ergonomic seats, contactless technologies, self-cleaning materials, IoT, virtual meetings platforms, mobile applications, etc.). A Reviving Pod can be located variably within a university campus. According to the poll results, we proposed a recreational zone design to accommodate the pods, as well as a diversity of activities that can encourage students to relieve their stresses and reinforce their health, consequently increasing their academic performance and supporting their well-being using the WELL Building Standard to promote better mental health, which is vital for students' success.

Depression and Anxiety in Patients with Cystic Fibrosis after Six Months on Elexacaftor-Tezacaftor-Ivacaftor

Background: Cystic fibrosis (CF) is a life-limiting disease with chronic, debilitating pulmonary, endocrine, gastrointestinal, and other symptoms. Patients with CF have higher rates of anxiety and depression than the general population (Quittner 2014). Elexacaftor-tezacaftor-ivacaftor (ETI) has resulted in significant improvement of physical CF symptoms by targeting defects in in the CF transmembrane regulator proteins transcribed by the deltaF508 mutation (Middleton 2019). This data is part of a 5 year study monitoring medical and psychiatric symptoms, especially anxiety and depression, in patients taking ETI. Method(s): This is a single center, Nationwide Children's Hospital IRB approved, longitudinal observational study evaluating the effects of ETI treatment on mood and anxiety. Eligible participants were recruited during routine CF clinic visits. Subjects are administered standardized validated measures for anxiety and depression at baseline, 1, 3, 6, 9, 12, 18, 24, 36, 48, and 60 months. Measures include the PHQ-9, GAD-7, adult and pediatric PROMIS Depression and Anxiety Scales. Result(s): 184 subjects (93 males, 91 females), completed all anxiety and depression measures at the 6 month mark. Thirty-two of 184 received pediatric measures. Linear mixed-effects model was used to evaluate changes of primary outcomes, PHQ-9, GAD-7, and PROMIS over the study visits. All statistical analyses are performed in R version 4.0 (R Core Team, Vienna, Austria). Normal range score rates at baseline then 6 months were: PHQ-9, 67%/78%;GAD-7, 71%/79%;adult PROMIS Depression, 87%/91%;pediatric PROMIS Depression, 91%/85%;adult PROMIS Anxiety, 83%/87%;pediatric PROMIS Anxiety, 91%/95%. Overall trends were toward stability to slight improvement on all measures, with only 5 respondents reporting shifts from "normal" to "severe" symptoms. No study participants required emergency or inpatient psychiatric care during this 6 month period. Discussion(s): A significant majority of 184 patients with CF demonstrated normal scores on measures of depression and anxiety during their first 6 months on ETI. These results indicate trends toward improvement in mental health upon initiation of ETI in this sample. While this does not reflect each individual case, it indicates that patients with CF collectively may have decreased anxiety and depression during this time period. While improvements in anxiety and depression as CF symptoms improve with ETI treatment make intuitive sense, the first 6 months of this study occurred during the COVID-19 pandemic. Hence, anxiety and depression may also have been affected by social isolation, changes in routine, and fear of contracting COVID-19. Conclusion/Implications: Continued follow-up is required to evaluate the relationships of CF medical symptoms, depression, anxiety, and ETI treatment over time. References: Middleton PG, et al. (2019). Elexacaftor-Tezacaftor-Ivacaftor for cystic fibrosis with a single Phe508del allele. NEJM, 381(19):1809-19. Quittner AL, et al. (2014). Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers. Thorax, 69:1090-97. Copyright © 2022

Infiltracao Medular Por Leucemia Mieloide Aguda (Lma) E Tumor Solido (Ts) Metastatico: Relato De Caso

Objetivo: Descrever um caso com duas neoplasias concomitantes infiltrando medula ossea (MO), sendo uma delas hematologica e outra, TS. Material e metodos: Relato de caso por meio de coleta de dados de prontuario de paciente acompanhado no HAC. Resultados: Paciente 67 anos, masculino, tabagista (100 anos/maco), ex-etilista, historia de inalacao de tintas com benzeno (pintor de carros por 30 anos), com astenia e anemia ha 4 meses, associado a perda de 25kg. Procurou atendimento em marco/22 com diagnostico de COVID-19 e necessidade de internacao hospitalar. Evoluiu com bicitopenia sendo transferido ao HAC para investigacao. Ao exame fisico: ECOG 3. Hemograma: bicitopenia (Hb 5.8 mg/dL;plaquetas 40000/mm3;leucocitos 13000/mm3;69% blastos). TC: derrame pleural a direita;raros micronodulos pulmonares;enfisema pulmonar difuso acentuado com areas de fibrose associadas;linfonodomegalias mediastinais e hilares, lesoes osteoliticas esparsas. Mielograma: dispoese das tres linhagens, com 24% de celulas blasticas, alem de grumos de celulas nao-hematologicas (TS). Em Citometria de Fluxo (Euroflow): 16% de mieloblastos patologicos, expressando CD7, CD13, CD33, CD34, CD38, CD44, CD71, CD97, CD123. Citogenetica: 47,XY,+8. Nao foi realizada avaliacao molecular. Biopsia de MO: infiltracao macica da medula ossea por tumor solido. Imunohistoquimica com positividade para: CK7 e TTF-1 e negatividade para: CK20, PSA, PAX-8, CD10, CDX-2, GATA-3. Diagnostico final: infiltracao da MO por adenocarcinoma, favorecido sitio pulmonar, e em area residual, infiltracao por Leucemia mieloide aguda, com alteracao citogenetica associada a mielodisplasia (ELN 2022). Como tratava-se de idoso fragil, sem possibilidade de tratamento intensivo das doencas leucemica e oncologica, proposto tratamento paliativo exclusivo, com medidas de suporte. Paciente faleceu apos 2 meses do diagnostico. Discussao: A associacao de LMA com TS nao e rara. O risco de um paciente previamente tratado para TS desenvolver LMA pode ser ate 10 vezes maior que a populacao normal. Relatos de casos de TS recidivados em MO e LMA concomitantes foram descritos, com desfechos sombrios. Contudo, nao ha na literatura a descricao de LMA de novo com TS infiltrando MO concomitantes ao diagnostico. Estudo chines de 2020, analisou 12 casos de LMA associada a TS primario sincronicos, sendo: 3 etiologia pulmonar, 1 mama, 1 mola, e 7 com neoplasia de TGI. O intervalo de tempo mediano para o diagnostico das duas neoplasias foi de 4 meses. O tratamento da LMA foi realizado com quimioterapia (QT) de alta intensidade ou agente hipometilante. A sobrevida global mediana foi de 12.5 meses (porem somente 4/12 tinham TS avancado). Um estudo americano em 2009 analisou 5 pacientes com LMA e tumor de pulmao (2 com doenca avancada) sincronicos. Todos foram tratados com QT de alta intensidade, e a sobrevida media foi de 5 meses (3-21). Conclusao: Este e o primeiro relato de caso de LMA e TS metastatico infiltrando MO concomitantemente ao diagnostico. A LMA deve ser tratada prioritariamente por ser doenca altamente agressiva, levando-se em conta as condicoes clinicas do paciente, com avaliacao individual. E mesmo com tratamento intensivo, o prognostico e reservado. Copyright © 2022

Determinants of COVID-19 Outcome as Predictors of Delayed Healthcare Services among Adults ≥50 Years during the Pandemic: 2006-2020 Health and Retirement Study.

BACKGROUND: The coronavirus disease 19 (COVID-19) was declared a global pandemic on 11 March 2020. To date, a limited number of studies have examined the impact of this pandemic on healthcare-seeking behaviors of older populations. This longitudinal study examined personal characteristics linked to COVID-19 outcomes as predictors of self-reported delayed healthcare services attributed to this pandemic, among U.S. adults, ≥50 years of age. METHODS: Secondary analyses were performed using cross-sectional data (1413 participants) and longitudinal data (2881 participants) from Health and Retirement Study (HRS) (2006-2018) linked to the 2020 HRS COVID-19 Project (57% female, mean age: 68 years). Demographic, socioeconomic, lifestyle and health characteristics were evaluated in relation to delayed overall, surgical and non-surgical healthcare services ("Since March 2020, was there any time when you needed medical or dental care, but delayed getting it, or did not get it at all?" and "What type of care did you delay") using logistic regression and Ensemble machine learning for cross-sectional data as well as mixed-effects logistic modeling for longitudinal data. RESULTS: Nearly 32.7% delayed healthcare services, 5.8% delayed surgical services and 31.4% delayed non-surgical services. Being female, having a college degree or higher and 1-unit increase in depression score were key predictors of delayed healthcare services. In fully adjusted logistic models, a history of 1 or 2 cardiovascular and/or metabolic conditions (vs. none) was associated with 60-70% greater odds of delays in non-surgical services, with distinct findings for histories of hypertension, cardiovascular disease, diabetes and stroke. Ensemble machine learning predicted surgical better than overall and non-surgical healthcare delays. CONCLUSION: Among older adults, sex, education and depressive symptoms are key predictors of delayed healthcare services attributed to the COVID-19 pandemic. Delays in surgical and non-surgical healthcare services may have distinct predictors, with non-surgical delays more frequently observed among individuals with a history of 1 or 2 cardiovascular and/or metabolic conditions.

Predictors of Mortality in Acute Respiratory Failure Patients Treated with Extracorporeal CO2 Removal

Extracorporeal CO2 removal (ECCO2R) is an effective therapy for correcting hypercapnia and respiratory acidosis. However, appropriate patient selection for optimal ECCO2R outcomes is not well defined. The goal of this retrospective, multicenter study was to determine patient and ECCO2R therapy characteristics which predict mortality in acute respiratory failure patients treated with the Hemolung ECCO2R system (ALung Technologies). The Hemolung Registry was queried for patients with acute respiratory failure. The Registry contains patient demographics, baseline and on- ECCO2R physiologic parameters, ICU survival and Hemolung performance data. Predictors of ICU survival were identified using a multivariable logistical regression analysis. 159 Hemolung patients were included in the analysis. Patients primarily had COVID-19 (55%) or non-COVID-19 ARDS (36%). Survival to ICU discharge was 41%. The median age of survivors was lower (49 vs 58 years), the use of adjunct therapies was lower in survivors (35.4% vs 64.9%), and a greater proportion of survivors received the recommended level of anticoagulation (43.1% vs 23.4%). ECCO2R complications were not significantly different between ICU survivors and non-survivors. COVID-19 diagnosis and a P/F < 100 at the start of Hemolung therapy were each independently associated with ICU mortality. This is the first study specifically evaluating patient and ECCO2R therapy characteristics that independently predict mortality in patients presenting with acute respiratory failure. The results of this study can provide insight in patient selection for future clinical trials and real-world use. Due to the retrospective nature of this study survival to hospital discharge data was not available.

Pelargonium sidoides Root Extract: Simultaneous HPLC Separation, Determination, and Validation of Selected Biomolecules and Evaluation of SARS-CoV-2 Inhibitory Activity.

This study aimed to establish a validated HPLC-UV analytical method for the determination of gallic acid, catechin, scopoletin, and umckalin in phytoformulations containing P. sidoides. Also, to assess the anti-SARS-CoV-2 effect of P. sidoides and these biomolecules in vitro. An HPLC-UV method was developed and verified by testing the commercial forms, Kalobin® and Umca®. It revealed low detectable scopoletin and high umckalin levels. Pelargonium sidoides exhibited a significant reduction of SARS-CoV-2-induced cytopathic effect in Vero E6 cells (IC50 13.79 µg/mL and selectivity index, SI 6.3), whereas scopoletin showed a remarkable anti-SARS-CoV-2 activity with better selectivity (IC50 17.79 µg/mL and SI 14.22). An in-silico prediction of the drugability indicated that the studied biomolecules are under the acceptable norms of Lipinski's rule, water-soluble, and showed high GIT absorption and bioavailability. Docking study towards the essential molecular targets for viral replication and entry of SARS-CoV-2 indicated good binding affinity of scopoletin (-6.4 Kcal/mol) towards the interface region between the SARS-CoV-2 spike protein RBD and the ACE2 surface receptor indicating the probability of interference with the viral entry to the human cells and showed H-bonding with His-41 in the active site of the main protease which may explain its high antiviral activity.

Barriers, facilitators, and preferences to exercise interventions in patients with metastatic breast cancer: A qualitative study in four European countries

Background: Exercise is a promising strategy to improve fatigue and quality of life in patients with metastatic breast cancer (MBC). However, little is known about patients’ barriers, facilitators, and preferences for supervised exercise programs. An in-depth understanding of the patients’ perspective could help to define the role of exercise professionals in this regard and support the development and implementation of successful exercise interventions. Methods: Eleven online focus groups were held, including a total of 44 participants from four European countries (DE, ESP, PL, SE). In semi-structured group sessions, patients were encouraged to discuss their reasons to participate in supervised exercise programs, experienced barriers and exercise preferences. Interviews were transcribed verbatim, translated into English, and coded based on a preliminary coding framework, supplemented by themes that emerged during the sessions. Results: Participants expressed positive attitudes towards exercise. Facilitating factors for participation in supervised programs included the benefits of social contact, professional guidance, and the experience of physical and psychological benefits. The main barriers cited were practical issues, physical limitations due to cancer and its treatment, and safety concerns due to Covid-19. Participants did not have a clear, shared preference regarding exercise type or setting, but would appreciate mixed exercises (i.e., aerobic, strength, and mind-body exercises) in flexible training modules. Individualized training programs and feedback from exercise professionals were strongly desired. Conclusions: While there was common ground regarding several barriers and facilitators, patients expressed mixed preferences for exercise programs. This related to benefits of social interaction in group exercise on the one hand, and the need for individualized tailoring to deal with physical restrictions on the other hand. Exercise professionals can play an important role in supporting exercise for MBC patients by identifying individual needs and providing training programs that are adjusted to patients' abilities and preferences. Legal entity responsible for the study: Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital. Funding: European Commission Research & Innovation Horizon 2020. Disclosure: A.M. May: Financial Interests, Institutional, Advisory Role, Paid to institution: COMPASS. K. Steindorf: Financial Interests, Personal, Expert Testimony, < €5,000: Institut National contre le cancer (INCA), Paris, France;Financial Interests, Personal, Expert Testimony, Member of Data Monitoring Board;< €1,000: Swiss Group for Clinical Research (SAAK), Switzerland;Financial Interests, Personal, Invited Speaker, < €1,000: Adviva, Heidelberg, Germany, Pierre Fabre, Freiburg, Germany, Takeda, Breast Cancer Care Center, Unna, Germany, Audi Health Care Insurance, Ingolstadt, Germany, University of Mainz, Germany;Financial Interests, Personal, Invited Speaker, Lecturer fee in Master Course, < €2,000: University of Heidelberg, Germany;Financial Interests, Personal, Expert Testimony, compensation of travel costs, no further fees: German Research Foundation (DFG), Bonn, Germany;Financial Interests, Personal, Expert Testimony, < €1,000: University of Vienna, Vienna, Austria. All other authors have declared no conflicts of interest.

Real-World Use of Extracorporeal CO2 Removal (ECCO2R) to Correct Respiratory Acidosis: Analysis of the Hemolung Registry

Hypercapnia and respiratory acidosis lead to increased morbidity and mortality in critically ill patients. Extracorporeal CO2 removal (ECCO2R) can rapidly correct pH and PaCO2 as a treatment for refractory, hypercapnic respiratory failure. Current clinical evidence for the benefits of ECCO2R is primarily limited to case series and single-center studies. The Hemolung (ALung Technologies, Inc., Pittsburgh, PA) is the only FDA cleared ECCO2R system and has been utilized to treat greater than 1,000 patients world-wide. The purpose of this study was to evaluate real-world evidence of the Hemolung ECCO2R system for the treatment of hypercapnic respiratory failure across a range of primary diagnoses. Methods: The Hemolung Registry was queried for patients with a baseline, pre-Hemolung pH < 7.35. Patients receiving either noninvasive or invasive ventilation were included in the analysis. Physiological benefits of Hemolung therapy were evaluated using a mixed model for repeated measures based on changes in pH and PaCO2 after 4-6 hrs and 16-35 hrs of Hemolung therapy compared to the baseline value. The model was used to calculate two-sided 95% confidence intervals and associated nominal p-values. Additional markers of clinical improvement included avoidance of intubation, survival to decannulation, and Hemolung CO2 removal rate and duration of use. Adverse events were also analyzed based on patient harm. Results: 176 Hemolung patients were included in the analysis. Multiple primary diagnoses were represented: 31% ARDS, 22% COPD exacerbation, 32% COVID-19, and 15% Other. Median CO2 removal by the Hemolung during the first day of therapy was 88 mL/min and resulted in a concomitant correction of pH from a median of 7.20 to 7.35 (p<0.001) and median PaCO2 correction of 81.7 to 57.0 mmHg (p<0.001). Correction of respiratory acidosis was independent of primary diagnosis, age, and BMI. 69% (112/162) of patients survived to de-cannulation. 86% (19/22) of patients failing NIV avoided intubation. There were no unanticipated complications, and the majority of adverse events did not require medical intervention or discontinuation of Hemolung therapy. 3 deaths associated with Hemolung therapy occurred. Conclusion: These data represent the largest reported analysis of ECCO2R therapy to treat a diverse population of hypercapnic respiratory failure patients. The results demonstrate significant correction of pH and PaCO2 within the first day of Hemolung therapy without significant adverse events. Data from forthcoming RCTs will shed further light on whether these physiologic benefits translate to improved outcomes compared to current standard of care.

Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties.

A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2'-pyrrolidine-3',3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d,h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties.

Real-World Evidence of ECCO2R to Correct Respiratory Acidosis: Analysis of the Hemolung Registry

Rationale: Hypercapnia and respiratory acidosis lead to increased morbidity and mortality in critically ill patients. Extracorporeal CO2 removal (ECCO2R) can rapidly correct pH and PaCO2 as a treatment for refractory, hypercapnic respiratory failure. Current clinical evidence for the benefits of ECCO2R is primarily limited to case series and single-center studies. The Hemolung (ALung Technologies) is the only FDA cleared ECCO2R system and has been utilized to treat greater than 1,000 patients world-wide. The purpose of this study was to evaluate real-world evidence of the Hemolung ECCO2R system for the treatment of hypercapnic respiratory failure across a range of primary diagnoses. Methods: The Hemolung Registry was queried for patients with a baseline, pre- Hemolung pH < 7.35. Patients receiving either noninvasive or invasive ventilation were included in the analysis. Physiological benefits of Hemolung therapy were evaluated using a mixed model for repeated measures based on changes in pH and PaCO2 after 4-6 hrs and 16-35 hrs of Hemolung therapy compared to the baseline value. The model was used to calculate two-sided 95% confidence intervals and associated nominal p-values. Additional markers of clinical improvement included avoidance of intubation, survival to decannulation, and Hemolung CO2 removal rate and duration. Adverse events were also analyzed based on patient harm. Results:176 Hemolung patients were included in the analysis. Multiple primary diagnoses were represented: 31% ARDS, 22% COPD exacerbation, 32% COVID-19, and 15% Other. Median duration of Hemolung therapy was 6.0 days. Median CO2 removal by the Hemolung during the first day of therapy was 88 mL/min and resulted in a concomitant correction of pH from a median of 7.20 to 7.35 (p<0.001) and median PaCO2 correction of 81.7 to 57.0 mmHg (p<0.001). Correction of respiratory acidosis was independent of primary diagnosis, age, and BMI. 69% (112/162) of patients survived to decannulation. 86% (19/22) of patients failing NIV avoided intubation. There were no unanticipated complications, and the majority of adverse events did not require medical intervention or discontinuation of Hemolung therapy. 3 deaths associated with Hemolung therapy occurred. Conclusions: These data represent the largest reported analysis of ECCO2R therapy to treat a diverse population of hypercapnic respiratory failure patients. The results demonstrate significant correction of pH and PaCO2 within the first day of Hemolung therapy without significant adverse events. Data from forthcoming RCTs will shed further light on whether these physiologic benefits translate to improved outcomes compared to current standard of care.

Spiro-3-indolin-2-ones: Synthesis, biological properties and computational studies (preprint)

A series of 1''-(alkylsulfonyl)-dispiro[indoline-3,2'-pyrrolidine-3',3''-piperidine]-2,4''-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d,h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties. 

Predictors of Covid-19 level of concern among older adults from the health and retirement study.

The purpose of this longitudinal study is to construct a prediction model for Covid-19 level of concern using established Covid-19 socio-demographic, lifestyle and health risk characteristics and to examine specific contributions of obesity-related cardiometabolic health characteristics as predictors of Covid-19 level of concern among a representative sample of U.S. older adults. We performed secondary analyses of existing data on 2872 2006-2020 Health and Retirement Study participants and examined 19 characteristics in relation to the outcome of interest using logistic regression and machine learning algorithms. In mixed-effects ordinal logistic regression models, a history of diabetes, stroke as well as 1-2 cardiometabolic risk factors and/or chronic conditions were associated with greater Covid-19 level of concern, after controlling for confounders. Female sex, birth cohort, minority race, Hispanic ethnicity and total wealth as well as depressive symptoms were associated with higher level of Covid-19 concern, and education was associated with lower level of Covid-19 concern in fully adjusted mixed-effects ordinal logistic regression models. The selected socio-demographic, lifestyle and health characteristics accounted for < 70% of the variability in Covid-19 level of concern based on machine learning algorithms. Independent risk factors for Covid-19 level of concern among U.S. older adults include socio-demographic characteristics and depressive symptoms. Advanced research is needed to identify relevant predictors and elucidate underlying mechanisms of observed relationships.

Comparative Single-Dose mRNA and ChAdOx1 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2, Including Variants of Concern: Test-Negative Design, British Columbia, Canada.

BACKGROUND: In British Columbia, Canada, most adults 50-69 years old became eligible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in April 2021, with chimpanzee adenoviral vectored vaccine (ChAdOx1) restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage. METHODS: Among adults 50-69 years old, single-dose messenger RNA (mRNA) and ChAdOx1 vaccine effectiveness (VE) against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between 4 April and 2 October 2021. RESULTS: Single-dose VE included 11 861 cases and 99 544 controls. Median of postvaccination follow-up was 32 days (interquartile range, 15-52 days). Alpha, Gamma, and Delta variants comprised 23%, 18%, and 56%, respectively, of genetically characterized viruses. At 21-55 days postvaccination, single-dose mRNA and ChAdOx1 VE (95% confidence interval [CI]) was 74% (71%-76%) and 59% (53%-65%) against any infection and 86% (80%-90%) and 94% (85%-97%) against hospitalization, respectively. VE (95% CI) was similar against Alpha and Gamma infections for mRNA (80% [76%-84%] and 80% [75%-84%], respectively) and ChAdOx1 (69% [60%-76%] and 66% [56%-73%], respectively). mRNA VE was lower at 63% (95% CI, 56%-69%) against Delta but 85% (95% CI, 71%-92%) against Delta-associated hospitalization (nonestimable for ChAdOx1). CONCLUSIONS: A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants of concern. ChAdOx1 VE was lower against infection, but 1 dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals.

Socio-demographic, lifestyle and health characteristics as predictors of self-reported Covid-19 history among older adults: 2006-2020 Health and Retirement Study.

BACKGROUND: To identify key socio-demographic, lifestyle, and health predictors of self-reported coronavirus disease 2019 (Covid-19) history, examine cardiometabolic health characteristics as predictors of self-reported Covid-19 history and compare groups with and without a history of Covid-19 on trajectories in cardiometabolic health and blood pressure measurements over time, among United States (U.S.) older adults. METHODS: Nationally representative longitudinal data on U.S. older adults from the 2006-2020 Health and Retirement Study were analyzed using logistic and mixed-effects logistic regression models. RESULTS: Based on logistic regression, number of household members (OR=1.26, 95% CI: 1.05, 1.52), depressive symptoms score (OR = 1.21, 95% CI: 1.04, 1.42) and number of cardiometabolic risk factors or chronic conditions ("1-2" vs "0") (OR = 0.27, 95% CI: 0.11, 0.67) were significant predictors of self-reported Covid-19 history. Based on mixed-effects logistic regression, several statistically significant predictors of Covid-19 history were identified, including female sex (OR = 3.06, 95% CI: 1.57, 5.96), other race (OR = 5.85, 95% CI: 2.37, 14.43), Hispanic ethnicity (OR = 2.66, 95% CI: 1.15, 6.17), number of household members (OR = 1.25, 95% CI: 1.10, 1.42), moderate-to-vigorous physical activity (1-4 times per month vs never) (OR = 0.38, 95% CI: 0.18, 0.78) and number of cardiometabolic risk factors or chronic conditions ("1-2" vs "0") (OR = 0.34, 95% CI: 0.19, 0.60). CONCLUSIONS: Number of household members, depressive symptoms and number of cardiometabolic risk factors or chronic conditions may be key predictors for self-reported Covid-19 history among U.S. older adults. In-depth analyses are needed to confirm preliminary findings.

COVID-19 Pandemic Impact on Trajectories in Cardiometabolic Health, Physical Activity, and Functioning Among Adults from the 2006-2020 Health and Retirement Study.

BACKGROUND: The aim of this study was to evaluate the impact of the COVID-19 pandemic on trajectories in cardiometabolic health, physical activity, and functioning among U.S. older adults, overall and according to selected baseline sociodemographic characteristics. METHODS: We performed secondary analyses using longitudinal data on 1,372 participants from the 2006-2020 Health and Retirement Study. Pre-post COVID-19 pandemic onset was examined in relation to body mass index (BMI), number of cardiometabolic risk factors and/or chronic conditions, physical activity, Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) using mixed-effects regression models and group-based trajectory models. RESULTS: The COVID-19 pandemic was associated with significantly increased BMI (ß = 1.39, 95% confidence interval [CI]: 0.74, 2.03). Furthermore, the odds of having at least one cardiometabolic risk factor and/or chronic disease increased pre-post COVID-19 onset (odds ratio 1.16, 95% CI: 1.00, 1.36), whereas physical functioning worsened pre-post COVID-19 onset (ADL: ß = 1.11, 95% CI: 0.94, 1.28; IADL: ß = 0.59, 95% CI: 0.46, 0.73). The pre-post COVID-19 period (2018-2020) showed a stable group of trajectories, with low, medium and high levels of the selected health indicators. Health disparities according to sex, race/ethnicity, educational level, work status, and total wealth are highlighted. CONCLUSIONS: The COVID-19 pandemic onset appears to worsen cardiometabolic health and physical functioning among U.S. older adults, with clusters of individuals defined by selected sociodemographic characteristics experiencing distinct trajectories pre-post COVID-19 pandemic onset.

Synthesis of aspirin-curcumin mimic conjugates of potential antitumor and anti-SARS-CoV-2 properties.

Series of piperidone-salicylate conjugates were synthesized through the reaction of 3E,5E-bis(arylidene)-4-piperidones with the appropriate acid chloride of acetylsalicylate in the presence of triethylamine. All the synthesized conjugates reveal antiproliferative properties against A431 (squamous skin) cancer cell line with potency higher than that of 5-fluorouracil. Many of the synthesized agents also exhibit promising antiproliferative properties against HCT116 (colon) cancer cell line, of which 5o and 5c are the most effective with 12.9, 9.8 folds potency compared with Sunitinib. Promising activity is also shown against MCF7 (breast) cancer cell line with 1.19, 1.12 folds relative to 5-fluorouracil. PI-flow cytometry of compound 5c supports the arrest of cell cycle at G1-phase. However, compound 5o and Sunitinib arrest the cell cycle at S-phase. The synthesized conjugates can be considered as multi-targeted tyrosine kinase inhibitors due to the promising properties against VEGFR-2 and EGFR in MCF7 and HCT116. CDOCKER studies support the EGFR inhibitory properties. Compounds 5p and 5i possessing thienylidene heterocycle are anti-SARS-CoV-2 with high therapeutic indices. Many of the synthesized agents show enhanced COX-1/2 properties than aspirin with better selectivity index towards COX-2 relative to COX-1. The possible applicability of the potent candidates discovered as antitumor and anti-SARS-CoV-2 is supported by the safe profile against normal (non-cancer, RPE1 and VERO-E6) cells.

Real-world use of ecco2r to correct respiratory acidosis: Analysis of the hemolung registry

Extracorporeal CO2 removal (ECCO2R) can benefit critically ill patients with hypercapnic acidosis by correcting pH and PaCO2. The Hemolung RAS (ALung Technologies) has provided ECCO2R therapy to over 1100 patients. The voluntary Hemolung Registry Program collects safety and benefit data from commercial use, US Emergency Use, and US Emergency Use Authorization therapies. 176 Hemolung patients were analyzed to evaluate the benefits and safety of Hemolung therapy. Multiple primary diagnoses were represented: 31% ARDS, 22% COPD exacerbation, 32% COVID-19, and 15% Other. Median duration of Hemolung therapy was 6.0 days. Median CO2 removal by the Hemolung during the first day of therapy was 88 mL/min and resulted in a concomitant correction of pH from a median of 7.20 to 7.35 (p<0.001) and median PaCO2 correction of 81.7 to 57.0 mmHg (p<0.001). Correction of respiratory acidosis was independent of primary diagnosis, age, and BMI. 69% (112/162) of patients survived to de-cannulation. 86% (19/22) of patients failing NIV avoided intubation. There were no unanticipated complications, and the majority of adverse events did not require medical intervention or discontinuation of Hemolung therapy. 3 deaths associated with Hemolung therapy occurred. To date, this is the largest analysis of ECCO2R to treat a diverse population of hypercapnic respiratory failure patients. The results demonstrate significant physiologic benefit from Hemolung therapy, and literature-based evidence suggests this benefit may result in improved outcomes, however data from RCTs are needed to determine whether these physiologic benefits translate to improved outcomes compared to current standard of care.

Impact of routine asymptomatic screening on COVID-19 incidence in a highly vaccinated university population (preprint)

Background: With the return of in-person classes, an understanding of COVID-19 transmission in vaccinated university campuses is essential. Given the context of high anticipated vaccination rates and other measures, there are outstanding questions of the potential impact of campus-based asymptomatic screening. Methods: We estimated the expected number of cases and hospitalizations in one semester using rates derived for British Columbia (BC), Canada up to September 15th, 2021 and age-standardizing to a University population. To estimate the expected number of secondary cases averted due to routine tests of unvaccinated individuals in a BC post-secondary institution, we used a probabilistic model based on the incidence, vaccination effectiveness, vaccination coverage and R0. We examined multiple scenarios of vaccine coverage, screening frequency, and pre-vaccination R0. Results: For one 12 week semester, the expected number of cases is 67 per 50,000 for 80\% vaccination coverage and 37 per 50,000 for 95\% vaccination coverage. Screening of the unvaccinated population averts an expected 6-16 cases per 50,000 at 80\% decreasing to 1-2 averted cases per 50,000 at 95\% vaccination coverage for weekly to daily screening. Further scenarios can be explored using a web-based application. Interpretation: Routine screening of unvaccinated individuals may be of limited benefit if vaccination coverage is 80\% or greater within a university setting.