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1.
HemaSphere ; 6:2024-2025, 2022.
Article in English | EMBASE | ID: covidwho-2032143

ABSTRACT

Background: MZL is the second most common lymphoma in older pts. Choosing an optimal treatment can be challenging because of patient-or disease-related risk factors and treatment-related toxicities (Curr Opin Oncol. 2019;31(5):386-393). Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition, which may improve efficacy outcomes and minimize toxicities, such as cardiac arrythmias and bleeding events. Zanubrutinib received accelerated approval from the United States FDA for the treatment of pts with R/R MZL (Haematologica . 2022;107(1):35-43). Aims: We aim to present a subgroup analysis of efficacy and safety of zanubrutinib in pts aged ≥65 years with R/R MZL enrolled in MAGNOLIA (BGB-3111-214;NCT03846427). Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The primary endpoint was overall response rate (ORR;complete response [CR] and partial response [PR]) determined by an independent review committee (IRC) in accordance with the Lugano classification. Secondary endpoints include ORR by investigator assessment (INV), duration of response (DOR), progression-free survival (PFS), and safety. All pts gave informed consent. Results: As of 18 January 2021, a total of 68 pts were enrolled (Table). Forty (61%) pts were ≥65 years old with a median age of 73 (range, 65-85);18 pts were ≥75 years old. Median number of prior therapies was 2 (range, 1-6) and 10 (25%) pts were refractory to last therapy. Most pts received prior rituximab + cyclophosphamide + vincristine + prednisone (48%) or bendamustine + rituximab (30%), while 5 (13%) pts received rituximab monotherapy. MZL subtypes included extranodal (n=17, 43%), nodal (n=14, 35%), and splenic (n=8, 20%). Median duration of treatment was 14.4 months (mo;range, 0.9-19.6). At a median follow-up of 15.8 mo (range, 2.8-21.8), ORR by IRC was 75% (CR 25%, PR 50%;Table). Responses were observed in all subtypes, with an ORR of 71%, 86%, and 75% in extranodal, nodal, and splenic subtypes, respectively (CR 41%, 21%, and 0%, respectively). Median DOR and PFS were not reached;15-month PFS was 87% and 12-month DOR was 93%. Most (63%) pts are continuing zanubrutinib. Treatment discontinuation due to disease progression was 28% by INV. Most common treatmentemergent adverse events (AEs) observed in ≥20% of pts include contusion (28%), diarrhea (25%), and constipation (20%). Grade ≥3 neutropenia occurred in 5% of pts. The most common infection was upper respiratory tract infection (10%). Two (5%) pts discontinued zanubrutinib due to unrelated fatal AEs (COVID-19 pneumonia and myocardial infarction in a patient with pre-existing coronary artery disease). Atrial fibrillation/flutter and hypertension occurred in 2 (5%) pts each and did not lead to treatment discontinuation. No pts required dose reductions, or experienced major or serious hemorrhage. Image: Summary/Conclusion: The safety profile of zanubrutinib observed in older pts was consistent with previously published results (Clin Cancer Res . 2021;27(23):6323-6332). Zanubrutinib was well tolerated and effective, as demonstrated by a high response rate and durable disease control in older pts with R/R MZL.

2.
JMIR Dermatology ; 5(3), 2022.
Article in English | Scopus | ID: covidwho-2022326

ABSTRACT

Background: Emoticons and emojis have become staple additions to modern-day communication. These graphical icons are now embedded in daily society through the various forms of popular social media and through users' personal electronic conversations. With ever-increasing use and inclusivity, exploration of the possible health care and dermatology applications of these tools is imperative. Objective: The goal of this narrative review was to provide and evaluate an up-to-date literature survey examining the utility of emoticons and emojis in medicine. Special attention was paid to their existing and potential uses in the field of dermatology, especially during the COVID-19 pandemic. Methods: A PubMed search of peer-reviewed publications was performed in mid-2021 to collect articles with emoticon or emoji keywords in combination with other health care-relevant or dermatology-relevant keywords. Screening of publications and described studies was performed by the authors with education and research experience in health care, dermatology, social media, and electronic communication trends. Selected articles were grouped based on common subjects for qualitative analysis and presentation for in-depth discussion. Results: From this extensive search, researchers were able to identify a wide variety of publications detailing the use of emoticons and emojis in general health care, pediatric health care, public health, and dermatology. Key subject areas that emerged from the investigation included the ability of emoticons and emojis to improve communication within pediatric health care, enhance mood and psychological assessment or mental health screening in adults, develop interventions to improve patient medication adherence, complement novel means of public health and COVID-19 surveillance, and bolster dermatology-specific applications. Conclusions: This review illuminated the repurposing of emojis and emoticons for a myriad of advantageous functions in health care and public health, with applications studied in many populations and situations. Dermatology-specific uses were relatively sparse in the literature, highlighting potential opportunities for growth in future studies and practices. The importance of diversity and inclusivity has extended to emojis, with the recent introduction of skin color customization and new emojis better representing the comprehensive spectrum of users' experiences. A continuously evolving and technology-driven population creates a unique niche for emoticons and emojis to ease worldwide communication and understanding, transcending the barriers of age, language, and background. We encourage future studies and innovations to better understand and expand their utility. © Mindy D Szeto, Cara Barber, Varun K Ranpariya, Jarett Anderson, Jonny Hatch, Jordan Ward, Megan N Aguilera, Shahzeb Hassan, Austin Hamp, Tyler Coolman, Robert P Dellavalle.

3.
Oxidative Medicine and Cellular Longevity ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-2020478

ABSTRACT

Bovine lactoferrin (bLf) is a multifunctional protein widely associated with anticancer activity. Prostate cancer is the second most frequent type of cancer worldwide. This study was aimed at evaluating the influence of bLf on cell viability, cell cycle progression, reactive oxygen species (ROS) production, and rate of apoptosis in the human prostate cancer cell line (DU-145). MTT assay and trypan blue exclusion were used to analyze cell viability. Morphological changes were analyzed through optical microscopy after 24 h and 48 h of bLf treatment. FITC-bLf internalization and cellular damage were observed within 24 h by confocal fluorescence microscopy. Cell cycle analyses were performed by flow cytometry and propidium iodide. For caspases 3/7 activation and reactive oxygen species production evaluation, cells were live-imaged using the high-throughput system Operetta. The cell viability assays demonstrated that bLf induces cell death and morphological changes after 24 h and 48 h of treatment compared to control on DU-145 cells. The bLf internalization was detected in DU-145 cells, G1-phase arrest of the cell cycle, caspase 3/7 activation, and increased oxidative stress on bLf-treated cells. Our data support that bLf has an important anticancer activity, thus offering new perspectives in preventing and treating prostate cancer.

4.
Open Forum Infectious Diseases ; 9(8):ofac419, 2022.
Article in English | MEDLINE | ID: covidwho-2018041

ABSTRACT

Immunocompromised patients with prolonged coronavirus disease 2019 symptoms present diagnostic and therapeutic challenges. We measured viral nucleocapsid antigenemia in 3 patients treated with anti-CD20 immunotherapy who acquired severe acute respiratory syndrome coronavirus 2 infection and experienced protracted symptoms. Our results support nucleocapsid antigenemia as a marker of persistent infection and therapeutic response.

5.
BMJ Nutrition, Prevention and Health ; 2022.
Article in English | EMBASE | ID: covidwho-1968290

ABSTRACT

Objectives: Intermittent fasting boosts some host defence mechanisms while modulating the inflammatory response. Lower-frequency fasting is associated with greater survival and lower risk from COVID-19-related comorbidities. This study evaluated associations of periodic fasting with COVID-19 severity and, secondarily, initial infection by SARS-CoV-2. Design: Prospective longitudinal observational cohort study. Setting: Single-centre secondary care facility in Salt Lake City, Utah, USA with follow-up across a 24-hospital integrated healthcare system. Participants: Patients enrolled in the INSPIRE registry in 2013-2020 were studied for the primary outcome if they tested positive for SARS-CoV-2 during March 2020 to February 2021 (n=205) or, for the secondary outcome, if they had any SARS-CoV-2 test result (n=1524). Interventions: No treatment assignments were made;individuals reported their personal history of routine periodic fasting across their life span. Main outcome measures: A composite of mortality or hospitalisation was the primary outcome and evaluated by Cox regression through February 2021 with multivariable analyses considering 36 covariables. The secondary outcome was whether a patient tested positive for SARS-CoV-2. Results: Subjects engaging in periodic fasting (n=73, 35.6%) did so for 40.4±20.6 years (max: 81.9 years) prior to COVID-19 diagnosis. The composite outcome occurred in 11.0% of periodic fasters and 28.8% of non-fasters (p=0.013), with HR=0.61 (95% CI 0.42 to 0.90) favouring fasting. Multivariable analyses confirmed this association. Other predictors of hospitalisation/mortality were age, Hispanic ethnicity, prior MI, prior TIA and renal failure, with trends for race, smoking, hyperlipidaemia, coronary disease, diabetes, heart failure and anxiety, but not alcohol use. In secondary analysis, COVID-19 was diagnosed in 14.3% of fasters and 13.0% of non-fasters (p=0.51). Conclusions: Routine periodic fasting was associated with a lower risk of hospitalisation or mortality in patients with COVID-19. Fasting may be a complementary therapy to vaccination that could provide immune support and hyperinflammation control during and beyond the pandemic. Trial registration: Clinicaltrials.gov, NCT02450006 (the INSPIRE registry).

6.
2022 Workshop on Open Challenges in Online Social Networks, OASIS 2022, held in conjunction with the 33rd ACM Conference on Hypertext and Social Media, HT 2022 ; : 39-49, 2022.
Article in English | Scopus | ID: covidwho-1962414

ABSTRACT

Online social networks (OSNs) are today a primary way to spread and consume information. Maybe the most important aspect of OSNs, both an opportunity and a weakness, is that OSNs are open: users can post anything, which leads to proliferation of information with various degrees of truthfulness. This impacts the volume of information, trending topics, and sentiment of users vis-à-vis of these topics. Our goal in this work is to analyze the spreading of information in Twitter, volume-wise and sentiment-wise (positive or negative), for COVID-19 vaccines overall, and for some specific brands. Our analysis was carried on over five 10-day time-windows in 2021, starting from February and until October. We also looked at what were the most popular tweets we collected during our predefined time-windows, and, by looking at the retweets counts, we observed how they trended over time. © 2022 ACM.

7.
Journal of New Zealand and Pacific Studies ; 10(1):3-5, 2022.
Article in English | Scopus | ID: covidwho-1923720

ABSTRACT

In 2017, the University of Opole and Adam Mickiewicz University in Poznań co-hosted an international conference entitled Redefining Australia and New Zealand: Historical Heritage and Contemporary Perspectives in Language, Culture, and Literature. This was the first of the planned series of Redefining Australia and New Zealand (RANZ) conferences aimed to promote Australian and New Zealand Studies in Poland, as well as to endorse Polish studies of Australia and New Zealand on an international scale. The 2nd RANZ International Conference, Redefining Australia and New Zealand: Changes, Innovations, Reversals, hosted by the University of Warsaw, foregrounded the prevalent and emergent thematic trends in Australian and New Zealand Studies. This included a comprehensive range of theoretical frameworks encompassing historical, traumaoriented, eco-critical, Indigenous, multicultural and gendered perspectives on Australian and New Zealand literature, film and arts, as analysed by both Polish and international scholars. The COVID-19 pandemic forced conference organizers to go online, with the 3rd RANZ International Conference entitled Insularity, Solidarity, Disunity. This was organized by the Adam Mickiewicz University of Poznań, and it resulted in further fruitful transnational discussions on the history and culture of Australia and New Zealand. © 2022. Intellect Ltd Editorial. English language. https://doi.org/10.1386/nzps_00088_2

8.
Clinical Infectious Diseases ; : 12, 2022.
Article in English | Web of Science | ID: covidwho-1895803

ABSTRACT

In hospitalized African women, both SARS-CoV-2 infection and pregnancy independently increased risks of morbidity and mortality. In addition, among pregnant and nonpregnant women with SARS-CoV-2 infection, HIV, prior tuberculosis, sickle cell anemia, and nongestational diabetes increased risk of ICU admission. Background Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. Methods We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models. Results Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38;95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86;95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00;95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0;95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57;95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03;95% CI: 1.79-14.13). Conclusions Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women.

9.
Gastrointestinal Endoscopy ; 95(6):AB65, 2022.
Article in English | EMBASE | ID: covidwho-1885778

ABSTRACT

DDW 2022 Author Disclosures: Louise Krott: NO financial relationship with a commercial interest ;Lynn Debels: NO financial relationship with a commercial interest ;Christophe Schoonjans: NO financial relationship with a commercial interest ;John Anderson: NO financial relationship with a commercial interest ;Roland Valori: NO financial relationship with a commercial interest ;Lobke Desomer: NO financial relationship with a commercial interest ;David Tate: NO financial relationship with a commercial interest Introduction: Colonoscopy is a complex practical skill, which is highly operator dependent. The consistent attainment of key performance indicators (KPIs) by a colonoscopist depends primarily upon training. Local factors, outside of a trainee’s control, may mean their training is unstructured and contingent upon the observed practice of a small number of trainers. This is particularly true given current travel restrictions imposed by the worldwide COVID-19 pandemic. We sought to demonstrate the feasibility and impact of a one-day virtual-live colonoscopy-training course with remote, experienced trainers. Aims and methods: 6 endoscopy trainees [Belgium] underwent a one-day course (the intervention) involving training by consciously competent colonoscopists who were physically remote [United Kingdom]. The intervention comprised 5 interactive sessions on colonoscopy theory combined with 6 live sessions, where trainees performed colonoscopy in their local endoscopy unit, receiving real-time instruction and performance enhancing feedback via a tele-conference monitor situated next to the endoscopic image. Trainers and the five trainees not doing the colonoscopy could follow the procedure in real-time including room view, view of the magnetic colonoscope imager and the endoscopic image. Colonoscopy KPIs were assessed on trainee-performed colonoscopies [unsedated or midazolam/fentanyl sedation] for 3 weeks prior and 4 weeks after the training. Qualitative trainee and trainer feedback regarding the course was obtained. Results: 6 experienced colonoscopy trainees (median 26 months prior-training) underwent the intervention. Trainees performed 60 colonoscopies, (33 pre-, and 27 post-training). Favorable trends in cecal intubation rate (CIR) and adenoma detection rate (ADR) were observed, (91% vs 96% (P=0.386), and 39% vs 63% (P=0.069) respectively). A trend to improved endoscopist-reported comfort scores ([Gloucester Comfort Score (GCS)>3] 18% vs 11% (P=0.375)) and nurse-reported comfort scores (GCS>3 22% vs 8% (P=0.189)) was observed (Table 1). Course participants and trainers alike reported globally favourable qualitative experiences with the expert trainers finding the format feasible and specifically mentioning they could focus on the training without distraction due to reduced cognitive load. Conclusions: Standardization of colonoscopy training is critical to the consistent attainment of KPIs by practicing colonoscopists and improving patient experience. This is the first demonstration of delivering live colonoscopy training remotely: an approach acceptable to trainees and trainers that has a positive impact on KPIs. Pending larger studies focused on efficacy, this approach has the potential to create a standardized curriculum for colonoscopy training, removing the barriers of travel, and allowing expanded exposure to consciously-competent expert trainers. [Formula presented]

10.
Occup Med (Lond) ; 72(5): 343-346, 2022 07 11.
Article in English | MEDLINE | ID: covidwho-1873978

ABSTRACT

BACKGROUND: Chlorhexidine is an antiseptic widely used in healthcare settings. There are increasing reports of significant hypersensitivity reactions associated with its use. Development of chlorhexidine allergy has been identified as an important occupational risk to healthcare workers (HCWs). AIMS: To evaluate the prevalence of sensitization to chlorhexidine amongst HCWs at a large tertiary hospital to assess the potential allergic safety risks associated with chlorhexidine exposure to staff. METHODS: Sensitization to chlorhexidine was evaluated by measurement of serum-specific immunoglobulin E (IgE) in samples collected from staff assessed after a sharps-injury incident and laboratory staff collected for quality assurance procedures. This test method has been shown to have high sensitivity and specificity in the diagnosis of chlorhexidine allergy. Prevalence of sensitization was additionally evaluated with reference to changes in exposure to chlorhexidine-based hand hygiene products because of infection control procedures and the coronavirus disease 2019 pandemic. RESULTS: A total of 320 samples were examined. The prevalence of positive chlorhexidine-specific IgE was 2%. Prevalence of sensitization in samples collected before and after increased chlorhexidine exposure was 1% and 3%. This did not represent a statistically significant difference. CONCLUSIONS: The prevalence figures for chlorhexidine sensitization in this study are higher than have been estimated previously for similar HCW cohorts. Increased exposure to chlorhexidine-based hand hygiene products was not demonstrated to increase sensitization in this group. Given the risk of severe reactions in sensitized individuals, this study indicates that evaluation of chlorhexidine allergy is important when investigating occupational allergy in HCWs.


Subject(s)
COVID-19 , Drug Hypersensitivity , Chlorhexidine/adverse effects , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/epidemiology , Health Personnel , Humans , Immunoglobulin E
11.
2022 CHI Conference on Human Factors in Computing Systems, CHI 2022 ; 2022.
Article in English | Scopus | ID: covidwho-1874710

ABSTRACT

Vaccine hesitancy has always been a public health concern, and anti-vaccine campaigns that proliferate disinformation have gained traction across the US in the last 25 years. The demographics of resistance are varied, with health, religious, and, increasingly, political concerns cited as reasons. With the COVID-19 pandemic igniting the fastest development of vaccines to date, mis- and disinformation about them have become inflammatory, with campaigning allegedly including racial targeting. Through a primarily qualitative investigation, this study inductively examines a large online vaccine discussion space that invokes references to the unethical Tuskegee Syphilis Study to understand how tactics of racial targeting of Black Americans might appear publicly. We find that such targeting is entangled with a genuine discussion about medical racism and vaccine hesitancy. Across 12 distinct voices that address race, medical racism, and vaccines, we discuss how mis- and disinformation sit alongside accurate information in a "polyvocal"space. © 2022 Owner/Author.

12.
Proceedings of the Crawford Fund ; 2021.
Article in English | CAB Abstracts | ID: covidwho-1863815

ABSTRACT

The Crawford Fund has supported a long-running program providing plant pathology and entomology support for smallholder farmers and provincial and district staff in southern Lao PDR. The program has involved over 32 volunteers, mentors and students covering 55 cash crops involved in poverty alleviation. The program has focused on identifying the key pests and diseases while working directly with the farmers to develop appropriate management practices. We endeavour to empower government advisers to work with farmers to alleviate poverty, for example through the production of high value horticulture crops. Activities have included workshops, establishment of small diagnostic laboratories, and the development of pest and disease checklists and extension materials. Benefits also flow to Australia, with volunteers and mentors gaining exposure to pests and diseases not present in Australia, and the opportunity to build professional networks. This case study describes the 'field to lab' approach that has characterised this program and made it successful. Dr Anderson visited Savannakhet and Champasak provinces in February and March 2019 as a volunteer with the Australian Volunteer Program. She worked with local government advisers to visit smallholder farmers and survey the leaf diseases that affect bananas in southern Lao PDR. In-field training for identification of banana leaf diseases was undertaken. Samples were taken to the laboratory for preliminary identification, providing the opportunity for training in specific techniques for working with banana leaf pathogens. Samples were sent to colleagues in internationally recognised laboratories for formal identification, making use of specialised resources not present in Lao PDR. During COVID, ongoing support for the identification of pest and diseases and their management has been through the use of social media such as WhatsApp which link the network of past volunteers, mentors and Lao counterparts.

13.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333097

ABSTRACT

Introduction LenusCOPD has been co-designed to enable digital transformation of COPD services for proactive preventative care. Patient-facing progressive web application, clinician dashboard and support website integrate patient-reported outcomes (PROs), self-management resources, structured clinical summary, wearable and home NIV data with asynchronous patient-clinician messaging. We commenced the implementation-effectiveness observational cohort RECEIVER trial in September 2019, with the primary endpoint of sustained patient usage and secondary endpoints including admissions, mortality, exacerbations, service workload and quality of life. We paused recruitment in March 2021 and provided LenusCOPD as routine care in the “DYNAMIC-SCOT” COVID-19 response service scale-up. Methods 83 RECEIVER trial participants and 142 DYNAMIC-SCOT participants had completed minimum 1 year follow-up when we censored data on 31 st August 2021. We established a control cohort with 5 patients matched per RECEIVER participant from de-identified contemporary routine clinical data. Results Sustained patient app utilisation was noted in both cohorts. Median time to admission or death was 43 days in control, 338 days in RECEIVER and 400 days in DYNAMIC-SCOT participants who had had a respiratory-related admission in the preceding year. The 12-month risk of admission or death was 74% in control patients, 53% in RECEIVER and 47% in the DYNAMIC-SCOT sub-cohort participants. There was a median of 2.5 COPD exacerbations per patient per year with stable quality of life across follow up and a manageable workload for clinical users. Conclusions A high proportion of people continued to use the co-designed LenusCOPD application during extended follow-up. Outcome data supports scale-up of this digital service transformation. Key messages What is the key question? Can sustained patient interaction and improved patient outcomes be achieved with digital transformation of a COPD service? What is the bottom line? Participants continue to use the LenusCOPD patient app, with an average of 3-3.5 interactions per person per week sustained >1-year post-onboarding. COPD- related hospital admissions and occupied bed days were reduced following LenusCOPD onboarding in participants with a history of a severe exacerbation in the previous year, with a median time to readmission of 380 days compared with 50 days in a contemporary matched control patient cohort. Why read on? Feasibility and utility results support scale-up adoption of these digital tools, to support optimised co-management of COPD and other long-term conditions within a continuous implementation-evaluation framework. This will establish a test-bed infrastructure for additional innovations including artificial intelligence-insights for MDT decision support.

14.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-332785

ABSTRACT

The slow pace of global vaccination and the rapid emergence of SARS-CoV-2 variants suggest recurrent waves of COVID-19 in coming years. Therefore, understanding why deaths from COVID-19 are highly concentrated among older adults is essential for global health. Severe COVID-19 T-cell lymphopenia is more common among older adults, and it entails poor prognosis. Much about the primary etiology of this form of lymphopenia remains unknown, but regardless of its causes, offsetting the decline in T-cell count during SARS-CoV-2 infection demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent. We have built a model that captures the effect of age-dependent TL shortening in hematopoietic cells and its effect on T-cell clonal expansion capacity. The model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity plummets by more than 90% over the next ten years. The collapse coincides with the steep increase in COVID-19 mortality with age. HCTL metrics may thus explain the vulnerability of older adults to COVID-19. That said, the wide inter-individual variation in HCTL across the general population means that some younger adults with inherently short HCTL might be at risk of severe COVID-19 lymphopenia and mortality from the disease. Significance Statement: Declining immunity with advancing age is a general explanation for the increased mortality from COVID-19 among older adults. This mortality far exceeds that from viral illnesses such as the seasonal influenza, and it thus requires specific explanations. One of these might be diminished ability with age to offset the development of severe T-cell lymphopenia (a low T-cell count in the blood) that often complicates COVID-19. We constructed a model showing that age-dependent shortening of telomeres might constrain the ability of T-cells of some older COVID-19 patients to undertake the massive proliferation required to clear the virus that causes the infection. The model predicts that individuals with short telomeres, principally seniors, might be at a higher risk of death from COVID-19.

15.
Biophysical Journal ; 121(3):386A-387A, 2022.
Article in English | Web of Science | ID: covidwho-1755680
16.
Open Forum Infectious Diseases ; 8(SUPPL 1):S343-S344, 2021.
Article in English | EMBASE | ID: covidwho-1746513

ABSTRACT

Background. Multi-system inflammatory syndrome in children (MIS-C) is a rare consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MIS-C shares features with common infectious and inflammatory syndromes and differentiation early in the course is difficult. Identification of early features specific to MIS-C may lead to faster diagnosis and treatment. We aimed to determine clinical, laboratory, and cardiac features distinguishing MIS-C patients within the first 24 hours of admission to the hospital from those who present with similar features but ultimately diagnosed with an alternative etiology. Methods. We performed retrospective chart reviews of children (0-20 years) who were admitted to Vanderbilt Children's Hospital and evaluated under our institutional MIS-C algorithm between June 10, 2020-April 8, 2021. Subjects were identified by review of infectious disease (ID) consults during the study period as all children with possible MIS-C require an ID consult per our institutional algorithm. Clinical, lab, and cardiac characteristics were compared between children with and without MIS-C. The diagnosis of MIS-C was determined by the treating team and available consultants. P-values were calculated using two-sample t-tests allowing unequal variances for continuous and Pearson's chi-squared test for categorical variables, alpha set at < 0.05. Results. There were 128 children admitted with concern for MIS-C. Of these, 45 (35.2%) were diagnosed with MIS-C and 83 (64.8%) were not. Patients with MIS-C had significantly higher rates of SARS-CoV-2 exposure, hypotension, conjunctival injection, abdominal pain, and abnormal cardiac exam (Table 1). Laboratory evaluation showed that patients with MIS-C had lower platelet count, lymphocyte count and sodium level, with higher c-reactive protein, fibrinogen, B-type natriuretic peptide, and neutrophil percentage (Table 2). Patients with MIS-C also had lower ejection fraction and were more likely to have abnormal electrocardiogram. Conclusion. We identified early features that differed between patients with MIS-C from those without. Development of a diagnostic prediction model based on these early distinguishing features is currently in progress.

20.
The Australian Journal of Music Therapy ; 32(1):42-51, 2021.
Article in English | ProQuest Central | ID: covidwho-1710461

ABSTRACT

Families faced lost or reduced employment, increased food and housing insecurity, limited ability to support schooling from home due to parental capacity and lack of technology, reduced social support, and increases in levels of domestic violence (Hand et al., 2020). Sing&Grow has also been found to improve parent mental health, parenting behaviours and children's social and communication development (Nicholson et al., 2008;Nicholson et al., 2010;Williams et al., 2012). A shared spreadsheet outlined the weekly workflow for all staff in preparation for 'delivery' the following week, and included allocation of tasks, due dates, digital platforms for content upload, and communication pathways. Family safety was also supported by the addition of an emergency contact to the Sing&Grow's registration form, as well as safety procedures should a music therapist witness anything concerning in a family's home.

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