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1.
Crit Care Explor ; 5(1): e0825, 2023 Jan.
Article in English | MEDLINE | ID: covidwho-2230150

ABSTRACT

Progressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the Pao2 to the Fio2 (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously (ratio of the Spo2 to the Fio2 [S/F ratio]), but it is affected by skin color and occult hypoxemia can occur in Black patients. Oxygen dissociation curves allow noninvasive estimation of P/F ratios (ePFRs) but remain unproven. OBJECTIVES: Measure overt and occult hypoxemia using ePFR. DESIGN SETTING AND PARTICIPANTS: We retrospectively studied COVID-19 hospital encounters (n = 5,319) at two academic centers (University of Virginia [UVA] and Emory University). MAIN OUTCOMES AND MEASURES: We measured primary outcomes (death or ICU transfer within 24 hr), ePFR, conventional hypoxemia measures, baseline predictors (age, sex, race, comorbidity), and acute predictors (National Early Warning Score [NEWS] and Sequential Organ Failure Assessment [SOFA]). We updated predictors every 15 minutes. We assessed predictive validity using adjusted odds ratios (AORs) and area under the receiver operating characteristic curves (AUROCs). We quantified disparities (Black vs non-Black) in empirical cumulative distributions using the Kolmogorov-Smirnov (K-S) two-sample test. RESULTS: Overt hypoxemia (low ePFR) predicted bad outcomes (AOR for a 100-point ePFR drop: 2.7 [UVA]; 1.7 [Emory]; p < 0.01) with better discrimination (AUROC: 0.76 [UVA]; 0.71 [Emory]) than NEWS (0.70 [both sites]) or SOFA (0.68 [UVA]; 0.65 [Emory]) and similar to S/F ratio (0.76 [UVA]; 0.70 [Emory]). We found racial differences consistent with occult hypoxemia. Black patients had better apparent oxygenation (K-S distance: 0.17 [both sites]; p < 0.01) but, for comparable ePFRs, worse outcomes than other patients (AOR: 2.2 [UVA]; 1.2 [Emory]; p < 0.01). CONCLUSIONS AND RELEVANCE: The ePFR was a valid measure of overt hypoxemia. In COVID-19, it may outperform multi-organ dysfunction models. By accounting for biased oximetry as well as clinicians' real-time responses to it (supplemental oxygen adjustment), ePFRs may reveal racial disparities attributable to occult hypoxemia.

2.
Critical care explorations ; 5(1), 2023.
Article in English | EuropePMC | ID: covidwho-2207586

ABSTRACT

IMPORTANCE: Progressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the Pao2 to the Fio2 (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously (ratio of the Spo2 to the Fio2 [S/F ratio]), but it is affected by skin color and occult hypoxemia can occur in Black patients. Oxygen dissociation curves allow noninvasive estimation of P/F ratios (ePFRs) but remain unproven. OBJECTIVES: Measure overt and occult hypoxemia using ePFR. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively studied COVID-19 hospital encounters (n = 5,319) at two academic centers (University of Virginia [UVA] and Emory University). MAIN OUTCOMES AND MEASURES: We measured primary outcomes (death or ICU transfer within 24 hr), ePFR, conventional hypoxemia measures, baseline predictors (age, sex, race, comorbidity), and acute predictors (National Early Warning Score [NEWS] and Sequential Organ Failure Assessment [SOFA]). We updated predictors every 15 minutes. We assessed predictive validity using adjusted odds ratios (AORs) and area under the receiver operating characteristic curves (AUROCs). We quantified disparities (Black vs non-Black) in empirical cumulative distributions using the Kolmogorov-Smirnov (K-S) two-sample test. RESULTS: Overt hypoxemia (low ePFR) predicted bad outcomes (AOR for a 100-point ePFR drop: 2.7 [UVA];1.7 [Emory];p < 0.01) with better discrimination (AUROC: 0.76 [UVA];0.71 [Emory]) than NEWS (0.70 [both sites]) or SOFA (0.68 [UVA];0.65 [Emory]) and similar to S/F ratio (0.76 [UVA];0.70 [Emory]). We found racial differences consistent with occult hypoxemia. Black patients had better apparent oxygenation (K-S distance: 0.17 [both sites];p < 0.01) but, for comparable ePFRs, worse outcomes than other patients (AOR: 2.2 [UVA];1.2 [Emory];p < 0.01). CONCLUSIONS AND RELEVANCE: The ePFR was a valid measure of overt hypoxemia. In COVID-19, it may outperform multi-organ dysfunction models. By accounting for biased oximetry as well as clinicians' real-time responses to it (supplemental oxygen adjustment), ePFRs may reveal racial disparities attributable to occult hypoxemia.

3.
ACR Open Rheumatol ; 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2112433

ABSTRACT

OBJECTIVE: Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other syndromes, making the diagnosis difficult for clinicians. We aimed to compare clinical differences between patients with and without clinical MIS-C diagnosis and develop a diagnostic prediction model to assist clinicians in identification of patients with MIS-C within the first 24 hours of hospital presentation. METHODS: A cohort of 127 patients (<21 years) were admitted to an academic children's hospital and evaluated for MIS-C. The primary outcome measure was MIS-C diagnosis at Vanderbilt University Medical Center. Clinical, laboratory, and cardiac features were extracted from the medical record, compared among groups, and selected a priori to identify candidate predictors. Final predictors were identified through a logistic regression model with bootstrapped backward selection in which only variables selected in more than 80% of 500 bootstraps were included in the final model. RESULTS: Of 127 children admitted to our hospital with concern for MIS-C, 45 were clinically diagnosed with MIS-C and 82 were diagnosed with alternative diagnoses. We found a model with four variables-the presence of hypotension and/or fluid resuscitation, abdominal pain, new rash, and the value of serum sodium-showed excellent discrimination (concordance index 0.91; 95% confidence interval: 0.85-0.96) and good calibration in identifying patients with MIS-C. CONCLUSION: A diagnostic prediction model with early clinical and laboratory features shows excellent discrimination and may assist clinicians in distinguishing patients with MIS-C. This model will require external and prospective validation prior to widespread use.

4.
mBio ; 13(4): e0145422, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-1950003

ABSTRACT

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.


Subject(s)
COVID-19 , Communicable Diseases , Severe acute respiratory syndrome-related coronavirus , Virus Diseases , Animals , Collaborative Cross Mice , Genome-Wide Association Study , Humans , Mice , Severe acute respiratory syndrome-related coronavirus/genetics , SARS-CoV-2/genetics
5.
Mayo Clin Proc ; 97(5): 951-990, 2022 05.
Article in English | MEDLINE | ID: covidwho-1814930

ABSTRACT

Coronary artery disease continues to be a major cause of morbidity and mortality despite significant advances in risk stratification and management. This has prompted the search for alternative nonconventional risk factors that may provide novel therapeutic targets. Psychosocial stress, or mental stress, has emerged as an important risk factor implicated in a higher incidence of cardiovascular events, and although our understanding of this far ranging and interesting phenomenon has developed greatly over recent times, there is still much to be learned regarding how to measure mental stress and how it may impact physical health. With the current coronavirus disease 2019 global pandemic and its incumbent lockdowns and social distancing, understanding the potentially harmful biological effects of stress related to life-changing events and social isolation has become even more important. In the current review our multidisciplinary team discusses stress from a psychosocial perspective and aims to define psychological stress as rigorously as possible; discuss the pathophysiologic mechanisms by which stress may mediate cardiovascular disease, with a particular focus to its effects on vascular health; outline existing methods and approaches to quantify stress by means of a vascular biomarker; outline the mechanisms whereby psychosocial stressors may have their pathologic effects ultimately transduced to the vasculature through the neuroendocrine immunologic axis; highlight areas for improvement to refine existing approaches in clinical research when studying the consequences of psychological stress on cardiovascular health; and discuss evidence-based therapies directed at reducing the deleterious effects of mental stress including those that target endothelial dysfunction. To this end we searched PubMed and Google Scholar to identify studies evaluating the relationship between mental or psychosocial stress and cardiovascular disease with a particular focus on vascular health. Search terms included "myocardial ischemia," "coronary artery disease," "mental stress," "psychological stress," "mental∗ stress∗," "psychologic∗ stress∗," and "cardiovascular disease∗." The search was limited to studies published in English in peer-reviewed journals between 1990 and the present day. To identify potential studies not captured by our database search strategy, we also searched studies listed in the bibliography of relevant publications and reviews.


Subject(s)
COVID-19 , Cardiovascular Diseases , Coronary Artery Disease , Cardiovascular Diseases/etiology , Communicable Disease Control , Humans , Stress, Psychological/complications
6.
Cancers (Basel) ; 14(7)2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1785529

ABSTRACT

BACKGROUND: Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) will have recurrence. The aim of this study was to develop a radiomic based model derived from baseline PET/CT to predict 2-year event free survival (2-EFS). METHODS: Patients with DLBCL treated with R-CHOP chemotherapy undergoing pre-treatment PET/CT between January 2008 and January 2018 were included. The dataset was split into training and internal unseen test sets (ratio 80:20). A logistic regression model using metabolic tumour volume (MTV) and six different machine learning classifiers created from clinical and radiomic features derived from the baseline PET/CT were trained and tuned using four-fold cross validation. The model with the highest mean validation receiver operator characteristic (ROC) curve area under the curve (AUC) was tested on the unseen test set. RESULTS: 229 DLBCL patients met the inclusion criteria with 62 (27%) having 2-EFS events. The training cohort had 183 patients with 46 patients in the unseen test cohort. The model with the highest mean validation AUC combined clinical and radiomic features in a ridge regression model with a mean validation AUC of 0.75 ± 0.06 and a test AUC of 0.73. CONCLUSIONS: Radiomics based models demonstrate promise in predicting outcomes in DLBCL patients.

7.
EClinicalMedicine ; 44: 101287, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1757288

ABSTRACT

BACKGROUND: We aimed to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in hospitalised children and young people (CYP), within a systematic review and individual patient meta-analysis. METHODS: We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies published between 1st January 2020 and 21st May 2021 which included all CYP admitted to hospital with ≥ 30 CYP with SARS-CoV-2 or ≥ 5 CYP with PIMS-TS or MIS-C. Eligible studies contained (1) details of age, sex, ethnicity or co-morbidities, and (2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted groupings of co-morbidities were eligible for narrative review. We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).PROSPERO: CRD42021235338. FINDINGS: 83 studies were included, 57 (21,549 patients) in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years (reference group), infants (aged <1 year) had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).The number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a step-wise fashion. Compared with CYP without comorbidity, odds ratios for critical care admission were: 1.49 (1.45-1.53) for 1 comorbidity; 2.58 (2.41-2.75) for 2 comorbidities; 2.97 (2.04-4.32) for ≥3 comorbidities. Corresponding odds ratios for death were: 2.15 (1.98-2.34) for 1 comorbidity; 4.63 (4.54-4.74) for 2 comorbidities and 4.98 (3.78-6.65) for ≥3 comorbidities. Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. IPD analysis demonstrated that, compared to children without co-morbidity, the risk difference of admission to critical care was increased in those with 1 comorbidity by 3.61% (1.87-5.36); 2 comorbidities by 9.26% (4.87-13.65); ≥3 comorbidities 10.83% (4.39-17.28), and for death: 1 comorbidity 1.50% (0.00-3.10); 2 comorbidities 4.40% (-0.10-8.80) and ≥3 co-morbidities 4.70 (0.50-8.90). INTERPRETATION: Hospitalised CYP at greatest vulnerability of severe disease or death with SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions. FUNDING: RH is in receipt of a fellowship from Kidney Research UK (grant no. TF_010_20171124). JW is in receipt of a Medical Research Council Fellowship (Grant No. MR/R00160X/1). LF is in receipt of funding from Martin House Children's Hospice (there is no specific grant number for this). RV is in receipt of a grant from the National Institute of Health Research to support this work (grant no NIHR202322). Funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript.

8.
Am J Health Promot ; 36(3): 458-471, 2022 03.
Article in English | MEDLINE | ID: covidwho-1650207

ABSTRACT

PURPOSE: To examine the feasibility and acceptability of a social network weight loss intervention delivered by lay health promoters (HPs) to immigrant populations. DESIGN: Single-arm, non-randomized, pilot study of a social network weight loss intervention developed by a community-based participatory research partnership and delivered by HPs. SETTING: Community-based setting in Southeastern Minnesota, United States. SAMPLE: Somali and Hispanic immigrants to the United States: 4 social networks of adults (2 Hispanic and 2 Somali) with 39 network participants. INTERVENTION: Twelve-week behavioral weight loss intervention delivered by HPs (4 weeks in-person and then 8 weeks virtual). MEASURES: Feasibility was assessed by recruitment and retention rates. Acceptability was assessed by surveys and focus groups with HPs and participants. Behavioral measures included servings of fruits and vegetables, drinking soda, and physical activity. Physiologic measures included weight, blood pressure, glucose, cholesterol, and triglycerides. ANALYSIS: Paired t-tests of pre- to post-intervention changes at the end of 12 weeks of treatment. RESULTS: Recruitment was feasible and post-intervention was 100%. Participants highly rated the intervention on satisfaction, motivation, and confidence to eat a healthy diet, be physically active, and lose weight. Participants were motivated by group social support and cohesion of their social networks. On average, participants lost weight (91.6 ± 15.9 to 89.7 ± 16.6 kg, P < .0001), lowered their systolic blood pressure (133.9±16.9 to 127.2 ± 15.8 mm Hg; P < .001), lowered their diastolic blood pressure (81 ± 9.5 to 75.8 ± 9.6 mm Hg; P < .0001), had more servings of vegetables per day (1.9 ± 1.2 to 2.6 ± 1.4; P < .001), and increased their physical activity (2690 ± 3231 to 6595 ± 7322 MET-minutes per week; P = .02). CONCLUSION: This pilot study of 2 immigrant communities who participated in a peer-led weight loss social network intervention delivered during the COVID-19 pandemic demonstrated high feasibility and acceptability. Participants lost weight, improved their health status, and improved their health behaviors.


Subject(s)
COVID-19 , Emigrants and Immigrants , Adult , Humans , Pandemics , Pilot Projects , SARS-CoV-2 , Social Networking , United States , Weight Loss
9.
Nat Med ; 28(1): 193-200, 2022 01.
Article in English | MEDLINE | ID: covidwho-1585817

ABSTRACT

Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective interventions. To address this question, we used data for all hospitalizations in England among 0-17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020-2021); hospitalizations due to all other non-traumatic causes in 2020-2021; hospitalizations due to all non-traumatic causes in 2019-2020; and hospitalizations due to influenza in 2019-2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15-17 year olds compared to 1-4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Ethnicity/statistics & numerical data , Intensive Care Units, Pediatric/statistics & numerical data , Systemic Inflammatory Response Syndrome/epidemiology , Adolescent , Age Factors , Asian People/statistics & numerical data , Black People/statistics & numerical data , Cardiovascular Diseases/epidemiology , Child , Child, Preschool , Comorbidity , England/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Neoplasms/epidemiology , Nervous System Diseases/epidemiology , Odds Ratio , Respiratory Tract Diseases/epidemiology , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Social Deprivation , White People/statistics & numerical data
10.
Telemed J E Health ; 27(12): 1385-1392, 2021 12.
Article in English | MEDLINE | ID: covidwho-1574377

ABSTRACT

Background: To examine clinician perspectives on the acceptability, appropriateness/suitability, and feasibility of video telehealth as a way to deliver mental health services during the COVID-19 pandemic. Materials and Methods: Mental health clinicians were surveyed with 27 Likert questions, using previously validated measures, on satisfaction and implementation experience with video telehealth visits between March and June 2020. Results: A total of 112 of 193 clinicians completed the survey (58.0%), including psychiatrists, psychologists, trainees (i.e., residents and fellows), advanced practice providers, and licensed mental health counselors. Clinicians reported high levels of acceptability, feasibility, and appropriateness of video telehealth; they also reported high levels of satisfaction with video telehealth visits. Seventy-nine and a half (79.5%) reported that their patients seemed highly satisfied with video telehealth visits, and 107 (95.5%) of clinicians responded that they would like video telehealth visits to represent at least 25% of their practice in the future. Discussion: Mental health clinicians showed positive attitudes toward the implementation of video telehealth visits, high levels of satisfaction with this care, and indicated strong interest in continuing this modality as a significant portion of clinical practice. Conclusions: This study demonstrates the ability of mental health clinicians to embrace new technology to expand access to care during the COVID-19 pandemic. Results indicate that telemental health is likely to be an integral part of clinic practice in the future.


Subject(s)
COVID-19 , Telemedicine , Humans , Pandemics , Personal Satisfaction , SARS-CoV-2
11.
Nat Med ; 28(1): 185-192, 2022 01.
Article in English | MEDLINE | ID: covidwho-1514420

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP, <18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally infected with the virus, we undertook a clinical review of all CYP deaths with a positive SARS-CoV-2 test from March 2020 to February 2021. The predominant SARS-CoV-2 variants were wild-type and Alpha. Here we show that, of 12,023,568 CYP living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to coronavirus disease 2019-the clinical disease associated with SARS-CoV-2 infection-and 3 were due to pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. In total, 99.995% of CYP with a positive SARS-CoV-2 test survived. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths. These results are important for guiding decisions on shielding and vaccinating children. New variants might have different mortality risks and should be evaluated in a similar way.


Subject(s)
COVID-19/complications , COVID-19/mortality , Ethnicity/statistics & numerical data , Systemic Inflammatory Response Syndrome/mortality , Adolescent , Age Distribution , Asian People/statistics & numerical data , Black People/statistics & numerical data , COVID-19/epidemiology , COVID-19/ethnology , Cause of Death , Child , Child, Preschool , England/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/ethnology , White People/statistics & numerical data
12.
Cell ; 184(21): 5432-5447.e16, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1454060

ABSTRACT

Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.

13.
Gastrointestinal Endoscopy ; 93(6):AB1-AB386, 2021.
Article in English | EMBASE | ID: covidwho-1298668

ABSTRACT

The proceedings contains 638 papers. The topics discussed include: 3526666 TUBULAR POUCHPLASTY TRANSORAL OUTLET REDUCTION (TTORE) IS SUPERIOR TO AND MORE DURABLE THAN TRADITIONAL TORE IN A LARGE COHORT STUDY;3522113 ENDOSCOPIC VERSUS SURGICAL GASTROJEJUNAL REVISION FOR WEIGHT REGAIN IN ROUX-EN-Y GASTRIC BYPASS PATIENTS: 5-YEAR SAFETY AND EFFICACY COMPARISON;3526904 PRIMARY OBESITY SURGERY ENDOLUMINAL 2 (POSE 2.0): AN INTERNATIONAL MULTICENTER PROSPECTIVE TRIAL WITH PLICATION DURABILITY ASSESSMENT;3523069 CHANGES IN INCRETINS, BILE ACIDS AND THE MICROBIOME AFTER DUODENAL MUCOSAL RESURFACING IN PATIENTS WITH TYPE 2 DIABETES;3523981 THE “ERAS” PROTOCOL REDUCES POST ENDOSCOPIC BARIATRIC PROCEDURE HEALTHCARE UTILIZATION;3520884 QUANTIFYING HEALTHCARE UTILIZATION AND DELAY IN TREATMENT OF GASTRIC STENOSIS FOLLOWING SLEEVE GASTRECTOMY;3523424 ENODOSCOPIC SLEEVE GASTROPLASTY (ESG) SUCCESSES AND FAILURES: PREDICTORS FOR ESG REVISION;3525620 ENDOSCOPIC SLEEVE GASTROPLASTY AS NEW HOPE FOR MILD OBESITY;3526737 HOW WELL MY PATIENT WILL DO? PERSONALITY TRAITS PREDICT WEIGHT LOSS AFTER ENDOSCOPIC SLEEVE GASTROPLASTY;3492486 SEMAGLUTIDE IN ASSOCIATION TO ENDOSCOPIC SLEEVE GASTROPLASTY: TAKING ENDOSCOPIC BATRIATRIC PROCEDURES OUTCOMES TO THE NEXT LEVEL;3520710 GLYCEMIC AND HEPATIC OUTCOMES AFTER ENDOSCOPIC DUODENAL MUCOSAL RESURFACING: A SYSTEMATIC REVIEW AND META-ANALYSIS;3525747 SHORT TERM OUTCOMES OF ENDOSCOPIC SLEEVE GASTROPLASTY (ESG) IN TYPE III OBESE PATIENTS: A CLINICAL, RETROSPECTIVE, SINGLE CENTER STUDY;3526510 ENDOSCOPIC SEPTOTOMY/STAPLE LINE RELEASE TO TREAT AN UNUSUAL CAUSE OF DYSPHAGIA AFTER SLEEVE GASTRECTOMY;3526579 MODIFIED ENDOSCOPIC SUBMUCOSAL DISSECTION – TRANSORAL OUTLET REDUCTION (ESD-TORE) FOR WEIGHT REGAIN;3522594 SAFETY AND FEASIBILITY OF SAME DAY DISCHARGE AFTER PER ORAL ENDOSCOPIC PYLOROMYOTOMY IN REFRACTORY GASTROPARESIS: A PILOT STUDY;3524289 IMPACT OF COVID-19 ON THE MANAGEMENT AND OUTCOMES OF SEVERE ACUTE CHOLANGITIS: FINDINGS FROM A NATIONWIDE CLINICAL DATA RESEARCH NETWORK

15.
Bone Jt Open ; 1(5): 137-143, 2020 May.
Article in English | MEDLINE | ID: covidwho-947961

ABSTRACT

AIMS: The current global pandemic due to COVID-19 is generating significant burden on the health service in the UK. On 23 March 2020, the UK government issued requirements for a national lockdown. The aim of this multicentre study is to gain a greater understanding of the impact lockdown has had on the rates, mechanisms and types of injuries together with their management across a regional trauma service. METHODS: Data was collected from an adult major trauma centre, paediatric major trauma centre, district general hospital, and a regional hand trauma unit. Data collection included patient demographics, injury mechanism, injury type and treatment required. Time periods studied corresponded with the two weeks leading up to lockdown in the UK, two weeks during lockdown, and the same two-week period in 2019. RESULTS: There was a 55.7% (12,935 vs 5,733) reduction in total accident and emergency (A&E) attendances with a 53.7% (354 vs 164) reduction in trauma admissions during lockdown compared to 2019. The number of patients with fragility fractures requiring admission remained constant (32 patients in 2019 vs 31 patients during lockdown; p > 0.05). Road traffic collisions (57.1%, n = 8) were the commonest cause of major trauma admissions during lockdown. There was a significant increase in DIY related-hand injuries (26% (n = 13)) lockdown vs 8% (n = 11 in 2019, p = 0.006) during lockdown, which resulted in an increase in nerve injuries (12% (n = 6 in lockdown) vs 2.5% (n = 3 in 2019, p = 0.015) and hand infections (24% (n = 12) in lockdown vs 6.2% (n = 8) in 2019, p = 0.002). CONCLUSION: The national lockdown has dramatically reduced orthopaedic trauma admissions. The incidence of fragility fractures requiring surgery has not changed. Appropriate provision in theatres should remain in place to ensure these patients can be managed as a surgical priority. DIY-related hand injuries have increased which has led to an increased in nerve injuries requiring intervention.

16.
Bone Jt Open ; 1(7): 424-430, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-937192

ABSTRACT

AIMS: To determine the impact of COVID-19 on orthopaediatric admissions and fracture clinics within a regional integrated care system (ICS). METHODS: A retrospective review was performed for all paediatric orthopaedic patients admitted across the region during the recent lockdown period (24 March 2020 to 10 May 2020) and the same period in 2019. Age, sex, mechanism, anatomical region, and treatment modality were compared, as were fracture clinic attendances within the receiving regional major trauma centre (MTC) between the two periods. RESULTS: Paediatric trauma admissions across the region fell by 33% (197 vs 132) with a proportional increase to 59% (n = 78) of admissions to the MTC during lockdown compared with 28.4% in 2019 (N = 56). There was a reduction in manipulation under anaesthetic (p = 0.015) and the use of Kirschner wires (K-wires) (p = 0.040) between the two time periods. The median time to surgery remained one day in both (2019 IQR 0 to 2; 2020 IQR 1 to 1). Supracondylar fractures were the most common reason for fracture clinic attendance (17.3%, n = 19) with a proportional increase of 108.4% vs 2019 (2019 n = 20; 2020 n = 19) (p = 0.007). While upper limb injuries and falls from play apparatus, equipment, or height remained the most common indications for admission, there was a reduction in sports injuries (p < 0.001) but an increase in lacerations (p = 0.031). Fracture clinic management changed with 67% (n = 40) of follow-up appointments via telephone and 69% (n = 65) of patients requiring cast immobilization treated with a 3M Soft Cast, enabling self-removal. The safeguarding team saw a 22% reduction in referrals (2019: n = 41, 2020: n = 32). CONCLUSION: During this viral pandemic, the number of trauma cases decreased with a change in the mechanism of injury, median age of presentation, and an increase in referrals to the regional MTC. Adaptions in standard practice led to fewer MUA, and K-wire procedures being performed, more supracondylar fractures managed through clinic and an increase in the use of removable cast.Cite this article: Bone Joint Open 2020;1-7:424-430.

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