Few pediatric cases of coronavirus disease 2019 (COVID-19) have been reported and we know little about the epidemiology in children, although more is known about other coronaviruses. We aimed to ...understand the infection rate, clinical presentation, clinical outcomes, and transmission dynamics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to inform clinical and public health measures.
We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in pediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched 3 databases and the COVID-19 resource centers of 11 major journals and publishers. English abstracts of Chinese-language papers were included. Data were extracted and narrative syntheses conducted.
Twenty-four studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, although radiological abnormalities are noted. Severe cases are not reported in detail and there are few data relating to transmission.
Children appear to have a low observed case rate of COVID-19 but may have rates similar to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention and be tested and counted in observed cases of COVID-19.
Abstract Background Previous reports suggest that acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is underdiagnosed in both adult and pediatric clinical practice. Underrecognition ...of this condition may be a barrier to instituting a low tidal volume ventilation strategy. This study aimed to determine the accuracy of clinical diagnoses of ARDS in daily practice using the American European Consensus Conference (AECC) criteria as a criterion standard and to investigate whether clinical recognition of ARDS altered ventilator management. Methods This retrospective study included intensive care unit (ICU) patients who died and underwent postmortem examination. Two independent reviewers assigned each patient to those with ALI/ARDS or no ALI. For those who met AECC criteria for ARDS, all patient records were reviewed for the presence of a documented diagnosis of the condition. The accuracy of the clinicians in diagnosing ALI/ARDS was determined, and ventilator settings between the clinically “diagnosed” and “non-diagnosed” groups were compared. The diagnostic accuracy in predetermined subgroups (those with diffuse alveolar damage, with ≥ 3 affected chest x-ray quadrants, with diagnosis ≥ 3 days, with pulmonary vs extrapulmonary cause) was also examined. Results Of 98 consecutive ICU patients who died and underwent autopsy, 51 met the inclusion criteria. Sixteen of 51 patients (31.3%) who had ALI/ARDS according to the AECC criteria had this recorded in their clinical notes. Those with histologic evidence of ALI/ARDS (diffuse alveolar damage) and with a more severe chest x-ray pattern or who satisfied the criteria for a number of consecutive days were no more likely to have a clinical diagnosis of ALI/ARDS recorded. However, those with a pulmonary cause of ALI/ARDS were more likely to have a diagnosis recorded. Tidal volumes, positive end-expiratory pressure, and mean airway pressure were higher in those with a clinical diagnosis of ARDS. Conclusions Acute respiratory distress syndrome is underrecognized by clinicians in ICU, and recognition does not result in lower tidal volume ventilation. Significant barriers remain to the recognition of ALI/ARDS and application of an evidence-based ventilator strategy.
The commensal microbiota, host immunity and metabolism participate in a signalling network, with diet influencing each component of this triad. In addition to diet, many elements of a modern ...lifestyle influence the gut microbiota but the degree to which exercise affects this population is unclear. Therefore, we explored exercise and diet for their impact on the gut microbiota.
Since extremes of exercise often accompany extremes of diet, we addressed the issue by studying professional athletes from an international rugby union squad. Two groups were included to control for physical size, age and gender. Compositional analysis of the microbiota was explored by 16S rRNA amplicon sequencing. Each participant completed a detailed food frequency questionnaire.
As expected, athletes and controls differed significantly with respect to plasma creatine kinase (a marker of extreme exercise), and inflammatory and metabolic markers. More importantly, athletes had a higher diversity of gut micro-organisms, representing 22 distinct phyla, which in turn positively correlated with protein consumption and creatine kinase.
The results provide evidence for a beneficial impact of exercise on gut microbiota diversity but also indicate that the relationship is complex and is related to accompanying dietary extremes.
Background:
The WHO definition of palliative care includes bereavement support as integral to palliative care, yet a previous survey of bereavement support in palliative care in Europe has shown a ...range of service responses to loss. A rigorous approach to agreeing and implementing a palliative care bereavement framework was required.
Aim:
The aim of this study was to develop consensus on best-practice recommendations for bereavement care principles, structures, processes and delivery based on current practice and evidence.
Design:
In accordance with Guidance on Conducting and Reporting Delphi Studies, a consensus-building five-round Delphi technique was performed. A scoping review of research literature informed drafting of 54 statements by the EAPC Bereavement Task Force. Evaluation of the statements was performed by an expert panel using a 5-point Likert scale. ⩾80% agreement were defined as essential items and 75%–79% agreement were defined as desirable items. Items with a consensus rating <75% were revised during the process.
Setting/participants:
The Delphi study was carried out by an expert panel among membership organisations of the European Association for Palliative Care.
Results:
In total, 376 email requests to complete Delphi questionnaire were distributed with a response rate of 23% (n = 87) and a follow-up response-rate of 79% (n = 69). Of the initial 54 statements in six dimensions, 52 statements were endorsed with 26 essential statements and 26 desirable statements.
Conclusions:
The six dimensions and 52 statements agreed through this Delphi study clarify a coherent direction for development of bereavement services in palliative care in Europe.
Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate ...cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples (n = 29). CTC count positively correlated with absolute total lymphocyte count (r2 = 0.1709, p = 0.0258) and NK-cell count (r2 = 0.49, p < 0.0001). There was also a positive correlation between platelet count and CTC count (r2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group (n = 123, p < 0.0001), the non-exercise group (n = 79, p = 0.001) and blood draw samples lacking platelet cloaking (n = 128, p < 0.0001). By flow cytometry, blood samples from the exercise group (n = 15) had a higher proportion of CD3+ T-lymphocytes (p = 0.0003) and lower proportions of B-lymphocytes (p = 0.0264) and NK-cells (p = 0.015) than the non-exercise group (n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis.
Objectives
The public health impact of the Irish Making Every Contact Count (MECC) brief intervention programme is dependent on delivery by health care professionals. We aimed to identify enablers ...and modifiable barriers to MECC intervention delivery to optimize MECC implementation.
Design
Online cross‐sectional survey design.
Methods
Health care professionals (n = 4050) who completed MECC eLearning were invited to complete an online survey based on the Theoretical Domains Framework (TDF). Multiple regression analysis identified predictors of MECC delivery (logistic regression to predict delivery or not; linear regression to predict frequency of delivery). Data were visualized using Confidence Interval‐Based Estimates of Relevance (CIBER).
Results
Seventy‐nine per cent of participants (n = 283/357) had delivered a MECC intervention. In the multiple logistic regression (Nagelkerke's R2 = .34), the significant enablers of intervention delivery were ‘professional role’ (OR = 1.86 1.10, 3.15) and ‘intentions/goals’ (OR = 4.75 1.97, 11.45); significant barriers included ‘optimistic beliefs about consequences’ (OR = .41 .18, .94) and ‘negative emotions’ (OR = .50 .32, .77). In the multiple linear regression (R2 = .29), the significant enablers of frequency of MECC delivery were ‘intentions/goals’ (b = 10.16, p = .02) and professional role (b = 6.72, p = .03); the significant barriers were ‘negative emotions’ (b = −4.74, p = .04) and ‘barriers to prioritisation’ (b = −5.00, p = .01). CIBER analyses suggested six predictive domains with substantial room for improvement: ‘intentions and goals’, ‘barriers to prioritisation’, ‘environmental resources’, ‘beliefs about capabilities’, ‘negative emotions’ and ‘skills’.
Conclusion
Implementation interventions to enhance MECC delivery should target intentions and goals, beliefs about capabilities, negative emotions, environmental resources, skills and barriers to prioritization.
Background
Clinic‐based biomarkers are effective in tracking disease progression in clinical research, but do not scale to support public health needs or large‐scale real‐world studies. Purely ...digital markers are scalable but lack the objectivity and neurobiological grounding of clinical measures. These first results of a real‐world feasibility study demonstrate that objective measures of a range of domains including EEG (Figure 1) are user‐friendly and suitable for repeated at‐home use by patients and older controls.
Method
60 patients and 60 matched controls are being recruited for a 1‐year repeated sampling study in the UK. Patients were clinically assessed to have mild Alzheimer’s type dementia. Participants were asked to complete about 30 minutes of behavioral tasks including memory, executive function, affective processing and language, while synchronized EEG was recorded using a self‐applied dry‐sensor headset. This interim data is from an initial 2‐week burst sampling period, for the first half of the cohorts.
Result
Adherence was 76% for the dementia group (N = 29, mean age = 75; ADAS = Cog 24.3) and 88% for the control group (N = 36, mean age = 71; ADAS = Cog 7.8). A symbol substitution task (executive function) differentiated strongly between groups (t(53) = 6.9), and correlated highly with a conventional pen‐and‐paper DSST benchmark (rho = 0.79). An associative memory task also patterned strongly with disease status (t(54) = 5.7) and correlated with the Verbal Paired Associates benchmark (rho = 0.76). The grand average P300 ERP, elicited by a gamified 2‐stimulus oddball task, showed characteristic features of sensory and higher cognitive processing (Figure 2). As expected in the patient group, the P300 was reduced and delayed; and the resting‐state EEG theta and alpha power were enhanced and reduced, respectively. Radar plots (Figure 3), illustrate the pattern observed across domains in one representative Alzheimer’s patient and one control. Data from a fronto‐temporal dementia sister study is included for comparison.
Conclusion
Interim data from this first‐in‐class study suggest that patients with mild Alzheimer’s disease dementia are capable and willing to participate in intensive home‐based functional neurophysiology studies, if technology is designed to be engaging and easy to use. Initial examination of the data aligns with established benchmarks, constituting positive early evidence for construct validity and technical feasibility.
Background
Clinic‐based biomarkers are effective in tracking disease progression in clinical research, but do not scale to support public health needs or large‐scale real‐world studies. Purely ...digital markers are scalable but lack the objectivity and neurobiological grounding of clinical measures. These first results of a real‐world feasibility study demonstrate that objective measures of a range of domains including EEG (Figure 1) are user‐friendly and suitable for repeated at‐home use by patients and older controls.
Method
60 patients and 60 matched controls are being recruited for a 1‐year repeated sampling study in the UK. Patients were clinically assessed to have mild Alzheimer’s type dementia. Participants were asked to complete about 30 minutes of behavioral tasks including memory, executive function, affective processing and language, while synchronized EEG was recorded using a self‐applied dry‐sensor headset. This interim data is from an initial 2‐week burst sampling period, for the first half of the cohorts.
Result
Adherence was 76% for the dementia group (N = 29, mean age = 75; ADAS = Cog 24.3) and 88% for the control group (N = 36, mean age = 71; ADAS = Cog 7.8). A symbol substitution task (executive function) differentiated strongly between groups (t(53) = 6.9), and correlated highly with a conventional pen‐and‐paper DSST benchmark (rho = 0.79). An associative memory task also patterned strongly with disease status (t(54) = 5.7) and correlated with the Verbal Paired Associates benchmark (rho = 0.76). The grand average P300 ERP, elicited by a gamified 2‐stimulus oddball task, showed characteristic features of sensory and higher cognitive processing (Figure 2). As expected in the patient group, the P300 was reduced and delayed; and the resting‐state EEG theta and alpha power were enhanced and reduced, respectively. Radar plots (Figure 3), illustrate the pattern observed across domains in one representative Alzheimer’s patient and one control. Data from a fronto‐temporal dementia sister study is included for comparison.
Conclusion
Interim data from this first‐in‐class study suggest that patients with mild Alzheimer’s disease dementia are capable and willing to participate in intensive home‐based functional neurophysiology studies, if technology is designed to be engaging and easy to use. Initial examination of the data aligns with established benchmarks, constituting positive early evidence for construct validity and technical feasibility.
Modulation of the NURR subfamily of nuclear receptors may be an important mechanism regulating pathways associated with inflammatory joint disease. We examined the signaling mechanisms through which ...inflammatory mediators, produced by rheumatoid arthritis (RA) synovial tissue, contribute to the regulation of the NURR subfamily. Markedly enhanced expression of NURR1 is observed in synovial tissue of patients with RA compared with normal subjects. Modulation by proinflammatory mediators in primary RA and normal synoviocytes shows that PGE(2), IL-1beta, and TNF-alpha markedly enhance NURR1 mRNA and protein levels in contrast to other subfamily members, NUR77 and NOR-1. We have established that transcriptional activation of the NURR1 gene by IL-1beta and TNF-alpha requires a proximal promoter region that contains a consensus NF-kappaB DNA-binding motif. IL-1beta- and TNF-alpha-induced NF-kappaB binding to this site is due predominantly to p65-p50 heterodimer and p50 homodimer subunit protein complexes. We further demonstrate a direct CREB-1-dependent regulation by PGE(2) situated at promoter region -171/-163. Moreover, analyses confirm the presence of CREB-1 and NF-kappaB p50 and p65 subunit binding to the NURR1 promoter under basal conditions in freshly explanted RA synovial tissue. In summary, enhanced NF-kappaB- and CREB-1-binding activity on the NURR1 promoter by inflammatory mediators delineates novel mechanisms in the regulation of NURR1 transcription. PGE(2)-, TNF-alpha-, and IL-1beta-dependent stimulation of the NURR1 gene implies that NURR1 induction represents a point of convergence of at least two distinct signaling pathways, suggesting an important common role for this transcription factor in mediating multiple inflammatory signals.
Introduction
The emergence of the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the coronavirus disease COVID-19 has impacted enormously on non-COVID-19-related ...hospital care. Curtailment of intensive care unit (ICU) access threatens complex surgery, particularly impacting on outcomes for time-sensitive cancer surgery. Oesophageal cancer surgery is a good example. This study explored the impact of the pandemic on process and short-term surgical outcomes, comparing the first wave of the pandemic from April to June in 2020 with the same period in 2019.
Methods
Data from all four Irish oesophageal cancer centres were reviewed. All patients undergoing resection for oesophageal malignancy from 1 April to 30 June inclusive in 2020 and 2019 were included. Patient, disease, and peri-operative outcomes (including COVID-19 infection) were compared.
Results
In 2020, 45 patients underwent oesophagectomy, and 53 in the equivalent period in 2019. There were no differences in patient demographics, co-morbidities, or use of neoadjuvant therapy. The median time to surgery from neoadjuvant therapy was 8 weeks in both 2020 and 2019. There were no significant differences in operative interventions between the two time periods. There was no difference in operative morbidity in 2020 and 2019 (28% vs 40%,
p
= 0.28). There was no in-hospital mortality in either period. No patient contracted COVID-19 in the perioperative period.
Conclusions
Continuing surgical resection for oesophageal cancer was feasible and safe during the COVID-19 pandemic in Ireland. The national response to this threat was therefore successful by these criteria in the curative management of oesophageal cancer.
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