Dyspnoea in patients receiving noninvasive ventilation for acute respiratory failure: prevalence, risk factors and prognostic impact: A prospective observational study

Dyspnoea is a frequent and intense symptom in intubated patients, but little attention has been paid to dyspnoea during noninvasive mechanical ventilation in the intensive care unit (ICU).The objectives of this study were to quantify the prevalence, intensity and prognostic impact of dyspnoea in patients receiving noninvasive ventilation (NIV) for acute respiratory failure (ARF) based on secondary analysis of a prospective observational cohort study in patients who received ventilatory support for ARF in 54 ICUs in France and Belgium. Dyspnoea was measured by a modified Borg scale.Among the 426 patients included, the median (interquartile range) dyspnoea score was 4 (3-5) on admission and 3 (2-4) after the first NIV session (p=0.001). Dyspnoea intensity ≥4 after the first NIV session was associated with the Sequential Organ Failure Assessment Score (odds ratio (OR) 1.12, p=0.001), respiratory rate (OR 1.03, p=0.032), anxiety (OR 1.92, p=0.006), leaks (OR 2.5, p=0.002) and arterial carbon dioxide tension (OR 0.98, p=0.025). Dyspnoea intensity ≥4 was independently associated with NIV failure (OR 2.41, p=0.001) and mortality (OR 2.11, p=0.009), but not with higher post-ICU burden and altered quality of life.Dyspnoea is frequent and intense in patients receiving NIV for ARF and is associated with a higher risk of NIV failure and poorer outcome

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

[A cross-sectional study of trait-anxiety in a group of 111 intellectually gifted children].

International audienceINTRODUCTION: Intellectually gifted children are often thought to display a high risk for psychopathology. However, this assertion has received only few direct arguments to date, and there is in fact a lack of knowledge on this subject. The aim of this study was to compare trait-anxiety - which is considered as a sensitive and early indicator of psychoaffective difficulties in children - in intellectually gifted children to the norm. METHODS: One hundred and eleven children aged 8 to 12 and with an intellectual quotient (IQ) higher than 129 participated in the study. They were recruited in a hospital department of child and adolescent psychiatry and through psychologists' private practice, where they attended consultation because of academic underachievement and/or social maladjustment. All the children were examined by trained psychiatrists and psychologists: none had a present or past medical or psychiatric condition and, additionally, none had an elevated score on the French version of the Children's Depressive Rating Scale Revised (Moor & Mack, 1982). Parents filled in a questionnaire for the collection of socio-demographic data and children answered the French version of the Revised-Children's Manifest Anxiety Scale (R-CMAS; Reynolds, 1999), a 37-items self-assessment of trait-anxiety, the psychometric properties of which have been validated in children with high IQ. DATA ANALYSIS: Mean scores and subscores on the R-CMAS in the whole studied group and as a function of gender and age were compared to French normative data (Reynolds, 1999) by calculation of 95% confidence intervals; subgroups were compared using Student's t-tests. Proportions of children who's score and subscores exceeded anxiety cut-off norms were compared to normative data using chi-square tests. Statistical significance was considered at the P<0.05 level. RESULTS: The studied group comprised mainly boys, and members of a sibling. Parents mainly lived as man and wife, had high academic levels, and had a professional activity. The confidence intervals of the R-CMAS scores and subscores all comprised their normative value, which denotes that no difference was statistically significant. Comparisons for age and gender showed no significant difference. Proportions of results exceeding the cut-off scores and subscores did not significantly differ from the norms. DISCUSSION: General and dimensional trait-anxiety levels in the studied group were comparable to normative data. These results are in accordance with previous studies of trait-anxiety in children and adolescents with high IQ, which all showed normal or decreased levels. These findings do not corroborate the hypothesis that intellectual giftedness constitutes a risk factor for psychopathology. LIMITS: The studied group was a clinical one, which could limit the generalisation of the results. However, mental disorders were ruled out, and the psychometric and socio-demographic characteristics of the group were in keeping with those described for the general population of gifted children. Moreover, considering that participant children displayed academic underachievement and/or social maladjustment, it can be supposed that their anxiety levels were not lower than those in the general population of gifted children. Secondly, the potentially confusing effect of socio-demographic variables (underrepresentation of low socio-economic levels and single-parent families) could not be statistically taken into account, due to the absence of a specific control group. CONCLUSION: Intellectually gifted children seem not to display increased trait-anxiety. However, further studies are necessary to investigate psychological functioning in gifted children and their risk for psychopathology

Reducing Radiation Dose at Chest CT: Comparison Among Model-based Type Iterative Reconstruction, Hybrid Iterative Reconstruction, and Filtered Back Projection.

The study aimed to evaluate the performances of two iterative reconstruction (IR) algorithms and of filtered back projection (FBP) when using reduced-dose chest computed tomography (RDCT) compared to standard-of-care CT. An institutional review board approval was obtained. Thirty-six patients with hematologic malignancies referred for a control chest CT of a known lung disease were prospectively enrolled. Patients underwent standard-of-care scan reconstructed with hybrid IR, followed by an RDCT reconstructed with FBP, hybrid IR, and iterative model reconstruction. Objective and subjective quality measurements, lesion detectability, and evolution assessment on RDCT were recorded. For RDCT, the CTDIvol (volumetric computed tomography dose index) was 0.43 mGy⋅cm for all patients, and the median [interquartile range] effective dose was 0.22 mSv [0.22-0.24]; corresponding measurements for standard-of-care scan were 3.4 mGy [3.1-3.9] and 1.8 mSv [1.6-2.0]. Noise significantly decreased from FBP to hybrid IR and from hybrid IR to iterative model reconstruction on RDCT, whereas lesion conspicuity and diagnostic confidence increased. Accurate evolution assessment was obtained in all cases with IR. Emphysema identification was higher with iterative model reconstruction. Although iterative model reconstruction offered better diagnostic confidence and emphysema detection, both IR algorithms allowed an accurate evolution assessment with an effective dose of 0.22 mSv