High Airway Occlusion Pressure Is Associated with Dyspnea and Increased Mortality in Critically Ill Mechanically Ventilated Patients.

Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H2O at enrollment, 24% had P0.1 values >3.5 cm H2O, 37% had P0.1 values between 1.5 and 3.5 cm H2O, and 39% had P0.1 values <1.5 cm H2O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea (P = 0.037), respiratory rate (P < 0.001), and PaO2 (P = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H2O versus 19% in those with P0.1 between 1.5 and 3.5 cm H2O and 17% in those with P0.1 < 1.5 cm H2O (P = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H2O, 1.19 [95% confidence interval, 1.04-1.37]; P = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H2O, 1.10 [95% confidence interval, 1.02-1.19]; P = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.

Social determinants associated with psychological distress in children and adolescents during and after the first COVID-19-related lockdown in France: results from the CONFEADO study.

BACKGROUND: This study aimed to analyze the parental socio-demographic characteristics of children and adolescents aged 9 to 18 years old, as well as the living and housing conditions associated with the psychological distress in these two sub-populations during and after France's first national COVID-19-related lockdown in spring 2020. METHODS: We used data from the cross-sectional, observational, web-based study CONFEADO, which collected data on children and adolescents' living and housing conditions and socio-demographic characteristics as well as those of their parents. It also collected data on children's and adolescents' health behaviors and psychological distress. We assessed psychological distress using the 10-item Children and Adolescents Psychological Distress Scale (CAPDS-10), and performed a multinomial logistic regression. RESULTS: A total of 2882 children and adolescents were included in the present study. Factors associated with moderate psychological distress included being a female, parental financial difficulties, a lack of a private living space at home for the child/adolescent, and the following child health behaviors: no leisure or recreational activities with adults in the household, doing less than one hour of school homework a day, and not going outside during the lockdown. Severe psychological distress was associated with the parent's occupation (especially essential frontline workers), a lack of a private living space at home for the child/adolescent, and the following child health behaviors: spending over 5 h a day on social media, doing less than one hour of school homework a day, and no leisure or recreational activities with adults in the household. CONCLUSIONS: This study emphasizes the impact of housing and living conditions, as well as parents' socio-economic characteristics on children's health behaviors and psychological needs during the first COVID-19-related lockdown in France. Our results suggest that health policies implemented during future pandemics should consider these structural social determinants to prevent severe psychological distress in children and adolescents.

Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.

Importance: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. Objective: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. Design, Setting, and Participants: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. Interventions: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. Results: Among 170 randomized patients (median age, 51 [IQR, 43-59] years; n = 60 women [35%]), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19-related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% [95% CI, -14.9% to 15.2%]; subdistribution hazard ratio, 1.11 [95% CI, 0.71-1.75]; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, -4.9 [95% CI, -11.2 to 1.5] days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 2.4% [95% CI, -13.9% to 18.6%]; P = .62). No serious adverse events were reported during the prone position procedure. Conclusions and Relevance: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. Trial Registration: ClinicalTrials.gov Identifier: NCT04607551.

REVOLUMAB: A phase II trial of nivolumab in recurrent IDH mutant high-grade gliomas.

BACKGROUND: Novel effective treatments are needed for recurrent IDH mutant high-grade gliomas (IDHm HGGs). The aim of the multicentric, single-arm, phase II REVOLUMAB trial (NCT03925246) was to assess the efficacy and safety of the anti-PD1 Nivolumab in patients with recurrent IDHm HGGs. PATIENTS AND METHODS: Adult patients with IDHm WHO grade 3-4 gliomas recurring after radiotherapy and ≥ 1 line of alkylating chemotherapy were treated with intravenous Nivolumab until end of treatment (12 months), progression, unacceptable toxicity, or death. The primary endpoint was the 24-week progression-free survival rate (24w-PFS) according to RANO criteria. RESULTS: From July 2019 to June 2020, 39 patients with recurrent IDHm HGGs (twenty-one grade 3, thirteen grade 4, five grade 2 with radiological evidence of anaplastic transformation; 39% 1p/19q codeleted) were enrolled. Median time since diagnosis was 5.7 years, and the median number of previous systemic treatments was two. The 24w-PFS was 28.2% (11/39, CI95% 15-44.9%). Median PFS and OS were 1.84 (CI95% 1.81-5.89) and 14.7 months (CI95% 9.18-NR), respectively. Four patients (10.3%) achieved partial response according to RANO criteria. There were no significant differences in clinical or histomolecular features between responders and non-responders. The safety profile of Nivolumab was consistent with prior studies. CONCLUSIONS: We report the results of the first trial of immune checkpoint inhibitors in IDHm gliomas. Nivolumab failed to achieve its primary endpoint. However, treatment was well tolerated, and long-lasting responses were observed in a subset of patients, supporting further evaluation in combination with other agents (e.g. IDH inhibitors).

Value of high-resolution full-field optical coherence tomography and dynamic cell imaging for one-stop rapid diagnosis breast clinic.

BACKGROUND: Full-field optical coherence tomography combined with dynamic cell imaging (D-FFOCT) is a new, simple-to-use, nondestructive, quick technique that can provide sufficient spatial resolution to mimic histopathological analysis. The objective of this study was to evaluate diagnostic performance of D-FFOCT for one-stop rapid diagnosis breast clinic. METHODS: Dynamic full-field optical coherence tomography was applied to fresh, untreated breast and nodes biopsies. Four different readers (senior and junior radiologist, surgeon, and pathologist) analyzed the samples without knowing final histological diagnosis or American College of Radiology classification. The results were compared to conventional processing and staining (hematoxylin-eosin). RESULTS: A total of 217 biopsies were performed on 152 patients. There were 144 breast biopsies and 61 lymph nodes with 101 infiltrative cancers (49.27%), 99 benign lesions (48.29%), 3 ductal in situ carcinoma (1.46%), and 2 atypias (0.98%). The diagnostic performance results were as follow: sensitivity: 77% [0.7;0.82], specificity: 64% [0.58;0.71], PPV: 74% [0.68;0.78], and NPV: 75% [0.72;0.78]. A large image atlas was created as well as a diagnosis algorithm from the readers' experience. CONCLUSION: With 74% PPV and 75% NPV, D-FFOCT is not yet ready to be used in clinical practice to identify breast cancer. This is mainly explained by the lack of experience and knowledge of this new technic by the four lectors. By training with the diagnosis algorithm and the image atlas, radiologists could have better outcomes allowing quick detection of breast cancer and lymph node involvement. Deep learning could also be used, and further investigation will follow.

Children and Adolescents Psychological Distress Scale During COVID-19 Pandemic: Validation of a Psychometric Instrument (CONFEADO Study).

Aim and Object Purpose of the Study: In March 2020, the WHO declared a pandemic (COVID-19) due to the SARS-CoV-2 virus. In France, school closures and lockdowns were implemented. In this unprecedented context for French adolescents and children, the CONFEADO study surveyed children aged 9 to 18 years to assess their mental health, psychological distress, and resilience during and after the lockdown in relation to their living and housing conditions. To assess psychological distress, a psychometric tool (Children and Adolescent Psychological Distress Scale-CAPDS-10) was specifically designed for the research. This article presents the psychometric validity of the CAPDS-10. Methods: This cross-sectional study collected data from June 9 to September 14, 2020, from children and adolescents (9 to 18 years of age) via an online questionnaire after sending it to a large network of partners. Psychological distress, resilience, and trait anxiety were assessed using the CAPDS-10, the Child and Youth Resilience Measure (CYRM), and the State-Trait Anxiety Inventory for Children (STAIC). The CAPDS-10 measured perceived psychological distress in the most recent 2 weeks (primary endpoint). The predictive power of the CAPDS-10 was determined by statistical analysis. We proceeded to a confirmatory factor analysis to validate the scale at a clinical level. We carried out a psychometric validation with a step to verify the uni-dimensionality of the scale (PCA analysis) and the calculation of convergent and divergent validity, correlation coefficient between items and subscales, Cronbach's alpha for reliability, determination of a cut-off score for the AUROC index. Results: Three thousand and forty eight children and adolescents completed the CAPDS-10. Analysis confirmed a three-factor model (anxiety, depression, and aggressive behavior) (RMSEA = 0.072 [0.067; 0.077], CFI = 0.954), with a correlation coefficient between items >0.4. PCA analysis concluded that the scale is unidimensional. Reliability was satisfactory with Cronbach's alpha coefficients >0.7 (0.86). In addition, prediction was good with an AUROC index equal to 0.73 and a threshold score for severe distress greater than or equal to 19. Conclusion: The CAPDS-10 measures psychological distress over the most recent 2-week period with good psychometric qualities. It could be used in crisis or prevention contexts in the general population or in clinical settings.