Although effective pertussis vaccines are available and have been incorporated into national immunization programs for infants and children, and adolescents and adults in some countries, pertussis remains endemic worldwide. Periodic outbreaks occur every 2 to 5 years. In 2013, France revised its pediatric vaccination program, transitioning from a 3 + 1 to a 2 + 1 schedule. The effects of this change have raised some concerns; however, data on the effectiveness of pediatric vaccines in France post 2013 remain limited. This matched case-control study aimed to estimate the effectiveness of vaccination against pertussis in children born in France between 2013 and 2019, using the French National Health Data System. Children were included in the study if they were alive and free of pertussis at 6 weeks of age, and if their mother-child linkage was available. Pertussis-related hospitalizations were captured using the International Classification of Diseases-10 codes (A37.0 and A37.9), and vaccine exposure status was confirmed using ATCC codes (J07CA02, J07CA06, and J07CA09). The odds ratio (OR) of exposure to vaccine against pertussis for 1, 2, and 3 effective doses was calculated using conditional logistic regression models. Vaccine effectiveness (VE) was estimated as (1-adjusted OR) × 100% in at-term infants. In total, 1,481,884 children were included in the study. When stratified by age groups, a gradient of increasing VE was observed, with highest VE (93.4%) observed among children aged 11.5 to 60 months who were fully vaccinated according to 2 + 1 schedule and lowest (24.1%) among children aged 2 to 4.5 months who received only the first dose. In sensitivity analyses, imputation of missing data on vaccinations potentially received outside the healthcare insurance setting (Protection maternelle et infantile) resulted in an approximately 6% increase in VE. Results demonstrated that adherence to the 2 + 1 schedule provided effective protection against pertussis in full term children in France.
Accurate size estimation of large (≥ 20 mm) colorectal laterally spreading tumors (LSTs) is essential for procedural planning, risk stratification, and predicting technical difficulty. Yet, the reliability of visual LST size assessment among endoscopists has not been systematically evaluated. 46 LSTs were recorded during colonoscopy. Twenty-four international expert endoscopists independently reviewed de-identified videos and provided visual estimates for (1) maximal diameter, (2) oral–anal axis, (3) left–right axis, and (4) percentage of colonic circumference involved. Each lesion was assessed twice in randomized order. Fleiss’s kappa, Krippendorff’s alpha, and intraclass correlation coefficients (ICC) were used to evaluate inter- and intra-rater agreement. A total of 1104 measurements were collected. Inter-endoscopist kappa agreement for maximal diameter was poor (κ = 0.16), with similarly poor agreement for the oral–anal (κ = 0.15) and left–right axes (κ = 0.14). The percentage of circumferential involvement demonstrated moderate reproducibility (ICC 0.74 and 0.70 across rounds). Subgroup analyses showed consistently poor agreement for larger lesions for diameter-based methods, whereas circumferential percentage estimation ranged from poor to good depending on LST size and morphology. Intra-endoscopist agreement for diameter- and axis-based approaches showed wide variability (κ range 0.01–0.67), while circumferential estimates achieved good to excellent agreement for most endoscopists. Visual estimation of large colorectal LST size is highly variable among expert endoscopists. Maximal diameter and axial lengths demonstrate poor inter- and intra-observer reliability. Circumferential extent is the most reproducible descriptor and may be the preferred approach for reporting LST size in clinical practice and research.
BACKGROUND:The proportion of patients aged ≥ 80 years with non-small-cell lung cancer (NSCLC) is rising, yet data on their management remain scarce. This study analysed changes in treatment and survival in this population over a decade. METHODS:The KBP-2010 and KBP-2020 cohorts are prospective, nationwide cohorts including patients diagnosed with primary lung cancer in France in 2010 and 2020, respectively. We compared the clinical characteristics, treatments and outcomes of KBP patients aged ≥ 80 years with NSCLC between 2010 and 2020. RESULTS:Among 8941 patients in KBP-2020, 7797 presented NSCLC and 1017 (13.0%) were ≥ 80 years, of whom 33.7% were women, 40.4% had ECOG performance status ≥ 2 and 32.4% were never-smokers. Most patients had metastatic disease (localized 18.9%, locally advanced 18.8%, metastatic 62.3%). Among patients who underwent molecular screening, the most frequent alterations were activating EGFR mutations (25.8%). Between 2010 and 2020, significant increases were seen in the numbers of patients undergoing surgery for localized disease (26.0% vs 46.4%) and chemoradiotherapy for locally advanced disease (10.6% vs 19.1%). In metastatic disease, the use of systemic therapy increased from 52.1% of patients in 2010-55.9% in 2020, with a shift towards targeted therapies (from 14.9% to 19.5%), while the use of chemotherapy decreased (from 51.2% to 24.6%). Four-year overall survival rate improved from 6.3% in 2010-13.1% in 2020 (p < 0.0001). CONCLUSION:Patients ≥ 80 years with NSCLC exhibit specific clinical and molecular profiles. Access to therapies improved over the decade 2010-2020, leading to significantly better survival outcomes.
Importance:Prone positioning has been shown to improve respiratory mechanics and oxygenation, but its clinical benefit in infants with acute viral bronchiolitis receiving high-flow nasal cannula (HFNC) support remains unknown. Objective:To investigate whether prone positioning in infants with moderate to severe acute bronchiolitis and HFNC support reduces escalation to noninvasive or invasive ventilation. Design, Setting, and Participants:Multicenter, randomized, open-label trial conducted in 15 pediatric intermediate or intensive care units in France. Infants aged 6 months or younger admitted for 24 hours or less with a diagnosis of acute bronchiolitis with moderate to severe respiratory distress requiring HFNC support were enrolled between January 2021 and November 2023 and followed up until hospital discharge (last patient discharged on December 11, 2023). Interventions:Participants were randomly assigned to the prone position (n = 221) or supine position (n = 230). Infants in the prone position group received prone positioning for 24 hours or longer during the first 48 hours. All participants received standardized HFNC support at 2 L/kg/min. Main Outcomes and Measures:The primary outcome was the need for escalation of care to noninvasive or invasive ventilation within the first 72 hours, according to prespecified criteria. Secondary outcomes included treatment failure, determined by an independent clinical adjudication committee; tolerance of prone positioning; length of hospital stay; duration of respiratory support; infant comfort; and adverse events. Results:Among 451 infants randomized, 446 were included in the primary analysis (median age, 41 [IQR, 19-72] days; 54% male). Escalation of care occurred in 80 infants (17.9%), with no significant difference between the prone position (33/220 [15.0%]) and supine position (47/226 [20.8%]) groups (adjusted odds ratio, 0.66 [95% CI, 0.40-1.07]; P = .09). Secondary outcomes did not differ significantly between the 2 groups. In the safety analysis, serious adverse events occurred in 2 of 180 infants (1.1%) in the prone position group and 2 of 264 (0.8%) in the supine position group. Conclusions and Relevance:Prone positioning in infants with moderate to severe bronchiolitis receiving HFNC support did not significantly reduce escalation of care. However, the wide 95% confidence interval around the observed odds ratio suggests that this study was not definitive and further research is warranted. Trial Registration:ClinicalTrials.gov Identifier: NCT03976895.
Background and ObjectivesDevelopmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort.MethodsWe retrospectively analyzed 110 patients with BS EEG enrolled from a database of 1,540 individuals with suspected genetic epilepsies (2008-2023). Clinical, EEG, and genetic data were systematically collected. Patients were stratified into 4 groups: KCNQ2, STXBP1, "other pathogenic variants," and "without a genetic diagnosis." EEG traces were reviewed independently, and outcomes were assessed through long-term follow-up.ResultsPathogenic or likely pathogenic variants were identified in 62.7% of patients and involved 23 genes, including 2 copy number variants. KCNQ2 (n = 24) and STXBP1 (n = 16) accounted for one-third of diagnoses, whereas SCN2A (n = 3) and KCNT1 (n = 2) were less frequent. In KCNQ2 cases, seizures and BS onset occurred earlier than in STXBP1 cases: mean 2 days vs 6 weeks for seizures and 3 days vs 2 months for BS, respectively. A typical BS pattern (bursts longer than suppressions) strongly correlated with KCNQ2 and STXBP1 variants. Novel associations were found with DPM1, GRIN2A, KCNT2, PIGO, PURA, WWOX, and candidate genes (KMT2E, SNAP25, and SYT1). Most variants were de novo heterozygous; however, recessive and X-linked inheritance patterns were also observed. Mortality was high (25%), primarily from status epilepticus and complications of severe disability. Most patients (72.5%) had persistent seizures at follow-up (a mean of 6.5 years), as well as profound intellectual disabilities, irrespective of genotype.DiscussionThis large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.
