Importance An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD ...incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. Objective To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus RSV and influenza cases) among children in France. Design, Setting, and Participants This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Exposures Implementation of NPIs during the COVID-19 pandemic. Main Outcomes and Measures The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. Results During the study period, 5113 children (median IQR age, 1.0 0.6-4.0 years; 2959 boys 57.9%) had IPD, and 6831 healthy children (median IQR age, 1.5 0.9-3.9 years; 3534 boys 51.7%) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, −82% to −43%;P < .001) and was similar for non–13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (−63%; 95% CI, −77% to −48%;P < .001) and low disease potential (−53%; 95% CI, −70% to −35%;P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (−12%; 95% CI, −37% to 12%;P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (−26%; 95% CI, −100% to 52%;P = .50) or low disease potential (−7%; 95% CI, −34% to 20%;P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, −74% to −97%;P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, −55% to −85%;P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, −28% to −78%;P < .001) and 40% (95% CI, −15% to −65%;P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, −7% to 15%;P = .49) of the decrease. Conclusions and Relevance In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.
Iron deficiency (ID) is considered the most frequent micronutrient deficiency in industrialized countries where strategies for its primary prevention vary widely and are insufficiently evaluated. We ...aimed to study the effectiveness for iron status of a national iron deficiency prevention strategy based on recommendations for young-child formula (YCF) use after age 12 months, taking into consideration other sources of iron and the family's socio-economic status.
In a cross-sectional observational study conducted in primary care pediatrician offices throughout France from 2016 to 2017, infants aged 24 months were consecutively included for a food survey and blood sampling. Associations between YCF consumption and serum ferritin (SF) level were studied by multivariable regression after adjustment on sociodemographic, perinatal and dietary characteristics, notably other intakes of iron.
Among the 561 infants analyzed, the ID prevalence was 6.6% (37/561; 95% confidence interval CI 4.7–9.0). Daily iron intake excluding YCF and total daily iron intake including YCF were below the 5-mg/day recommended average requirements for 63% and 18% of children, respectively. ID frequency was significantly decreased (or SF level was independently higher) with any YCF consumption after age 10 months (odds ratio 0.15, 95% CI 0.07–0.31), current YCF consumption at age 24 months (median SF level 29 vs 21 μg/L if none), prolonged YCF consumption (28 μg/L if >12 months vs 17 μg/L if none), and increasing daily volume of YCF consumed at age 24 months from a small volume (e.g., 29 μg/L if <100 mL/day vs 21 μg/L if none).
Current or past YCF use was independently associated with a better iron status at age 24 months than non-use. The strategy recommending YCF use at weaning after age 12 months seems effective in the general population.
NCT02484274.
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Background:
Adequate evaluation of iron status in young children is of paramount importance given the frequency of iron deficiency (ID) and its potential short- and long-term neurocognitive adverse ...effects when occurs early. Iron metabolism is complex and the correct evaluation of iron status may be difficult, notably when inflammation is present. Soluble transferrin receptor (sTfR) is not modified by inflammation but lacks specificity in ID, and its combination with serum ferritin (SF) by the TfR-F index (TfR/logSF) has been proposed to improve diagnosis performances Punnonen Blood 1997. Hepcidin has been identified in the two last decades has the key regulator of iron homeostasis mainly by controlling iron release from macrophages via ferroportin degradation, as well as enterocytes absorption Ganz Blood 2011. Scarce studies have been published on hepcidin in healthy children in industrialized countries Uijterschout Pediatr Res 2014. The distribution of sTfR and hepcidin in healthy young children is unknown, including according to gender.
Aims:
Our objective was to describe hepcidin, sTfR and other iron status biomarkers (serum ferritin SF, hemoglobin (Hb), transferrin saturation, zinc protoporphyrin ZnPP) distributions in a population of healthy infants aged 2 years old.
Methods:
In a cross-sectional observational study conducted in primary care pediatricians' offices throughout France from 2016 to 2017, infants aged 2 years old were consecutively included to undergo a blood sampling in the morning fasting. They were excluded if they were affected by a chronical disease involving iron metabolism, had fever in the last 15 days or biological inflammation defined as a CRP≥10 mg/L, and had no measurement for hepcidin. Hepcidin and ZnPP in erythrocytes were measured after a <24 hours frozen transport at -80°C in the dark by liquid chromatography-tandem mass spectrometry (LC-MS/MS, limit of detection = 0.75 ng/mL, intra- and inter-assay precision ≤ 12.3% and 9.9% Lefebvre Clin Chem Lab Med 2015) and by a fluorimetric method, respectively. Hb and mean corpuscular Hb concentration were measured immediately after the sample by spectrophotometric methods. The other iron biomarkers were immediately measured after refrigerated or frozen transport using immuno-turbidimetric method for transferrin (limit of detection = 0.1 g/L, intra- and inter-assay precision ≤1.2 and 2.6%) and sTfR (limit of detection 0.5 mg/L, intra- and inter-assay precision ≤2.1 and 3.6%), and electro‐chemiluminescence immunoassay for SF (limit of detection = 0.5 μg/L, intra- and inter-assay precision ≤1.1% and 5.7%). The distribution of biomarkers were described, including after classical mathematical transformation.
Results:
Among the 539 included children, the mean age was 24 months (SD 0.6), 49% were girls. Prevalence of ID (SF <10 µg/L) and anemia (Hb <11 g/dL) was 7% (37/539, 95% CI 4.9-9.3) and 3% (19/536, 95% CI 2.1-5.5), respectively. Hepcidin (ng/mL) median was 3.3 (IQR: 1.0-7.1; min-max: 0.75-104.1) and its mean was 6.7 (SD 10.7). Hepcidin was neither normally nor log-normally distributed (Figure 1.A, 1.B). sTfR median was 4.1 (IQR: 3.6-4.8; min-max: 1.2-13.5) and its mean was 4.2 (SD 1.1). TfR-F index median was 1.2 (IQR: 1.0-1.5; min-max: 0.3-8.4) and its mean was 1.4 (SD 0.6). No statistically significant difference was found between girls and boys for hepcidin, sTfR, and TfR-F index distributions (all p t-tests > 0.3). Distributions of other iron biomarkers were closed to those reported in the literature.
Conclusion:
We described for the first time in a nationwide ambulatory study hepcidin and TfR/logSF distributions in a population of 2 year-old healthy infants with a low ID prevalence. Hepcidin had a right-skewed distribution and its normalisation was not obtained by usual transformations. Low values, partly corresponding to the limit of detection, were over-represented despite the low proportion of ID defined by SF level. High values were also observed despite the exclusion of infants with CRP>10 mg/L. We did not find significant variations according to gender. Our results will help define normal values at this age to better interpret iron status.
Sacri:Secteur Francais des Aliments de l Enfance: Research Funding; French Ministry of Health DGOS PHRC regional 2014 no. AOR14053: Research Funding. De Montalembert:Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Addmedica: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Chalumeau:French Ministry of Health DGOS PHRC regional 2014 no. AOR14053: Research Funding; Secteur Francais des Aliments de l Enfance: Research Funding.
To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline ...compliance.
This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).
We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with “timely long-term prophylaxis” as compared with “delayed long-term prophylaxis”: hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with “long-term prophylaxis guideline compliance” vs “long-term prophylaxis anticipation.”
This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
Introduction
Recombinant factor IX Fc fusion protein (rFIXFc) is an extended half‐life concentrate for the treatment of haemophilia B (HB). rFIXFc activity monitoring is crucial in several clinical ...situations. However, differences were observed between one‐stage clotting (OSC) and chromogenic assays, but not for all factor IX (FIX) concentrations.
Aims
To compare rFIXFc measurements obtained using different instruments and common OSC and chromogenic asssays.
Methods
FIX:C measurements were performed in rFIXFc‐spiked plasma aliquots (targeted FIX levels of 1.5, 1, 0.5, 0.2, 0.05, 0.02 and 0.01 IU/mL) and plasma samples collected from two patients with HB at various time points after rFIXFc infusion, using three instruments (STA‐R MAX, ACLTOP700 and CS2100i) and common clotting and chromogenic FIX:C assays.
Results
The same reagent could give different FIX:C measurements when adapted to different instruments. Moreover, the same reagent/instrument combination could give different results depending of the FIX concentration. For OSC assays, only STA‐Cephascreen on STA‐R MAX and CS2100i, SynthAFax on ACLTOP 700 and Actin on CS2100i provided acceptable recoveries for all rFIXFc concentrations. The chromogenic assays ROX‐FIX and Biophen FIX:C underestimated rFIXFc for concentrations lower than 0.05 and 0.2 IU/mL, respectively.
Conclusions
Our study demonstrates that the same reagent adapted to different instruments could lead to different rFIXFc values. As rFIXFc under/overestimation could be associated with inappropriate treatment or biased calculation of pharmacokinetic parameters, the reagent/instrument combination used by haemostasis laboratories should be considered and regularly evaluated by external quality assessment programmes.
Intracranial haemorrhage (ICH) is known to be a severe although uncommon complication of haemophilia. A national survey has been conducted in France in order to collect information about ICHs which ...occurred in haemophiliacs between 1991 and 2001 and to propose recommendations for the diagnostic and treatment of ICH. Within this period, 123 episodes of ICH were recorded from 106 patients. Two‐thirds of ICH concerned patients with severe haemophilia. Half of the cases occurred in patients under 15 years of age, 67.2% of which were post‐traumatic. Ten cases occurred in neonates with three fatal outcomes. Overall mortality was high (21.9%) suggesting that availability of clotting factor concentrates has not improved the prognosis of this event. Morbidity was also high with 60% of long‐term sequelae. The following parameters have been identified as prognostic factors for death: thrombocytopenia, HCV infection, intraventricular or intraparenchymatous haemorrhage. A delay in diagnosis was mentioned in 43.3% of cases, often related to the lack of recognition of the initial symptoms, which may be very common (apathy, tearfulness in young children and headache in elder patients). Delayed replacement therapy was recorded in 37.2% of cases. Emergency units initially dealt with half of these patients. Information concerning recognition and management of these episodes, not only in severe haemophilia, but also in moderate and mild forms, should be regularly supplied to paediatricians in maternity and physicians from emergency units, as well as to patients and their relatives.
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