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Objectives SARS-CoV-2 induces a broad spectrum of clinical manifestations, which overlap with other viral infections very common in children. We aimed to describe the percentage of positive SARS-CoV-2 RT-PCR tests in symptomatic and asymptomatic ambulatory children and to determine the predictive factors for positivity. Patients and Methods From June 1 to July 31, 2020, we conducted a cross-sectional prospective, multicenter study (13 hospital emergency units and 59 ambulatory pediatricians) throughout France. Children under 15 years of age with a prescription of nasopharyngeal SARS-CoV-2 RT-PCR test were enrolled. Results Among the 1,553 RT-PCR tests, 22 were positive (1.4%; 95%CI [0.9; 2.1]). In both univariate and multivariate analyses, the predictive factors for positivity were age below 2 years (OR: 4.5 [1.6; 12.7]) and history of contact (OR: 12.3 [4.6; 32.8]). Conclusions In an epidemic stage with low SARS-CoV-2 circulation, sampling of children with nonspecific symptoms and without known contact could be questioned.

Background: The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify participants at risk of developing mild cognitive impairment due to Alzheimer's disease within 5 years, and to evaluate the safety and efficacy of low-dose pioglitazone to delay onset of mild cognitive impairment in these at-risk participants. Methods: In this phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled cognitively healthy, community living participants aged 65–83 years from 57 academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. By use of the BRAA, participants were grouped as high risk or low risk. Participants at high risk were randomly assigned 1:1 to receive oral pioglitazone (0·8 mg/day sustained release) or placebo, and all low-risk participants received placebo. Study investigators, site staff, sponsor personnel, and study participants were masked to genotype, risk assignment, and treatment assignment. The planned study duration was the time to accumulate 202 events of mild cognitive impairment due to Alzheimer's disease in White participants who were at high risk (the population on whom the genetic analyses that informed the BRAA development was done). Primary endpoints were time-to-event comparisons between participants at high risk and low risk given placebo (for the BRAA objective), and between participants at high risk given pioglitazone or placebo (for the efficacy objective). The primary analysis included all participants who were randomly assigned, received at least one dose of study drug, and had at least one valid post-baseline visit, with significance set at p=0·01. The safety analysis included all participants who were randomly assigned and received at least one dose of study medication. An efficacy futility analysis was planned for when approximately 33% of the anticipated events occurred in the high-risk, White, non-Hispanic or Latino group. This trial is registered with ClinicalTrials.gov, NCT01931566. Findings: Between Aug 28, 2013, and Dec 21, 2015, we enrolled 3494 participants (3061 at high risk and 433 at low risk). Of those participants, 1545 were randomly assigned to pioglitazone and 1516 to placebo. 1104 participants discontinued treatment (464 assigned to the pioglitazone group, 501 in the placebo high risk group, and 139 in the placebo low risk group). 3399 participants had at least one dose of study drug or placebo and at least one post-baseline follow-up visit, and were included in the efficacy analysis. 3465 participants were included in the safety analysis (1531 assigned to the pioglitazone group, 1507 in the placebo high risk group, and 427 in the placebo low risk group). In the full analysis set, 46 (3·3%) of 1406 participants at high risk given placebo had mild cognitive impairment due to Alzheimer's disease, versus four (1·0%) of 402 participants at low risk given placebo (hazard ratio 3·26, 99% CI 0·85–12·45; p=0·023). 39 (2·7%) of 1430 participants at high risk given pioglitazone had mild cognitive impairment, versus 46 (3·3%) of 1406 participants at high risk given placebo (hazard ratio 0·80, 99% CI 0·45–1·40; p=0·307). In the safety analysis set, seven (0·5%) of 1531 participants at high risk given pioglitazone died versus 21 (1·4%) of 1507 participants at high risk given placebo. There were no other notable differences in adverse events between groups. The study was terminated in January, 2018, after failing to meet the non-futility threshold. Interpretation: Pioglitazone did not delay the onset of mild cognitive impairment. The biomarker algorithm demonstrated a 3 times enrichment of events in the high risk placebo group compared with the low risk placebo group, but did not reach the pre-specified significance threshold. Because we did not complete the study as planned, findings can only be considered exploratory. The conduct of this study could prove useful to future clinical development strategies for Alzheimer's disease prevention studies. Funding: Takeda and Zinfandel.

Objectives To assess whether a retail sales database could be used to monitor antibiotic utilization in the outpatient setting at the national level. Methods We extracted 2012–17 outpatient antibiotic extrapolated retail sales (IQVIA’s Xponent) and reimbursement data from the National Health Insurance (SNDS) in metropolitan France. We compared estimates of antibiotic use and consumption [number of antibiotic drug deliveries (DrID) and defined daily doses (DID) per 1000 inhabitants per day]. We relied on relative differences, Pearson’s r statistics and time series using autoregressive integrated moving average (ARIMA) modelling to study: (i) differences in point estimates, (ii) correlation, and (iii) consistency in time trends between Xponent and SNDS. The analysis was conducted overall and in subgroups (age groups, therapeutic classes, major antimicrobial agents and regions). Results We analysed approximately 377 million antibiotic drug deliveries, comprising nearly 3.4 billion DDDs. Overall, Xponent slightly overestimated SNDS point estimates with yearly relative differences of +3.5% for DrID and +3.3% for DID. Peaks in relative differences were observed for July and August months. Relative differences were Conclusions IQVIA’s Xponent and SNDS data were highly consistent. Xponent database seems suitable for monitoring outpatient antibiotic utilization in France.

BACKGROUND/OBJECTIVES Transfusion reactions (TRs) may cause or contribute to death. Cardiopulmonary TRs are distressing, and collectively account for most transfusion fatalities, though the degree to which they alter survival more broadly is unclear. Deaths (and their timing) after TRs may provide further insights. MATERIALS/METHODS Adult (tri-hospital network) haemovigilance data (2013-2016) recorded referrals with conclusions ranging from unrelated to transfusion (UTR) to entities such as: septic TRs, serologic/haemolytic reactions, transfusion-associated circulatory overload (TACO), transfusion-associated dyspnoea (TAD), transfusion-related acute lung injury (TRALI), allergic transfusion reaction (ATR), and others. For (in- or out-patient) visits involving suspected TRs (VISTRs), all-cause mortalities (% [95% confidence interval]) and associated time-to-death (TTD) (median days, [interquartile range]) were compared. Diagnoses were defined inclusively (possible-to-definite) or strictly (probable-to-definite). RESULTS Of 1144 events, rank order VISTR mortality following (possible-to-definite) TRs, and associated TTDs, were led by: DHTR 33% [6-19], 1 death at 123d; TRALI 32% [15-54], 6 deaths: 3d [2-20]; BaCon 21% [14-31], 17 deaths: 10d [3-28]; TACO 18% [12-26], 23 deaths: 16d [6-28]; TAD 17% [11-26]: 18 deaths, 6d [3-12]. Higher-certainty TRs ranked similarly (DHTR 50% [9-91]; BaCon 29% [12-55], 4 deaths: 12d [3-22]; and TACO 25% [16-38], 15 deaths: 21d [6-28]). VISTR mortality after TACO or TRALI significantly exceeded ATR (3·3% [2·4-5·8], P

Background Maintaining a high vaccination coverage rate (VCR) throughout the lifetime and complying with the National Immunization Program are essential to optimize the protection of the population. The study objectives were to evaluate the evolution of the VCRs and the compliance with the vaccination visits for the diphtheria, tetanus, poliomyelitis and pertussis boosters in France since the changes implemented in the 2013 National Immunization Program. Methods Cumulative booster VCRs were estimated at all vaccination visits, from 2013 to 2017, among persons eligible for a booster vaccination from a 1/97th random sample of French claims data. Broader age groups around the recommended ages by the vaccination schedule (6, 11–13, 25, 45, 65, 75, 85, 95y) were used: all persons aged 5 to 8, 10 to 15, 21 to 29, 41 to 49, 61 to 69, 71 to 79, 81 to 89 and 91 to 99. Results Over the study period, the diphtheria-tetanus-poliomyelitis booster VCRs increased, reaching in 2017: 73.3% at 8 years old, 75.6% at 15 years old, 46.6% at 29 years old, 38.4% at 49 years old, 36.3% at 69 years old, 30.8% at 79 years old, 22.1% at 89 years old and 11.0% at 99 years old. The pertussis VCRs were also increasing at all vaccination visits, in particular at the vaccination visits at 6 and 11–13 years old (from 16.4% to 63.8% and from 50.3% to 61.2%, respectively). Delayed vaccinations were observed at all vaccination visits. Conclusion VCRs for Diphtheria, Tetanus, Poliomyelitis and Pertussis booster vaccination increased from 2013 to 2017 while remaining suboptimal across all ages and lower in the adult populations. The analysis also shows that the introduction in 2013 of a pertussis vaccination at 6 years of age was relatively well-established in 2017 while other changes in recommendations were slowly or partially implemented.

Background Platelet transfusions are used to prevent or control bleeding in patients with thrombocytopenia or platelet dysfunction. The pretransfusion platelet count threshold has been studied extensively in multiple patient settings yielding high-quality evidence that has been summarized in several comprehensive evidence-based platelet guidelines. Study design and methods A prospective 12-week audit of consecutive platelet transfusions using validated and evidence-based adjudication criteria was conducted. Patient demographic, laboratory, and transfusion details were collected with an electronic audit tool. Each order was adjudicated either electronically or independently by two transfusion medicine physicians. The aim was to determine platelet transfusion appropriateness and common scenarios with deviations from guidelines. Results Fifty-seven (38%) of 150 hospitals provided data on 1903 platelet orders, representing 90% of platelet usage in the region during the time period. Overall, 702 of 1693 adult (41.5%) and 133 of 210 pediatric orders (63.3%) were deemed inappropriate. The most common inappropriate platelet order was for prophylaxis in the absence of bleeding or planned procedure in patients with hypoproliferative thrombocytopenia and a platelet count over 10 x 109 /L (53% of inappropriate orders in adults and 45% in pediatrics). Platelet transfusions ordered with either a preprinted transfusion order set (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.44-2.73) or technologist prospective screening (OR, 1.40; 95% CI, 1.10-1.78) were more likely to be appropriate. Conclusion There is a discrepancy between clinical practice and evidence-based platelet guidelines. Broad educational and system changes will be needed to align platelet transfusion practice with guideline recommendations.

Background Alloimmunization can impact both the fetus and neonate. Study objectives (a) calculate the incidence of clinically significant RBC isoimmunization during pregnancy, (b) review maternal management and neonatal outcomes, (c) assess the value of prenatal and postnatal serological testing in predicting neonatal outcomes. Study design and methods A retrospective audit of consecutive alloimmunized pregnancies was conducted. Data collected included demographics, clinical outcomes, and laboratory results. Outcomes included: incidence of alloimmunization; outcomes for neonates with and without the cognate antigen; and sensitivity and specificity of antibody titration testing in predicting hemolytic disease of the fetus and newborn (HDFN). Results Over 6 years, 128 pregnant women (0.4%) were alloimmunized with 162 alloantibodies; anti-E was the most common alloantibody (51/162; 31%). Intrauterine transfusions (IUTs) were employed in 2 (3%) of 71 mothers of cognate antigen positive (CoAg+) neonates. Of 74 CoAg+ neonates, 58% required observation alone, 23% intensive phototherapy, 9% top up transfusion, and 3% exchange transfusion; no fetal or neonatal deaths occurred. HDFN was diagnosed in 28% (21/74) of neonates; anti-D was the most common cause. The sensitivity and specificity of the critical gel titer >32 in predicting HDFN were 76% and 75%, respectively (negative predictive value 95%; positive predictive value 36%). The sensitivity and specificity of a positive direct antiglobulin test (DAT) in predicting HDFN were 90% and 58%, respectively (NPV 97%; PPV 29%). Conclusion Morbidity and mortality related to HDFN was low; most alloimmunized pregnancies needed minimal intervention. Titers of >32 by gel warrant additional monitoring during pregnancy.

Summary Background Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. Methods We did a quasi-experimental interrupted time series analysis over the past 15 years in a tertiary paediatric centre in the Paris region, a French epicentre of the COVID-19 outbreak. The main outcome was the number of Kawasaki disease cases over time, estimated by quasi-Poisson regression. In the same centre, we recorded the number of hospital admissions from the emergency department (2005–2020) and the results of nasopharyngeal multiplex PCR to identify respiratory pathogens (2017–2020). These data were compared with daily hospital admissions due to confirmed COVID-19 in the same region, recorded by Public Health France. Findings Between Dec 1, 2005, and May 20, 2020, we included 230 patients with Kawasaki disease. The median number of Kawasaki disease hospitalisations estimated by the quasi-Poisson model was 1·2 per month (IQR 1·1–1·3). In April, 2020, we identified a rapid increase of Kawasaki disease that was related to SARS-CoV-2 (six cases per month; 497% increase [95% CI 72–1082]; p=0·0011), starting 2 weeks after the peak of the COVID-19 epidemic. SARS-CoV-2 was the only virus circulating intensely during this period, and was found in eight (80%) of ten patients with Kawasaki disease since April 15 (SARS-CoV-2-positive PCR or serology). A second peak of hospital admissions due to Kawasaki disease was observed in December, 2009 (six cases per month; 365% increase ([31–719]; p=0.0053), concomitant with the influenza A H1N1 pandemic. Interpretation Our study further suggests that viral respiratory infections, including SAR-CoV-2, could be triggers for Kawasaki disease and indicates the potential timing of an increase in incidence of the disease in COVID-19 epidemics. Health-care providers should be prepared to manage an influx of patients with severe Kawasaki disease, particularly in countries where the peak of COVID-19 has recently been reached. Funding French National Research Agency.

Objective(s): Blood cultures (BC), when performed in children seen in the emergency department with community-acquired pneumonia (CAP), are most of the time sterile. We described the diagnostic accuracy of white blood cells (WBC), absolute neutrophils count (ANC), C-reactive protein (CRP), and procalcitonin (PCT) to predict blood culture (BC) result in childhood CAP.Study Design: Secondary analysis of a prospective study carried out in eight pediatric emergency departments (France, 2009–2018), including children (≤15 years) with CAP. Analyses involved univariate comparisons and ROC curves.Results: We included 13,752 children with CAP. BC was positive in 137 (3.6%) of the 3,829 children (mean age 3.7 years) in whom it was performed, mostly with Streptococcus pneumoniae (n = 107). In children with bacteremia, ANC, CRP and PCT levels were higher (median 12,256 vs. 9,251/mm3, 223 vs. 72 mg/L and 8.6 vs. 1.0 ng/mL, respectively; p ≤ 0.002), but WBC levels were not. The area under the ROC curve of PCT (0.73 [95%CI 0.64–0.82]) was significantly higher (p ≤ 0.01) than that of WBC (0.51 [0.43–0.60]) and of ANC (0.55 [0.46–0.64]), but not than that of CRP (0.66 [0.56–0.76]; p = 0.21). CRP and PCT thresholds that provided a sensitivity of at least 90% were 30 mg/L and 0.25 ng/mL, respectively, for a specificity of 25.4 and 23.4%, respectively. CRP and PCT thresholds that provided a specificity of at least 90% were 300 mg/L and 20 ng/mL, respectively, for a sensitivity of 31.3 and 28.9%, respectively.Conclusions: PCT and CRP are the best routinely available predictive biomarkers of bacteremia in childhood CAP.

Non-pharmaceutical interventions (NPIs) were implemented to reduce the spread of coronavirus disease 2019 (COVID-19). A first national lockdown was decided in France on the 17 March 2020. These measures had an impact on other viral and non-viral infectious diseases. We aimed to assess this impact on community-acquired pneumonia (CAP) in children. We performed a quasi-experimental interrupted time series analysis. We used data from a French prospective surveillance system of six pediatric emergency departments (PEDs). All visits from 1 January 2017 to 31 December 2020 were included. Pre-intervention period was before 17 March 2020 and post-intervention period was after 18 March 2020. We estimated the impact on the weekly number of visits for CAP and CAP admission using quasi-Poisson regression modeling. A total of 981,782 PEDs visits were analyzed, among them, 8318 visits were associated with CAP, and 1774 of these were followed by a hospital admission. A major decrease was observed for CAP visits (−79.7% 95% CI [−84.3, −73.8], p &lt, 0.0001), and CAP admission (−71.3% 95 CI [−78.8, −61.1], 0.0001). We observed a dramatic decrease of CAP in children following NPIs implementation. Further studies are required to assess the long-term impact of these measures.

International audience

Background: A worldwide voluntary recall of valsartan in July 2018 due to the potential carcinogen N-nitrosodimethylamine received extensive media and public attention. This was followed by more Food and Drug Administration (FDA) recalls regarding other contaminated ARB (angiotensin receptor blocker) products. Our study investigated the association between the FDA recalls and ARB neoplasm adverse events (AEs) reported to the FDA adverse event reporting system. Methods: In this cross-sectional study, data were retrospectively collected from the FDA adverse event reporting system database from January 2015 to December 2019. Reporting odds ratios (RORs) were estimated to detect signals of association between ARBs (valsartan, irbesartan, and losartan) and reported neoplasm AEs using negative (amoxicillin and sertraline) and positive (omeprazole and ranitidine) control exposures. The χ 2 was used to compare categorical variables. Results: A total of 2 181 524 AEs, including 10 461 nonmetastatic neoplasm AEs were analyzed. Monthly RORs (95% CI) of valsartan-associated neoplasms versus controls (ROR*: valsartan/negative exposures; ROR†: valsartan/omeprazole; and ROR‡: valsartan/ranitidine) showed the highest signals after the recall date in July 2018 (7.64 [4.78–12.19]*; 4.77 [3.36–6.79]†; 4.13 [2.50–6.84]‡) and August 2018 (7.87 [5.19–11.94]*; 5.65 [4.12–7.75]†; and 7.20 [4.46–11.63]‡). In contrast, the highest cancer signals for the irbesartan and losartan recalls detected in March 2019 (4.80*; 4.06†; and 3.38‡) and April 2019 (3.63*; 3.69†; and 2.52‡) respectively, were lower. One-year postrecall reported neoplasm AEs were ≈2-fold higher for valsartan than irbesartan (OR, 1.77 [95% CI, 1.47–2.13], P P Conclusions: Significantly more postrecall neoplasms were reported for valsartan, with higher valsartan-associated cancer signals compared with irbesartan and losartan, although they all contained the same carcinogenic contaminant. Extensive media coverage of the FDA valsartan recall may have alarmed patients and generated these abrupt, biologically infeasible cancer signals.

Background Prenatal antibody titers for alloimmunized patients are subject to multiple sources of variation. A parallel titer on the previous sample at the same time as the current sample is recommended. The purpose of this study was to determine the added value of parallel titers. Study design and methods This is a retrospective study of samples from consecutive prenatal patients with at least two prenatal antibody titers performed in the same pregnancy at a single institution between October 2010 and March 2017. Prenatal titers were performed using gel technology. Data were collected to determine the sensitivity and specificity of a clinically significant increase (twofold or greater) in serial titers compared with the gold standard of using parallel titers. Results There were 155 serial prenatal titers performed in 59 alloimmunized pregnant women. Nineteen samples (12%) had a serial titer increase of twofold or greater with eight false positive samples (increase less than twofold when using parallel titers). Thirty-six samples (23%) had a serial titer increase of onefold with two false negative samples (increase of twofold or greater using parallel titers). One hundred samples (65%) had no increase (or a decrease) in serial titer with none having an increase of twofold or greater using parallel titers. The sensitivity of a twofold or greater increase in serial titers was 84.6% (95% CI 55-98%) and the specificity was 94.4% (95% CI 89-98%) when compared with parallel titers. Conclusion This study questions the value of parallel titers on every prenatal titer performed. When no increase in serial titers was observed, parallel titers added no new information.

BACKGROUND & OBJECTIVES Serologic testing after transfusion reactions (TRs) aims to find accountable immune haemolytic incompatibility. Our hospital policies recommend serologic testing in all TR, except for low-risk fevers (subclinical temperature

The transfusion chain is susceptible to error at every step. Accurate patient registration is a key first step that links a patient with their historical medical profile, yet patient registration is marked by its own challenges. Registration errors are deviations from standard operating procedures that occur during the process of patient registration. A frequent consequence of registration errors is the obfuscation of historical information and patient misidentification. Through duplicate registrations, patient information can be spread across multiple records and through hybrid registrations information from multiple patients can be combined into a single record. Patients with the same core identifiers, and the misuse of health insurance information also pose a threat to accurate registration. In the context of transfusion, this can lead to ABO discrepancies, failing to match for previously identified alloantibodies, and redundant serological investigations. Other consequences include missed billing opportunities and the inadvertent sharing of medical information. Reducing the occurrence of registration errors can be achieved through a multifaceted approach combining targeted educational efforts with technological improvements to the registration system. A recent development being the use of biometric identifiers. Despite their frequency, published reports on the occurrence and underlying cause of registration errors are rare. Most reports are found within articles on general medical errors or misidentification events and consequently, the true rate of registration errors among health information systems is not known. Here we summarize literature pertaining to how and why registration errors occur and their implications in the context of blood transfusion.

A multi-partner effort in Uganda and Zambia employed a districtwide health systems strengthening approach, with supply- and demand-side interventions, to address timely use of appropriate, quality maternity care. Between 2012 and 2016, maternal mortality declined by approximately 40% in both partnership-supported facilities and districts in each country. This experience has useful lessons for other low-resource settings., Background: Ending preventable maternal and newborn deaths remains a global health imperative under United Nations Sustainable Development Goal targets 3.1 and 3.2. Saving Mothers, Giving Life (SMGL) was designed in 2011 within the Global Health Initiative as a public–private partnership between the U.S. government, Merck for Mothers, Every Mother Counts, the American College of Obstetricians and Gynecologists, the government of Norway, and Project C.U.R.E. SMGL's initial aim was to dramatically reduce maternal mortality in low-resource, high-burden sub-Saharan African countries. SMGL used a district health systems strengthening approach combining both supply- and demand-side interventions to address the 3 key delays to accessing effective maternity care in a timely manner: delays in seeking, reaching, and receiving quality obstetric services. Implementation: The SMGL approach was piloted from June 2012 to December 2013 in 8 rural districts (4 each) in Uganda and Zambia with high levels of maternal deaths. Over the next 4 years, SMGL expanded to a total of 13 districts in Uganda and 18 in Zambia. SMGL built on existing host government and private maternal and child health platforms, and was aligned with and guided by Ugandan and Zambian maternal and newborn health policies and programs. A 35% reduction in the maternal mortality ratio (MMR) was achieved in SMGL-designated facilities in both countries during the first 12 months of implementation. Results: Maternal health outcomes achieved after 5 years of implementation in the SMGL-designated pilot districts were substantial: a 44% reduction in both facility and districtwide MMR in Uganda, and a 38% decrease in facility and a 41% decline in districtwide MMR in Zambia. Facility deliveries increased by 47% (from 46% to 67%) in Uganda and by 44% (from 62% to 90%) in Zambia. Cesarean delivery rates also increased: by 71% in Uganda (from 5.3% to 9.0%) and by 79% in Zambia (from 2.7% to 4.8%). The average annual rate of reduction for maternal deaths in the SMGL-supported districts exceeded that found countrywide: 11.5% versus 3.5% in Uganda and 10.5% versus 2.8% in Zambia. The changes in stillbirth rates were significant (−13% in Uganda and −36% in Zambia) but those for pre-discharge neonatal mortality rates were not significant in either Uganda or Zambia. Conclusion: A district health systems strengthening approach to addressing the 3 delays to accessing timely, appropriate, high-quality care for pregnant women can save women's lives from preventable causes and reduce stillbirths. The approach appears not to significantly impact pre-discharge neonatal mortality.

International audience; Since the beginning of the COVID-19 pandemic, reduced incidence of many viral and bacterial infections has been reported in children: bronchiolitis, varicella, measles, pertussis, pneumococcal and meningococcal invasive diseases. The purpose of this opinion paper is to discuss various situations that could lead to larger epidemics when the non-pharmaceutical interventions (NPI) imposed by the SARS-CoV-2 epidemic will no longer be necessary.While NPIs limited the transmission of SARS-CoV-2, they also reduced the spread of other pathogens during and after lockdown periods, despite the re-opening of schools since June 2020 in France. This positive collateral effect in the short term is welcome as it prevents additional overload of the healthcare system. The lack of immune stimulation due to the reduced circulation of microbial agents and to the related reduced vaccine uptake induced an "immunity debt" which could have negative consequences when the pandemic is under control and NPIs are lifted. The longer these periods of "viral or bacterial low-exposure" are, the greater the likelihood of future epidemics. This is due to a growing proportion of "susceptible" people and a declined herd immunity in the population. The observed delay in vaccination program without effective catch-up and the decrease in viral and bacterial exposures lead to a rebound risk of vaccine-preventable diseases.With a vaccination schedule that does not include vaccines against rotavirus, varicella, and serogroup B and ACYW Neisseria meningitidis, France could become more vulnerable to some of these rebound effects.

International audience; Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P =.008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P =.004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design..

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution. METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement. RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children

Background:Multisystem inflammatory syndrome in children (MIS-C) is the most severe form associated with SARS-CoV-2 infection in children. To reduce the spread of SARS-CoV-2 at the population level, educational setting closure have been implemented in many countries. However, the direct benefit of school closure on the MIS-C burden remains to be explored. We aimed to assess the role of educational settings in SARS-CoV-2 transmission among children with MIS-C.Methods:We conducted a French national prospective surveillance of MIS-C, coordinated by Public Health France, from April 2020 to March 2021. During this period, we included all children with MIS-C fulfilling the WHO definition who were reported to Public Health France. For each child, we traced the source of SARS-CoV-2 transmission. The main outcome was the proportion of children with MIS-C, with educational setting-related SARS-CoV-2 infection, during the period of school opening.Results:We included 142 children fulfilling WHO criteria for MIS-C: 104 (70%) cases occurred during school opening periods. In total, 62/104 children (60%, 95%CI [50; 69]) had been contaminated by a household contact and 5/104 in educational settings (5%, 95%CI [2; 11]). Among children with MIS-C occurring during school closure periods, the proportion of household transmission remained similar (66%, 25/38).Conclusion:Children with MIS-C were mainly infected by SARS-CoV-2 within their family environment, and the educational setting played a marginal role in this transmission. This suggests that mitigating school attendance may not reduce substantially the burden of MIS-C.

Background: This study aimed to evaluate whether the high frequency of reported statin adverse effects (AEs) may be associated with the nocebo effect. We compared nocebo-related subjective AEs with objective AEs and investigated factors potentially associated with the nocebo effect. Methods: A retrospective cohort study was conducted using the Food and Drug Administration Adverse Event Reporting System between January 2010 and December 2019 for statins, including, atorvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin. Subjective AEs included fatigue, subjective muscular, and nervous system AEs. Objective AEs were defined as hepatic and objective muscular AEs. We compared the number of subjective and objective AEs using the Mann-Whitney U test and examined trends in the frequency of subjective versus objective reports over time using linear regression with interaction terms. We evaluated the association between AEs and gender and country using linear regression. Quantitative detection of signals was estimated using proportional reporting ratio and reporting odds ratio for simvastatin. Results: Of 2 994 487 overall AE reports, more subjective than objective AEs were reported per quarter (mean±SD: 4777±1375.45 versus 999±276.95; P P P =0.035; subjective muscular AE: 417.95, P P P Conclusions: This study found that significantly more subjective than objective AEs are reported for statins. Subjective statin AEs, potentially related to the nocebo effect are reported more often by women than by men, and in the United States than in other countries.

Naso-pharyngeal RT-PCR is the gold standard for the diagnosis of COVID-19, but there is a need for rapid and reliable tests. Some validation studies have used frozen aliquots mainly from adults. The aim of this real-life study was to test the performance of a SARS-CoV-2 rapid antigen test (SC2-RAT) in children. Symptomatic patients aged 0 to 17 years were recruited in the emergency department of the University Hospital of Creteil and in primary care pediatric practices from October 10, 2020 for 7 weeks. Each enrolled child had a SARS-CoV-2 RT-PCR test and a SC2-RAT from two distinct nasopharyngeal swabs. Among the 308 patients (mean [SD] age 4.9 [5.3] years), fever was the main symptom (73.4%), with no difference between COVID-19–negative and –positive groups. The prevalence of COVID-19 was 10.7% (95% CI 7.5–14.7). On the whole cohort, the sensitivity and specificity of the SC2-RAT compared to RT-PCR was 87.9% (95% CI 71.8–96.6) and 98.5% (95% CI 96.3–99.6). Considering samples with cycle threshold >25, the sensibility was lower: 63.6% (95% CI 30.8–89.1) and the specificity 99.6% (95% CI 98.0–100.0). The mean delay to obtain an SC2-RAT result was n = 21, 61.6%, vs. n = 64, 24.6%; p < 0.01). In real life, SC2-RAT seems reliable for symptomatic children, allowing to detect contagious children.

BackgroundSeveral studies indicated that children seem to be less frequently infected with SARS-CoV-2 and are potentially less contagious than adults. To examine the spread of SARS-CoV-2, we combined both Reverse transcription-PCR testing and serology in children in the most affected region in France, Paris, during the COVID-19 epidemic.MethodsFrom 14 April 2020 to 12 May 2020, we conducted a cross-sectional, prospective, multicentre study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory paediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by Reverse transcription-PCR and a microsample of blood for micromethod serology.ResultsAmong the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) were symptomatic. Reverse transcription-PCR and serology results were positive for 11 (1.8%) and 65 (10.7%) children, respectively, with no significant difference between asymptomatic and pauci-symptomatic children. Only three children were Reverse transcription-PCR-positive without any antibody response detected. The frequency of Reverse transcription-PCR SARS-CoV-2 positivity was significantly higher for children with positive than negative serology results (12.3% vs 0.6%, pConclusionIn an area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with Reverse transcription-PCR SARS-CoV-2 positivity was very low (1.8%), but that of serology positivity was higher (10.7%). Most children with positive Reverse transcription-PCR results also had positive serology results.Trial registration numberNCT04318431.

Introduction: A worldwide recall of valsartan due to the potential carcinogen N-nitrosodimethylamine in July 2018 received extensive public attention. This was followed by more FDA recalls of other contaminated angiotensin receptor blocker (ARB) products. Our study investigated the association between the FDA recalls and ARB neoplasm adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS). Methods: Data was retrospectively collected from the FAERS database for reports from 1/2015-12/2019. Reporting odds ratios (ROR) were estimated to detect signals for association between ARBs (valsartan, losartan, and irbesartan) and reported neoplasm AEs using negative (amoxicillin and sertraline) and positive (omeprazole and ranitidine) control exposures. Chi-square test was used to compare categorical variables. Results: A total of 2,181,524 AEs, including 19,287 neoplasm AEs were analyzed. 1-year post-recall reported neoplasm AEs were higher for valsartan than losartan ( p p * : valsartan/negative exposure; ROR † : valsartan/omeprazole; ROR † : valsartan/ranitidine) showed the highest numerical signals post-recall in 7/2018 [7.64 (4.78-12.19) * ; 4.77 (3.36-6.79) † ; 4.13 (2.50-6.84) † ] and 8/2018 [(7.87 (5.19-11.94) * ; 5.65 (4.12-7.75) † ; 7.20 (4.46-11.63) † ]. In contrast, the highest post-recall cancer signals for irbesartan and losartan detected in 3/2019 (4.80 * ; 4.06 † ; 3.38 † ) and 4/2019 (3.63 * ; 3.69 † ; 2.52 † ) respectively, were lower. Conclusion: Significantly more post-recall neoplasms were reported for valsartan, with higher valsartan-associated cancer signals compared with losartan and irbesartan, even though they all contained the same carcinogenic contaminant. Extensive media coverage of the FDA valsartan recall may have alarmed patients and generated these abrupt, biologically infeasible cancer signals.

Introduction: Comparison of blinded and nonblinded statin trials have confirmed a nocebo effect, most commonly presenting as subjective muscle and nervous system adverse events (AEs). This study evaluated whether the increase in reported statin AEs over time was associated with the nocebo effect by comparing nocebo-related subjective with objective AEs. Method: A retrospective cohort study was conducted using the FDA Adverse Event Reporting System (FAERS) of statin-associated AEs from 1/2010-12/2019. Statins selected for analysis were atorvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin. Subjective AEs included fatigue, subjective muscular, and nervous system AEs. Objective AEs were hepatic and objective muscular AEs. We compared the number of subjective and objective AEs using Mann-Whitney U, and evaluated the association between AEs and gender and country using linear regression. Quantitative detection of signals was estimated using reporting odds ratio (ROR). Institutional Review Board review was exempt since we used de-identified public data. Results: Of 2,994,487 statin AE reports, more subjective than objective AEs were reported per quarter (mean ± SD: 4777 ± 1375.45 vs 999 ± 276.95; p Conclusion: This study found that significantly more subjective than objective AEs are reported for statins. Subjective statin AEs, potentially related to the nocebo effect are reported more often by females than by males, and in the US than in other countries.

International audience; Primary infection with varicella-zoster virus (VZV) causes chickenpox, a benign and self-limited disease in healthy children. In patients with primary or acquired immunodeficiencies, primary infection can be life-threatening, due to rapid dissemination of the virus to various organs [lung, gastrointestinal tract, liver, eye, central nervous system (CNS)]. We retrospectively described and compared the clinical presentations and outcomes of disseminated varicella infection (DV) in patients with acquired (AID) (n= 7) and primary (PID) (n= 12) immunodeficiencies. Patients with AID were on immunosuppression (mostly steroids) for nephrotic syndrome, solid organ transplantation or the treatment of hemopathies, whereas those with PID had combined immunodeficiency (CID) or severe CID (SCID). The course of the disease was severe and fulminant in patients with AID, with multiple organ failure, no rash or a delayed rash, whereas patients with CID and SICD presented typical signs of chickenpox, including a rash, with dissemination to other organs, including the lungs and CNS. In the PID group, antiviral treatment was prolonged until immune reconstitution after bone marrow transplantation, which was performed in 10/12 patients. Four patients died, and three experienced neurological sequelae. SCID patients had the worst outcome. Our findings highlight substantial differences in the clinical presentation and course of DV between children with AID and PID, suggesting differences in pathophysiology. Prevention, early diagnosis and treatment are required to improve outcome.

Objectives To assess recent community antibiotic prescribing for French children and identify areas of potential improvement. Methods We analysed 221 768 paediatric ( Results GPs prescribed more antibiotics than paediatricians [prescription rate 26.1 (95% CI 25.9–26.3) versus 21.6 (95% CI 21.0–22.2) per 100 visits, respectively; P Conclusions Future antibiotic stewardship campaigns should target presumed viral RTIs, broad-spectrum antibiotic use and GPs aged ≥50 years.

Objective: Nearly half of children who undergo tympanostomy tube (TT) insertion may experience otorrhea following surgery. We sought to review the evidence for the role of bacterial biofilms in post-tympanostomy tube otorrhea (PTTO) and the accumulated experience regarding the preventive measures for biofilm formation/adhesion on TTs. Methods: English literature search for relevant MeSH keywords was conducted in the following databases: MEDLINE (via PubMed), Ovid Medline, Google Scholar, and Clinical Evidence (BMJ Publishing) between January 1, 1995, and December 31, 2019. Subsequently, articles were reviewed and included if biofilm was evident in PTTO. Results: There is an increased evidence supporting the role of biofilms in PTTO. Studies on TT design and material suggest that nitinol and/or silicone TTs had a lower risk for PTTO and that biofilms appeared in specific areas, such as the perpendicular junction of the T-tubes and the round rims of the Paparella-type tubes. Biofilm-component DNAB-II protein family was present in half of children with PTTO, and targeting this protein may lead to biofilm collapse and serve as a potential strategy for PTTO treatment. Novel approaches for the prevention of biofilm-associated PTTO include changing the inherent tube composition; tube coating with antibiotics, polymers, plant extracts, or other biofilm-resistant materials; impregnation with antimicrobial compounds; and surface alterations by ion-bombardment or surface ionization, which are still under laboratory investigation. Conclusions: Currently, there is no type of TT on which bacteria will not adhere. The challenges of treating PTTO indicate the need for further research in optimization of TT design, composition, and coating.

Diarrheal disease remains a leading cause of child death globally, especially in low and middle-income countries. Use of oral rehydration solution (ORS) for treatment of diarrhea in children, a very cost-effective intervention, remains below 50% in many countries. Here we use a multi-level longitudinal model to reveal important predictors of ORS use at the national level. The findings suggest that increasing government effectiveness along with increased implementation and affordability of community-based health programs can lead to substantial increases in ORS use. Key informant interviews with national health leaders in countries that significantly improved ORS coverage support these quantitative findings.

The circumareolar (periareolar) mastopexy is an extremely versatile technique that can facilitate multiple types of aesthetic improvements of the breast, including elevation of the nipple areolar complex (NAC), reduction of areola size, improvement of breast symmetry, tightening of the skin envelope, and compression of a herniated areola as in the case of tuberous breasts. The technique also avoids a vertical scar on the breast, which is a significant benefit for many patients concerned about visible scars. The technique has earned a bad reputation for scar spread and distortion of the breast due to overaggressive skin resection or use in cases where a vertical mastopexy is more appropriate. This chapter will discuss how to assess patients based on their anatomy and determine whether a circumareolar mastopexy is an appropriate technique to use. It will also discuss how to design the skin resection pattern and execute the procedure in a way that minimizes risks of scar spread, wound healing issues and other complications.

International audience; The objective of this study was to determine the number of cases of pediatric meningitis or purpura fulminans associated with an incorrect vaccination status from 2011 to 2013 in France. A total of 48 children with vaccine-preventable meningitis or purpura fulminans, including three deaths, had an incorrect vaccination status: 26 cases were due to Neisseria meningitidis group C (54.2%), 19 to Streptococcus pneumoniae (39.6%), and three to Haemophilus influenzae type b (6.3%). The majority of patients (n = 35, 72.9%) had received no injection of the vaccine concerned. Over a 3-year period, 48 cases of bacterial meningitis or purpura fulminans in children could have been avoided if the French immunization schedule had been followed.

Many ambulatory networks in several countries have established syndromic surveillance systems to detect outbreaks of different illnesses. Here, we describe a new Pediatric and Ambulatory Research in Infectious diseases network that combined automated data extraction from the computers of primary care pediatricians.Pediatricians who used the same software, AxiSanté 5-Infansoft for electronic medical records were specially trained in infectious diseases, encouraged to comply with French treatments' recommendations, use of point-of-care tests and vaccination guidelines. Infectious disease diagnoses in children16 years old in the records triggered automatic data extraction of complete records. A quality control process and external validation were developed.From September 2017 to February 2020, 107 pediatricians enrolled 57,806 children (mean age 2.9 ± 2.6 years at diagnosis) with at least one infectious disease diagnosis among those followed by the network. Among the 118,193 diagnoses, the most frequent were acute otitis media (n = 44,924, 38.0%), tonsillopharyngitis (n = 13,334, 11.3%), gastroenteritis (n = 12,367, 10.5%), influenza (n = 11,062, 9.4%), bronchiolitis (n = 10,531, 8.9%), enteroviral infections (n = 8474, 7.2%) and chickenpox (n = 6857, 5.8%). A rapid diagnostic test was performed in 84.7% of cases of tonsillopharyngitis and was positive in 44%. The antibiotic recommendations from French guidelines were strictly followed: amoxicillin was the most prescribed antibiotic and less than 10% of presumed viral infections were treated.This "tailor-made" network set up with quality controls and external validation represents a new approach to the surveillance of pediatric infectious diseases in the digital era and could highly optimize pediatric practices.

Objectives To assess time trends of outpatient antibiotic utilization using different measures and explore their discrepancies. Methods Based on French sales data from the IQVIA SDM database, 2009-16, we assessed time trends in outpatient antibiotic utilization using PrID, DID, PID and SID (defined as the number of prescriptions, DDDs, packages and standard units per 1000 inhabitants per day, respectively). We explored discrepancies between trends in PrID and DID by modelling the number of DDDs per prescription. Results Outpatient antibiotic utilization (n = 538.2 million projected prescriptions) decreased in terms of PrID, PID and SID (-10%, -8% and -8%, respectively; negative regression slopes; P

Hypothermia (36°C) exacerbates trauma-induced coagulopathy and worsens morbidity and mortality among severely injured trauma patients; there is a paucity of published data describing how well trauma centres adhere to standards regarding measurement of temperature, and best practices for preventing and treating hypothermia.We completed a retrospective quality audit of all severely injured trauma patients (Injury Severity Score (ISS≥20)) who had urgent surgery at Sunnybrook Health Sciences Centre (SHSC) between 2010 and 2014. Information regarding temperature monitoring was evaluated over the course of the initial resuscitation and admission. Independent risk factors for in-hospital mortality were elucidated through a multivariable regression analysis.Out of a total of 4492 trauma patients, 495 were severely-injured and went to the operating room (OPR) after being treated in the trauma bay (TB) at SHSC between 2010 and 2014. The majority of the patients were male (n=384, 77.6%) and had a blunt mechanism of injury (n=391, 79.0%). The median ISS score was 29 (interquartile range (IQR) 26, 35). Eighty-nine (17.9%) patients died; 26 (5.2%) of these patients died intra-operatively. Less than one fifth of patients (n=82,16.6%) received a temperature measurement during pre-hospital transport phase. Upon arrival to the TB, almost two-thirds (n=301, 60.8%) of patients had their temperature recorded and a similar proportion (n=175, 58.1%) of those patients were hypothermic (36°C). In the OPR, close to 80% (n=389, 78.6%) of patients had their temperature measured on both arrival; almost 60% (n=223, 57.3%) were hypothermic on arrival. Almost all patients had their temperature measured upon arrival to the ICU or specialized ward (n=450, 98.3%). Warming initiatives were documented in only 36 (7.3%) patients in the TB, yet documented in almost all patients in OR (n=464, 93.7%). An increased risk of in-hospital mortality was correlated with not taking a temperature measurement in the TB (Odds Ratio (OR) 2.86 (95% Confidence Interval (CI) [1.64-4.99]) or OPR (OR 4.66 (95% CI [2.50-8.69]).A majority of severely injured trauma patients are hypothermic well into the perioperative period after initial admission. An absence of having temperature measurement during initial hospitalization is associated with increased in-hospital mortality amongst this patient group. Quality improvement initiatives should aim to strive for ongoing temperature measurement as a key performance indicator and early prevention and treatment of hypothermia during initial resuscitation.

Acute gastroenteritis (AGE) are usually caused by viruses, especially Rotavirus and Norovirus. Among the bacterial causes, very few warrant antibiotic treatment, mainly Shigella, Vibrio cholerae, Campylobacter (only for severe cases, particularly in the initial phase) and severe cases of Salmonella infection. The antimicrobial treatments proposed in this guide follow the latest guidelines of the European Society of Pediatric Infectious Diseases and the European Society of Pediatric Gastroenterology and Nutrition. Azithromycin is the preferred antibiotic for infections due to Shigella and Campylobacter. Ceftriaxone and ciprofloxacin are recommended for salmonellosis when antibiotic treatment is indicated. In most cases, empirical treatment without bacteriological documentation should be avoided.

Shiga toxin-producing Escherichia coli (STEC) infection can cause simple diarrhoea but also life-threatening haemolytic and uraemic syndrome (HUS) in infants. Diagnosis is based on amplification of genes encoding the Shiga toxin ( stx ) on stools.1 The increasing ability to detect STEC due to the availability of multiplex PCR raises questions concerning the interpretation by clinicians of a positive PCR for patients with acute diarrhoea. Therefore, knowledge of the rate of asymptomatic carriage among young infants is needed. We assessed the rate of STEC carriage in a large cohort of children less than 2 years old, at risk of HUS in France, irrespective of their modality of care. This work is an ancillary study of a longitudinal survey of faecal Enterobacterales antimicrobial resistance performed in children aged 6–24 …

The occurrence of meningitis in children5 years old may be associated with specific predisposing factors that can be anatomic, such as cerebrospinal fluid fistula or breach, or related to genetic susceptibility or N inborn or acquired immunologic defect. This study aimed to assess the anatomical and immunologic risk factors in children5 years old with pneumococcal meningitis and prospectively enrolled in the French national meningitis network.We analyzed all data for children who were 5-15 years old with a diagnosis of pneumococcal meningitis between 2001 and 2013. We describe the frequency and typology of the anatomic or immunologic risk factors, the clinical features and the pneumococcal serotypes.Among the 316 patients with pneumococcal meningitis, the mortality rate was 9.5% and 23.1% of cases presented complications (abscess, coma, hemodynamic failure, thrombophlebitis cerebral or deafness). In total, 108 children (34%) showed risk factors, the most frequent being anatomic: 70 cases (22.8%) were related to a cerebrospinal fluid breach or fistula and 55 (17.9%) to immunodeficiency, primary or acquired. Serotype data were available for 207 pneumococcal isolates (65.5%). The most frequent serotypes were as follows: 3, 18C, 19A and 19F between 2001 and 2009 and 19F, 3, 19A, 12F, 22F, 17F and 24F after 2009.We describe the largest cohort of children5 years old with pneumococcal meningitis. One third of the children had risk factors justifying a complete immunologic and radiologic work-up.

The high level of effectiveness of pneumococcal conjugate vaccines (PCVs) was demonstrated initially in high-income countries (HICs). However, because the burden of pneumococcal diseases (PDs) is greater in non-high-income countries (NHICs) than HICs, the assessment of these vaccines in this latter setting is crucial. Areas covered: PubMed was used to search for literature related to the effectiveness of PCVs. Several studies described the effectiveness of PCVs in NHICs, and we compare the impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and pneumonia in HICs and NHICs. Expert commentary: Implementation of PCVs has been effective in both HICs and NHICs. The decline in overall incidence of PD is due to the disappearance of most vaccine serotypes, which is straightforward and comparable across the different settings. As expected, the decrease in overall incidence of PD was eroded in part by the increasing incidence of IPD due to non-vaccine serotypes. We need to continue a multi-faceted surveillance of IPD and carriage.

BACKGROUND Febrile nonhemolytic transfusion reactions (FNHTRs) are characterized by a post-transfusion temperature rise (of ≥ 1°C, to ≥ 38°C) or chills/rigors unrelated to the underlying condition. FNHTRs are provoked by inflammatory cytokines in the product or by host antileukocyte antibodies against residual donor leukocytes. FNHTRs are among the most commonly reported transfusion disturbances and are generally deemed nonserious events. However, their impact on patients and hospitals may be underestimated. STUDY DESIGN AND METHODS A search through two hemovigilance databases identified all known possible-to-definite FNHTRs over 3 years (2013-2015) at four academic hospitals using prestorage leukoreduced components. FNHTRs were assessed for frequency by product (red blood cells [RBCs], platelets [PLTs], intravenous immunoglobulin), diagnostics (bedside, chest imaging, serology, microbiology), and management (medications, disposition change). The definition of FNHTR was derived from Canada's Transfusion-Transmitted Injuries Surveillance System. RESULTS For 437 FNHTRs, the overall per-product rate across all sites was 0.24%, or 0.17% with RBCs alone and 0.25% with PLTs alone. One-third of patients had significant fevers (≥ 39.0°C or a rise by ≥ 2.0°C). Approximately one-quarter underwent chest imaging within 48 hours, and 79% had blood cultures. A hospital admission directly attributable to the FNHTR, to exclude other causes of fever, occurred in 15% of FNHTR outpatients. CONCLUSION An analysis of FNHTRs reveals a substantial burden of postreaction clinical activity in addition to the disturbance itself. Efforts to avoid this adverse event may save resources, reduce patient distress, and encourage compliance with more restrictive transfusion strategies.

Supplemental Digital Content is available in the text., Background: Acute otitis media (AOM) is an important cause of childhood morbidity and antibiotic prescriptions. However, the relative importance of the well-known otopathogens, Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hflu), remains unclear because of a limited number of tympanocentesis-based studies that vary significantly in populations sampled, case definitions and heptavalent pneumococcal conjugate vaccine use. Methods: We conducted a pooled analysis of results from 10 AOM etiology studies of similar design, the protocols of which were derived from a common protocol and conducted in children 3 months to 5 years of age in different countries. Generalized estimating equations were used to account for within-study correlations. Results: The majority, 55.5% (95% confidence interval: 47.0%–65.7%) of 1124 AOM episodes, were bacterial pathogen positive: 29.1% (24.8%–34.1%) yielded Hflu and 23.6% (19.0%–29.2%) Spn. Proportions of Hflu and Spn were higher and lower, respectively, in heptavalent pneumococcal conjugate vaccine–vaccinated children. Hflu and Spn were each isolated from 20% to 35% of children in every 1-year age range. Hflu was less likely to be isolated from first (vs. subsequent) episodes [relative risk (RR): 0.71 (0.60–0.84)]. Spn was more often isolated from sporadic (vs. recurrent) cases [RR: 0.76 (0.61–0.97)]; the opposite was true for Hflu [RR: 1.4 (1.00–1.96)]. Spn cases were more likely to present with severe (vs. mild) symptoms [RR: 1.42 (1.01–2.01)] and Hflu cases with severe tympanic membrane inflammation [RR: 1.35 (1.06–1.71)]. Conclusions: Spn and Hflu remain the leading otopathogens in all populations examined. While associated with overlapping symptoms and severity, they exhibit some differences in their likelihood to cause disease in specific subpopulations.

Objective Vaccination of pregnant women against seasonal influenza is recommended in France since 2010. We currently do not have any vaccination coverage (VC) data to assess the implementation of this recommendation. Methods Vaccinoscopie ® is an annual study conducted online using a self-administered questionnaire. A section dedicated to parents’ vaccination was included in 2014 and aimed at interviewing 300 mothers of infants aged Results While 56% of mothers reported to have been informed of the importance of vaccination by a healthcare professional (HCP) during their last pregnancy, only 11% reported having been informed of the importance of influenza vaccination. Overall, 49% of mothers reported willing to be vaccinated during their next pregnancy to protect their baby, if the vaccination were to be recommended by a HCP. However, this rate was only 32% for influenza vaccination. In contrast, 52% of mothers reported willing to be vaccinated against pertussis during pregnancy if the vaccination were to be recommended by a HCP. The influenza VC estimates in pregnant women was 7%. Conclusion Although influenza vaccination has been recommended for all French pregnant women for the past five years, HCPs rarely recommend this vaccination – hence, the low VC. Informing and raising awareness among HCPs seems to be crucial to improve this coverage.

Introduction: Vancomycin remains the reference antibiotic in neonates for care-related infections caused by ß-lactam–resistant Gram-positive bacteria. Achieving the optimal serum vancomycin level is challenging because of high inter-individual variability and the drug's narrow therapeutic window. Continuous infusion might offer pharmacokinetic and practical advantages, but we lack consensus on the dosing regimen. The aim was to determine the proportion of neonates achieving an optimal therapeutic vancomycin level at the first vancomycin concentration assay and which dosing regimen is the most suitable for neonates.Methods: All neonates receiving continuous-infusion vancomycin (loading dose 15 mg/kg and maintenance dose 30 mg/kg/d) in a neonatal intensive care unit were retrospectively analyzed. The proportion of neonates reaching the target serum vancomycin level was calculated. After reviewing the literature to identify all published articles proposing a dosing regimen for continuous-infusion vancomycin for neonates, regimens were theoretically applied to our population by using maintenance doses according to covariate(s) proposed in the original publication.Results: Between January 2013 and December 2014, 75 neonates received 91 vancomycin courses by continuous infusion. Median gestational age, birth weight, and postnatal age were 27 weeks (interquartile range 26–30.5), 815 g (685–1,240), and 15 days (9–33). At the first assay, only 28/91 (30.8%) courses resulted in vancomycin levels between 20 and 30 mg/L (target level), 23/91 (25.3%) >30 mg/L and 40/91 (43.9%)