Since the beginning of the COVID-19 pandemic, other respiratory illnesses decreased worldwide. This study described the consequences of public health measures on respiratory syncytial virus (RSV) severe infections in France, where an interseasonal resurgence of RSV occurred recently. All patients admitted to Necker Hospital (Paris) between August 2018 and April 2021 with a diagnosis of RSV-associated acute lung respiratory infection (ALRI) were enrolled. Characteristics of subjects with RSV-associated ALRI in 2020/2021 were compared to those infected during the two previous outbreaks. Overall, 664 inpatients were diagnosed with RSV-associated ALRI: 229, 183, and 252 during the 2018/2019, 2019/2020, and 2020/2021 outbreaks, respectively. During autumn 2020, a national lockdown began in France but schools remained open. A 3-month delayed RSV epidemic occurred at the end of this lockdown. Compared to previous outbreaks, the 2020/2021 epidemics involved more children aged 6 to 11 months (25.8% versus 13.1%, p < 0.0001), but less infants aged < 6 months (41.3% versus 56.6%, p < 0.0001) and less adults (0.0 versus 2.7%, p < 0.0001). Shorter length of stay at hospital, less frequent requirement of admission to intensive care unit, use of non-invasive ventilation, and/or high-flow nasal oxygen were observed in 2020/2021 than during previous epidemics ( p < 0.0001). Delayed RSV outbreak was associated with more hospitalizations for ALRI, higher age of pediatric inpatients, but milder median clinical phenotype. Reinforced public health measures (even while keeping nurseries and schools open with mandatory face masks since six years of age) could impact, at least transiently, the burden of RSV-related hospitalizations. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04323-1.
Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.
This study was performed to investigate placental transfer of nucleoside analogue reverse transcriptase inhibitors (NRTIs) and their concentrations in amniotic fluid when given to human immunodeficiency virus (HIV)-infected pregnant women. A total of 100 HIV type 1-infected mothers receiving antiretroviral therapy, including one or more NRTIs, for clinical indications at the time of delivery were enrolled. Maternal blood samples and amniotic fluid were obtained during delivery or cesarean section, and paired cord blood samples were obtained by venipuncture immediately after delivery. Drug concentrations were measured by using high-performance liquid chromatography. A significant relationship between concentrations in maternal and cord plasma samples was found for zidovudine, lamivudine, stavudine, and didanosine. The ratio between the concentrations in cord and maternal plasma samples (R) was high for zidovudine (R ؍ 1.22), its glucuronide metabolite (3-azido-3-deoxythymidine--D-glucuronide) (R ؍ 1.01), stavudine (R ؍ 1.32), lamivudine (R ؍ 0.93), and abacavir (R ؍ 1.03) and was low for didanosine (R ؍ 0.38). The ratio between the concentrations in amniotic fluid and cord plasma samples was high for zidovudine (R ؍ 2.24), its glucuronide metabolite (R ؍ 2.83), stavudine (R ؍ 4.87), and lamivudine (R ؍ 3.99) and was lower for didanosine (R ؍ 1.14). These findings indicate that most NRTIs cross the placenta by simple diffusion and are concentrated in the amniotic fluid, probably through fetal urinary excretion. The efficacy or toxicity of NRTIs may vary according to placental transfer.
The parents signed consent forms without having fully understood all the elements specific to the experimental protocol. Rather, the parents based their decision on their confidence in the medical team, even when their child's life was at risk.
We found an association between daily asthma exacerbation in paediatric visits to the ED and fine particulate air pollutants.
Aims: To assess parental understanding and memorisation of the information given when seeking for consent to their child's participation to clinical research, and to identify the factors of significant influence on parents' decision making process. Methods: Sixty eight parents who had been approached for enrolling their child in a clinical oncology or HIV study were asked to complete an interview. Their understanding was measured by a score which included items required to obtain a valid consent according to French legislation. Results: Items that were best understood by parents were the aims of the study (75%), the risks (70%), the potential benefits to their child (83%), the potential benefits to other children (70%), the right to withdraw (73%), and voluntariness (84%). Items that were least understood were the procedures (44%), the possibility of alternative treatments (53%), and the duration of participation (39%). Less than 10% of the parents had understood all these points. Ten parents (15%) did not remember that they had signed up for a research protocol. Thirty three parents (48%) reported no difficulty in making their decision. Twenty four parents (38%) declared that they made their decision together with the investigator; 26 (41%) let the physician decide. Fifty four parents (78%) felt that the level of information given was satisfactory. Conclusion: There was an apparent discrepancy between parents' evaluation of the adequacy of the information delivered and evaluation of their understanding and memorisation. The majority of parents preferred that the physician take as much responsibility as possible in the decision making process.
According to the European AIDS Clinical Society, tenofovir disoproxil fumarate can be used in HIV-infected pregnant women if started prior to pregnancy, although no data are available on the pharmacokinetics of tenofovir (TFV) during pregnancy. The aim of this study was to describe TFV pharmacokinetics in HIV-infected women and to evaluate the effect of pregnancy on TFV disposition. Samples were collected according to a therapeutic drug monitoring in 186 women, including 46 pregnant women treated with TFV and retrospectively analyzed by a population approach. TFV pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. The mean population parameter estimates (between-subject variability) were as follows: absorption rate constant, 0.56 h ؊1 ; elimination clearance, 59.9 liters h ؊1 (0.436); central volume of distribution, 552 liters (1.96); intercompartmental clearance, 172 liters/h; and peripheral volume of distribution, 1,390 liters. Pregnant women had a 39% higher apparent clearance compared to nonpregnant women. Apparent clearance significantly decreased with age. In order to obtain an exposure similar to the known exposure in adults and guarantee similar trough concentrations (C min ) as observed in adults, an increase in the TFV dose should be considered for women from the second trimester to delivery. Because of the lack of data on the use of tenofovir disoproxil fumarate (TDF) in pregnancy and concerns over possible bone toxicity, U.S. guidelines recommend that TDF-based highly active antiretroviral therapy (HAART) should be used only after careful considerations of alternatives (8). However, for women who were already treated by TDF prior to pregnancy, European AIDS Clinical Society guidelines recommend to continue the TDF treatment during pregnancy. Thus, in these therapeutic drug monitoring data, some women were taking TDF during their pregnancy in the first, second, and third trimester.TDF is already taken during pregnancy at the same dose as in adults although physiological changes associated with pregnancy can lead to significant variations in pharmacokinetics (modified absorption, distribution, and elimination). No pharmacokinetic data on the use of TDF before the 38th week of pregnancy are available. Two studies restricted to late pregnancy and labor suggest that tenofovir (TFV) exposure is lower than nonpregnant adult exposure (9, 16).We performed here a population pharmacokinetic study of women during pregnancy, at delivery, and out of pregnancy in order to investigate TFV pharmacokinetics throughout pregnancy. MATERIALS AND METHODSPatients and treatments. The population included nonpregnant women, pregnant women, and women on the day of delivery receiving oral TFV for treatment of HIV infection and whose antiretroviral drug plasma concentrations were monitored on a routine basis. TFV was administered chronically using a 300-mg once-daily regimen. For each woman, the time elapsed between administration and sampling times, the time of dosing, the bod...
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