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Background: France implemented a combination of non-pharmaceutical interventions (NPIs) to manage the COVID-19 pandemic between September 2020 and June 2021. These included a lockdown in the fall 2020 – the second since the start of the pandemic – to counteract the second wave, followed by a long period of nighttime curfew, and by a third lockdown in the spring 2021 against the Alpha wave. Interventions have so far been evaluated in isolation, neglecting the spatial connectivity between regions through mobility that may impact NPI effectiveness. Methods: Focusing on September 2020–June 2021, we developed a regionally-based epidemic metapopulation model informed by observed mobility fluxes from daily mobile phone data and fitted the model to regional hospital admissions. The model integrated data on vaccination and variants spread. Scenarios were designed to assess the impact of the Alpha variant, characterized by increased transmissibility and risk of hospitalization, of the vaccination campaign and alternative policy decisions. Results: The spatial model better captured the heterogeneity observed in the regional dynamics, compared to models neglecting inter-regional mobility. The third lockdown was similarly effective to the second lockdown after discounting for immunity, Alpha, and seasonality (51% vs 52% median regional reduction in the reproductive number R0, respectively). The 6pm nighttime curfew with bars and restaurants closed, implemented in January 2021, substantially reduced COVID-19 transmission. It initially led to 49% median regional reduction of R0, decreasing to 43% reduction by March 2021. In absence of vaccination, implemented interventions would have been insufficient against the Alpha wave. Counterfactual scenarios proposing a sequence of lockdowns in a stop-and-go fashion would have reduced hospitalizations and restriction days for low enough thresholds triggering and lifting restrictions. Conclusions: Spatial connectivity induced by mobility impacted the effectiveness of interventions especially in regions with higher mobility rates. Early evening curfew with gastronomy sector closed allowed authorities to delay the third wave. Stop-and-go lockdowns could have substantially lowered both healthcare and societal burdens if implemented early enough, compared to the observed application of lockdown-curfew-lockdown, but likely at the expense of several labor sectors. These findings contribute to characterize the effectiveness of implemented strategies and improve pandemic preparedness. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic and paucisymptomatic infections account for a substantial portion of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions. The value of intensified screening strategies, especially in emergency departments (EDs), in reaching asymptomatic and paucisymptomatic patients and helping to improve detection and reduce transmission has not been documented. The objective of this study was to evaluate in EDs whether an intensified SARS-CoV-2 screening strategy combining nurse-driven screening for asymptomatic/paucisymptomatic patients with routine practice (intervention) could contribute to higher detection of SARS-CoV-2 infections compared to routine practice alone, including screening for symptomatic or hospitalized patients (control). Methods and findings: We conducted a cluster-randomized, two-period, crossover trial from February 2021 to June 2021 in 18 EDs in the Paris metropolitan area, France. All adults visiting the EDs were eligible. At the start of the first period, 18 EDs were randomized to the intervention or control strategy by balanced block randomization with stratification, with the alternative condition being applied in the second period. During the control period, routine screening for SARS-CoV-2 included screening for symptomatic or hospitalized patients. During the intervention period, in addition to routine screening practice, a questionnaire about risk exposure and symptoms and a SARS-CoV-2 screening test were offered by nurses to all remaining asymptomatic/paucisymptomatic patients. The primary outcome was the proportion of newly diagnosed SARS-CoV-2–positive patients among all adults visiting the 18 EDs. Primary analysis was by intention-to-treat. The primary outcome was analyzed using a generalized linear mixed model (Poisson distribution) with the center and center by period as random effects and the strategy (intervention versus control) and period (modeled as a weekly categorical variable) as fixed effects with additional adjustment for community incidence. During the intervention and control periods, 69,248 patients and 69,104 patients, respectively, were included for a total of 138,352 patients. Patients had a median age of 45.0 years [31.0, 63.0], and women represented 45.7% of the patients. During the intervention period, 6,332 asymptomatic/paucisymptomatic patients completed the questionnaire; 4,283 were screened for SARS-CoV-2 by nurses, leading to 224 new SARS-CoV-2 diagnoses. A total of 1,859 patients versus 2,084 patients were newly diagnosed during the intervention and control periods, respectively (adjusted analysis: 26.7/1,000 versus 26.2/1,000, adjusted relative risk: 1.02 (95% confidence interval (CI) [0.94, 1.11]; p = 0.634)). The main limitation of this study is that it was conducted in a rapidly evolving epidemiological context. Conclusions: The results of this study showed that intensified screening for SARS-CoV-2 in EDs was unlikely to identify a higher proportion of newly diagnosed patients. Trial registration: Trial registration number: ClinicalTrials.gov NCT04756609. Judith Leblanc and co-workers report a cluster-randomized trial evaluating intensive screening for SARS-CoV-2 infection in emergency departments. Author summary: Why was this study done?: Undetected asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections or paucisymptomatic infections with mild symptoms are responsible for a substantial portion of transmissions, which has been a major challenge in managing the Coronavirus Disease 2019 (COVID-19) pandemic. Free and widely available screening has been offered in many countries to reach asymptomatic/paucisymptomatic infectious individuals and improve detection, reduce transmission, and help contain the pandemic. To our knowledge, the value of systematically offering screening during medical consultations, particularly in emergency departments (EDs), to identify asymptomatic/paucisymptomatic infectious individuals has not been evaluated. What did the researchers do and find?: The objective of this trial was to evaluate whether an intensified screening strategy involving screening for asymptomatic/paucisymptomatic patients and routine screening of symptomatic and hospitalized patients (intervention) could lead to a higher proportion of new diagnoses compared with routine screening (control) in 18 EDs in the Paris metropolitan region. During the intervention period, 4,283 asymptomatic/paucisymptomatic patients were screened, leading to 224 new diagnoses. Overall, 1,859 patients were newly diagnosed during the intervention period versus 2,084 during the control period, corresponding, after analysis, to 26.7 new diagnoses/1,000 patients versus 26.2/1,000. The proportion of new diagnoses among asymptomatic/paucisymptomatic patients in EDs was higher than that in community screenings in the region. Comparison with findings from a mathematical model indicated that ED data allowed the estimation of regional incidences for asymptomatic/paucisymptomatic infections. What do these findings mean?: The results of this study showed that the intensified screening strategy was unlikely to bring a substantial benefit to the detection of SARS-CoV-2 infections. The population screened in EDs appeared to be more affected by SARS-CoV-2 than the general population screened in the region. Intensified screening in EDs could allow access to individuals who are less likely to be reached by the general screening system. The main limitation of this study is that it was conducted in a changing epidemiological context, which encourages further exploration of screening strategies for asymptomatically transmitted respiratory viruses to better define the observatory role of EDs in emerging epidemics. [ABSTRACT FROM AUTHOR]

Urgent action is needed to ensure humanity's future under climate change. Agriculture faces major challenges as it is both influenced by and contributes to climate change. Conservation agriculture sequesters carbon (C) in the soil due to practices such as reduced tillage and planting of cover crops. This study assessed effects of an innovative conservation agriculture popcorn (Zea mays) and wheat (Triticum aestivum) crop rotation in south-western France on soil C sequestration, GHG emissions and several environmental impacts. Two complementary approaches were used: i) a comparison based on field data and expert judgement to assess short-term effects and ii) modelling of three scenarios to quantify long-term outcomes. In both approaches Life cycle assessment (LCA) was used to compare popcorn and wheat rotations. The conventional rotation used ploughing, and its soil was bare between wheat harvest and popcorn sowing. Conservation agriculture used reduced tillage, cover crops, and compost of green waste. Impacts of compost production were allocated mainly to its waste treatment function, based on waste treatment cost and compost price. Simulation modelling of soil C was used to estimate the amount of C sequestered by the conservation and conventional crop rotations. LCA was combined with soil C modelling over 100 years to assess the long-term climate change impact of three scenarios for the popcorn and wheat rotation. These scenarios were 1) Conventional agriculture, 2) Conservation agriculture with cover crops only, 3) Conservation agriculture with cover crops + compost. Mean annual C sequestration and net climate change impact were -0.24 t/ha and 3867 kg CO2-eq./ha, respectively, for the conventional rotation and 0.91 t/ha and 434 kg CO2-eq./ha, respectively, for the conservation rotation. The climate change impact of the conservation rotation depended strongly on the allocation of composting impacts between the waste treatment and compost production functions. Compared to the conventional rotation, the conservation rotation had a lower marine eutrophication impact (-7%) but higher impacts for terrestrial acidification (+9%), land competition (+3%), and cumulative energy demand (+2%). Modelling over 100 years revealed that, at near soil C equilibrium, a conventional scenario lost 9% of soil C, whereas conservation agriculture scenarios gained 14% (only cover crop) and 26% of soil C (cover crop + compost). Conservation agriculture resulted in soil C sequestration over several decades, until a new soil C equilibrium was reached. [ABSTRACT FROM AUTHOR]

Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like "where" and "when" still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increase. However, the public health costs associated with these delays tend to grow with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality, and stress on the healthcare system. [ABSTRACT FROM AUTHOR]

Background: Several countries are implementing COVID-19 booster vaccination campaigns. The objective of this study was to model the impact of different primary and booster vaccination strategies. Methods: We used a compartmental model fitted to hospital admission data in France to analyze the impact of primary and booster vaccination strategies on morbidity and mortality, assuming waning of immunity and various levels of virus transmissibility during winter. Results: Strategies prioritizing primary vaccinations were systematically more effective than strategies prioritizing boosters. Regarding booster strategies targeting different age groups, their effectiveness varied with immunity and virus transmissibility levels. If the waning of immunity affects all adults, people aged 30 to 49 years should be boosted in priority, even for low transmissibility levels. Conclusions: Increasing the primary vaccination coverage should remain a priority. If a plateau has been reached, boosting the immunity of younger adults could be the most effective strategy, especially if SARS-CoV-2 transmissibility is high. [ABSTRACT FROM AUTHOR]

Background: Vaccination is expected to change the epidemiology and management of SARS-CoV-2 epidemics.Methods: We used an age-stratified compartmental model calibrated to French data to anticipate these changes and determine implications for the control of an autumn epidemic. We assumed vaccines reduce the risk of hospitalization, infection, and transmission if infected by 95%, 60%, and 50%, respectively.Results: In our baseline scenario characterized by basic reproduction number R0=5 and a vaccine coverage of 70-80-90% among 12-17, 18-59, and ≥ 60 years old, important stress on healthcare is expected in the absence of measures. Unvaccinated adults ≥60 years old represent 3% of the population but 43% of hospitalizations. Given limited vaccine coverage, children aged 0-17 years old represent a third of infections and are responsible for almost half of transmissions. Unvaccinated individuals have a disproportionate contribution to transmission so that measures targeting them may help maximize epidemic control while minimizing costs for society compared to non-targeted approaches. Of all the interventions considered including repeated testing and non-pharmaceutical measures, vaccination of the unvaccinated is the most effective.Conclusions: With the Delta variant, vaccinated individuals are well protected against hospitalization but remain at risk of infection and should therefore apply protective behaviors (e.g., mask-wearing). Targeting non-vaccinated individuals may maximize epidemic control while minimizing costs for society. Vaccinating children protects them from the deleterious effects of non-pharmaceutical measures. Control strategies should account for the changing SARS-CoV-2 epidemiology. [ABSTRACT FROM AUTHOR]

In France, social distancing measures have been adopted to contain the spread of COVID-19, culminating in national Lockdowns. The use of hand washing, hydro-alcoholic rubs and mask-wearing also increased over time. As these measures are likely to impact the transmission of many communicable diseases, we studied the changes in common infectious diseases incidence in France during the first year of COVID-19 circulation. We examined the weekly incidence of acute gastroenteritis, chickenpox, acute respiratory infections and bronchiolitis reported in general practitioner networks since January 2016. We obtained search engine query volume for French terms related to these diseases and sales data for relevant drugs over the same period. A periodic regression model was fit to disease incidence, drug sales and search query volume before the COVID-19 period and extrapolated afterwards. We compared the expected values with observations made in 2020. During the first lockdown period, incidence dropped by 67% for gastroenteritis, by 79% for bronchiolitis, by 49% for acute respiratory infection and 90% for chickenpox compared to the past years. Reductions with respect to the expected incidence reflected the strength of implemented measures. Incidence in children was impacted the most. Reduction in primary care consultations dropped during a short period at the beginning of the first lockdown period but remained more than 95% of the expected value afterwards. In primary care, the large decrease in reported gastroenteritis, chickenpox or bronchiolitis observed during the period where many barrier measures were implemented imply that the circulation of common viruses was reduced and informs on the overall effect of these measures. [ABSTRACT FROM AUTHOR]

As countries in Europe implement strategies to control the COVID-19 pandemic, different options are chosen regarding schools. Through a stochastic age-structured transmission model calibrated to the observed epidemic in Île-de-France in the first wave, we explored scenarios of partial, progressive, or full school reopening. Given the uncertainty on children's role, we found that reopening schools after lockdown may increase COVID-19 cases, yet protocols exist to keep the epidemic controlled. Under a scenario with stable epidemic activity if schools were closed, reopening pre-schools and primary schools would lead to up to 76% [67, 84]% occupation of ICU beds if no other school level reopened, or if middle and high schools reopened later. Immediately reopening all school levels may overwhelm the ICU system. Priority should be given to pre- and primary schools allowing younger children to resume learning and development, whereas full attendance in middle and high schools is not recommended for stable or increasing epidemic activity. Large-scale test and trace is required to keep the epidemic under control. Ex-post assessment shows that progressive reopening of schools, limited attendance, and strong adoption of preventive measures contributed to a decreasing epidemic after lifting the first lockdown. The role of children in the spread of COVID-19 is not fully understood, and the circumstances under which schools should be opened are therefore debated. Here, the authors demonstrate protocols by which schools in France can be safely opened without overwhelming the healthcare system. [ABSTRACT FROM AUTHOR]

Introduction: Living donor kidney transplant (LDKT) is one of the best therapeutic options for end-stage kidney disease (ESKD). Guidelines identify different estimated glomerular filtration rate (eGFR) thresholds to determine the eligibility of donors. The aim of our study was to evaluate whether pretransplant donor eGFR was associated with kidney function in the recipient. Methods: We retrospectively studied LDKT recipients who received a kidney graft between September 1, 2005, and June 30, 2016 in the same transplant center in France and that had eGFR data available at 3, 12, 24, and 36 months posttransplant. Results: We studied 90 donor-recipient pairs. The average age at time of transplant was 51.47 ± 10.95 for donors and 43.04 ± 13.52 years for recipients. Donors' average eGFR was 91.99 ± 15.37 mL/min/1.73 m2. Donor's age and eGFR were significantly correlated (p < 0.0001, r2 0.023). Donor's age and eGFR significantly correlated with recipient's eGFR at 3, 12, and 24 months posttransplant (age: p < 0.001 at all intervals; eGFR p = 0.001, 0.003, and 0.016, respectively); at 36 months, only donor's age significantly correlated with recipient's eGFR. BMI, gender match, and year of kidney transplant did not correlate with graft function. In the multivariable analyses, donor's eGFR and donor's age were found to be associated with graft function; correlation with eGFR was lost at 36 months; and donor's age retained a strong correlation with graft function at all intervals (p < 0.001). Conclusions: Donor's eGFR and age are strong predictors of recipient's kidney function at 3 years. We suggest that donor's eGFR should be clinically balanced with other determinants of kidney function and in particular with age. [ABSTRACT FROM AUTHOR]

Background: More than half of the global population is under strict forms of social distancing. Estimating the expected impact of lockdown and exit strategies is critical to inform decision makers on the management of the COVID-19 health crisis.Methods: We use a stochastic age-structured transmission model integrating data on age profile and social contacts in Île-de-France to (i) assess the epidemic in the region, (ii) evaluate the impact of lockdown, and (iii) propose possible exit strategies and estimate their effectiveness. The model is calibrated to hospital admission data before lockdown. Interventions are modeled by reconstructing the associated changes in the contact matrices and informed by mobility reductions during lockdown evaluated from mobile phone data. Different types and durations of social distancing are simulated, including progressive and targeted strategies, with large-scale testing.Results: We estimate the reproductive number at 3.18 [3.09, 3.24] (95% confidence interval) prior to lockdown and at 0.68 [0.66, 0.69] during lockdown, thanks to an 81% reduction of the average number of contacts. Model predictions capture the disease dynamics during lockdown, showing the epidemic curve reaching ICU system capacity, largely strengthened during the emergency, and slowly decreasing. Results suggest that physical contacts outside households were largely avoided during lockdown. Lifting the lockdown with no exit strategy would lead to a second wave overwhelming the healthcare system, if conditions return to normal. Extensive case finding and isolation are required for social distancing strategies to gradually relax lockdown constraints.Conclusions: As France experiences the first wave of COVID-19 pandemic in lockdown, intensive forms of social distancing are required in the upcoming months due to the currently low population immunity. Extensive case finding and isolation would allow the partial release of the socio-economic pressure caused by extreme measures, while avoiding healthcare demand exceeding capacity. Response planning needs to urgently prioritize the logistics and capacity for these interventions. [ABSTRACT FROM AUTHOR]

Background: Although it is rarely fatal in developed countries, acute gastroenteritis (AGE) still induces significant morbidity and economic costs. The objective of this study was to identify factors associated with AGE in winter in the general population.Methods: A prospective study was performed during winter seasons from 2014 to 2015 to 2016-2017. Participants filled an inclusion survey and reported weekly data on acute symptoms. Factors associated with having at least one AGE episode per winter season were analyzed using the generalized estimating equations (GEE) approach.Results: They were 13,974 participants included in the study over the three seasons. On average, 8.1% of participants declared at least one AGE episode during a winter season. People over 60 declared fewer AGE episodes (adjusted OR (aOR) = 0.76, 95% CI [0.64; 0.89]) compared to individuals between 15 and 60 years old, as well as children between 10 and 15 (aOR = 0.60 [0.37; 0.98]). Overweight (aOR = 1.25 [1.07; 1.45]) and obese (aOR = 1.47 [1.19; 1.81]) individuals, those having frequent cold (aOR = 1.63 [1.37; 1.94]) and those with at least one chronic condition (aOR = 1.35 [1.16; 1.58]) had more AGE episodes. Living alone was associated with a higher AGE episode rate (aOR = 1.31 [1.09; 1.59]), as well as having pets at home (aOR = 1.23 [1.08; 1.41]).Conclusions: Having a better knowledge of AGE determinants will be useful to adapt public health prevention messages. [ABSTRACT FROM AUTHOR]

Annual incidence rates of varicella infection in the general population in France have been rather stable since 1991 when clinical surveillance started. Rates however show a statistically significant increase over time in children aged 0–3 years, and a decline in older individuals. A significant increase in day-care enrolment and structures’ capacity in France was also observed in the last decade. In this work we investigate the potential interplay between an increase of contacts of young children possibly caused by earlier socialization in the community and varicella transmission dynamics. To this aim, we develop an age-structured mathematical model, informed with historical demographic data and contact matrix estimates in the country, accounting for longitudinal linear increase of early childhood contacts. While the reported overall varicella incidence is well reproduced independently of mixing variations, age-specific empirical trends are better captured by accounting for an increase in contacts among pre-school children in the last decades. We found that the varicella data are consistent with a 30% increase in the number of contacts at day-care facilities, which would imply a 50% growth in the contribution of 0-3y old children to overall yearly infections in 1991–2015. Our findings suggest that an earlier exposure to pathogens due to changes in day-care contact patterns, represents a plausible explanation for the epidemiological patterns observed in France. Obtained results suggest that considering temporal changes in social factors in addition to demographic ones is critical to correctly interpret varicella transmission dynamics. [ABSTRACT FROM AUTHOR]

Background: Pregnancy is a risk factor for severe influenza resulting in increased risks of hospitalisation and death in mothers and their new-borns. Our objective was to assess the representativeness and participation of French women to a new web-based collaborative tool for data collection and monitoring of Influenza Like Illness (ILI) during pregnancy.Methods: During the 2014/2015 influenza season, pregnant women living in metropolitan France were enrolled through a web platform ( https://www.grippenet.fr/). Then throughout the season, participants were asked to report, on a weekly basis, if they had experienced symptoms of ILI. Representativeness was assessed by comparing the characteristics of participants to those of the French National Perinatal Survey. For each participant, the participation rate was the number of weekly questionnaires completed, divided by the length of follow-up (in weeks). Predictors of active participation (participation rate >15%) were assessed by multivariate logistic regression.Results: A total of 153 women were enrolled. Participants were older (mean age 34 years vs. 29 years) and more highly educated (high school level 89% versus 52%) than the general population of pregnant women in France, but the sample did not differ on pregnancy-related characteristics (parity, history of hospitalisation during a previous pregnancy). The median rate of participation was high (78%, interquartile range: 34-96). Higher educational level and participation to a previous GrippeNet.fr season were associated with active participation.Conclusion: Despite small sample size and lack of representativeness, the retention rate was high, suggesting that pregnant women are prone to adhere to a longitudinal follow-up of their health status via the Internet. [ABSTRACT FROM AUTHOR]

The increasing Internet coverage and the widespread use of digital devices offer the possibility to develop new digital surveillance systems potentially capable to provide important aid to epidemiological and public health monitoring and research. In France, a new nationwide surveillance system for influenza-like illness, GrippeNet.fr, was introduced since the 2011/2012 season based on an online participatory mechanism and open to the general population. We evaluate the recruitment and participation of users to the first pilot season with respect to similar efforts in Europe to assess the feasibility of establishing a participative network of surveillance in France. We further investigate the representativeness of the GrippeNet.fr population along a set of indicators on geographical, demographic, socio-economic and health aspects. Participation was widespread in the country and with rates comparable to other European countries with partnered projects running since a longer time. It was not representative of the general population in terms of age and gender, however all age classes were represented, including the older classes (65+ years old), generally less familiar with the digital world, but considered at high risk for influenza complications. Once adjusted on demographic indicators, the GrippeNet.fr population is found to be more frequently employed, with a higher education level and vaccination rate with respect to the general population. A similar propensity to commute for work to different regions was observed, and no significant difference was found for asthma and diabetes. Results show the feasibility of the system, provide indications to inform adjusted epidemic analyses, and highlight the presence of specific population groups that need to be addressed by targeted communication strategies to achieve a higher representativeness in the following seasons. [ABSTRACT FROM AUTHOR]

Mitotane is used as a post-operative adjuvant treatment for patients with adrenocortical carcinoma. Monitoring of plasma mitotane concentrations is recommended, but we do not know what impact target concentrations have on patient outcome. To answer this question, we retrospectively analyzed patient records in the Lysosafe Online® database (HRA Pharma, France) for patients who were treated for ≥6 months and who had ≥3 measurements of plasma mitotane levels during follow-ups at 11 tertiary centers in Italy from 2005 to 2017. We identified 110 patients treated with adjuvant mitotane for a median of 46 months (IQR, interquartile range, 28–62) with a median maintenance dose of 2.0 g/day (IQR 1.5–2.5). Achievement of target mitotane concentrations (≥14 mg/L) required a median of 8 months (IQR 5–19). Female sex was associated inversely with the dose, while body mass index (BMI) was correlated positively. Multivariate analysis showed that the Ki67 index and time to achieve the target range of plasma mitotane were independent predictors of recurrence-free survival (RFS). In a separate multivariate model, considering only the maintenance phase (month 7 to month 36, M7–M36) of treatment, the time in the target range of plasma mitotane was associated with a significantly lower risk of recurrence (Hazard Ratio, HR = 0.93; 0.88–0.98, p < 0.01). The prognostic implications of the time in target range and the time needed to reach target mitotane concentrations support the use of mitotane monitoring and may inform practice. [ABSTRACT FROM AUTHOR]