Shift in emergency department utilization by frequent attendees with sickle cell disease during the COVID-19 pandemic: A multicentre cohort study.

While the coronavirus disease-2019 (COVID-19) might have increased acute episodes in people living with sickle cell disease (SCD), it may also have changed their reliance on emergency department (ED) services. We assessed the impact of the COVID-19 pandemic and lockdowns on ED visits in adult SCD people followed in five French reference centres, with a special focus on 'high users' (≥10 visits in 2019). We analysed the rate of ED visits from 1 January 2015 to 31 December 2021, using a self-controlled case series. Among 1530 people (17 829 ED visits), we observed a significant reduction in ED visits during and after lockdowns, but the effect vanished over time. Compared to pre-pandemic, incidence rate ratios for ED visits were 0.59 [95% CI 0.52-0.67] for the first lockdown, 0.66 [95% CI 0.58-0.75] for the second and 0.85 [95% CI 0.73-0.99] for the third. High users (4% of people but 33.7% of visits) mainly drove the reductions after the first lockdown. COVID-19 lockdowns were associated with reduced ED visits. While most people returned to their baseline utilization by April 2021, high users had a lasting decrease in ED visits. Understanding the factors driving the drop in ED utilization among high users might inform clinical practice and health policy.

Performances of statistical methods for the detection of seasonal influenza epidemics using a consensus-based gold standard.

Influenza epidemics are monitored using influenza-like illness (ILI) data reported by health-care professionals. Timely detection of the onset of epidemics is often performed by applying a statistical method on weekly ILI incidence estimates with a large range of methods used worldwide. However, performance evaluation and comparison of these algorithms is hindered by: (1) the absence of a gold standard regarding influenza epidemic periods and (2) the absence of consensual evaluation criteria. As of now, performance evaluations metrics are based only on sensitivity, specificity and timeliness of detection, since definitions are not clear for time-repeated measurements such as weekly epidemic detection. We aimed to evaluate several epidemic detection methods by comparing their alerts to a gold standard determined by international expert consensus. We introduced new performance metrics that meet important objective of influenza surveillance in temperate countries: to detect accurately the start of the single epidemic period each year. Evaluations are presented using ILI incidence in France between 1995 and 2011. We found that the two performance metrics defined allowed discrimination between epidemic detection methods. In the context of performance detection evaluation, other metrics used commonly than the standard could better achieve the needs of real-time influenza surveillance.

Clinical and microbiological determinants of severe and fatal outcomes in patients infected with Enterobacteriaceae producing extended-spectrum ß-lactamase.

Although extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae have become a worldwide public health concern, little is known regarding the clinical course of colonized or infected individuals. Our objective was to characterize the determinants of fatal outcomes related to ESBL-producing microorganisms at a large hospital in Paris, France. In 2012-2013, all consecutive patients with clinical samples testing positive for ESBL-producing Enterobacteriaceae at Saint-Antoine Hospital were identified. Patient clinical data were obtained at hospital entry, while information on intensive care unit (ICU) admissions and death were prospectively collected. Risk-factors for fatal 1-year outcomes were assessed using logistic regression. In total, 643/4684 (13%) ESBL-positive samples were observed, corresponding to 516 episodes (n = 206, 40% treated) among 330 patients. Most episodes were nosocomial-related (n = 347/516, 67%) involving Escherichia coli (n = 232/516, 45%) or Klebsiella pneumoniae (n = 164/516, 32%). Empirical antibiotic therapy was adequate in 89/206 (43%) infections, while the median length of hospital stay was 30 days [interquartile range (IQR) = 11-55] and 39/201 (19%) were admitted to the ICU. Overall, 104/241 patients (43%) with available data died within 1 year. In the multivariable analysis, 1-year death was associated with age >80 years (p = 0.01), concomitant comorbidity (p = 0.001), nosocomial-acquired infection (p = 0.002), and being infected rather than colonized (p < 0.001). In this series of patients with identified samples of ESBL-producing Enterobacteriaceae, hospital burden was large and 1-year mortality rates high. Understanding which patients in this setting would benefit from broad-spectrum empirical antibiotic therapy should be further examined.

Hepatitis C virus seroprevalence in adults in Africa: a systematic review and meta-analysis.

With the introduction of more efficient treatments for hepatitis C virus (HCV), improved epidemiological information is required at the country level to allow evidence-based policymaking for elaboration of national strategies and HCV resources planning. We present a systematic review with meta-analysis of HCV seroprevalence data in adults in African countries. We conducted a systematic review of all HCV seroprevalence estimates reported in African countries from 2000 to 2014 in MEDLINE, AJOL and grey literature. We assessed studies performed in the general population and among blood donors, pregnant women and HIV-positive patients. A meta-regression analysis was used to provide adjusted estimates of HCV seroprevalence in the general adult population in each country, accounting for the heterogeneity in sample age structure and population types in the included studies. We identified 775 national-level estimations, among which 184 were included. Estimates of HCV seroprevalence were produced for 38 countries, in addition to the results from nationwide representative surveys available in Egypt and Libya. Next to Egypt, which clearly stands out, the highest levels of seroprevalence were found in Middle Africa (e.g. Cameroon, Gabon and Angola) and some West African countries (e.g. Burkina Faso, Benin), and the largest absolute numbers of infected adults were found in Nigeria, Ethiopia and Democratic Republic of Congo. This study exposes the diversity of HCV epidemiology among African countries. Egypt and several countries of West and Middle Africa present a HCV burden that will require strong governmental commitment to promote efficient preventive and curative interventions.

Decrease in the incidence of culture-positive meningitis and cerebral tuberculomas in France from 1990 to 2007.

We evaluated the incidence rate of culture-positive central nervous system tuberculosis (CNS TB) in France in 2007 and its time trend between 1990 and 2007. We used a capture-recapture analysis by using data recorded in 2007 by the mandatory notification system and the national network of the National Reference Centre (NRC). The 2007 sensitivity of the NRC was 79·4%. The previous sensitivity for 2000 (75·6%) and that for 2007 yielded a pooled estimate of 77·4% (95% confidence interval 64·8-88·0), which was used to extrapolate the number of culture-positive CNS TB cases from those reported in four surveys (1990, 1995, 2000, 2007). The extrapolated number of culture-positive CNS TB cases fell from 90 to 35 between 1990 and 2007, and the extrapolated incidence rates fell from 1·6 to 0·55 cases/million (P < 0·001). This favourable trend should be closely monitored following the change of the BCG vaccination policy in 2007.

Local and regional spread of chikungunya fever in the Americas.

Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is currently affecting several areas in the Caribbean. The vector is found in the Americas from southern Florida to Brazil, and the Caribbean is a highly connected region in terms of population movements. There is therefore a significant risk for the epidemic to quickly expand to a wide area in the Americas. Here, we describe the spread of CHIKV in the first three areas to report cases and between areas in the region. Local transmission of CHIKV in the Caribbean is very effective, the mean number of cases generated by a human case ranging from two to four. There is a strong spatial signature in the regional epidemic, with the risk of transmission between areas estimated to be inversely proportional to the distance rather than driven by air transportation. So far, this simple distance-based model has successfully predicted observed patterns of spread. The spatial structure allows ranking areas according to their risk of invasion. This characterisation may help national and international agencies to optimise resource allocation for monitoring and control and encourage areas with elevated risks to act.

Assessment of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in the Middle East and risk of international spread using a novel maximum likelihood analysis approach.

The emergence of the novel Middle East (ME) respiratory syndrome coronavirus (MERS-CoV) has raised global public health concerns regarding the current situation and its future evolution. Here we propose an integrative maximum likelihood analysis of both cluster data in the ME and importations in a set of European countries to assess the transmission scenario and incidence of sporadic infections. Our approach is based on a spatial-transmission model integrating mobility data worldwide and allows for variations in the zoonotic/environmental transmission and under-ascertainment. Maximum likelihood estimates for the ME, considering outbreak data up to 31 August 2013, indicate the occurrence of a subcritical epidemic with a reproductive number R of 0.50 (95% confidence interval (CI): 0.30-0.77) associated with a daily rate of sporadic introductions psp of 0.28 (95% CI: 0.12-0.85). Infections in the ME appear to be mainly dominated by zoonotic/environmental transmissions, with possible under-ascertainment (ratio of estimated to observed (0.116) sporadic cases equal to 2.41, 95% CI: 1.03-7.32). No time evolution of the situation emerges. Analyses of flight passenger data from ME countries indicate areas at high risk of importation. While dismissing an immediate threat for global health security, this analysis provides a baseline scenario for future reference and updates, suggests reinforced surveillance to limit under-ascertainment, and calls for alertness in high importation risk areas worldwide.

Micro and macro population effects in disease transmission: the case of varicella.

Profiles of varicella-zoster virus (VZV) seroprevalence have shown large variability in European countries in which vaccination has not been implemented. Differences in micro and macro population structures (e.g. household and municipality, respectively) may explain such variability, which is the focus of a population-based study of varicella in 12,000 children from 7800 French households in Corsica. The cumulative incidence was 89% at age 11 years, as the median age at infection was 5 years in first-born children, but decreased to 3.9 years in younger siblings. Hazard of infection in households increased as the first-born child initially enrolled in primary school. Age at infection was higher in less populated areas. Household attack rates increased with age (55% in <6 months, >90% in >3 years) and household secondary attack rate was approximately 70%. Several levels of population structure independently affect age at varicella infection.

Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom.

The size of the variant Creutzfeldt-Jakob Disease (vCJD) epidemic in the United Kingdom is a major public health concern and a subject of speculation. The cases are young (mean age = 28). Assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.7 years [95% confidence interval (CI): 12.4 to 23.2] and that the total number of cases will be 205 (upper limit of the 95% CI: 403).

A preliminary estimation of the reproduction ratio for new influenza A(H1N1) from the outbreak in Mexico, March-April 2009.

As of 12 May 2009, 5,251 cases of the new influenza A(H1N1) have been officially reported to the World Health Organization (WHO) from 30 countries, with most of the identified cases exported from Mexico where a local epidemic has been going on for the last two months. Sustained human-to-human transmission is necessary to trigger influenza pandemic and estimating the reproduction ratio (average number of secondary cases per primary case) is necessary for forecasting the spread of infection. We use two methods to estimate the reproduction ratio from the epidemic curve in Mexico using three plausible generation intervals (the time between primary and secondary case infection). As expected, the reproduction ratio estimates were highly sensitive to assumptions regarding the generation interval, which remains to be estimated for the current epidemic. Here, we suggest that the reproduction ratio was less than 2.2 - 3.1 in Mexico, depending on the generation interval. Monitoring and updating the reproduction ratio estimate as the epidemic spreads outside Mexico into different settings should remain a priority for assessing the situation and helping to plan public health interventions.

Early estimates of 2009 pandemic influenza A(H1N1) virus activity in general practice in France: incidence of influenza-like illness and age distribution of reported cases.

In the end of August 2009, an unusually elevated level of influenza-like illness (ILI) activity was reported to the French Sentinel Network. We quantified the observed excess in ILI cases in France during summer 2009 and characterised age patterns in reported cases. An excess of cases has been observed since 5 July, with a time increasing trend. The cumulated estimated excess number of ILI cases was 269,935 [179,585; 316,512], corresponding to 0.5% French population over the period. Compared to the same period in the past years, relative cumulated incidence was greater among young subjects and lower among subjects over 65 years old. Compared to past epidemics, the relative cumulated incidence was greater in children less than 5 years old. This excess of cases may reflect the current spread of the A(H1N1) virus in France, subject to the following limitations: estimates were based on clinical cases consulting a GP; large media coverage may have led to a non specific increase in consultation rates.

Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling.

We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.

Investigating transmission in a two-wave epidemic of Chikungunya fever, Réunion Island.

An epidemic of Chikungunya fever, a mosquito-borne viral disease, spectacularly swept through Réunion Island (population 780,000) in 2005-2006. There were 3,000 cases in a first wave (March-June 2005) and more than 250,000 cases in a second (December 2005-April 2006). Adapting newly developed epidemiological tools to vector-borne diseases, we show that despite this massive difference in magnitude, the transmission potential as measured by the number of secondary cases per index case (or reproduction number), remained similar during the two consecutive waves. The best estimate for the initial reproduction number R(0) was 3.7, with a possible range from 2 to 11 depending on incubation duration and lifespan of the mosquito. We conclude that an increase in virulence between the two seasons was not necessary to explain the change in magnitude of the epidemics, and that the attack rate may be well over 50% in Chikungunya fever epidemics in the absence of intervention.

[Theoretical epidemiology and vaccine]. / Epidémiologie théorique et vaccination.

BACKGROUND: We describe important findings in theoretical epidemiology related to mass vaccination, including herd immunity and vaccine efficacy measures. POINTS: Through a review of recent publications, we address the following questions: is there optimal vaccine coverage? Is it possible to achieve optimal coverage through individual choice? What are the consequences of a suboptimal vaccination? What is vaccine efficacy and how is it measured? PERSPECTIVES: These results define a framework for analysing how successful mass vaccination may be from a public health perspective.

[Inguinal hernia repair: time interval between surgical repair and recurrence]. / Hernies inguinales: délais d'apparition des récidives.

This study seeks to evaluate the time interval between initial inguinal hernia repair and the appearance of recurrent hernia in patients undergoing re-operation. Recurrent hernia was identified in 94 (6.4%) of 1,474 patients having undergone initial hernia repair at our institution. Recurrence appeared within two years in 40 patients (42%). Recurrences were noted beyond five years in 32 patients (34%), and after 20 years in 18 patients (19%). 75% of recurrences had occurred within 15 years. We conclude that almost two-thirds of recurrences occur later than five years after the initial intervention and a quarter occur at an interval of more than fifteen years. Most studies underestimate hernia recurrence due to an insufficient period of post-operative observation.

Can a second wave of new variant of the CJD be discarded in absence of observation of clinical non Met-Met cases?

BACKGROUND: Presently, all patients with clinical variant Creutzfeldt-Jakob disease in the United Kingdom have been Met-Met at codon 129 of the PrP gene. There is much worry about the possibility of a second wave of the epidemic in the 60% of the United Kingdom population which are not Met-Met. METHODS: A mathematical model of a putative United Kingdom variant Creutzfeldt-Jakob disease epidemic that could occur in non Met-Met is derived. The risk of infection is assumed to parallel the Met-Met risk which has been previously modelled. The reason for the present absence of clinical non Met-Met cases is assumed to be a longer incubation period in these subjects than in others. The incubation period is assumed to be lognormally distributed. The means and coefficients of variation compatible with the present absence of clinical cases are systematically searched. RESULTS: We show that the present absence of clinical cases of variant Creutzfeldt-Jakob disease in the Met-Val or Val-Val population can be compatible with a second wave only if the mean incubation period is more than 25 years. The best estimates of the size of the second wave are always below 250. A fraction of these cases however will never be observed, as they will die from other causes before the onset of the new variant. CONCLUSION: The mean incubation period values compatible with the absence of non Met-Met clinical cases that we found are not implausible, and the possibility of a second wave cannot yet be ruled out. However, should this second wave occur, it would be below 250 in the worst hypothesis.

[Apnea of prematurity: risk factors and ambulatory treatment with caffeine citrate]. / Apnées tardives du prématuré: facteurs de risque, traitement ambulatoire par citrate de caféine.

INTRODUCTION: Apnea of prematurity develop during the first days of life and usually resolve by the time the infant reaches 36-37 weeks postmenstrual age. In a few cases, they persist beyond term, especially in infants delivered at the youngest gestational ages (24-28 GA), and require specific care. In our unit, those preterm babies are discharged home with caffeine citrate treatment. Discontinuing the treatment is performed in hospital when they achieve a postmenstrual age of at least 42 weeks. OBJECTIVE: To identify predictive factors of persistent apnea in preterm babies. MATERIAL AND METHODS: Retrospective study comparing a population of 41 preterm infants discharged with treatment to 123 preterm babies discharged without treatment to identify predictors of persistent apnea. RESULTS: Factors significantly associated were: birth weight<1500 g, initial hypotension, gastroesophageal reflux, need for continuous positive airway pressure and multiparity. At home, no infant died and no adverse effect was reported by parents. CONCLUSION: Persistent apnea can be responsible for prolonged hospitalization. Risk factors can be identified in some children. Discharging with treatment can be an alternative to their hospitalization.

[Morbidity and cost of rotavirus infections in France]. / Morbidité et coût des infections à rotavirus en France.

BACKGROUND: Rotavirus is the most common cause of severe diarrhea in children. Morbidity and mortality related to rotavirus infection is not well known in temperate countries in general, and in France in particular. OBJECTIVES: The aim of this study was estimate the morbidity, mortality, and cost related to the rotavirus infection in France, in order to assess the potential impact of a vaccination program. METHODS: A birth cohort was followed until 5 years of age using a decision tree model. Rotavirus infection incidence rates were modeled according to age, seasons, and breast-feeding status. RESULTS: Based on estimates from a decision model, we found that in France, rotavirus infection was responsible for 300,000 annual episodes of acute diarrhea, 138,000 visits to general practitioners, 18,000 hospitalizations, and 9 deaths. The annual direct cost related to rotavirus infection care was estimated at 28 million euros. CONCLUSION: This study demonstrates the high morbidity and cost of care associated with rotavirus infection in France. The decision tree model developed in this study could be used in the future to estimate the potential effectiveness, cost and cost-effectiveness of childhood vaccination strategies using new rotavirus vaccines.

Occupational determinants of methicillin-resistant Staphylococcus aureus colonization among healthcare workers: a longitudinal study in a rehabilitation center.

BACKGROUND Staphylococcus aureus carriage among healthcare workers (HCWs) is a concern in hospital settings, where it may provide a reservoir for later infections in both patients and staff. Earlier studies have shown that the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in HCWs is highly variable, depending notably on location, hospital department type, MRSA prevalence among patients, and type of contacts with patients. However, MRSA incidence in HCWs and its occupational determinants have seldom been studied. METHODS A prospective, observational cohort study was conducted between May and October 2009 in a French rehabilitation center hospital. HCWs and patients were screened weekly for S. aureus nasal carriage. Methicillin-susceptible S. aureus and MRSA prevalence and incidence were estimated and factors associated with MRSA acquisition were identified using generalized estimating equation regression methods. RESULTS Among 343 HCWs included in the analysis, the average prevalence was 27% (95% CI, 24%-29%) for methicillin-susceptible S. aureus and 10% (8%-11%) for MRSA. We observed 129 MRSA colonization events. According to the multivariable analysis, high MRSA prevalence level among patients and HCW occupation were significantly associated with MRSA acquisition in HCWs, with assistant nurses being more at risk than nurses (odds ratio, 2.2; 95% CI, 1.4-3.6). CONCLUSIONS Our findings may help further our understanding of the transmission dynamics of MRSA carriage acquisition in HCWs, suggesting that it is notably driven by carriage among patients and by the type of contact with patients.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

BACKGROUND: Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES: To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS: The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS: Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 µg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 µg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS: A CTnI level of > 0.25 µg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.