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.

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.

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.

Factors associated with humoral immune response to pandemic A/H1N1(v) 2009 influenza vaccine in cystic fibrosis.

Influenza vaccination is recommended in cystic fibrosis patients. The objective of this study was to assess the immunogenicity of vaccination against 2009 pandemic A/H1N1 influenza and to study the factors associated with the immune response in patients with cystic fibrosis. 122 patients with cystic fibrosis were enrolled in a prospective study and received 1 dose of 2009/H1N1v adjuvanted vaccine, or for children <2 years and lung-transplanted patients, two doses of non-adjuvanted 2009/H1N1v vaccine administered 21 days apart. Hemagglutination inhibition antibodies were assessed before and 21 days after vaccination and at least 6 months after vaccination. After vaccination, 85% of the patients had an influenza antibody titer ≥1:40 and 69% seroconverted. 13% of the transplanted patients seroconverted compared with 72% of the non-transplanted patients. In this latter group, non-adjuvanted vaccine and low body mass index were independently associated with lower response to vaccination. 86% of the non-transplanted patients with normal BMI and receiving adjuvanted vaccine seroconverted. Persistence of seroprotection 10 months after vaccination was found in 50% of the patients. In patients with cystic fibrosis, malnutrition and receipt of non-adjuvanted vaccine were associated with lower immune response to pandemic influenza vaccination. Our data also suggest a potential defect in the immune response to influenza vaccination of patients with cystic fibrosis and raise the question of whether a different immunization strategy is needed.

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.

Capillary refill time exploration during septic shock.

BACKGROUND: During septic shock management, the evaluation of microvascular perfusion by skin analysis is of interest. We aimed to study the skin capillary refill time (CRT) in a selected septic shock population. METHODS: We conducted a prospective observational study in a tertiary teaching hospital. After a preliminary study to calculate CRT reproducibility, all consecutive patients with septic shock during a 10-month period were included. After initial resuscitation at 6 h (H6), we recorded hemodynamic parameters and analyzed their predictive value on 14-day mortality. CRT was measured on the index finger tip and on the knee area. RESULTS: CRT was highly reproducible with an excellent inter-rater concordance calculated at 80% [73-86] for index CRT and 95% [93-98] for knee CRT. A total of 59 patients were included, SOFA score was 10 [7-14], SAPS II was 61 [50-78] and 14-day mortality rate was 36%. CRT measured at both sites was significantly higher in non-survivors compared to survivors (respectively 5.6 ± 3.5 vs 2.3 ± 1.8 s, P < 0.0001 for index CRT and 7.6 ± 4.6 vs 2.9 ± 1.7 s, P < 0.0001 for knee CRT). The CRT at H6 was strongly predictive of 14-day mortality as the area under the curve was 84% [75-94] for the index measurement and was 90% [83-98] for the knee area. A threshold of index CRT at 2.4 s predicted 14-day outcome with a sensitivity of 82% (95% CI [60-95]) and a specificity of 73% (95% CI [56-86]). A threshold of knee CRT at 4.9 s predicted 14-day outcome with a sensitivity of 82% (95% CI [60-95]) and a specificity of 84% (95% CI [68-94]). CRT was significantly related to tissue perfusion parameters such as arterial lactate level and SOFA score. Finally, CRT changes during shock resuscitation were significantly associated with prognosis. CONCLUSION: CRT is a clinical reproducible parameter when measured on the index finger tip or the knee area. After initial resuscitation of septic shock, CRT is a strong predictive factor of 14-day mortality.

Peripheral microcirculatory exploration during mechanical ventilation weaning.

BACKGROUND: Weaning from mechanical ventilation is a daily challenge in intensive care patients. Our objective was to explore microcirculatory perfusion during mechanical ventilation weaning and to evaluate its predictive value on the weaning outcome. METHODS: Prospective observational study. All consecutive patients, older than 18 years, under mechanical ventilation that met the criteria for weaning were enrolled. Patients underwent a T-piece Spontaneous Breath Trial (SBT) for 60 minutes and the usual clinical parameters were recorded every 5 minutes. Microcirculatory perfusion was evaluated using the mottling score and the Tissue Oxygen Saturation (StO2) measured by Near Infrared Spectroscopy technology on the thenar and knee area. RESULTS: Seventy-three patients were studied (age: 67±15 years, men: 40, SAPS II: 47±15) after a duration of mechanical ventilation of 3 (1-6) days. Forty-five patients succeeded the first SBT. The mottling score severity recorded just before ventilator disconnection (baseline) was associated with weaning failure (P=0.03). Moreover, the mottling score increase during SBT was significantly associated with weaning failure (80% vs. 28%, P=0.001; Odds ratio 10.5 [2.0-54.8]). Baseline thenar StO2 was not different according to weaning outcome (failure 76±13% vs. success 77±7%, P=0.90) whereas baseline knee StO2 was significantly lower in patients who failed the first SBT (67±13% vs. 75±12%, P<0.01). This difference was apparent since the very beginning of the SBT and lasted throughout the trial (P=0.0001). CONCLUSION: In unselected mechanically ventilated patients undergoing SBT, mottling score and knee StO2 are early predictors of weaning failure.

Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge.

BACKGROUND AND PURPOSE: Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. EXPERIMENTAL APPROACH: We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. KEY RESULTS: In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg(-1), i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1ß levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1ß levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. CONCLUSIONS AND IMPLICATIONS: Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases.

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.

High prevalence of undiagnosed diabetes and high risk for diabetes using HbA1c criteria in middle-aged patients undergoing cataract surgery.

AIM: This study assessed the prevalence of undiagnosed diabetes and a high risk for diabetes using glycated haemoglobin (HbA(1c)) values in middle-aged patients undergoing cataract surgery. METHODS: The study comprised 137 consecutive patients, aged 40 to 65 years, with no known diabetes undergoing cataract surgery at a French national eye centre. Fasting glucose, obesity parameters, and vascular and ocular cataract risk factors were recorded. HbA1c was measured on the day of cataract surgery. Prevalence of undiagnosed diabetes (HbA(1c) ≥ 6.5%) and a high risk of diabetes (≥ 6.0% but < 6.5%) in the study population was compared with recently published estimates from general French, Dutch and US populations. RESULTS: In the study population, undiagnosed diabetes was found in 12 patients (9%; 95% CI: 4-14%) and a high risk for diabetes in 47 (34%; 95% CI: 26-42%). These prevalences were four to 11 times higher than the corresponding population-based estimates, whereas obesity parameters recorded in the general populations and in our study population were similar according to HbA1c subcategories. Of the 125 patients with HbA1c less than 6.5%, values were higher in patients without ocular cataract risk factors (n = 73; 58%) than in those with cataract risk factors (n = 52; 42%) at 5.92 ± 0.30% and 5.57 ± 0.29%, respectively (P < 0.001), thereby suggesting a significant role for blood glucose levels in cataractogenesis. CONCLUSION: Middle-aged patients undergoing cataract surgery showed a high prevalence of diabetes and a high risk for diabetes not recognized before surgery, suggesting that this patient population should be targeted for diabetes screening and prevention.

Estimating influenza latency and infectious period durations using viral excretion data.

Influenza infection natural history is often described as a progression through four successive stages: Susceptible-Exposed/Latent-Infectious-Removed (SEIR). The duration of each stage determines the average generation time, the time between infection of a case and infection of his/her infector. Recently, several authors have justified somewhat arbitrary choices in stage durations by how close the resulting generation time distribution was to viral excretion over time after infection. Taking this reasoning one step further, we propose that the viral excretion profile over time can be used directly to estimate the required parameters in an SEIR model. In our approach, the latency and infectious period distributions are estimated by minimizing the Kullback-Leibler divergence between the model-based generation time probability density function and the normalized average viral excretion profile. Following this approach, we estimated that the latency and infectious period last respectively 1.6 and 1.0 days on average using excretion profiles from experimental infections. Interestingly, we find that only 5% of cases are infectious for more than 2.9 days. We also discuss the consequences of these estimates for the evaluation of the efficacy of control measures such as isolation or treatment. We estimate that, under a best-case scenario where symptoms appear at the end of the latency period, index cases must be isolated or treated at most within 16h after symptoms onset to avoid 50% of secondary cases. This study provides the first estimates of latency and infectious period for influenza based directly on viral excretion data. It provides additional evidence that isolation or treatment of cases would be effective only if adopted shortly after symptoms onset, and shows that four days of isolation may be enough to avoid most transmissions.

Knee area tissue oxygen saturation is predictive of 14-day mortality in septic shock.

PURPOSE: Thenar eminence tissue oxygen saturation (StO(2)) was developed to assess organ perfusion. However, mottling, a strong predictor of mortality in septic shock, develops preferentially around the knee. We aimed to evaluate the prognostic value of StO(2) measured around the knee in septic shock patients and compare it to thenar StO(2). METHODS: This was a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included. Parameters were recorded when vasopressors were started (H0) and every 6 h during 24 h. Their predictive value was assessed on 14-day mortality. RESULTS: Fifty-two patients were included. SOFA score was 11 (9-15) and SAPS II was 56 (40-72). At 6 h after ICU admission (H6), mean arterial pressure, cardiac index, and central venous pressure were not different between non-survivors and survivors; but non-survivors had higher arterial lactate level (8.8 ± 5.0 vs. 2.2 ± 1.5 mmol/l, P < 0.001), lower urinary output (0.22 ± 0.45 vs. 0.70 ± 0.50 ml/kg/h, P < 0.001) and ScvO(2) (62 ± 20 vs. 72 ± 9 %, P = 0.03). At H6, StO(2) was lower in non-survivors; this difference was not significant for thenar StO(2) (70 ± 15 vs. 77 ± 12 %, P = 0.10) but was very pronounced for knee StO(2) (39 ± 23 vs. 71 ± 12 %, P < 0.001). At H6, a low knee StO(2) was associated with a higher mottling score (P < 0.01), a higher lactate level (P < 0.002, R (2) = 0.2), and a lower urinary output (P = 0.02, R (2) = 0.12). CONCLUSION: After initial septic shock resuscitation, StO(2) measured around the knee is a strong predictive factor of 14-day mortality.

Mottling score predicts survival in septic shock.

BACKGROUND: Experimental and clinical studies have identified a crucial role of microcirculation impairment in severe infections. We hypothesized that mottling, a sign of microcirculation alterations, was correlated to survival during septic shock. METHODS: We conducted a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included during a 7-month period. After initial resuscitation, we recorded hemodynamic parameters and analyzed their predictive value on mortality. The mottling score (from 0 to 5), based on mottling area extension from the knees to the periphery, was very reproducible, with an excellent agreement between independent observers [kappa = 0.87, 95% CI (0.72-0.97)]. RESULTS: Sixty patients were included. The SOFA score was 11.5 (8.5-14.5), SAPS II was 59 (45-71) and the 14-day mortality rate 45% [95% CI (33-58)]. Six hours after inclusion, oliguria [OR 10.8 95% CI (2.9, 52.8), p = 0.001], arterial lactate level [<1.5 OR 1; between 1.5 and 3 OR 3.8 (0.7-29.5); >3 OR 9.6 (2.1-70.6), p = 0.01] and mottling score [score 0-1 OR 1; score 2-3 OR 16, 95% CI (4-81); score 4-5 OR 74, 95% CI (11-1,568), p < 0.0001] were strongly associated with 14-day mortality, whereas the mean arterial pressure, central venous pressure and cardiac index were not. The higher the mottling score was, the earlier death occurred (p < 0.0001). Patients whose mottling score decreased during the resuscitation period had a better prognosis (14-day mortality 77 vs. 12%, p = 0.0005). CONCLUSION: The mottling score is reproducible and easy to evaluate at the bedside. The mottling score as well as its variation during resuscitation is a strong predictor of 14-day survival in patients with septic shock.

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.

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.

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.