Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an

Effet de la réponse inflammatoire à la phase aigüe du sepsis sur l’induction de la réponse SOS bactérienne

Sepsis is defined as a dysregulated immune response to infection, and in severe cases is associated to an increase in the proportion of circulating Immature Granulocytes (IG), secondary to an emergency granulopoiesis. Pathogen control functions such as phagocytosis and reactive oxygen species (ROS) production are decreased in GIs compared to Neutrophils (Neut). However, these functions could trigger the bacterial SOS response, a genetic network triggered by DNA damage and responsible for the DNA repair. Additionally to the DNA repair functions, the SOS response facilitates bacterial adaptation to hostile environments by, among others, the expression and dissemination of antimicrobial resistance genes. We hypothesized that during the innate immune response of sepsis, ROS produced by Neut and GI may induce the bacterial SOS response and consequently facilitate the development of antibiotic resistance. We developed an in vitro and ex vivo incubation model to evaluate the interaction between Neut/GI and E. coli as model bacteria. This allowed us to test simultaneously the phagocytic function and ROS production by granulocytes, as well as the induction of the SOS response using a bacterial fluorescence system. In this work, we demonstrated the induction of the SOS response in the GI of septic patients and showed the increased expression of the qnrB2 gene, conferring quinolone resistance in an SOS-dependent manner. An in vitro model to assess the excision frequency of the Integron’s integrase among phagocyted bacteria was also studied and optimized.Le sepsis est caractérisé par une dérégulation de la réponse immune associée à une augmentation du nombre de Granulocytes Immatures (GI) dans la circulation sanguine, ce qui est observé dans la granulopoïèse d’urgence. Les fonctions de défense face aux pathogènes telles que la phagocytose et la production d’espèces réactives de l’oxygène (ROS) sont diminuées chez les GI par rapport aux Neutrophiles (Neut). Toutefois, ces fonctions pourraient déclencher la réponse SOS bactérienne, responsable de la réparation de l’ADN endommagé par ces ROS. En plus de son activité réparatrice, la réponse SOS facilite l’adaptation bactérienne aux milieux hostiles, par l’expression et dissémination des gènes de résistance aux antibiotiques. Nous avons émis l’hypothèse que pendant la réponse immune innée du sepsis, les ROS produites par les Neut et les GI peuvent induire la réponse SOS bactérienne et en conséquence, faciliter l’apparition des résistances aux antibiotiques. Nous avons développé un modèle in vitro et ex vivo d’incubation pour évaluer l’interaction entre les Neut/GI et E. coli comme bactérie modèle. Cela nous a permis de tester à la fois la fonction phagocytaire et la production des ROS par les granulocytes, ainsi que l’induction de la réponse SOS par l’utilisation d’un système de fluorescence bactérien. Dans ce travail, nous avons mis en évidence l’induction de la réponse SOS chez les GI des patients septiques et nous avons montré l’augmentation d‘expression du gène qnrB2, conférant la résistance aux quinolones de façon SOS-dépendante. Un modèle in vitro pour évaluer l’activité d’excision de l’intégrase de l’intégron parmi les bactéries phagocytées a été également optimisée

Effet de la réponse inflammatoire à la phase aigüe du sepsis sur l’induction de la réponse SOS bactérienne

Sepsis is defined as a dysregulated immune response to infection, and in severe cases is associated to an increase in the proportion of circulating Immature Granulocytes (IG), secondary to an emergency granulopoiesis. Pathogen control functions such as phagocytosis and reactive oxygen species (ROS) production are decreased in GIs compared to Neutrophils (Neut). However, these functions could trigger the bacterial SOS response, a genetic network triggered by DNA damage and responsible for the DNA repair. Additionally to the DNA repair functions, the SOS response facilitates bacterial adaptation to hostile environments by, among others, the expression and dissemination of antimicrobial resistance genes. We hypothesized that during the innate immune response of sepsis, ROS produced by Neut and GI may induce the bacterial SOS response and consequently facilitate the development of antibiotic resistance. We developed an in vitro and ex vivo incubation model to evaluate the interaction between Neut/GI and E. coli as model bacteria. This allowed us to test simultaneously the phagocytic function and ROS production by granulocytes, as well as the induction of the SOS response using a bacterial fluorescence system. In this work, we demonstrated the induction of the SOS response in the GI of septic patients and showed the increased expression of the qnrB2 gene, conferring quinolone resistance in an SOS-dependent manner. An in vitro model to assess the excision frequency of the Integron’s integrase among phagocyted bacteria was also studied and optimized.Le sepsis est caractérisé par une dérégulation de la réponse immune associée à une augmentation du nombre de Granulocytes Immatures (GI) dans la circulation sanguine, ce qui est observé dans la granulopoïèse d’urgence. Les fonctions de défense face aux pathogènes telles que la phagocytose et la production d’espèces réactives de l’oxygène (ROS) sont diminuées chez les GI par rapport aux Neutrophiles (Neut). Toutefois, ces fonctions pourraient déclencher la réponse SOS bactérienne, responsable de la réparation de l’ADN endommagé par ces ROS. En plus de son activité réparatrice, la réponse SOS facilite l’adaptation bactérienne aux milieux hostiles, par l’expression et dissémination des gènes de résistance aux antibiotiques. Nous avons émis l’hypothèse que pendant la réponse immune innée du sepsis, les ROS produites par les Neut et les GI peuvent induire la réponse SOS bactérienne et en conséquence, faciliter l’apparition des résistances aux antibiotiques. Nous avons développé un modèle in vitro et ex vivo d’incubation pour évaluer l’interaction entre les Neut/GI et E. coli comme bactérie modèle. Cela nous a permis de tester à la fois la fonction phagocytaire et la production des ROS par les granulocytes, ainsi que l’induction de la réponse SOS par l’utilisation d’un système de fluorescence bactérien. Dans ce travail, nous avons mis en évidence l’induction de la réponse SOS chez les GI des patients septiques et nous avons montré l’augmentation d‘expression du gène qnrB2, conférant la résistance aux quinolones de façon SOS-dépendante. Un modèle in vitro pour évaluer l’activité d’excision de l’intégrase de l’intégron parmi les bactéries phagocytées a été également optimisée

Effect of the innate immune response in sepsis on the induction of the SOS bacterial response

Le sepsis est caractérisé par une dérégulation de la réponse immune associée à une augmentation du nombre de Granulocytes Immatures (GI) dans la circulation sanguine, ce qui est observé dans la granulopoïèse d’urgence. Les fonctions de défense face aux pathogènes telles que la phagocytose et la production d’espèces réactives de l’oxygène (ROS) sont diminuées chez les GI par rapport aux Neutrophiles (Neut). Toutefois, ces fonctions pourraient déclencher la réponse SOS bactérienne, responsable de la réparation de l’ADN endommagé par ces ROS. En plus de son activité réparatrice, la réponse SOS facilite l’adaptation bactérienne aux milieux hostiles, par l’expression et dissémination des gènes de résistance aux antibiotiques. Nous avons émis l’hypothèse que pendant la réponse immune innée du sepsis, les ROS produites par les Neut et les GI peuvent induire la réponse SOS bactérienne et en conséquence, faciliter l’apparition des résistances aux antibiotiques. Nous avons développé un modèle in vitro et ex vivo d’incubation pour évaluer l’interaction entre les Neut/GI et E. coli comme bactérie modèle. Cela nous a permis de tester à la fois la fonction phagocytaire et la production des ROS par les granulocytes, ainsi que l’induction de la réponse SOS par l’utilisation d’un système de fluorescence bactérien. Dans ce travail, nous avons mis en évidence l’induction de la réponse SOS chez les GI des patients septiques et nous avons montré l’augmentation d‘expression du gène qnrB2, conférant la résistance aux quinolones de façon SOS-dépendante. Un modèle in vitro pour évaluer l’activité d’excision de l’intégrase de l’intégron parmi les bactéries phagocytées a été également optimisée.Sepsis is defined as a dysregulated immune response to infection, and in severe cases is associated to an increase in the proportion of circulating Immature Granulocytes (IG), secondary to an emergency granulopoiesis. Pathogen control functions such as phagocytosis and reactive oxygen species (ROS) production are decreased in GIs compared to Neutrophils (Neut). However, these functions could trigger the bacterial SOS response, a genetic network triggered by DNA damage and responsible for the DNA repair. Additionally to the DNA repair functions, the SOS response facilitates bacterial adaptation to hostile environments by, among others, the expression and dissemination of antimicrobial resistance genes. We hypothesized that during the innate immune response of sepsis, ROS produced by Neut and GI may induce the bacterial SOS response and consequently facilitate the development of antibiotic resistance. We developed an in vitro and ex vivo incubation model to evaluate the interaction between Neut/GI and E. coli as model bacteria. This allowed us to test simultaneously the phagocytic function and ROS production by granulocytes, as well as the induction of the SOS response using a bacterial fluorescence system. In this work, we demonstrated the induction of the SOS response in the GI of septic patients and showed the increased expression of the qnrB2 gene, conferring quinolone resistance in an SOS-dependent manner. An in vitro model to assess the excision frequency of the Integron’s integrase among phagocyted bacteria was also studied and optimized

Community-acquired Staphylococcus aureus bacteriuria: a warning microbiological marker for infective endocarditis?

International audienceBACKGROUND:Urinary tract infection (UTI) is frequently diagnosed in the Emergency Department (ED). Staphylococcus aureus (SA) is an uncommon isolate in urine cultures (0.5-6% of positive urine cultures), except in patients with risk factors for urinary tract colonization. In the absence of risk factors, community-acquired SA bacteriuria may be related to deep-seated SA infection including infective endocarditis. We hypothesized that SA bacteriuria could be a warning microbiological marker of unsuspected infective endocarditis in the ED.METHODS:This is a retrospective chart review of consecutive adult patients between December 2005 and February 2018. All patients admitted in the ED with both SA bacteriuria (104 CFU/ml SA isolated from a single urine sample) and SA bacteremia, without risk factors for UT colonization (i.e., < 1 month UT surgery, UT catheterization) were analyzed. Diagnosis of infective endocarditis was based on the Duke criteria.RESULTS:During the study period, 27 patients (18 men; median age: 61 [IQR: 52-73] years) were diagnosed with community-acquired SA bacteriuria and had subsequently documented bacteremia and SA infective endocarditis. Only 5 patients (18%) had symptoms related to UT infection. Median delay between ED admission and SA bacteriuria identification was significantly shorter than that between ED admission and the diagnosis of infective endocarditis (1.4 ± 0.8 vs. 4.3 ± 4.2 days: p = 0.01). Mitral and aortic valves were most frequently involved by infective endocarditis (93%). Mortality on day 60 reached 56%.CONCLUSIONS:This study suggests that community-acquired SA bacteriuria should warn the emergency physician about a potentially associated left-sided infective endocarditis in ED patients without risk factors for UT colonization

Is prehospital endobronchial intubation a risk factor for subsequent ventilator associated pneumonia? A retrospective analysis

International audienceMore than half of patients under mechanical ventilation in the intensive care unit (ICU) are field-intubated, which is a known risk factor for ventilator associated pneumonia (VAP). We assessed whether field endobronchial intubation (EBI) is associated with the development of subsequent VAP during the ICU stay. This retrospective, nested case-control study was conducted in a cohort of field-intubated patients admitted to an ICU of a teaching hospital during a three-year period. Cases were defined as field-intubated patients with EBI and controls corresponded to field-intubated patients with proper position of the tracheal tube on admission chest X-ray. Primary endpoint was the development of early VAP. Secondary endpoints included the development of early ventilator associated tracheo-bronchitis, late VAP, duration of mechanical ventilation, length of stay and mortality in the ICU. A total of 145 patients were studied (mean age: 54 ± 19 years; men: 74%). Reasons for field intubation were predominantly multiple trauma (49%) and cardiorespiratory arrest (38%). EBI was identified in 33 patients (23%). Fifty-three patients (37%) developed early or late VAP. EBI after field intubation was associated with a nearly two-fold increase of early VAP, though not statistically significant (30% vs. 17%: p = 0.09). No statistically significant difference was found regarding secondary outcomes. The present study suggests that inadvertent prehospital EBI could be associated with a higher incidence of early-onset VAP. Larger studies are required to confirm this hypothesis. Whether strategies aimed at decreasing the incidence and duration of EBI could reduce the incidence of subsequent VAP remains to be determined

Phagosomal granulocytic ROS in septic patients induce the bacterial SOS response

International audienceSeptic patients with worst clinical prognosis have increased circulating immature granulocytes (IG), displaying limited phagocytosis and reactive oxygen species (ROS) production. Here, we developed an ex vivo model of incubation of human granulocytes, from septic patients or healthy donors, with Escherichia coli. We showed that the ROS production in Sepsis-IG is lower due to decreased activation and protein expression of the NADPH oxidase complex. We also demonstrated that the low level of ROS production and lower phagocytosis of IG in sepsis induce the bacterial SOS response, leading to the expression of the SOS-regulated quinolone resistance gene qnrB2. Without antimicrobial pressure, the sepsis immune response alone may promote antibiotic resistance expression