Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

The DNAJB6 and DNAJB8 Protein Chaperones Prevent Intracellular Aggregation of Polyglutamine Peptides

Fragments of proteins containing an expanded polyglutamine (polyQ) tract are thought to initiate aggregation and toxicity in at least nine neurodegenerative diseases, including Huntington's disease. Because proteasomes appear unable to digest the polyQ tract, which can initiate intracellular protein aggregation, preventing polyQ peptide aggregation by chaperones should greatly improve polyQ clearance and prevent aggregate formation. Here we expressed polyQ peptides in cells and show that their intracellular aggregation is prevented by DNAJB6 and DNAJB8, members of the DNAJ (Hsp40) chaperone family. In contrast, HSPA/Hsp70 and DNAJB1, also members of the DNAJ chaperone family, did not prevent peptide-initiated aggregation. Intriguingly, DNAJB6 and DNAJB8 also affected the soluble levels of polyQ peptides, indicating that DNAJB6 and DNAJB8 inhibit polyQ peptide aggregation directly. Together with recent data showing that purified DNAJB6 can suppress fibrillation of polyQ peptides far more efficiently than polyQ expanded protein fragments in vitro, we conclude that the mechanism of DNAJB6 and DNAJB8 is suppression of polyQ protein aggregation by directly binding the polyQ tract

Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM-1

Upon inflammation, leukocytes leave the circulation by crossing the endothelial monolayer at specific transmigration “hotspot” regions. Although these regions support leukocyte transmigration, their functionality is not clear. We found that endothelial hotspots function to limit vascular leakage during transmigration events. Using the photoconvertible probe mEos4b, we traced back and identified original endothelial transmigration hotspots. Using this method, we show that the heterogeneous distribution of ICAM-1 determines the location of the transmigration hotspot. Interestingly, the loss of ICAM-1 heterogeneity either by CRISPR/Cas9-induced knockout of ICAM-1 or equalizing the distribution of ICAM-1 in all endothelial cells results in the loss of TEM hotspots but not necessarily in reduced TEM events. Functionally, the loss of endothelial hotspots results in increased vascular leakage during TEM. Mechanistically, we demonstrate that the 3 extracellular Ig-like domains of ICAM-1 are crucial for hotspot recognition. However, the intracellular tail of ICAM-1 and the 4th Ig-like dimerization domain are not involved, indicating that intracellular signaling or ICAM-1 dimerization is not required for hotspot recognition. Together, we discovered that hotspots function to limit vascular leakage during inflammation-induced extravasation

Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM-1

Upon inflammation, leukocytes leave the circulation by crossing the endothelial monolayer at specific transmigration “hotspot” regions. Although these regions support leukocyte transmigration, their functionality is not clear. We found that endothelial hotspots function to limit vascular leakage during transmigration events. Using the photoconvertible probe mEos4b, we traced back and identified original endothelial transmigration hotspots. Using this method, we show that the heterogeneous distribution of ICAM-1 determines the location of the transmigration hotspot. Interestingly, the loss of ICAM-1 heterogeneity either by CRISPR/Cas9-induced knockout of ICAM-1 or equalizing the distribution of ICAM-1 in all endothelial cells results in the loss of TEM hotspots but not necessarily in reduced TEM events. Functionally, the loss of endothelial hotspots results in increased vascular leakage during TEM. Mechanistically, we demonstrate that the 3 extracellular Ig-like domains of ICAM-1 are crucial for hotspot recognition. However, the intracellular tail of ICAM-1 and the 4th Ig-like dimerization domain are not involved, indicating that intracellular signaling or ICAM-1 dimerization is not required for hotspot recognition. Together, we discovered that hotspots function to limit vascular leakage during inflammation-induced extravasation

Coronary Artery Calcifications Are Associated With More Severe Multiorgan Failure in Patients With Severe Coronavirus Disease 2019 Infection: Longitudinal Results of the Maastricht Intensive Care COVID Cohort

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is regarded as a multisystemic disease. Patients with preexisting cardiovascular disease have an increased risk for a more severe disease course. This study aimed to investigate if a higher degree of coronary artery calcifications (CAC) on a standard chest computed tomography (CT) scan in mechanically ventilated patients was associated with a more severe multiorgan failure over time. MATERIALS AND METHODS: All mechanically ventilated intensive care unit patients with SARS-CoV-2 infection who underwent a chest CT were prospectively included. CT was used to establish the extent of CAC using a semiquantitative grading system. We categorized patients into 3 sex-specific tertiles of CAC: lowest, intermediate, and highest CAC score. Daily, the Sequential Organ Failure Assessment (SOFA) scores were collected to evaluate organ failure over time. Linear mixed-effects regression was used to investigate differences in SOFA scores between tertiles. The models were adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, cardiovascular risk factors, and chronic liver, lung, and renal disease. RESULTS: In all, 71 patients were included. Patients in the highest CAC tertile had, on average, over time, 1.8 (0.5-3.1) points higher SOFA score, compared with the lowest CAC tertile (P=0.005). This association remained significant after adjustment for age, sex, and APACHE II score (1.4 [0.1-2.7],P=0.042) and clinically relevant after adjustment for cardiovascular risk factors (1.3 [0.0-2.7],P=0.06) and chronic diseases (1.3 [-0.2 to 2.7],P=0.085). CONCLUSION: A greater extent of CAC is associated with a more severe multiorgan failure in mechanically ventilated coronavirus disease 2019 patients

Coronary Artery Calcifications Are Associated With More Severe Multiorgan Failure in Patients With Severe Coronavirus Disease 2019 Infection:Longitudinal Results of the Maastricht Intensive Care COVID Cohort

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is regarded as a multisystemic disease. Patients with preexisting cardiovascular disease have an increased risk for a more severe disease course. This study aimed to investigate if a higher degree of coronary artery calcifications (CAC) on a standard chest computed tomography (CT) scan in mechanically ventilated patients was associated with a more severe multiorgan failure over time. MATERIALS AND METHODS: All mechanically ventilated intensive care unit patients with SARS-CoV-2 infection who underwent a chest CT were prospectively included. CT was used to establish the extent of CAC using a semiquantitative grading system. We categorized patients into 3 sex-specific tertiles of CAC: lowest, intermediate, and highest CAC score. Daily, the Sequential Organ Failure Assessment (SOFA) scores were collected to evaluate organ failure over time. Linear mixed-effects regression was used to investigate differences in SOFA scores between tertiles. The models were adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, cardiovascular risk factors, and chronic liver, lung, and renal disease. RESULTS: In all, 71 patients were included. Patients in the highest CAC tertile had, on average, over time, 1.8 (0.5-3.1) points higher SOFA score, compared with the lowest CAC tertile (P=0.005). This association remained significant after adjustment for age, sex, and APACHE II score (1.4 [0.1-2.7], P=0.042) and clinically relevant after adjustment for cardiovascular risk factors (1.3 [0.0-2.7], P=0.06) and chronic diseases (1.3 [−0.2 to 2.7], P=0.085). CONCLUSION: A greater extent of CAC is associated with a more severe multiorgan failure in mechanically ventilated coronavirus disease 2019 patients

Advances in reference materials and measurement techniques for greenhouse gas atmospheric observations

We present the global research landscape which aims to deliver a measurement infrastructure to underpin atmospheric observations of key greenhouse gases governing changes in the Earth’s climate. These measurements present a significant challenge to the metrological community, analytical laboratories and major producers of reference materials. The review focuses on the progress made in the Gas Analysis Working Group of the Consultative Committee for Amount of Substance: Metrology in Chemistry and Biology (CCQM-GAWG) in establishing the primary realisation of the amount-of-substance fraction for carbon dioxide, methane and nitrous oxide in an air matrix. It also focuses on the importance of providing traceable measurements of isotopic composition of these components for commutability of reference materials and for isotope ratio measurements for greenhouse gas source attribution. The review examines the developments in the Global Atmosphere Watch (GAW) Programme of the World Meteorological Organisation (WMO) for providing the framework for the development and implementation of integrated greenhouse gas observations, which is vital for understanding the global carbon cycle and the role greenhouse gases play in climate change. The developments in analytical techniques are also discussed which have shaped the direction of the metrology required to meet the evolving and future needs of stakeholders