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

Per- and poly-fluoroalkyl substances (PFASs) in follicular fluid from women experiencing infertility in Australia

Per- and poly-fluoroalkyl substances (PFASs) have been widely used and detected in human matrices. Evidence that PFAS exposure may be associated with adverse human reproductive health effects exists, however, data is limited. The use of a human matrix such as follicular fluid to determine chemical exposure, along with reproductive data will be used to investigate if there is a relationship between PFAS exposure and human fertility. Objective: This study aims to: (1) assess if associations exist between PFAS concentrations and/or age and fertilisation rate (as determined in follicular fluid of women in Australia who received assisted reproductive treatment (ART)); and (2) assess if associations exist between PFAS concentrations and infertility aetiology. Methods: Follicular fluids were originally collected from participants who underwent fully stimulated ART treatment cycles at an in vitro fertilisation (IVF) clinic in the period 2006–2009 and 2010–11 in Queensland, Australia. The samples were available for analysis of 32 PFASs including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). 97 samples were matched with limited demographic data (age and fertilisation rate) and five infertility factors (three known female factors): 1) endometriosis, 2) polycystic ovarian syndrome (PCOS), and 3) genital tract infections - tubal/pelvic inflammation disease; as well as 4) male factor, and 5) idiopathic or unknown from either males or females. SPSS was used for linear regression analysis. Results: PFASs were detected in all follicular fluid samples with the mean concentrations of PFOS and PFOA, 4.9, and 2.4 ng/ml, respectively. A lower fertilisation rate was observed at higher age when age was added as a covariate, but there was no relationship between PFAS concentrations and fertilisation rate. There were few statistically significant associations between PFAS concentrations in follicular fluid and infertility factors. Log-transformed PFHxS concentrations were lower in females with endometriosis (factor 1) than in women who had reported ‘male factors’ as a reason of infertility, while PFHpA was higher in women who had infertile due to female factors (factor 1–3) compared to those who had infertile due to male factor. Conclusion: PFASs were detected in follicular fluid of Australian women who had been treated at an IVF clinic. PFAS exposure found in follicular fluids is linked to increased risk of some infertility factors, and increased age was associated with decreased fertilisation rate in our data. But there was no relationship between PFAS and ferlitisation rate. Further large-scale investigations of PFAS and health effects including infertility are warranted

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Keratocyte apoptosis and not myofibroblast differentiation mark the graft/host interface at early time-points post-DSAEK in a cat model.

To evaluate myofibroblast differentiation as an etiology of haze at the graft-host interface in a cat model of Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK).DSAEK was performed on 10 eyes of 5 adult domestic short-hair cats. In vivo corneal imaging with slit lamp, confocal, and optical coherence tomography (OCT) were performed twice weekly. Cats were sacrificed and corneas harvested 4 hours, and 2, 4, 6, and 9 days post-DSAEK. Corneal sections were stained with the TUNEL method and immunohistochemistry was performed for α-smooth muscle actin (α-SMA) and fibronectin with DAPI counterstain.At all in vivo imaging time-points, corneal OCT revealed an increase in backscatter of light and confocal imaging revealed an acellular zone at the graft-host interface. At all post-mortem time-points, immunohistochemistry revealed a complete absence of α-SMA staining at the graft-host interface. At 4 hours, extracellular fibronectin staining was identified along the graft-host interface and both fibronectin and TUNEL assay were positive within adjacent cells extending into the host stroma. By day 2, fibronectin and TUNEL staining diminished and a distinct acellular zone was present in the region of previously TUNEL-positive cells.OCT imaging consistently showed increased reflectivity at the graft-host interface in cat corneas in the days post-DSAEK. This was not associated with myofibroblast differentiation at the graft-host interface, but rather with apoptosis and the development of a subsequent acellular zone. The roles of extracellular matrix changes and keratocyte cell death and repopulation should be investigated further as potential contributors to the interface optical changes

Methods of Corneal Optical Coherence Tomography (OCT) Analysis.

<p>(<b>A</b>) OCT image of an <i>in vivo</i> cat cornea 4 hours after Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK). Note the greater intensity of backscatter at the graft-host interface (solid arrows) relative to the adjacent stromata. The perpendicular lines superimposed over the OCT image indicate the location of the areas analyzed for backscatter intensity (white and black) and thickness (red, orange, and maroon). Four perpendicular lines (white and black), 20 pixels wide and located +/−100 and +/−200 pixels from the central specular reflection were used to generate a pixel brightness profile. As depicted along the black line, intensity line graphs generated from each of the four perpendicular lines were then used to identify and measure intensity over three defined corneal regions; a 10 pixel thick region of interface (yellow), a 40 pixel thick region of the adjacent host stroma (green), and a 40 pixel thick region of the adjacent donor stroma (blue). Total corneal (red), host stromal (orange), and donor stromal (maroon) thickness measurements were taken in the central cornea as depicted by the central line. (<b>B</b>) A representative plot of normalized backscattered light intensity through a cat cornea post-DSAEK at a single time-point. This profile was generated as described above. These graphs were constructed for each of the line locations. Note the intensity peak at the interface (yellow) in comparison to that of the adjacent host (green) and donor stroma (blue).</p

Interface Intensity and Corneal Thickness Post-DSAEK.

<p>(<b>A</b>) Corneal optical coherence tomography (OCT) images of an <i>in vivo</i> cat cornea pre-operatively and at early post-Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK) time-points. Note the easily discernible post-operative interface between the host and donor stromata appears brighter than the adjacent tissue. The host stroma also has increased thickness immediately post-operatively, which improves with time. (<b>B</b>) Corneal OCT image-derived backscatter intensity at the graft-host interface (yellow) in comparison to the adjacent host stroma (green) and donor stroma (blue) at early post-DSAEK time points. Note that the graft-host interface was consistently brighter than the adjacent host stroma and adjacent donor stroma. This result was statistically significant at the majority of time-points; between interface and adjacent host stroma at days 0 (p = 0.0078), 2/3 (p = 0.0053), 4/5 (p = 0.0019) and 6/7 (p = 0.0003), and between interface and adjacent donor stroma at days 0 (p = 0.0078), 2/3 (p = 0.0005), and 6/7 (p = 0.0155). This difference was no longer observed at the 8/9 day time point. * = significant difference between mean interface and mean host stromal intensity. † = significant difference between mean interface and mean donor stromal intensity. (<b>C</b>) OCT image-derived corneal thickness measurements across early post-DSAEK time-points. Note the brisk increase in total thickness from pre-operative levels (Pre-Op) to immediate post-operative (0) levels associated with the addition of the donor tissue, and the subsequent gradual decline in total thickness to day 6/7.</p

Immunohistochemistry for detection of alpha-smooth muscle actin (α-SMA) and fibronectin post-Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK).

<p>Corneal sections were stained with antibodies against α-SMA (red) to label myofibroblasts, antibodies against fibronectin (green), and 4′6′-diamidino-2-phenylondole dihydrochloride (DAPI) (blue) was used to label cell nuclei. (<b>A–C</b>) Photomicrographs of <i>ex vivo</i> cat corneal sections of the graft-host interface (arrows) on post-operative days 0 (<b>A</b>), 4 (<b>B</b>), and 9 (<b>C</b>)(scale bar for A – C = 0.2 mm). (<b>D and E</b>) The graft-host interface on days 0 (<b>D</b>) and 9 (<b>E</b>) (scale bar for D & E = 0.2 mm). (<b>F</b>) The central stroma of an unoperated cat cornea demonstrated an absence of α-SMA and mild diffuse fibronectin staining. (<b>G and H</b>) Incisional paracenteses wounds on day 0 (<b>G</b>) and day 9 (<b>H</b>) (scale bar for F – H = 0.4 mm). (<b>I</b>) An incisional paracentesis wound on day 9 at high magnification (scale bar for I = 0.2 mm). Note the lack of α-SMA staining at the graft-host interface (<b>C and E</b>), but positive α-SMA staining at the incisional wound (<b>H and I</b>) on day 9. On day 0, 4 hours after DSAEK, fibronectin staining was present extracellularly along the interface and also appeared to co-localize with DAPI in the cells of the adjacent host stroma (<b>A and D</b>). On day 9 post-DSAEK, there was faint fibronectin staining near the host stromal cells, but the interface fibronectin staining is much fainter and more consistent with the unoperated control.</p

Incidence of acute myeloid leukemia and hepatocellular carcinoma in mice irradiated with 1 GeV/nucleon 56Fe Ions

Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the leukemogenic efficacy of one such HZE species, 1 GeV Fe-56 ions, a component of space radiation, in a mouse model for radiation-induced acute myeloid leukemia. CBA/CaJ mice were irradiated with 1 GeV/nucleon Fe-56 ions or Cs-56 gamma rays and followed until they were moribund or to 800 days of age. We found that 1 GeV/nucleon Fe-56 ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia (AML). However, Fe-56-ion-irradiated mice had a much higher incidence of hepatocellular carcinoma (HCC) than gamma-irradiated mice, with an estimated RBE of approximately 50. These data suggest a difference in the effects of HZE iron ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. (C) 2009 by Radiation Research Societ