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

Managing overlap of primary study results across systematic reviews: practical considerations for authors of overviews of reviews

Background Overviews often identify and synthesise a large number of systematic reviews on the same topic, which is likely to lead to overlap (i.e. duplication) in primary studies across the reviews. Using a primary study result multiple times in the same analysis overstates its sample size and number of events, falsely leading to greater precision in the analysis. This paper aims to: (a) describe types of overlapping data that arise from the same primary studies reported across multiple reviews, (b) describe methods to identify and explain overlap of primary study data, and (c) present six case studies illustrating different approaches to manage overlap. Methods We first updated the search in PubMed for methods from the MOoR framework relating to overlap of primary studies. One author screened the studies titles and abstracts, and any full-text articles retrieved, extracted methods data relating to overlap of primary studies and mapped it to the overlap methods from the MOoR framework. We also describe six case studies as examples of overviews that use specific overlap methods across the steps in the conduct of an overview. For each case study, we discuss potential methodological implications in terms of limitations, efficiency, usability, and resource use. Results Nine methods studies were found and mapped to the methods identified by the MOoR framework to address overlap. Overlap methods were mapped across four steps in the conduct of an overview – the eligibility criteria step, the data extraction step, the assessment of risk of bias step, and the synthesis step. Our overview case studies used multiple methods to reduce overlap at different steps in the conduct of an overview. Conclusions Our study underlines that there is currently no standard methodological approach to deal with overlap in primary studies across reviews. The level of complexity when dealing with overlap can vary depending on the yield, trends and patterns of the included literature and the scope of the overview question. Choosing a method might be dependent on the number of included reviews and their primary studies. Gaps in evaluation of methods to address overlap were found and further investigation in this area is needed.Medicine, Faculty ofNon UBCAnesthesiology, Pharmacology and Therapeutics, Department ofReviewedFacult

Pictograms for Safer Medication Management by Health Care Workers

ABSTRACTBackground: Inherent risks are associated with the preparation and administration of medications. As such, a key aspect of medication safety is to ensure safe medication management practices.Objective: To identify key medication safety issues and high-alert drug classes that might benefit from implementation of pictograms, for use by health care providers, to enhance medication administration safety. This study was the first step in the development of such pictograms.Methods: Self-identified medication management experts participated in a modified Delphi process to achieve consensus on situations where safety pictograms are required for labelling to optimize safe medication management. The study was divided into 3 phases: issue generation, issue reduction, and issue selection. Issues achieving at least 80% consensus and deemed most essential were selected for future studies. Retained issues were subjected to semiotic analysis, and preliminary pictograms were developed.Results: Of the 87 health care professionals (pharmacists, pharmacy technicians, nurses, and physicians) invited to participate in the Delphi process, 30 participated in all 3 phases. A total of 55 situations that could potentially benefit from safety pictograms were generated initially. Through the Delphi process, these were narrowed down to 10 situations where medication safety might be increased with the use of safety pictograms. For most of the retained issues, between 3 and 6 pictograms were designed, based on the results of the semiotic analysis.Conclusions: The pharmacists, pharmacy technicians, nurses, and physicians participating in this study reached consensus and identified 10 medication administration safety issues that might benefit from the development and implementation of safety pictograms. Pictograms were developed for a total of 9 issues. In follow-up studies, these pictograms will be validated for comprehension and evaluated for effectiveness.RÉSUMÉContexte : Il y a des risques inhérents associés à la préparation et à l’administration de médicaments. Pour cette raison, l’un des principaux aspects de la sécurité des médicaments est d’assurer des pratiques de gestion des médicaments sécuritaires.Objectif : Déterminer les principales questions de sécurité des médicaments et les classes de médicaments de niveau d’alerte élevé pour lesquelles l’ajout de pictogrammes, destinés aux fournisseurs de soins de santé, permettrait de rendre l’administration de médicaments plus sécuritaire. La présente étude représentait la première étape dans l’élaboration de ces pictogrammes.Méthodes : Des professionnels qui se définissaient comme experts en gestion de médicaments ont participé à un processus Delphi modifié dans le but d’arriver à un consensus à propos des situations où des pictogrammes de sécurité doivent être ajoutés à l’étiquette afin d’optimiser la gestion sécuritaire des médicaments. L’étude a été divisée en trois phases : génération de questions de sécurité, élimination de questions de sécurité et sélection de questions de sécurité. Les questions qui atteignaient un consensus d’au moins 80 % et qui étaient considérées comme les plus essentielles ont été retenues pour des études ultérieures. Les questions de sécurité retenues ont été soumises à une analyse sémiotique, puis des ébauches de pictogrammes ont été créées.Résultats : Parmi les 87 professionnels de la santé (notamment des pharmaciens, des techniciens en pharmacie, du personnel infirmier et des médecins) invités à participer au processus Delphi, 30 ont pris part aux trois étapes. Au total, 55 situations pour lesquelles il pourrait être avantageux d’utiliser des pictogrammes de sécurité ont été générées au départ. Grâce au processus Delphi, ce nombre a été réduit à 10 situations pour lesquelles la sécurité des médicaments pourrait être accrue à l’aide de pictogrammes de sécurité. Pour la plupart des questions retenues, entre trois et six pictogrammes ont été conçus à l’aide des résultats de l’analyse sémiotique.Conclusion : Les pharmaciens, les techniciens en pharmacie, le personnel infirmier et les médecins qui ont participé à l’étude ont atteint un consensus sur dix questions au sujet de l’administration sécuritaire des médicaments pour lesquelles l’élaboration et la mise en place de pictogrammes de sécurité pourraient être avantageuses. Ensuite, des pictogrammes ont été conçus pour neuf questions au total. Dans les études ultérieures, il faudra évaluer l’efficacité des pictogrammes et s’assurer qu’ils sont interprétés correctement

Altered patterns of epigenetic changes in systemic lupus erythematosus and auto-antibody production: is there a link?

International audienceThe prominent feature of immunological defects in systemic lupus erythematosus (SLE) is the production of autoantibodies (auto-Abs) to nuclear antigens including DNA, histones and RNP. In addition, there is growing evidence that epigenetic changes play a key role in the pathogenesis of SLE. Autoreactive CD4(+) T cells and B cells in patients with SLE have evidence of altered patterns of DNA methylation as well as post-translational modifications of histones and ribonucleoproteins (RNP). A key question that has emerged from these two characteristic features of SLE is whether the two processes are linked. New data provide support for such a link. For example, there is evidence that hypomethylated DNA is immunogenic, that anti-histone auto-Abs in patients with SLE bind epigenetic-sensitive hot spots and that epigenetically-modified RNP-derived peptides can modulate lupus disease. All in all, the available evidence indicates that a better understanding of dysregulation in epigenetics in SLE may offer opportunities to develop new biomarkers and novel therapeutic strategies

Clinical and pharmacokinetic/dynamic outcomes of prolonged infusions of beta-lactam antimicrobials: An overview of systematic reviews.

ObjectiveThis overview of reviews aims to map and compare of objectives, methods, and findings of existing systematic reviews to develop a greater understanding of the information available about prolonged beta-lactam infusions in hospitalized patients with infection.DesignOverview of systematic reviews.Data sourcesMedline, Embase, PROSPERO and the Cochrane Library were systematically searched from January, 1990 to June, 2019 using a peer reviewed search strategy. Grey literature was also searched for relevant reviews.Eligibility criteria for selecting reviewsSystematic reviews were sought that compared two or more infusion strategies for intravenous beta-lactam antimicrobials and report clinical cure or mortality. Populations of included reviews were restricted to hospitalized patients with infection, without restrictions on age, infection type, or disease.Data extraction and analysisAbstract screening, data extraction, quality and risk of bias assessment were conducted by two independent reviewers. Overlap between reviews was assessed using a modified corrected covered area. Overview findings are reported in accordance with Cochrane's recommendation for overview conduct. Clinical outcomes extracted included survival, clinical cure, treatment failure, microbiological cure, length of stay, adverse events, cost, and emergence of resistance.ResultsThe search strategy identified 3327 unique citations from which 21 eligible reviews were included. Reviews varied by population, intervention and outcomes studied. Between reviews, overlap of primary studies was generally high, methodologic quality generally low and risk of bias variable. Nine of 14 reviews that quantitatively evaluated mortality and clinical cure identified a benefit with prolonged infusions of beta lactams when compared with intermittent infusions. Evidence of mortality and clinical cure benefit was greater among critically ill patients when compared to less sick patients and lower in randomized controlled trials when compared with observational studies.ConclusionsFindings from our review demonstrate a consistent and reproducible lack of harm with prolonged infusions of beta-lactam antibiotics with variability in effect size and significance of benefits. Despite 21 systematic reviews addressing prolonged infusions of beta-lactams, this overview supports the continued need for a definitive systematic review given variability in populations, interventions and outcomes in the current systematic reviews. Subsequent systematic reviews should have more rigorous and transparent methods, only include RCTs and evaluate the proposed benefits found in various subgroup-analyses-i.e. high risk of mortality.Trial registrationProspero registry, CRD42019117118

DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus.

International audienceAbstract Systemic lupus erythematosus (SLE) disease is an autoimmune disease of unknown aetiology that affects predominantly women of child bearing age. Since previous studies, including ours, have demonstrated that CD4+ T cells and B cells from SLE patients are defective in their ability to methylate their DNA upon antigen stimulation, the aim of this study was to investigate whether DNA demethylation affects the transcription of HRES-1 in B cells. HRES-1 is the prototype of Human Endogenous Retrovirus (HERV) overexpressed in SLE. We have observed that SLE B cells were characterized by their incapacity to methylate the HRES-1 promoter, both in unstimulated and in anti-IgM stimulated B cells. In turn, HRES-1/p28 expression was increased in SLE B cells after B cell receptor engagement, but not in controls. In SLE B cells the Erk/DNMT1 pathway was defective. In addition, blocking the autocrine-loop of IL-6 in SLE B cells with an anti-IL-6 receptor monoclonal antibody restores DNA methylation and control of HRES-1/p28 expression became effective. As a consequence, a better understanding of HERV dysregulation in SLE reinforces our comprehension of the disease and opens new therapeutic perspectives

Clinical utility of overviews on adverse events of pharmacological interventions

Background Overviews (i.e., systematic reviews of systematic reviews, meta-reviews, umbrella reviews) are a relatively new type of evidence synthesis. Among others, one reason to conduct an overview is to investigate adverse events (AEs) associated with a healthcare intervention. Overviews aim to provide easily accessible information for healthcare decision-makers including clinicians. We aimed to evaluate the clinical utility of overviews investigating AEs. Methods We used a sample of 27 overviews exclusively investigating drug-related adverse events published until 2021 identified in a prior project. We defined clinical utility as the extent to which overviews are perceived to be useful in clinical practice. Each included overview was assigned to one of seven pharmacological experts with expertise on the topic of the overview. The clinical utility and value of these overviews were determined using a self-developed assessment tool. This included four open-ended questions and a ranking of three clinical utility statements completed by clinicians. We calculated frequencies for the ranked clinical utility statements and coded the answers to the open-ended questions using an inductive approach. Results The overall agreement with the provided statements was high. According to the assessments, 67% of the included overviews generated new knowledge. In 93% of the assessments, the overviews were found to add value to the existing literature. The overviews were rated as more useful than the individual included systematic reviews (SRs) in 85% of the assessments. The answers to the open-ended questions revealed two key aspects of clinical utility in the included overviews. Firstly, it was considered useful that they provide a summary of available evidence (e.g., along with additional assessments, or across different populations, or in different settings that have not been evaluated together in the included SRs). Secondly, it was found useful if overviews conducted a new meta-analysis to answer specific research questions that had not been answered previously. Conclusions Overviews on drug-related AEs are considered valuable for clinical practice by clinicians. They can make available evidence on AEs more accessible and provide a comprehensive view of available evidence. As the role of overviews evolves, investigations such as this can identify areas of value.Medicine, Faculty ofNon UBCReviewedFacultyResearche