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

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

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

Divergent small viral fusogens use different strategies to hijack the actin cytoskeleton to drive cell-cell fusion

Cell-cell fusion is indispensable for numerous stages of development, from fertilization to tissue development and maintenance. It is typically driven by fusogenic membrane proteins that have tall (&gt;10 nm) ectodomains that bridge the distance between plasma membranes. These tall fusogens often resemble those involved in enveloped viral entry and undergo conformational changes that pull the two membranes into close contact and drive fusion. In contrast, some cell-cell fusogens, such as the fusion-associated small transmembrane (FAST) proteins from reovirus, have ectodomains that are short (&lt;2 nm), smaller than the repulsive hydration barrier that prevents membranes from coming into close contact.In this dissertation, I investigated the mechanism of FAST protein-mediated cell-cell fusion. In the first part, I discovered that p14, the FAST protein from reptilian reovirus, hijacks the actin cytoskeleton by binding to the adaptor Grb2 through a phosphorylation-dependent motif in its cytoplasmic tail to drive cell-cell fusion. In the second part, I examined a related FAST protein that arose from a distinct gain-of-function evolutionary event more than 500 million years ago might and found that it also usurped the cellular actin machinery to drive cell-cell fusion. Findings from both studies suggest that these short cell-cell fusogens use force generated from localized actin assembly to overcome the intermembrane gap and bring the two membranes in close contact for fusion. This work establishes how short, non-canonical fusogens can use an alternative, non-conformational change-based mechanism to drive fusion of crowded plasma membranes, providing a mechanistic model for other short, physiological cell-cell fusogens like myomixer and myomaker

A systematic review and meta-analysis of pharmacotherapy and psychotherapy for anxiety disorders and obsessive-compulsive disorder in children and adolescents

Background Anxiety and obsessive-compulsive disorder (OCD) are two significant and potentially disabling mental health problems in youth. Prompt and optimal management of these disorders reduce disease burden on the individual, family and society. Pharmacotherapy, psychotherapy and combined treatment are well-established modalities for treating these disorders, yet evidence for their comparative efficacies is limited and warrants further study. Objectives To assess the relative efficacies of pharmacotherapy, psychotherapy and combination treatment in the management of anxiety and OCD in children and adolescents. Search strategy Electronic searches of Medline(1946-), EMBASE(1947-) and PsycINFO(1967-) were performed in May 2015. Various electronic registries were searched for ongoing and unpublished studies. Reference lists of included studies were also perused. Selection criteria All randomised controlled trials (RCTs) of pharmacotherapy versus psychotherapy, and combination therapy versus pharmacotherapy/psychotherapy for anxiety and OCD in youth. Data collection and analysis A solo researcher undertook a systematic review and meta-analysis to address the research objectives. Systematic review and meta-analysis encompass rigorous examination of all relevant evidence using standardised criteria in literature search, study selection, bias assessment, quantitative data extraction and outcome appraisal. In this review, primary outcomes included remission and treatment response. Post-treatment severity, quality of life, treatment tolerability and major adverse effects were secondary outcomes. Main results Five studies on anxiety (822 participants) and six studies on OCD (364 participants) were included in the meta-analysis. Comparison between pharmacotherapy and psychotherapy for anxiety revealed inconclusive results, although summary effects tended to favour psychotherapy. Remission and treatment response insignificantly favoured psychotherapy over pharmacotherapy. Anxiety severity was insignificantly lower in patients receiving psychotherapy than pharmacotherapy [Standardised Mean Difference (SMD) 0.25, 95% Confidence Interval (CI) -0.73 to 1.23]. Findings were more consistently showing the superiority of combination therapy over psychotherapy for anxiety. Remission and treatment response were both significantly greater for combination than psychotherapy, while post-treatment severity was insignificantly lower (SMD -0.46, 95% CI -1.02 to 0.11). Findings in OCD mostly echoed with those of anxiety. Remission almost reached statistical significance favouring combination over psychotherapy [Odds Ratio (OR) 1.88, 95% CI 0.79 to 4.43]. Treatment response insignificantly favoured combination over pharmacotherapy (OR 3.36, 95% CI 0.86 to 13.20). Post-treatment severity was significantly lower for combination compared with pharmacotherapy (SMD -0.52, 95% CI -0.82 to -0.22), but not with psychotherapy (SMD -0.13, 95% CI -0.53 to 0.27); while those who received psychotherapy had insignificantly lower severity compared with medications alone (SMD 0.36, 95% CI -0.01 to 0.73). Author’s conclusions This review offers cautious support for psychotherapy over pharmacotherapy in both paediatric anxiety and OCD. Evidence favouring combination therapy over monotherapy is stronger, especially in patients with higher baseline severity and co-morbidities, where earlier commencement of combination therapy might have been more desirable. Further research is needed to assess different therapeutic subclasses, discern predictors and moderators to response, and evaluate long-term outcomes.published_or_final_versionPublic HealthMasterMaster of Public Healt

Design and synthesis of luminescent branched multinuclear platinum(II)alkynyl complexes and the study of their two-photon absorptionproperties

published_or_final_versionChemistryDoctoralDoctor of Philosoph

Help-seeking and antibiotic prescribing for acute cough in a Chinese primary care population: a prospective multicentre observational study

Acute cough is a common reason to prescribe antibiotics in primary care. This study aimed to explore help-seeking and antibiotic prescribing for acute cough in Chinese primary care population. This is a prospective multicentre observational study that included adults presenting with acute cough. Clinicians recorded patients' presenting symptoms, examination findings and medication prescription. Patients completed symptom diaries for up to 28 days by charting their symptom severity and recovery. Adjusted binary logistic regression models identified factors independently associated with antibiotic prescription. Primary care clinicians (n=19) recruited 455 patients. A total of 321 patients (70.5%) returned their completed symptom diaries. Concern about illness severity (41.6%) and obtaining a prescription for symptomatic medications (45.9%), rather than obtaining a prescription for antibiotics, were the main reasons for consulting. Antibiotics were prescribed for 6.8% (n=31) of patients, of which amoxicillin was the most common antimicrobial prescribed (61.3%), as it was associated with clinicians' perception of benefit from antibiotic treatment (odds ratio (OR): 25.9, 95% confidence interval (CI): 6.7-101.1), patients' expectation for antibiotics (OR: 5.1, 95% CI: 1.7-11.6), anticipation (OR: 5.1, 95% CI: 1.6-15.0) and request for antibiotics (OR 15.7, 95% CI: 5.0-49.4), as well as the severity of respiratory symptoms (cough, sputum, short of breath and wheeze OR: 2.7-3.7, all P<0.05). There was a significant difference in antibiotic prescription rates between private primary care clinicians and public primary care clinicians (17.4 vs 1.6%, P=0.00). Symptomatic medication was prescribed in 98.0% of patients. Mean recovery was 9 days for cough and 10 days for all symptoms, which was not significantly associated with antibiotic treatment. Although overall antibiotic-prescribing rates were low, there was a higher rate of antibiotic prescribing among private primary care clinicians, which warrants further exploration and scope for education and interventio

Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications

Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515 μm and stiffness ranging from 190 to 1600 Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Dinuclear Platinum(II) Terpyridyl Complexes with a <i>para</i>-Diselenobenzoquinone Organometallic Linker: Synthesis, Structures, and Room-Temperature Phosphorescence

We report the synthesis of a unique class of luminescent heterotrinuclear complexes of the general formulas [Pt­(terpy)­{Cp*Ir-<i>p</i>-(η⁴-C₆H₄Se₂)}­Pt­(terpy)]­[X]₄ (X = OTf, <b>3a</b>; PF₆, <b>3b</b>; BF₄, <b>3c</b>; ClO₄, <b>3d</b>; BPh₄, <b>3e</b>). In these coordination assemblies two Pt­(terpy) moieties are held by a stable η⁴-diseleno-<i>p</i>-benzoquinone complex [Cp*Ir-<i>p</i>-(η⁴-C₆H₄Se₂)]. The molecular structures of solvates of <b>3a</b> and <b>3b</b> were ascertained by single-crystal X-ray diffraction study and confirmed the formation of the target molecules. The solid-state packing of two of these complexes confirms the presence of π–π and Pt···Pt interactions among individual units providing a 1D supramolecular chain for <b>3a</b>, while a dimer species is obtained for <b>3b</b>, illustrating the effect of the counterion on directing the crystal packing of the individual molecules. All compounds show phosphorescence in the red region (685–705 nm) in fluid solution and in the solid state at room temperature, unlike the analogous compound Pt­(terpy)­{Cp*Ir-<i>p</i>-(η⁴-C₆H₄S₂)}­Pt­(terpy)]­[CF₃SO₃]₄ obtained with a dithiobenzoquinone organometallic linker, which is only luminescent at low temperature