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

Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis

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

Residual fibroglandular breast tissue after mastectomy is associated with an increased risk of a local recurrence or a new primary breast cancer"

Abstract Background Residual fibroglandular breast tissue (RFGT) following a mastectomy has been claimed to be associated with the occurrence of an in-breast local recurrence (IBLR) or new primary tumor (NP). Yet, scientific evidence proving this assumption is lacking. The primary aim of the study was to verify whether RFGT following a mastectomy is a risk factor for an IBLR or NP. Methods This retrospective analysis included all patients that underwent a mastectomy and were followed up at the Department of Obstetrics and Gynecology of the Medical University of Vienna between 01.01.2015 and 26.02.2020. RFGT volume (assessed on magnetic resonance imaging) was correlated with the prevalence of an IBLR and a NP. Results A total of 105 patients (126 breasts) following a therapeutic mastectomy were included. After a mean follow-up of 46.0 months an IBLR had occurred in 17 breasts and a NP in 1 breast. A significant difference in RFGT volume was observed between the disease-free cohort and the subgroup with an IBLR or NP (p = .017). A RFGT volume of ≥ 1153 mm3 increased the risk by the factor 3.57 [95%CI 1.27; 10.03]. Conclusions RFGT volume is associated with an increased risk for an IBLR or NP

Das Konzept der Ökosystemleistungen – eine Chance für Integratives Gewässermanagement

The planning and implementation of management measures to improve the status of freshwaters and the natural flood retention potential of rivers and floodplains (Water Framework Directive, Natura2000, Floods directive) are often challenging due to the various users and diverse legal frameworks involved. The decision-making process could benefit from the assessment and evaluation of ecosystem services (ES) though the complementary knowledge about the effects of management options. ES can be understood as the direct and indirect contributions of ecosystems to human well-being. Research is needed on how the ES concept could be applied in riverine landscapes. Hence, the RESI (River Ecosystem Service Index) project developed a concept and a method for the assessment and evaluation of ES in rivers and floodplains in inter- and transdisciplinary cooperation across both theory and practice. Based on literature and feedback from experts in water management, the project aimed at defining key conceptual terms (such as offered ES, used ES, and human input) and an ES classification that is adapted to the application on riverine landscapes. For the resulting list of provisioning, regulating and cultural ES, methods for the spatially explicit assessment and evaluation were developed, which are presented here by the example of the regulating ES flood regulation and the cultural ES unspecific interaction with the riverine landscape. The results and the reflection of the practical relevance of ES show that the ES concept is applicable for river and floodplain management, and at the same time, stakeholders are interested in using it. The application of the RESI in planning scenarios created a crosssectoral basis for communication and knowledge exchange among all stakeholders, which facilitates the development of integrative management options and thus enables solving conflicts of interest.Die Planung und die Umsetzung von Bewirtschaftungsmaßnahmen zur Verbesserung des Gewässerzustands und des natürlichen Hochwasserrückhalts an Flüssen und Auen gemäß EG-Wasserrahmenrichtlinie (EU-WRRL), Flora-Fauna-Rahmenrichtlinie (FFH-RL) und Hochwasser-Risiko-Management-Richtlinie (HWRM-RL) sind häufig schwierig. Gründe dafür sind verschiedene Nutzungsansprüche und diverse rechtliche Rahmensetzungen. Die entsprechenden Entscheidungsprozesse können von einer Erfassung und Bewertung von Ökosystemleistungen (ÖSL) profitieren, indem ergänzende Informationen zu den Auswirkungen der Bewirtschaftungsoptionen bereitgestellt werden. ÖSL werden hier verstanden als direkte und indirekte Beiträge von Ökosystemen zum menschlichen Wohlbefinden. Allerdings wurde das ÖSL-Konzeptes bisher kaum in Flussauenlandschaften angewendet. Im Projekt RESI (River Ecosystem Service Index) wurde daher in Zusammenarbeit zwischen Wissenschaft und Praxis ein Konzept und eine Methodik zur Erfassung und Bewertung von ÖSL in Flüssen und Auen entwickelt. Ziel dabei war es, vor dem Hintergrund der aktuellen Literatur und des Feedbacks von Experten im Gewässermanagement anwendbare konzeptionelle Kernbegriffe wie bereitgestellte ÖSL, genutzte ÖSL und menschliche Beiträge zur Nutzbarmachung zu definieren und eine auf Flusslandschaften angepasste Klassifikation von ÖSL zu erstellen. Für die resultierende Liste der versorgenden, regulierenden und kulturellen ÖSL wurden geeignete Methoden zur Erfassung und Bewertung entwickelt, die hier am Beispiel der regulativen ÖSL „Hochwasserregulation“ und kulturellen ÖSL „unspezifische Interaktion mit der Flusslandschaft“ dargestellt werden. Die Ergebnisse sowie die Reflektion der Praxisrelevanz von ÖSL zeigen, dass das Konzept für die Bewirtschaftung von Flüssen und Auen anwendbar ist und in der Praxis auf großes Interesse stößt. Die Anwendung des RESI für Planungsszenarien schafft eine sektorenübergreifende Kommunikations- und Informationsbasis, in die alle Akteure einbezogen werden können, was die Ableitung integrativer Bewirtschaftungsoptionen erleichtert und somit die Lösung von Interessenskonflikten unterstützt

PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.

BACKGROUND:Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients. METHODS:Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months. RESULTS:Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS. CONCLUSION:In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS

PTEN expression and its association with histopathological parameters and clinical outcome.

<p>PTEN expression and its association with histopathological parameters and clinical outcome.</p

Patients and tumour characteristics, including type and line of trastuzumab-based therapy for these patients in the metastatic setting.

<p>Patients and tumour characteristics, including type and line of trastuzumab-based therapy for these patients in the metastatic setting.</p

Tumor characteristics by immunohistochemistry of 115 breast cancers.

<p>Tumor characteristics by immunohistochemistry of 115 breast cancers.</p