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

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

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

Nucleus accumbens dopamine tracks aversive stimulus duration and prediction but not value or prediction error

There is active debate on the role of dopamine in processing aversive stimuli, where inferred roles range from no involvement at all, to signaling an aversive prediction error (APE). Here, we systematically investigate dopamine release in the nucleus accumbens core (NAC), which is closely linked to reward prediction errors, in rats exposed to white noise (WN, a versatile, underutilized, aversive stimulus) and its predictive cues. Both induced a negative dopamine ramp, followed by slow signal recovery upon stimulus cessation. In contrast to reward conditioning, this dopamine signal was unaffected by WN value, context valence, or probabilistic contingencies, and the WN dopamine response shifted only partially toward its predictive cue. However, unpredicted WN provoked slower post-stimulus signal recovery than predicted WN. Despite differing signal qualities, dopamine responses to simultaneous presentation of rewarding and aversive stimuli were additive. Together, our findings demonstrate that instead of an APE, NAC dopamine primarily tracks prediction and duration of aversive events

Potential of Mobile Health Technology to Reduce Health Disparities in Underserved Communities.

INTRODUCTION: Mobile health (mHealth) has the potential to change how patients make healthcare decisions. We sought to determine the readiness to use mHealth technology in underserved communities. METHODS: We conducted a cross-sectional survey of patients presenting with low-acuity complaints to an urban emergency department (ED) with an underserved population. Patients over the age of two who presented with low-acuity complaints were included. We conducted structured interview with each patient or parent (for minors) about willingness to use mHealth tools for guidance. Analysis included descriptive statistics and univariate analysis based on age and gender. RESULTS: Of 560 patients included in the survey, 80% were adults, 64% female, and 90% Black. The mean age was 28 ± 9 years for adults and 9 ± 5 years for children. One-third of patients reported no primary care physician, and 55% reported no access to a nurse or clinician for medical advice. Adults were less likely to have access to phone consultation than parents of children (odds ratio [OR] 0.49, 95% confidence interval [CI], 0.32 - 0.74), as were males compared to females (OR 0.52, 95% CI, 0.37-0.74). Most patients (96%) reported cellular internet access. Two-thirds of patients reported using online references. When asked how they would behave if an mHealth tool advised them that their current health problem was low risk, 69% of patients responded that they would seek care in an outpatient clinic instead of the ED (30%), stay home and not seek urgent medical care (28%), or use telehealth (11%). CONCLUSION: In this urban community we found a large capacity and willingness to use mHealth technology in medical triage

Potential of Mobile Health Technology to Reduce Health Disparities in Underserved Communities

Introduction: Mobile health (mHealth) has the potential to change how patients make healthcare decisions. We sought to determine the readiness to use mHealth technology in underserved communities.Methods: We conducted a cross-sectional survey of patients presenting with low-acuity complaints to an urban emergency department (ED) with an underserved population. Patients over the age of two who presented with low-acuity complaints were included. We conducted  structured interview with each patient or parent (for minors) about willingness to use mHealth tools for guidance. Analysis included descriptive statistics and univariate analysis based on age and gender.Results: Of 560 patients included in the survey, 80% were adults, 64% female, and 90% Black. The mean age was 28 ± 9 years for adults and 9 ± 5 years for children. One-third of patients reported no primary care physician, and 55% reported no access to a nurse or clinician for medical advice. Adults were less likely to have access to phone consultation than parents of children (odds ratio [OR] 0.49, 95% confidence interval [CI], 0.32 – 0.74), as were males compared to females (OR 0.52, 95% CI, 0.37– 0.74). Most patients (96%) reported cellular internet access. Two-thirds of patients reported using online references. When asked how they would behave if an mHealth tool advised them that their current health problem was low risk, 69% of patients responded that they would seek care in an outpatient clinic instead of the ED (30%), stay home and not seek urgent medical care (28%), or use telehealth (11%).Conclusion: In this urban community we found a large capacity and willingness to use mHealth technology in medical triage

Potential of Mobile Health Technology to Reduce Health Disparities in Underserved Communities

INTRODUCTION: Mobile health (mHealth) has the potential to change how patients make healthcare decisions. We sought to determine the readiness to use mHealth technology in underserved communities. METHODS: We conducted a cross-sectional survey of patients presenting with low-acuity complaints to an urban emergency department (ED) with an underserved population. Patients over the age of two who presented with low-acuity complaints were included. We conducted structured interview with each patient or parent (for minors) about willingness to use mHealth tools for guidance. Analysis included descriptive statistics and univariate analysis based on age and gender. RESULTS: Of 560 patients included in the survey, 80% were adults, 64% female, and 90% Black. The mean age was 28 ± 9 years for adults and 9 ± 5 years for children. One-third of patients reported no primary care physician, and 55% reported no access to a nurse or clinician for medical advice. Adults were less likely to have access to phone consultation than parents of children (odds ratio [OR] 0.49, 95% confidence interval [CI], 0.32 - 0.74), as were males compared to females (OR 0.52, 95% CI, 0.37-0.74). Most patients (96%) reported cellular internet access. Two-thirds of patients reported using online references. When asked how they would behave if an mHealth tool advised them that their current health problem was low risk, 69% of patients responded that they would seek care in an outpatient clinic instead of the ED (30%), stay home and not seek urgent medical care (28%), or use telehealth (11%). CONCLUSION: In this urban community we found a large capacity and willingness to use mHealth technology in medical triage