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

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Effect of three modalities on emergence agitation among post-traumatic stress disorder patients undergoing laparoscopy: a randomized controlled study

Abstract Background and aim Emergence agitation (EA) after general anesthesia is common in patients with post-traumatic stress disorder (PTSD). Due to the recent worldwide events such as the Covid-19 pandemic and wars, PTSD is not rare. Accordingly, a reliable, cost-effective anesthetic protocol to lower the incidence of EA is crucial. Therefore, we aimed to compare three different interventions for avoiding EA in PTSD patients undergoing gynecological laparoscopic surgery. Participants were divided into four groups: 1: performing pre-operative relaxation techniques (deep breathing exercise and progressive muscle relaxation [PMR]); 2: administrating intra-operative Ketamine; 3: applying both previously mentioned strategies and 4 as controls. Methods This study was carried out on 144 adult women scheduled for gynecological laparoscopy, randomly allocated into four groups: three intervention groups and a control group (36 each). Women aged 18-45 years old, with a diagnosis of PTSD were included in the study. Patients with a positive history of major neurological, cardiovascular, metabolic, respiratory, or renal disease were excluded. Any patient who reported the use of psychiatric drugs were also excluded from the study. Data was analyzed using IBM SPSS Statistics software version 26. Kolmogorov- Smirnov was used to verify the normality of the distribution of variables. Odds ratio was calculated to clarify the strength and direction of the association between intervention groups and control. Data was deemed significant at a p-value ≤0.05. Results Heart rate (HR) and Mean Arterial Blood Pressure (MABP) intra-operative and post-operative till 24 hours were significantly lower in groups 1, 2, and 3 compared to group 4 (p<0.001). There was a significant statistical difference in the intraoperative HR percentage decrease. MABP percentage decrease post-operative was higher in all the intervention groups with no statistically significant difference, except for group 1 compared to group 4, which was statistically significant (12.28 ± 11.77 and 6.10 ± 7.24, p=0.025). Visual Analogue Scale measurements were significantly less in the intervention groups 1, 2, and 3 compared to group 4. On Riker sedation–agitation scores, group 1 was 85 times more likely to be non-agitated (85 (15.938 – 453.307), p<0.001), group 2 was 175 times more likely to be non-agitated (175 (19.932–1536.448), p<0.001) and group 3 was protected against agitation. Conclusion Pre-operative relaxation techniques (breathing exercises and PMR) significantly lowered HR, MABP, VAS score, and EA than controls. These effects were not significantly different from intra-operative ketamine injection or the combination of both (relaxation techniques and ketamine). We recommend routine pre-operative screening for PTSD and the application of relaxation techniques (breathing exercises and PMR) in the pre-operative preparation protocol of PTSD-positive cases as well as routine practical application of preoperative relaxation techniques. Further studies on using pre-operative relaxation techniques in general could be cost-effective

Is neuregulin-1 (NRG-1) a potential blood biomarker linking depression to obesity? A case-control study

Abstract Background and aim No definite biomarker linking depression and obesity has been found yet. Our study aimed to investigate neuregulin-1 (NRG-1) as a potential blood biomarker for this association. Methods A case–control study was conducted on 108 obese subjects assigned for laparoscopic sleeve gastrectomy and 100 non-obese controls. Depression was assessed pre- and post-operatively. Serum NRG-1 was measured. Results Pre-operatively depression was significantly higher among obese compared to non-obese patients. After the operation, 1.9% of the severely depressed subjects reported no depression, while 5.6% became moderately depressed; about 6% of the moderately depressed and 16% of the mildly depressed became not depressed. Serum NRG-1 level was significantly lower among obese and severely depressed compared to the controls. It was negatively correlated to the level of depression pre- and post-operative (r = -0.764 and -0.467 respectively). The sensitivity of serum NRG1 as a predictor for depression pre- and post-operative was 92.45% and 52.94% respectively. Specificity was 69.09% and 79.73% respectively at cut-off values of ≤ 3.5 and ≤ 2.5 ng/ml. Conclusion NRG-1 is a possible biomarker for the diagnosis of depression pre-bariatric surgery and the prediction of its prognosis post-operatively

Adult skin fibroblast state change in murine wound healing

Abstract Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play major roles in skin wound healing such as in wound contraction and release of growth factors which are of importance in angiogenesis and tissue remodeling. Abnormal fibroblast phenotypes have been identified in patients with chronic wounds. In this work, we analyzed scRNA-seq datasets of normal and wounded skin from mice at day 4 post-wound to investigate fibroblast heterogeneity during the proliferative phase of wound healing. Compositional analysis revealed a specific subset of fibroblast (cluster 3) that primarily increased in wounded skin (14%) compared to normal skin (3.9%). This subset was characterized by a gene signature marked by the plasma membrane proteins Sfrp2 + Sfrp4 + Sfrp1 + and the transcription factors Ebf1 + Prrx1 + Maged1 + . Differential gene expression and enrichment analysis identified epithelial to mesenchymal transition (EMT) and angiogenesis to be upregulated in the emerging subset of fibroblasts of the wounded skin. Using two other datasets for murine wounded skin confirmed the increase in cluster 3-like fibroblasts at days 2, 7 and 14 post-wounding with a peak at day 7. By performing a similarity check between the differential gene expression profile between wounded and normal skin for this emerging fibroblast subset with drug signature from the ConnectivityMap database, we identified drugs capable of mimicking the observed gene expression change in fibroblasts during wound healing. TTNPB, verteprofin and nicotinic acid were identified as candidate drugs capable of inducing fibroblast gene expression profile necessary for wound healing. On the other hand, methocarbamol, ifosfamide and penbutolol were recognized to antagonize the identified fibroblast differential expression profile during wound healing which might cause delay in wound healing. Taken together, analysis of murine transcriptomic skin wound healing datasets suggested a subset of fibroblasts capable of inducing EMT and further inferred drugs that might be tested as potential candidates to induce wound closure

Knowledge and attitudes of medical students toward death: a cross-sectional comparative study between an Arab and a Western University

Abstract Background Cultural factors influence attitudes toward death, and gender disparities are evident. Prior studies show that medical students have limited knowledge about death and are uncomfortable with it. Moreover, there is limited research that has examined factors that influence medical students’ knowledge and attitudes toward death. Objectives The objectives of the study were to compare cultural and gender differences in relation to knowledge and attitudes toward loss and grief and to screen for complicated grief among medical students at the Arabian Gulf University and the University of Toronto. Methods A cross-sectional study was disseminated to medical students at both universities in 2022. The variables in the survey included four parts: demographic characteristics of the participants, religious observance, history of encountering loss of a loved one, grief following loss, attitude toward death, and learning about how to deal with grief and death during medical school. The brief grief questionnaire and the death attitude profile-revised scales were used. Results The study sample consisted of 168 medical students, with 74.1% being female. Complicated grief scores were higher among Arabian Gulf University students (3.87 ± 2.39) than among University of Toronto students (2.00 ± 1.93) and were higher for participants with a higher degree of religious observance in both schools (p < 0.05). Death avoidance (p = 0.003), approach acceptance (p < 0.001), and escape acceptance (p = 0.038) domains were significantly higher among Arabian Gulf University students than among University of Toronto students. Almost three-quarters of University of Toronto students reported not being taught about grief, compared to 54% of Arabian Gulf University students. Conclusions Arabian Gulf University medical students scored higher on complicated grief, most likely due to cultural and religious factors. Females at both institutions as well as those who indicated a higher level of religious observance reported higher scores of complicated grief. The study highlights how cultural and religious beliefs influence medical students’ attitudes toward death and bereavement. It provides valuable insight into the knowledge and attitudes of medical students toward loss

Urinary monocyte chemoattractant protein-1 as a biomarker of lupus nephritis activity in children

Systemic lupus erythematosus (SLE) is a life-long, life-limiting and multi-systemic autoimmune disease. Glomerulonephritis is one of the most serious manifestations of SLE. Younger children have an increased incidence, severity and morbidity of lupus nephritis (LN) compared with adult-onset disease. Monocyte chemoattractant protein-1 (MCP-1) enhances leukocyte adhesiveness and endothelial permeability in the kidneys of murine and human LN models. Our study aimed to assess the role of urinary MCP-1 in the early diagnosis of LN activity. Sixty children, of whom 45 children aged from six to 12 years old and of both sexes (15 SLE patients without nephritis, 15 active LN and 15 inactive LN) fulfilling the American College of Rheumatology Classification Criteria for SLE were studied in comparison with 15 healthy subjects. We investigated the serum and urinary MCP-1 in all groups using the enzyme-linked immunosorbent assay test. Urinary MCP-1 was significantly higher in active LN in comparison with inactive LN and controls, and also significantly higher in inactive LN in comparison with SLE without nephritis and controls. There was also a significant difference between SLE without nephritis and controls. Serum MCP-1 was significantly higher in the group with active LN in comparison with the inactive group and SLE without nephritis and controls, but there was no significant difference between SLE and controls. The urinary MCP-1 level correlated well with SLE disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary MCP-1 correlates positively with proteinuria, blood urea nitrogen level and creatinine and negatively with hemoglobin and creatinine clearance. We concluded that measurement of MCP-1 in urine may be useful for monitoring the severity of renal involvement in SLE. We recommend measuring urinary MCP-1 in pediatric SLE for the early diagnosis of LN and for the evaluation of the severity of renal involvement

Engineering nanomedicines for immunogenic eradication of cancer cells: Recent trends and synergistic approaches

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment (TME) leading to failure of immune response. Numerous therapeutic strategies including chemotherapy, radiotherapy, photodynamic, photothermal, magnetic, chemodynamic, sonodynamic and oncolytic therapy, have been developed to induce immunogenic cell death (ICD) of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response. However, many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response. Here, we outline the current state of using nanomedicines for boosting ICD of cancer cells. Moreover, synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints, phagocytosis, macrophage polarization, tumor hypoxia, autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed. We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses. Endoplasmic reticulum localized ICD, focused ultrasound hyperthermia, cell membrane camouflaged nanomedicines, amplified reactive oxygen species (ROS) generation, metallo-immunotherapy, ion modulators and engineered bacteria are among the most innovative approaches. Various challenges, merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy

Additional file 1 of Knowledge and attitudes of medical students toward death: a cross-sectional comparative study between an Arab and a Western University

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