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Here, we report on the emergence and spread of multidrug-resistant NDM-1-producing P. aeruginosa isolates from patients hospitalized in the Attica region, Greece, in 2022 to provide data on their resistome, their virulome, the genetic environment of bla NDM-1 , and their molecular epidemiology. A total of 17 carbapenem-resistant P. aeruginosa isolates identified as NDM-producers by immunochromatography at the hospital level were sent to the Central Public Health Laboratory, in the frame of the laboratory surveillance of carbapenem-resistant pathogens, for further characterization. The initial screening for genetic AMR determinants was carried out by PCR and the MDR Direct Flow Chip assay. Typing was performed by MLST and DLST, the latter in a subset of isolates. Further analysis was performed by whole-genome sequencing (WGS) of six isolates from both hospitals to analyze their entire genomes and elucidate their genetic relatedness. All isolates were allocated to international high-risk clones, sixteen to ST773 and one to ST308. Five ST773 and the sole ST308 isolate were found to harbor the bla NDM-1 gene, along with various other ARGs integrated into their chromosomes, as well as with a wide variety of virulence genes. The bla NDM-1 gene was located in the integrative and conjugative elements ICE 6600 -like and ICE Tn4371 6385 in ST773 and ST308 isolates, respectively. Single-nucleotide polymorphism analysis of the five ST773 isolates indicated their clonal spread in both hospitals. These results suggested that two different molecular events contributed to the emergence of NDM-1-producing P. aeruginosa isolates in Athenian hospitals, highlighting the need for ongoing surveillance.

From 2019 (pre-COVID-19) to 2022 (COVID-19 years), three tertiary Greek hospitals monitored MDRO bloodstream infection (BSI) and hospital acquisition relying on laboratory data. Surveillance covered carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA), vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA), in intensive care units (ICUs) and non-ICUs. Non-ICUs experienced significant increases in CRE, CRAB and VRE during the pandemic. In ICUs, CRE increased in 2021, CRAB in 2020 and 2021, and VRE in 2021 and 2022. KPC predominated among CRE. MDRO BSI and hospital acquisition incidence rates increased, driven by CRE and CRAB., (© 2024. The Author(s).)

Background: Ketamine is an anesthetic and analgesic known for its psychotomimetic properties, such as dissociation and altered perception. Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) are characterized by unwanted memories, intrusive thoughts, and dissociative flashbacks following an acute traumatic event. It is unknown how analgesic ketamine affects the symptomatology of ASD when administered to patients in the posttraumatic period., Objective and Methods: In this article, we present the case of a 26-year-old man who sustained gunshot wounds and developed worsened ASD after receiving analgesic ketamine. We also present a review of the current literature on peritraumatic ketamine and its subsequent effect on ASD and PTSD., Results: In 2 out of 3 articles examining ketamine and ASD, ketamine was associated with worsened symptomatology of ASD. There were 6 articles examining ketamine and PTSD. In 1 of 6 articles, ketamine was associated with increased incidence and/or severity of PTSD, and in 2 of 6, it was associated with decreased incidence and/or severity of PTSD. There was no relationship between ketamine and subsequent PTSD in 3 of 6 articles., Conclusion: We conclude that ketamine's psychotomimetic properties may exacerbate the dissociative and perceptual symptoms of ASD, but its long-term effects on PTSD are still unclear. In patients with preexisting ASD, the potential risks and benefits of using analgesic ketamine must be weighed carefully., (Copyright © 2023 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To produce a qualitative description of the impact of moral injury on medical providers during the COVID-19 pandemic., Methods: A convergent mixed-methods study design was used to explore experiences of health care workers during the first 12 months of the COVID-19 pandemic. Participants completed the Moral Injury Symptom Scale-HP (MISS-HP) and a 60-minute interview, in which they described their work experiences from March 2020 through January 2021. The study was conducted between May 2021 and August 2021., Results: Eight physicians and 6 nurses were interviewed. Most participants (71%) worked in the emergency department, while 29% worked in the medical intensive care unit (MICU). MISS-HP scores were 49 on average and ranged from 29 to 73. Among the demographic groups, MICU participants scored the highest (56) and men scored the lowest (40). There were no significant differences in scores between any demographic group. The analysis of interview data showed how omissions and commissions in one's professional duties created internal conflicts, which were inextricably linked to a deeper sense of feelings of guilt and blame around experiences of betraying or being betrayed and an inability to uphold one's moral values., Conclusions: The pandemic upended a previously reliable and imperceptible experience of a background of safety, in which the provision of both material resources and human presence was expected without question. Future directions generated from this study might examine the role of dependency on leadership structures and relationships with self and others that create the conditions for moral injury., Prim Care Companion CNS Disord 2024;26(1):23m03651 ., Author affiliations are listed at the end of this article., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Background: Omicron-1 COVID-19 is less invasive in the general population than previous viral variants. However, clinical course and outcome of hospitalised patients with SARS-CoV-2 pneumonia during the shift of the predominance from Delta to Omicron variants are not fully explored., Methods: During January 2022 consecutively hospitalised patients with SARS-CoV-2 pneumonia were analysed. SARS-CoV-2 variants were identified by a 2-step pre-screening protocol and randomly confirmed by whole genome sequencing analysis. Clinical, laboratory and treatment data split by type of variant were analysed along with logistic regression of factors associated to mortality., Results: 150 patients [mean age (SD) 67.2(15.8) years, male 54%] were analysed. Compared to Delta ( n  = 46), Omicron-1 patients ( n  = 104) were older [mean age (SD): 69.5(15.4) vs 61.9(15.8) years, p  = 0.007], with more comorbidities (89.4% vs 65.2%, p  = 0.001), less obesity (BMI >30Kg/m 2 in 24% vs 43.5%, p  = 0.034) but higher vaccination rates for COVID-19 (52.9% vs 8.7%, p  < 0.001). Severe pneumonia (48.7%), pulmonary embolism (4.7%), need for invasive mechanical ventilation (8%), administration of dexamethasone (76%) and 60-day mortality (22.6%) did not significantly differ. Severe SARS-CoV-2 pneumonia independently predicted mortality [OR 8.297 (CI95% 2.080-33.095), p  = 0.003]. Remdesivir administration ( n  = 135) was protective from death both in unadjusted and adjusted models [OR 0.157 (CI95% 0.026-0.945), p  = 0.043., Conclusions: In a COVID-19 department the severity of pneumonia that did not differ between Omicron-1 and Delta variants predicted mortality whilst remdesivir remained protective in all analyses. Death rates did not differ between SARS-CoV-2 variants. Vigilance and consistency with prevention and treatment guidelines for COVID-19 is mandatory regardless of the predominant SARS-CoV-2 variant.

Objective: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals report higher rates of exposure to traumatic events and posttraumatic stress disorder (PTSD) compared with heterosexual and cisgender individuals. No treatment outcomes research has focused on PTSD in the LGBTQ population. Trauma-focused psychodynamic psychotherapy (TFPP) is a brief, manualized, attachment- and affect-focused psychotherapy for PTSD. TFPP explicitly incorporates broad identity-related and societal factors into its conceptualization of trauma and its consequences, which may be especially helpful for LGBTQ patients with minority stress who seek affirmative care., Methods: Fourteen LGBTQ patients with PTSD, assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), received 24 sessions of twice-weekly (12 weeks) TFPP via teletherapy provided by supervised early-career therapists inexperienced in the modality. Sessions were videotaped to monitor therapists' treatment adherence. Patients were assessed at baseline, week 5, termination (week 12), and 3 months posttreatment for PTSD symptoms (assessed with the CAPS-5) and secondary outcomes., Results: TFPP was well tolerated by patients, with 12 (86%) completing the intervention. CAPS-5-measured PTSD symptoms, including dissociation, significantly improved during treatment (mean decrease=-21.8, d=-1.98), and treatment gains were maintained at follow-up. Most patients experienced PTSD clinical response (N=10, 71%) or diagnostic remission (N=7, 50%). Patients generally experienced significant, concomitant improvements in complex PTSD symptoms, general anxiety, depression, and psychosocial functioning. Adherence to the intervention among therapists was high, with 93% of rated sessions meeting adherence standards., Conclusions: TFPP shows promise in the treatment of PTSD among sexual and gender minority patients seeking LGBTQ-affirmative PTSD care., Competing Interests: Dr. Milrod is a coauthor of Trauma-Focused Psychodynamic Psychotherapy: A Step-by-Step Treatment Manual and receives royalties from Oxford University Press. The other authors report no financial relationships with commercial interests.

Obesity, defined as a body mass index (BMI) ≥ 30, is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated BMI is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear because of inconsistent findings from epidemiological studies and a lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelia of women carrying a BRCA mutation is positively correlated with BMI and with biomarkers of metabolic dysfunction. In addition, RNA sequencing showed obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which affected neighboring breast epithelial cells. In breast tissue explants cultured from women carrying a BRCA mutation, we found that blockade of estrogen biosynthesis or estrogen receptor activity decreased DNA damage. Additional obesity-associated factors, including leptin and insulin, increased DNA damage in human BRCA heterozygous epithelial cells, and inhibiting the signaling of these factors with a leptin-neutralizing antibody or PI3K inhibitor, respectively, decreased DNA damage. Furthermore, we show that increased adiposity was associated with mammary gland DNA damage and increased penetrance of mammary tumors in Brca1 +/- mice. Overall, our results provide mechanistic evidence in support of a link between elevated BMI and breast cancer development in BRCA mutation carriers. This suggests that maintaining a lower body weight or pharmacologically targeting estrogen or metabolic dysfunction may reduce the risk of breast cancer in this population.

Graphene and its derivatives are attractive materials envisaged to enable a wealth of novel applications in many fields including energy, electronics, composite materials or health. A comprehensive understanding of the potential adverse effects of graphene-related materials (GRM) in humans is a prerequisite to the safe use of these promising materials. Here, we exploited gene expression profiling to identify transcriptional responses and toxicity pathways induced by graphene oxide (GO) and graphene nanoplatelets (GNP) in human macrophages. Primary human monocyte-derived macrophages (MDM) and a human macrophage cell line, i.e. differentiated THP-1 cells, were exposed to 5 or 20 μg/mL GO and GNP for 6 and 24 h to capture early and more persistent acute responses at realistic or slightly overdose concentrations. GO and GNP induced time-, dose- and macrophage type-specific differential expression of a substantial number of genes with some overlap between the two GRM types (up to 384 genes (9.6%) or 447 genes (20.4%) in THP-1 or MDM, respectively) but also a high number of genes exclusively deregulated from each material type. Furthermore, GRM responses on gene expression were highly different from those induced by inflammogenic material crystalline quartz (maximum of 64 (2.3%) or 318 (11.3%) common genes for MDM treated with 20 μg/mL GO and GNP, respectively). Further bioinformatics analysis revealed that GNP predominantly activated genes controlling inflammatory and apoptotic pathways whereas GO showed only limited inflammatory responses. Interestingly, both GRM affected the expression of genes related to antigen processing and presentation and in addition, GO activated pathways of neutrophil activation, degranulation and immunity in MDM. Overall, this study provides an extensive resource of potential toxicity mechanisms for future safety assessment of GRM in more advanced model systems to verify if the observed changes in gene expression in human macrophages could lead to long-term consequences on human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

To support a safe application of graphene-related materials (GRMs) it is necessary to understand the potential negative impacts they could have on human health, in particular on the lung - one of the most sensitive exposure routes. Machine learning (ML) approaches can help analyse the results of multiple toxicity studies to understand the structure-activity relationship and the effect of experimental conditions, thus supporting predictive nanotoxicology. In this work we collected in vitro cytotoxicity data obtained from studies using lung cells; we then fitted multiple regression models to predict this endpoint based on the material properties and experimental conditions. Moreover, the data set was used to calculate the Benchmark Dose Lower Confidence Interval (BMDL), a dose descriptor widely used in risk assessment. Regression and classification models were applied for the prediction of the BMDL value and BMDL range. The analyses show that both cytotoxicity and the BMDL range can be predicted well (Q 2  = 0.77 and accuracy = 0.71, respectively). Both physico-chemical characteristics such as the lateral size, number of layers, and functionalization, and experimental conditions such as the assay and media used were important predicting features, confirming the need for thorough characterization and reporting of these parameters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Bloodstream infections (BSI) caused by highly resistant pathogens in non-ICU COVID-19 departments pose important challenges. Methods: We performed a comparative analysis of incidence and microbial epidemiology of BSI in COVID-19 vs. non-COVID-19, non-ICU departments between 1 September 2020-31 October 2021. Risk factors for BSI and its impact on outcome were evaluated by a case-control study which included COVID-19 patients with/without BSI. Results: Forty out of 1985 COVID-19 patients developed BSI. The mean monthly incidence/100 admissions was 2.015 in COVID-19 and 1.742 in non-COVID-19 departments. Enterococcus and Candida isolates predominated in the COVID-19 group (p < 0.001 and p = 0.018, respectively). All Acinetobacter baumannii isolates were carbapenem-resistant (CR). In the COVID-19 group, 33.3% of Klebsiella pneumoniae was CR, 50% of Escherichia coli produced ESBL and 19% of Enterococcus spp. were VRE vs. 74.5%, 26.1% and 8.8% in the non-COVID-19 group, respectively. BSI was associated with prior hospitalization (p = 0.003), >2 comorbidities (p < 0.001), central venous catheter (p = 0.015), severe SARS-CoV-2 pneumonia and lack of COVID-19 vaccination (p < 0.001). In the multivariate regression model also including age and multiple comorbidities, only BSI was significantly associated with adverse in-hospital outcome [OR (CI95%): 21.47 (3.86−119.21), p < 0.001]. Conclusions: BSI complicates unvaccinated patients with severe SARS-CoV-2 pneumonia and increases mortality. BSI pathogens and resistance profiles differ among COVID-19/non-COVID-19 departments, suggesting various routes of pathogen acquisition.

Background: Scabies is a global health concern disproportionately affecting vulnerable populations such as refugees and asylum seekers. Greece is a main point of entry in Europe for refugees, but epidemiological data on scabies in this population are scarce. We aimed to describe the epidemiology of scabies, including trends over the study period., Methodology/principal Findings: Data were collected from June, 2016 to July, 2020, using the surveillance system of the Greek National Public Health Organization. Daily reports on scabies and other infectious diseases were submitted by staff at health centers for refugees/asylum seekers. Observed proportional morbidity for scabies was calculated using consultations for scabies as a proportion of total consultations. There were a total of 13118 scabies cases over the study period. Scabies was the third most frequently observed infectious disease in refugees/asylum seekers population after respiratory infections and gastroenteritis without blood in the stool. The scabies monthly observed proportional morbidity varied between 0.3% (August 2017) to 5.7% (January 2020). Several outbreaks were documented during the study period. The number of cases increased from October 2019 until the end of the study period, with a peak of 1663 cases in January 2020, related to an outbreak at one center. Spearman correlation test between the number of reported scabies cases and time confirmed an increasing trend (ρ = 0.67)., Conclusions/significance: Scabies is one of the most frequently reported infectious diseases by health care workers in refugee/asylum seekers centers in Greece. Observed proportional morbidity for scabies increased over time and there were several outbreaks. The current surveillance system with daily reports of the new cases effectively detects new cases in an early stage. Public health interventions, including mass drug administration, should be considered to reduce the burden of scabies in refugee/migrant populations., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Numerous studies show increased prevalence of MDR bacteria amongst asylum seekers, but data on the molecular profiles of such strains are limited. We aimed to evaluate the molecular profiles of ESBL-producing Escherichia coli (ESBL-E. coli) strains isolated from asylum seekers and investigate their phylogenetic relatedness., Methods: WGS data of ESBL-E. coli isolates from asylum seekers, retrieved from 1 January to 31 December 2016, were analysed to assess MLST STs, fim types, phylogroups and resistance genes. Fifty-two ESBL-E. coli isolates from the Dutch-German border region were used for genome comparison purposes as a control group., Results: Among 112 ESBL-E. coli isolates from asylum seekers, originating mostly from Syria (n = 40) and Iraq (n = 15), the majority belonged to ST131 (21.4%) and ST10 (17.0%). The predominant gene for β-lactam resistance was blaCTX-M-15 (67.9%), followed by the often co-detected blaTEM-1B (39.3%). No mcr or carbapenemase genes were detected. The majority of the strains belonged to phylogroups B2 (38.4%) and A (32.1%), carrying fimH27 (25%) and fimH30 (19.6%). A core genome MLST minimum spanning tree did not reveal clusters containing strains from the asylum seekers and the control group. Five clusters were formed within the asylum seeker group, by strains isolated from people originating from different countries., Conclusions: The most frequently isolated clones in this study were isolated on a regular basis within the Dutch population before the increase in the asylum seeker population. No mcr- or carbapenemase-producing clones were detected among the asylum seeker population. Minor clustering was observed amongst the asylum seeker strains., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: Digitally delivering healthcare services is very attractive for tuberculosis (TB) management as this disease has a complex diagnosis and lengthy management and involves multiple medical and nonmedical specialists. Especially in low- and middle-income countries, eHealth could potentially offer cost-effective solutions to bridge financial, social, time, and distance challenges., Objective: The goal of the research is to understand what would make eHealth globally applicable and gain insight into different TB situations, opportunities, and challenges., Methods: We performed focus group interviews with TB experts and patients from 6 different countries on 4 different continents. The focus group interviews followed the theory of planned behavior framework to offer structured recommendations for a versatile eHealth solution. The focus group interviews were preceded by a general demographic and technology use questionnaire. Questionnaire results were analyzed using basic statistics in Excel (Microsoft Corporation). Focus group interview data were analyzed using ATLAS.ti 8 (ATLAS.ti Scientific Software Development GmbH) by assigning codes to quotations and grouping codes into the 5 domains within the framework., Results: A total of 29 patients and 32 medical staff members were included in our study. All medical staff had used the internet, whereas 31% (9/61) of patients had never been online. The codes with the most quotations were information in relation to eHealth (144 quotations) and communication (67 quotations). The consensus among all participants from all countries is that there are important communication and information gaps that could be bridged by an eHealth app. Participants from different countries also highlighted different challenges, such as a majority of asylum-seeker patients or lack of infrastructure that could be addressed with an eHealth app., Conclusions: Within the 6 countries interviewed, there is high enthusiasm toward eHealth in TB. A potential app could first target information and communication gaps in TB, with additional modules aimed at setting-specific challenges., (©Ioana Margineanu, Christina Louka, Maria Vincenti-Gonzalez, Antonia Morita Iswari Saktiawati, Johannes Schierle, Kabiru Mohammed Abass, Onno Akkerman, Jan-Willem Alffenaar, Adelita V Ranchor, Ymkje Stienstra. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 02.11.2020.)

Introduction: Europe has been dealing with an increasing number of refugees during the past 5 years. The timing of screening and vaccination of refugees is debated by many professionals, however refugees' perspectives on health issues are infrequently taken into account. In this study, we aimed to investigate asylum seekers' perspectives on infectious diseases screening and vaccination policies., Materials and Methods: Interviews were conducted in Greece and the Netherlands. Asylum seekers and recently arrived refugees were approached and informed with the help of interpreters; consent forms were acquired. The survey focused on demographic data, vaccination status, screening policies and prevention of infectious diseases., Results: A total of 61 (43 male, 70.5%) refugees (30 Afghanis, 16 Syrian, 7 Erithrean) were interviewed. Mean age was 35.2 years (SD 13.5) and 50% had received primary or secondary education, while 24.6% received none. Median time after arrival in Greece and the Netherlands was 24 months (IQR 8.5-28). 44 out of 61 (72.1) participants were willing to be vaccinated after arrival in Europe, 26 preferred vaccination and screening to be performed at the point of entry. The need for screening and vaccination was perceived higher amongst participants in Greece (100% vs 43.3%) due to living conditions leading to increased risk of outbreaks., Conclusion: Participants were willing to communicate their perspectives and concerns. Screening and vaccination programs could be more effective when implemented shortly after arrival and by involving asylum seekers and refugees when developing screening and vaccination interventions., Competing Interests: The authors have declared that no competing interests exist.

Background: Several studies have shown a high prevalence of multi-drug resistant organisms (MDRO) amongst asylum seekers when compared to the general population. The aim of this study is to assess the duration of MDRO carriage in this population., Methods: Data were retrospectively collected between January 1st 2014 through December 31st 2016. Study material included screening samples for MDRO carriage and clinical samples from asylum seekers in need of medical care. The study focused on methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Enterobacteriaceae (MDRE). The rates of MRSA and MDRE detected were calculated every four weeks after arrival in the Netherlands., Results: Samples from 2091 asylum seekers were included. 1270 (60.7%) were female, median age was 26 years (IQR 20-34) and median number of days in the Netherlands until first sample was 67 (IQR 4-235). In the patients' first obtained samples, the rate of MRSA varied between 4.5 and 13.0% per time interval after arrival. The rate of MDRE fluctuated between 7.4% and 25.0%. No particular decline in positivity rates in first obtained samples was observed after arrival in the Netherlands. In the group of asylum seekers who arrived more than one year ago, MRSA was isolated in a percentage of 5.1% ( n  = 273, median months after arrival 34.1 (IQR 16.5-63.1)) and MDRE in 9.4% ( n  = 276, median months after arrival 35.4 (IQR 17-65))., Conclusion: To our knowledge, this is the first study demonstrating that carriage rate of MDRO in asylum seekers remains high even after prolonged stay in the Netherlands. Longitudinal data on MDRO carriage after arrival in countries with a low MDRO prevalence are needed to determine optimal screening strategies, infection control measures and empirical antibiotic therapy., Competing Interests: This study was evaluated by the ethics committee and was waived in accordance with Dutch legislation owing to its retrospective nature (University Medical Center Groningen, METc number 2016/516). No written informed consent was obtained from patients for the use of retrospective data but patient information was anonymised and de-identified prior to analysis.NAJWR consults for IDbyDNA.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

A Syrian asylum seeker with multidrug-resistant tuberculosis (TB) developed a bronchopleural fistula after pneumonectomy. Although screening tests were negative on admission, carbapenemase-producing Enterobacteriaceae were cultured after a few months of TB treatment. Prevalence of multidrug-resistant organisms is reported to be increased in asylum seekers compared with the general Dutch population. Arduous conditions during transit and interrupted health care delivery in our patient led to multiple-resistant microorganisms that complicated treatment.