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Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.
To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.
Multicenter prospective surveillance study.
Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.
From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.
We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.
Acute respiratory tract infections (ARIs) are commonly diagnosed and major drivers of antibiotic prescribing. Clinician-focused interventions can reduce unnecessary antibiotic prescribing for ARIs. We elicited clinician feedback to design sustainable interventions to improve ARI management by understanding the mental framework of clinicians surrounding antibiotic prescribing within Veterans’ Health Administration clinics.
We conducted one-on-one interviews with clinicians (n = 20) from clinics targeted for intervention at 5 facilities. The theory of planned behavior guided interview questions. Interviews were audio recorded and transcribed for qualitative analysis. An iterative coding approach identified 6 themes.
Emergent themes: (1) barriers to appropriate prescribing are multifactorial and include challenges of behavior change; (2) antibiotic prescribing decisions are perceived as autonomous yet, diagnostic uncertainty and perceptions of patient demand can make prescribing decisions difficult; (3) clinicians perceive variation in peer prescribing practices and influences; (4) clinician-focused interventions are valuable if delivered with sensitivity; (5) communication strategies for educating patients are preferred to a shared decisions process; and (6) team standardization of practice and communication are key to facilitate appropriate prescribing. Clinicians perceived audit-and-feedback with peer comparison, academic detailing, and enhanced patient communication strategies as viable approaches to improving appropriate prescribing.
Implementation strategies that enable clinicians to overcome diagnostic uncertainty, perceived patient demand, and improve patient education are desired. Implementation strategies were welcomed, and some were more readily accepted (eg, audit feedback) than others (eg, shared decision making). Implementation strategies should address clinicians’ perceptions of antibiotic prescribing practices and should enhance their patient communication skills.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
Haplosporidian protist parasites are a major concern for aquatic animal health, as they have been responsible for some of the most significant marine epizootics on record. Despite their impact on food security, aquaculture and ecosystem health, characterizing haplosporidian diversity, distributions and host range remains challenging. In this study, water filtering bivalve species, cockles Cerastoderma edule, mussels Mytilus spp. and Pacific oysters Crassostrea gigas, were screened using molecular genetic assays using deoxyribonucleic acid (DNA) markers for the Haplosporidia small subunit ribosomal deoxyribonucleic acid region. Two Haplosporidia species, both belonging to the Minchinia clade, were detected in C. edule and in the blue mussel Mytilus edulis in a new geographic range for the first time. No haplosporidians were detected in the C. gigas, Mediterranean mussel Mytilus galloprovincialis or Mytilus hybrids. These findings indicate that host selection and partitioning are occurring amongst cohabiting bivalve species. The detection of these Haplosporidia spp. raises questions as to whether they were always present, were introduced unintentionally via aquaculture and or shipping or were naturally introduced via water currents. These findings support an increase in the known diversity of a significant parasite group and highlight that parasite species may be present in marine environments but remain undetected, even in well-studied host species.
The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Despite knowing for many decades that depressive psychopathology is common in first-episode schizophrenia spectrum disorders (FES), there is limited knowledge regarding the extent and nature of such psychopathology (degree of comorbidity, caseness, severity) and its demographic, clinical, functional and treatment correlates. This study aimed to determine the pooled prevalence of depressive disorder and caseness, and the pooled mean severity of depressive symptoms, as well as the demographic, illness, functional and treatment correlates of depressive psychopathology in FES.
This systematic review, meta-analysis and meta-regression was prospectively registered (CRD42018084856) and conducted in accordance with PRISMA and MOOSE guidelines.
Forty studies comprising 4041 participants were included. The pooled prevalence of depressive disorder and caseness was 26.0% (seven samples, N = 855, 95% CI 22.1–30.3) and 43.9% (11 samples, N = 1312, 95% CI 30.3–58.4), respectively. The pooled mean percentage of maximum depressive symptom severity was 25.1 (38 samples, N = 3180, 95% CI 21.49–28.68). Correlates of depressive psychopathology were also found.
At least one-quarter of individuals with FES will experience, and therefore require treatment for, a full-threshold depressive disorder. Nearly half will experience levels of depressive symptoms that are severe enough to warrant diagnostic investigation and therefore clinical intervention – regardless of whether they actually fulfil diagnostic criteria for a depressive disorder. Depressive psychopathology is prominent in FES, manifesting not only as superimposed comorbidity, but also as an inextricable symptom domain.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
The study examined (a) whether alcohol use subgroups could be identified among African Americans assessed from adolescence through early adulthood, and (b) whether subgroup membership was associated with the interaction between internalizing symptoms and antisocial behavior polygenic risk scores (PRSs) and environmental characteristics (i.e., parental monitoring, community disadvantage). Participants (N = 436) were initially recruited for an elementary school-based prevention trial in a Mid-Atlantic city. Youths reported on the frequency of their past year alcohol use from ages 14–26. DNA was obtained from participants at age 21. Internalizing symptoms and antisocial behavior PRSs were created based on a genome-wide association study (GWAS) conducted by Benke et al. (2014) and Tielbeek et al. (2017), respectively. Parental monitoring and community disadvantage were assessed at age 12. Four classes of past year alcohol use were identified: (a) early-onset, increasing; (b) late-onset, moderate use; (c) low steady; and (d) early-onset, decreasing. In high community disadvantaged settings, participants with a higher internalizing symptoms PRS were more likely to be in the early-onset, decreasing class than the low steady class. When exposed to elevated community disadvantage, participants with a higher antisocial behavior PRS were more likely to be in the early-onset, increasing class than the early-onset, decreasing and late-onset, moderate use classes.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated.
We used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods.
Bacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%–14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change.
Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
This study examined the effectiveness of a formal postdoctoral education program designed to teach skills in clinical and translational science, using scholar publication rates as a measure of research productivity.
Participants included 70 clinical fellows who were admitted to a master’s or certificate training program in clinical and translational science from 1999 to 2015 and 70 matched control peers. The primary outcomes were the number of publications 5 years post-fellowship matriculation and time to publishing 15 peer-reviewed manuscripts post-matriculation.
Clinical and translational science program graduates published significantly more peer-reviewed manuscripts at 5 years post-matriculation (median 8 vs 5, p=0.041) and had a faster time to publication of 15 peer-reviewed manuscripts (matched hazard ratio = 2.91, p=0.002). Additionally, program graduates’ publications yielded a significantly higher average H-index (11 vs. 7, p=0.013).
These findings support the effectiveness of formal training programs in clinical and translational science by increasing academic productivity.
Objectives: The self-reference effect (SRE), enhanced memory for self-related information, has been studied in healthy young and older adults but has had little investigation in people with age-related memory disorders, such as amnestic mild cognitive impairment (aMCI). Self-referential encoding may help to improve episodic memory in aMCI. Additionally, self-referential processing has been shown to benefit recollection, the vivid re-experiencing of past events, a phenomenon that has been termed the self-reference recollection effect (SRRE; Conway & Dewhurst, 1995). Furthermore, it remains unclear whether the valence of stimuli influences the appearance of the SRE and SRRE. Methods: The current study investigated the SRE and SRRE for trait adjective words in 20 individuals with aMCI and 30 healthy older adult controls. Ninety trait adjective words were allocated to self-reference, semantic, or structural encoding conditions; memory was later tested using a recognition test. Results: While healthy older adults showed a SRE, individuals with aMCI did not benefit from self-referential encoding over and above that of semantic encoding (an effect of “deep encoding”). A similar pattern was apparent for the SRRE; healthy controls showed enhanced recollection for words encoded in the self-reference condition, while the aMCI group did not show specific benefit to recollection for self-referenced over semantically encoded items. No effects of valence were found. Conclusions: These results indicate that while memory for trait adjective words can be improved in aMCI with deep encoding strategies (whether self-reference or semantic), self-referencing does not provide an additional benefit. (JINS, 2018, 24, 821–832)
Chondrichthyan teeth from a new locality in the Scottish Borders supply additional evidence of Early Carboniferous chondrichthyans in the UK. The interbedded dolostones and siltstones of the Ballagan Formation exposed along Whitrope Burn are interpreted as representing a restricted lagoonal environment that received significant amounts of land-derived sediment. This site is palynologically dated to the latest Tournaisian–early Viséan. The diverse dental fauna documented here is dominated by large crushing holocephalan toothplates, with very few, small non-crushing chondrichthyan teeth. Two new taxa are named and described. Our samples are consistent with worldwide evidence that chondrichthyan crushing faunas are common following the Hangenberg extinction event. The lagoonal habitat represented by Whitrope Burn may represent a temporary refugium that was host to a near-relict fauna dominated by large holocephalan chondrichthyans with crushing dentitions. Many of these had already become scarce in other localities by the Viséan and become extinct later in the Carboniferous. This fauna provides evidence of early endemism or niche separation within European chondrichthyan faunas at this time. This evidence points to a complex picture in which the diversity of durophagous chondrichthyans is controlled by narrow spatial shifts in niche availability over time.
Foodborne non-typhoidal salmonellosis causes approximately 1 million illnesses annually in the USA. In April 2015, we investigated a multistate outbreak of 65 Salmonella Paratyphi B variant L(+) tartrate(+) infections associated with frozen raw tuna imported from Indonesia, which was consumed raw in sushi. Forty-six (92%) of 50 case-patients interviewed ate sushi during the week before illness onset, and 44 (98%) of 45 who specified ate sushi containing raw tuna. Two outbreak strains were isolated from the samples of frozen raw tuna. Traceback identified a single importer as a common source of tuna consumed by case-patients; this importer issued three voluntary recalls of tuna sourced from one Indonesian processor. Four Salmonella Weltevreden infections were also linked to this outbreak. Whole-genome sequencing was useful in establishing a link between Salmonella isolated from ill people and tuna. This outbreak highlights the continuing foodborne illness risk associated with raw seafood consumption, the importance of processing seafood in a manner that minimises contamination with pathogenic microorganisms and the continuing need to ensure imported foods are safe to eat. People at higher risk for foodborne illness should not consume undercooked animal products, such as raw seafood.
Stress is an event that threatens homoeostasis and thus causes physiological and behavioural responses to reinstate equilibrium. Excessive and/or chronic stress can be psychologically and physiologically detrimental. Examinations can represent a significant source of stress for students. The hypothalamic–pituitary–adrenal axis (HPA) is the core endocrine stress system. Investigations into the HPA response to examinations have yielded inconsistent results. The aim of this study is to further explore the relationship between examination stress, HPA axis activity, mood, sleep and exercise in students undergoing a naturalistic examination period stressor.
In total, 16 medical students participated. Students completed self-reported stress, anxiety, mood, sleep and physical activity questionnaires, and provided saliva samples during an examination-free period and an examination period 1 month later. The cortisol awakening response, representative of HPA activity, was determined from saliva samples by enzyme-linked immunosorbent assay.
Anxiety levels increased (p=0.04) and mood decreased (p=0.05) during the examination period. There was concomitant decease in physical activity levels (p=0.02). There was no significant increase in HPA activity during the examination period (p=0.29). Sleep quality did not significantly worsen (p=0.55) during the examination period.
Examination periods are associated with increased anxiety levels, lower mood and decreased physical activity. Future studies incorporating examination results and cognitive function may help to identify potential protective interventional strategies, while optimising performance.