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Critical Reviews in Microbiology Apr 2024This brief review explores the intricate interplay between bacteriophages and plasmids in the context of antibiotic resistance gene (ARG) dissemination. Originating from... (Review)
Review
This brief review explores the intricate interplay between bacteriophages and plasmids in the context of antibiotic resistance gene (ARG) dissemination. Originating from studies in the late 1950s, the review traces the evolution of knowledge regarding extrachromosomal factors facilitating horizontal gene transfer and adaptation in bacteria. Analyzing the gene repertoires of plasmids and bacteriophages, the study highlights their contributions to bacterial evolution and adaptation. While plasmids encode essential and accessory genes influencing host characteristics, bacteriophages carry auxiliary metabolic genes (AMGs) that augment host metabolism. The debate on phages carrying ARGs is explored through a critical evaluation of various studies, revealing contrasting findings from researchers. Additionally, the review addresses the interplay between prophages and plasmids, underlining their similarities and divergences. Based on the available literature evidence, we conclude that plasmids generally encode ARGs while bacteriophages typically do not contain ARGs. But extra-chromosomaly present prophages with plasmid characteristics can encode and disseminate ARGs.
PubMed: 38651513
DOI: 10.1080/1040841X.2024.2339262 -
Human Vaccines & Immunotherapeutics Dec 2024Dengvaxia is the first dengue vaccine recommended in the United States (U.S.). It is recommended for children aged 9-16 y with laboratory-confirmed previous dengue...
Dengvaxia is the first dengue vaccine recommended in the United States (U.S.). It is recommended for children aged 9-16 y with laboratory-confirmed previous dengue infection and living in areas where dengue is endemic. We conducted focus groups with parents and in-depth interviews with key informants (i.e. practicing pediatricians, physicians from immunization clinics, university researchers, and school officials) in Puerto Rico (P.R.) to examine acceptability, barriers, and motivators to vaccinate with Dengvaxia. We also carried out informal meetings and semi-structured interviews to evaluate key messages and educational materials with pediatricians and parents. Barriers to vaccination included lack of information, distrust toward new vaccines, vaccine side effects and risks, and high cost of/lack of insurance coverage for laboratory tests and vaccines. Motivators included clear information about the vaccine, a desire to prevent future dengue infections, the experience of a previous dengue infection or awareness of dengue fatality, vaccine and laboratory tests covered by health insurance, availability of rapid test results and vaccine appointments. School officials and parents agreed parents would pay a deductible of $5-20 for Dengvaxia. For vaccine information dissemination, parents preferred an educational campaign through traditional media and social media, and one-on-one counseling of parents by healthcare providers. Education about this vaccine to healthcare providers will help them answer parents' questions. Dengvaxia acceptability in P.R. will increase by addressing motivators and barriers to vaccination and by disseminating vaccine information in plain language through spokespersons from health institutions in P.R.
Topics: Child; Humans; Dengue; Dengue Vaccines; Parents; Puerto Rico; United States; Vaccination; Vaccines; Adolescent
PubMed: 38599678
DOI: 10.1080/21645515.2024.2323264 -
Nature Communications Aug 2023Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish...
Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We analysed two decades of bla evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the bla gene across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. We showed how an initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability of bla to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, bla persisted through diversification of genetic settings that resulted from transfer of bla plasmids between bacterial hosts and of the integron carrying bla between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.
Topics: Integrons; beta-Lactamases; Bacterial Proteins; Plasmids; Serratia marcescens; Carbapenems; Genomics; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37553339
DOI: 10.1038/s41467-023-39915-2 -
Journal of Hospital Medicine Dec 2023Although the transfer of patients between acute care hospitals (interhospital transfer, IHT) is common, health information exchange (HIE) during IHT remains inadequate,...
INTRODUCTION
Although the transfer of patients between acute care hospitals (interhospital transfer, IHT) is common, health information exchange (HIE) during IHT remains inadequate, with fragmented communication and unreliable access to clinical information. This study aims to design, implement, and rigorously evaluate the implementation of a HIE platform to improve data access during IHT.
METHODS AND ANALYSIS
Study subjects include patients aged >18 transferred to the medical, cardiology, oncology, or intensive care unit (ICU) services at an 800-bed quaternary care hospital; and healthcare workers involved in their care. The first aim of this study is to optimize clinician workflow, data visualization, and interoperability through user-centered design sessions for HIE platform development. The second aim is to evaluate the impact of the intervention on clinician-reported medical errors among 500 pre- and 500 postintervention IHT patients using interrupted time series methodology, adjusting for confounding variables and temporal trends. The third aim is to evaluate intervention fidelity, use and perceived usability of the platform, and barriers and facilitators of implementation from interprofessional stakeholder input, using mixed-methods evaluation. The fourth aim is to consolidate key findings to create a toolkit for spread and sustainability.
ETHICS AND DISSEMINATION
We will track patient safety endpoints and clinician workflow burdens and ensure the protection of patient data throughout the study. We will disseminate our findings via the creation of a toolkit for spread and sustainability, partnering with our funder (AHRQ) for dissemination, and communicating our results via abstracts and publications.
Topics: Humans; Patient Transfer; Interrupted Time Series Analysis; Communication; Health Information Exchange
PubMed: 37846028
DOI: 10.1002/jhm.13221 -
Cancer Letters Jun 2024Tumor cells disseminate in various distant organs at early stages of cancer progression. These disseminated tumor cells (DTCs) can stay dormant/quiescent without causing... (Review)
Review
Tumor cells disseminate in various distant organs at early stages of cancer progression. These disseminated tumor cells (DTCs) can stay dormant/quiescent without causing patient symptoms for years or decades. These dormant tumor cells survive despite curative treatments by entering growth arrest, escaping immune surveillance, and/or developing drug resistance. However, these dormant cells can reactivate to proliferate, causing metastatic progression and/or relapse, posing a threat to patients' survival. It's unclear how cancer cells maintain dormancy and what triggers their reactivation. What are better approaches to prevent metastatic progression and relapse through harnessing cancer dormancy? To answer these remaining questions, we reviewed the studies of tumor dormancy and reactivation in various types of cancer using different model systems, including the brief history of dormancy studies, the intrinsic characteristics of dormant cells, and the external cues at the cellular and molecular levels. Furthermore, we discussed future directions in the field and the strategies for manipulating dormancy to prevent metastatic progression and recurrence.
Topics: Humans; Neoplasms; Animals; Neoplasm Metastasis; Tumor Microenvironment; Disease Progression; Signal Transduction; Neoplasm Recurrence, Local; Cell Proliferation
PubMed: 38649107
DOI: 10.1016/j.canlet.2024.216899 -
The Journal of Mental Health Policy and... Dec 2023In the US, much of the research into new intervention and delivery models for behavioral health care is funded by research institutes and foundations, typically through... (Review)
Review
BACKGROUND
In the US, much of the research into new intervention and delivery models for behavioral health care is funded by research institutes and foundations, typically through grants to develop and test the new interventions. The original grant funding is typically time-limited. This implies that eventually communities, clinicians, and others must find resources to replace the grant funding -otherwise the innovation will not be adopted. Diffusion is challenged by the continued dominance in the US of fee-for-service reimbursement, especially for behavioral health care.
AIMS
To understand the financial challenges to disseminating innovative behavioral health delivery models posed by fee-for-service reimbursement, and to explore alternative payment models that promise to accelerate adoption by better addressing need for flexibility and sustainability.
METHODS
We review US experience with three specific novel delivery models that emerged in recent years. The models are: collaborative care model for depression (CoCM), outpatient based opioid treatment (OBOT), and the certified community behavioral health clinic (CCBHC) model. These examples were selected as illustrating some common themes and some different issues affecting diffusion. For each model, we discuss its core components; evidence on its effectiveness and cost-effectiveness; how its dissemination was funded; how providers are paid; and what has been the uptake so far.
RESULTS
The collaborative care model has existed for longest, but has been slow to disseminate, due in part to a lack of billing codes for key components until recently. The OBOT model faced that problem, and also (until recently) a regulatory requirement requiring physicians to obtain federal waivers in order to prescribe buprenorphine. Similarly, the CCBHC model includes previously nonbillable services, but it appears to be diffusing more successfully than some other innovations, due in part to the approach taken by funders.
DISCUSSION
A common challenge for all three models has been their inclusion of services that were not (initially) reimbursable in a fee-for-service system. However, even establishing new procedure codes may not be enough to give providers the flexibility needed to implement these models, unless payers also implement alternative payment models.
IMPLICATIONS FOR HEALTH CARE PROVISION AND USE
For providers who receive time-limited grant funding to implement these novel delivery models, one key lesson is the need to start early on planning how services will be sustained after the grant ends.
IMPLICATIONS FOR HEALTH POLICY
For research funders (e.g., federal agencies), it is clearly important to speed up the process of obtaining coverage for each novel delivery model, including the development of new billable service codes, and to plan for this as early as possible. Funders also need to collaborate with providers early in the grant period on sustainability planning for the post-grant environment. For payers, a key lesson is the need to fold novel models into stable existing funding streams such as Medicaid and commercial insurance coverage, rather than leaving them at the mercy of revolving time-limited grants, and to provide pathways for contracting for innovations under new payment models.
IMPLICATIONS FOR FURTHER RESEARCH
For researchers, a key recommendation would be to pay greater attention to the payment environment when designing new delivery models and interventions.
Topics: United States; Humans; Fee-for-Service Plans; Medicaid; Ambulatory Care Facilities
PubMed: 38113385
DOI: No ID Found -
Journal of Bone Oncology Feb 2024Epigenetic alterations, including DNA methylation and post translational modifications to histones, drive tumorigenesis and metastatic progression. In the context of...
Epigenetic alterations, including DNA methylation and post translational modifications to histones, drive tumorigenesis and metastatic progression. In the context of bone metastasis, epigenetic modifications in tumor cells can modulate dissemination of cancer cells to the bone, tumor progression in the bone marrow, and may be associated with patient survival rates. Bone disseminated tumor cells may enter a dormant state or stimulate osteolysis through the "vicious cycle" of bone metastasis where bone disseminated tumor cells disrupt the bone microenvironment, which fuels tumor progression. Epigenetic alterations may either exacerbate or abrogate the vicious cycle by regulating tumor suppressors and oncogenes, which alter proliferation of bone-metastatic cancer cells. This review focuses on the specific epigenetic alterations that regulate bone metastasis, including DNA methylation, histone methylation, and histone acetylation. Here, we summarize key findings from researchers identifying epigenetic changes that drive tumor progression in the bone, along with pre-clinical and clinical studies investigating the utility of targeting aberrant epigenetic alterations to treat bone metastatic cancer.
PubMed: 38304486
DOI: 10.1016/j.jbo.2024.100524 -
BMJ Open Dec 2023Four years after the devastating Ebola outbreak, governments in West Africa were quick to implement non-pharmaceutical interventions (NPIs) in response to the rapid...
INTRODUCTION
Four years after the devastating Ebola outbreak, governments in West Africa were quick to implement non-pharmaceutical interventions (NPIs) in response to the rapid spread of SARS-CoV-2. The NPIs implemented included physical distancing, closure of schools and businesses, restrictions on public gatherings and mandating the use of face masks among others. In the absence of widely available vaccinations, NPIs were the only known means to try to slow the spread of COVID-19. While numerous studies have assessed the effectiveness of these NPIs in high-income countries, less is known about the processes that lead to the adoption of policies and the factors that influence their implementation and adherence in low-income and middle-income countries. The objective of this scoping review is to understand the extent and type of evidence in relation to the policy formulation, decision-making and implementation stages of NPIs in West Africa.
METHODS AND ANALYSIS
A scoping review will be undertaken following the guidance developed by Arskey and O'Malley, the Joanna Briggs Institute (JBI) methodology for scoping reviews and the PRISMA guidelines for Scoping Reviews. Both peer-reviewed and grey literature will be searched using Web of Science, Embase, Scopus, APA PsycInfo, WHO Institutional Repository for Information Sharing, JSTOR and Google Advanced Search, and by searching the websites of the WHO, and the West African Health Organisation. Screening will be conducted by two reviewers based on inclusion and exclusion criteria, and data will be extracted, coded and narratively synthesised.
ETHICS AND DISSEMINATION
We started this scoping review in May 2023, and anticipate finishing by April 2024. Ethics approval is not required since we are not collecting primary data. This protocol was registered at Open Science Framework (https://osf.io/gvek2/). We plan to disseminate this research through publications, conference presentations and upcoming West African policy dialogues on pandemic preparedness and response.
Topics: Humans; COVID-19; SARS-CoV-2; Pandemics; Academies and Institutes; Africa, Western; Research Design; Systematic Reviews as Topic; Review Literature as Topic
PubMed: 38072480
DOI: 10.1136/bmjopen-2023-079810 -
Cancer Letters Nov 2023
PubMed: 37839626
DOI: 10.1016/j.canlet.2023.216446 -
Expert Review of Anti-infective Therapy 2024is a major agent of healthcare-associated infections and a cause of some community-acquired infections, including severe bacteremic infections associated with... (Review)
Review
INTRODUCTION
is a major agent of healthcare-associated infections and a cause of some community-acquired infections, including severe bacteremic infections associated with metastatic abscesses in liver and other organs. Clinical relevance is compounded by its outstanding propensity to evolve antibiotic resistance. In particular, the emergence and dissemination of carbapenem resistance in has posed a major challenge due to the few residual treatment options, which have only recently been expanded by some new agents. The epidemiological success of carbapenem-resistant (CR-Kp) is mainly linked with clonal lineages that produce carbapenem-hydrolyzing enzymes (carbapenemases) encoded by plasmids.
AREAS COVERED
Here, we provide an updated overview on the mechanisms underlying the emergence and dissemination of CR-Kp, focusing on the role that plasmids have played in this phenomenon and in the co-evolution of resistance and virulence in .
EXPERT OPINION
CR-Kp have disseminated on a global scale, representing one of the most important contemporary public health issues. These strains are almost invariably associated with complex multi-drug resistance (MDR) phenotypes, which can also include recently approved antibiotics. The heterogeneity of the molecular bases responsible for these phenotypes poses significant hurdles for therapeutic and diagnostic purposes.
Topics: Humans; Klebsiella pneumoniae; Plasmids; beta-Lactamases; Anti-Bacterial Agents; Carbapenems; Carbapenem-Resistant Enterobacteriaceae; Klebsiella Infections
PubMed: 38236906
DOI: 10.1080/14787210.2024.2305854