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Identify essential components of a curriculum on antimicrobial stewardship (AS) for pediatric residents.
Design:
Survey.
Setting:
Academic tertiary care children’s hospital.
Participants:
Pediatric residents and infectious diseases (ID)/AS content experts (CE), including pediatric ID faculty, fellows, nurse practitioners, and pharmacists.
Methods:
Residents were surveyed to assess prior AS experiences and usefulness of education in different AS domains (e.g., antimicrobial resistance [AMR]). CE was surveyed to identify content to include in an AS curriculum. A specific topic (e.g., resistance in Staphylococcus aureus) achieved consensus if ≥80% of CE identified the topic as “very” or “extremely” important.
Results:
Thirty-three of 110 pediatric residents responded to the resident survey (response rate 30%). Spectrum of activity (97%), empiric therapy (94%), and duration of therapy (94%) were the domains identified by the most residents as “very” or “extremely” useful. All CE responded to the CE survey (n=26). Thirty-nine of 105 topics (37%) met the consensus threshold. The domains with most topics achieving consensus were empiric therapy (11/13 topics, 85%) and duration of therapy (5/8 topics, 63%). Only one topic was identified within the domains of antibiotic allergies, diagnostics, and AMR, reflecting 18%, 14%, and 6% of the potential topics within each domain, respectively.
Conclusions:
A pediatric AS curriculum focused on empiric therapy and duration of therapy is likely to meet the needs of both learners and CEs.
The regulation of electron heat transport in high-$\beta$, weakly collisional, magnetized plasma is investigated. A temperature gradient oriented along a mean magnetic field can induce a kinetic heat-flux-driven whistler instability (HWI), which back-reacts on the transport by scattering electrons and impeding their flow. Previous analytical and numerical studies have shown that the heat flux for the saturated HWI scales as $\beta _e^{-1}$. These numerical studies, however, had limited scale separation and consequently large fluctuation amplitudes, which calls into question their relevance at astrophysical scales. To this end, we perform a series of particle-in-cell simulations of the HWI across a range of $\beta _e$ and temperature-gradient length scales under two different physical set-ups. The saturated heat flux in all of our simulations follows the expected $\beta _e^{-1}$ scaling, supporting the robustness of the result. We also use our simulation results to develop and implement several methods to construct an effective collision operator for whistler turbulence. The results point to an issue with the standard quasi-linear explanation of HWI saturation, which is analogous to the well-known $90^{\circ }$ scattering problem in the cosmic-ray community. Despite this limitation, the methods developed here can serve as a blueprint for future work seeking to characterize the effective collisionality caused by kinetic instabilities.
Approximately five million people live with diabetes in the UK. The cost of this is approximately 10 percent of the National Health Service (NHS) budget. Wales has the highest prevalence of diabetes of any country in the UK. Educating people on how to best manage their condition can minimize associated complications. Digital platforms can aid self-management and improve risk factors.
Methods
This rapid review aimed to address the following research question: What is the clinical and cost effectiveness of digital platforms for personalized diabetes management to inform decision-making and guidance in the NHS? Digital platforms for this rapid review can be driven using artificial intelligence, machine learning, or through the application of data rules. Clinical evidence published since 2008 on health economics and patient, carer, and family perspectives relevant to Wales was identified by searching relevant databases such as MEDLINE. One relevant economic analysis was conducted using the UK Prospective Diabetes Study Outcomes Model 2.
Results
Outcomes included improvements in glycemic control, healthcare resource use (e.g., number of total general practitioner and emergency department visits per year), reduction in body weight among participants, reduction in cholesterol levels, and positive patient-reported outcome measures. An economic analysis identified in the literature review found that a digital platform was more effective and less costly than routine diabetes care and was, therefore, dominant. The analysis was based on observed reductions in glycosylated hemoglobin levels from a database of people with diabetes in NHS Scotland.
Conclusions
The evidence suggests there are benefits in using digital platforms to aid self-management among people with diabetes. Studies reporting on glycosylated hemoglobin levels found statistically significant and clinically important benefits from using digital platforms. Digital platforms also have the potential to be more effective and less costly than routine diabetes care in Wales and the UK.
Young stellar objects (YSOs) are protostars that exhibit bipolar outflows fed by accretion disks. Theories of the transition between disk and outflow often involve a complex magnetic field structure thought to be created by the disk coiling field lines at the jet base; however, due to limited resolution, these theories cannot be confirmed with observation and thus may benefit from laboratory astrophysics studies. We create a dynamically similar laboratory system by driving a $\sim$1 MA current pulse with a 200 ns rise through a $\approx$2 mm-tall Al cylindrical wire array mounted to a three-dimensional (3-D)-printed, stainless steel scaffolding. This system creates a plasma that converges on the centre axis and ejects cm-scale bipolar outflows. Depending on the chosen 3-D-printed load path, the system may be designed to push the ablated plasma flow radially inwards or off-axis to make rotation. In this paper, we present results from the simplest iteration of the load which generates radially converging streams that launch non-rotating jets. The temperature, velocity and density of the radial inflows and axial outflows are characterized using interferometry, gated optical and ultraviolet imaging, and Thomson scattering diagnostics. We show that experimental measurements of the Reynolds number and sonic Mach number in three different stages of the experiment scale favourably to the observed properties of YSO jets with $Re\sim 10^5\unicode{x2013}10^9$ and $M\sim 1\unicode{x2013}10$, while our magnetic Reynolds number of $Re_M\sim 1\unicode{x2013}15$ indicates that the magnetic field diffuses out of our plasma over multiple hydrodynamical time scales. We compare our results with 3-D numerical simulations in the PERSEUS extended magnetohydrodynamics code.
Highly portable and accessible MRI technology will allow researchers to conduct field-based MRI research in community settings. Previous guidance for researchers working with fixed MRI does not address the novel ethical, legal, and societal issues (ELSI) of portable MRI (pMRI). Our interdisciplinary Working Group (WG) previously identified 15 core ELSI challenges associated with pMRI research and recommended solutions. In this article, we distill those detailed recommendations into a Portable MRI Research ELSI Checklist that offers practical operational guidance for researchers contemplating using this technology.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.
Invasive haemodynamics are often performed for initiating and guiding pulmonary artery hypertension therapy. Little is known about the predictive value of invasive haemodynamic indices for long-term outcomes in children with pulmonary artery hypertension. We aimed to evaluate invasive haemodynamic data to help predict outcomes in paediatric pulmonary artery hypertension.
Methods:
Patients with pulmonary artery hypertension who underwent cardiac catheterisation (2006–2019) at a single centre were included. Invasive haemodynamic data from the first cardiac catheterisation and clinical outcomes were reviewed. The combined adverse outcome was defined as pericardial effusion (due to right ventricle failure), creation of a shunt for pulmonary artery hypertension (atrial septal defect or reverse Pott’s shunt), lung transplant, or death.
Results:
Among 46 patients with a median [interquartile range (IQR)] age of 13.2 [4.1–44.7] months, 76% had CHD. Median mean pulmonary artery pressure was 37 [28–52] mmHg and indexed pulmonary vascular resistance was 6.2 [3.6–10] Woods units × m2. Median pulmonary artery pulsatility index was 4.0 [3.0–4.7] and right ventricular stroke work index was 915 [715–1734] mmHg mL/m2. After a median follow-up of 2.4 years, nine patients had a combined adverse outcome (two had a pericardial effusion, one underwent atrial level shunt, one underwent reverse Pott’s shunt, and six died). Patients with an adverse outcome had higher systolic and mean pulmonary artery pressures, higher diastolic and transpulmonary pressure gradients, higher indexed pulmonary vascular resistance, higher pulmonary artery elastance, and higher right ventricular stroke work index (p < 0.05 each).
Conclusion:
Invasive haemodynamics (especially mean pulmonary artery pressure and diastolic pressure gradient) obtained at first cardiac catheterisation in children with pulmonary artery hypertension predicts outcomes.
Mobile phone reminding apps can be used by people with acquired brain injury (ABI) to compensate for their memory impairments. However off-the-shelf apps may be difficult to use. ApplTree has been developed to be accessible to this group, compared to off-the-shelf reminding apps such as Google Calendar. This pilot feasibility trial aimed to establish the feasibility of running (and issues that should be addressed to complete) a randomised controlled trial comparing ApplTree to Google Calendar in an ABI community treatment setting.
Participants and Methods:
Adults with self or other reported memory difficulty after an ABI were enrolled (n=39). Those who completed the baseline phase were randomised (n=29) and randomly allocated to the Google Calendar or ApplTree intervention. They were shown a 30 minute video tutorial of the app and an assessment on their ability to use it. Timely completion of everyday memory tasks were measured for a 3 week pre-intervention baseline and 3 week post-intervention follow-up phase. Participants also completed neuropsychological tests assessing memory, attention and executive function and gave qualitative feedback on the app and their experience in the trial.
Results:
Recruitment rate was 58% of the target (29 were randomised, n=50 was the target in 2 years). Retention rate was 65.5% and adherence rate was 57.9%. While the feasibility trial was not powered to calculate efficacy, there was a 13% increase in everyday memory tasks completed on time for those in the ApplTree group (n=10) compared to baseline and no change for the Google Calendar group (n=9). Feasibility results indicate 72 participants would need to fully complete a trial to detect the minimum clinically important difference (12.5% increase in successful performance of everyday memory tasks) in the efficacy of ApplTree compared to Google Calendar, should such a difference exist.
Conclusions:
The challenges with recruitment of people receiving community care for ABI are highlighted in this trial and discussed along with the impact of the Covid-19 pandemic. Methodological considerations for researchers or clinicians looking to measure everyday memory ability are discussed. The majority (19 of 21) of participants who were given an app were capable of learning to use it during an hour-long session. This indicates it is a feasible intervention that community ABI services could offer. Participant feedback highlighted the merits of design features implemented in ApplTree that can improve the uptake and utility of reminding apps.
‘Newsround’ offers a platform for new discoveries that do not appear within the specialist contributions of this year’s Archaeological Reports, but which nevertheless warrant emphasis, either as a result of their particular characteristics or for the contribution they make to broader archaeological narratives. This section is not intended to be exhaustive, but rather an overview of archaeological research in Greece. It comprises largely preliminary reports (results of excavations that took place up to and including August 2023, where possible) that complement the digital content made available through Archaeology in Greece Online (https://chronique.efa.gr). Due to the diachronic nature of a number of the sites, and for ease of reference, the material is organized geographically in the first instance and then chronologically (earliest to latest) within each section as far as possible.
People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown.
Methods:
We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other.
Results:
Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone.
Conclusions:
CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
OBJECTIVES/GOALS: We aim to discover safer and more effective therapeutics for CNS disorders. Current therapeutic development is hindered by dosing out drugs for safe consumption. By identifying proteins with narrow functional roles in the brain (i.e., behavioral control), we can develop drugs targeting these proteins for improved treatment safety and efficacy. METHODS/STUDY POPULATION: We focused on an evolutionarily new, non-neuronal, non-synaptic glutamate signaling mechanism, system xc- (Sxc). Sxc activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc). To confirm Sxc mutation, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on behavioral control, such as impulse control and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on behavioral control were impaired. MSxc rats displayed deficits in impulse control and behavioral flexibility. We hypothesize that MSxc rats will also show deficits in response inhibition using the stop signal reaction time task, a common metric used in clinical populations. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on impulse control, without impacting development or simple brain function. These results show the potential of targeting Sxc to restore behavioral control without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.
Vascular dementia (VD) is one of the more common types of dementia. Much is known about VD in older adults in terms of survival and associated risk factors, but comparatively less is known about VD in a younger population. This study aimed to investigate survival in people with young-onset VD (YO-VD) compared to those with late-onset VD (LO-VD) and to investigate predictors of mortality.
Design:
Retrospective file review from 1992 to 2014.
Setting:
The inpatient unit of a tertiary neuropsychiatry service in Victoria, Australia.
Participants:
Inpatients with a diagnosis of VD.
Measurements and methods:
Mortality information was obtained from the Australian Institute of Health and Welfare. Clinical variables included age of onset, sex, vascular risk factors, structural neuroimaging, and Hachinksi scores. Statistical analyses used were Kaplan–Meier curves for median survival and Cox regression for predictors of mortality.
Results:
Eighty-four participants were included with few clinical differences between the LO-VD and YO-VD groups. Sixty-eight (81%) had died. Median survival was 9.9 years (95% confidence interval 7.9, 11.7), with those with LO-VD having significantly shorter survival compared to those with YO-VD (6.1 years and 12.8 years, respectively) and proportionally more with LO-VD had died (94.6%) compared to those with YO-VD (67.5%), χ2(1) = 9.16, p = 0.002. The only significant predictor of mortality was increasing age (p = 0.001).
Conclusion:
While there were few clinical differences, and older age was the only factor associated with survival, further research into the effects of managing cardiovascular risk factors and their impact on survival are recommended.
Carer burden is common in younger-onset dementia (YOD), often due to the difficulty of navigating services often designed for older people with dementia. Compared to Alzheimer’s disease (AD), the burden is reported to be higher in behavioral variant frontotemporal dementia (bvFTD). However, there is little literature comparing carer burden specifically in YOD. This study hypothesized that carer burden in bvFTD would be higher than in AD.
Design:
Retrospective cross-sectional study.
Setting:
Tertiary neuropsychiatry service in Victoria, Australia.
Participants:
Patient-carer dyads with YOD.
Measurements:
We collected patient data, including behaviors using the Cambridge Behavioral Inventory-Revised (CBI-R). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI-12). Descriptive statistics and Mann-Whitney U tests were used to analyze the data.
Results:
Carers reported high burden (ZBI-12 mean score = 17.2, SD = 10.5), with no significant difference in burden between younger-onset AD and bvFTD. CBI-R stereotypic and motor behaviors, CBI-R everyday skills, and total NUCOG scores differed between the two groups. There was no significant difference in the rest of the CBI-R subcategories, including the behavior-related domains.
Conclusion:
Carers of YOD face high burden and are managing significant challenging behaviors. We found no difference in carer burden between younger-onset AD and bvFTD. This could be due to similarities in the two subtypes in terms of abnormal behavior, motivation, and self-care as measured on CBI-R, contrary to previous literature. Clinicians should screen for carer burden and associated factors including behavioral symptoms in YOD syndromes, as they may contribute to carer burden regardless of the type.
We detected no correlation between standardized antimicrobial administration ratios (SAARs) and healthcare facility-onset Clostridioides difficile infection (HO-CDI) rates in 102 acute-care Veterans Affairs medical centers over 16 months. SAARs may be useful for investigating trends in local antimicrobial use, but no ratio threshold demarcated HO-CDI risk.
Physical activity interventions can confer a range of physical and mental health benefits among young people with mental disorders. In some contexts, such as Ireland, integrated physical activity is not easily available within child and adolescent mental health services. Therefore, an interagency pilot intervention was established in a child and adolescent mental health service in Ireland with the integration of a novel exercise practitioner into the multidisciplinary mental health team.
Objective:
A qualitative evaluation was conducted to understand the impact of the pilot intervention and to understand issues of implementation that arose throughout.
Methods:
In-depth qualitative interviews with service users’ parents/guardians (N = 3) and a single focus group with existing service providers (N = 3), framed by the RE-AIM framework were conducted to evaluate the pilot intervention. Data were analysed using thematic analysis to explore themes.
Results:
Three overarching themes were identified. These were as follows: (i) Making changes toward healthier physical activity behaviours; (ii) An intervention of therapeutic holism; and (iii) The integrated service delivery.
Conclusions:
This research provides insight on the value of a novel integrated exercise practitioner in outpatient young persons’ mental health services in Ireland, indicating an enhanced and complimentary therapeutic service. These findings will be helpful for integrating Exercise Practitioners in this setting going forward.
To investigate factors that influence antibiotic prescribing decisions, we interviewed 49 antibiotic stewardship champions and stakeholders across 15 hospitals. We conducted thematic analysis and subcoding of decisional factors. We identified 31 factors that influence antibiotic prescribing decisions. These factors may help stewardship programs identify educational targets and design more effective interventions.