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Hyperkalemia (HK) is common and potentially a life-threatening condition. If untreated, HK can progress to ventricular arrhythmia and cardiac arrest. Early treatment reduces mortality in HK. This study evaluates a novel protocol for identification and empiric management of presumed HK in the prehospital setting.
This was a retrospective, observational chart review of a single, large, suburban Emergency Medical Services (EMS) system. Patients treated for presumed HK, with both a clinical concern for HK and electrocardiogram (ECG) changes consistent with HK, from February 2018 through February 2021 were eligible for inclusion. Patients were excluded if found to be in cardiac arrest on EMS arrival. Empiric treatment of HK included administration of calcium, sodium bicarbonate, and albuterol. Post-treatment, patients were placed on cardiac monitoring and adverse events recorded enroute to receiving hospital. Protocol compliance was assessed by two independent reviewers. Serum potassium (K) level was obtained from hospital medical records.
A total of 582 patients were treated for HK, of which 533 patients were excluded due to cardiac arrest prior to EMS arrival. The remaining 48 patients included in the analysis had a mean age of 56 (SD = 20) years and were 60.4% (n = 29) male with 77.1% (n = 37) Caucasian, 10.4% (n = 5) African American, and 12.5% (n = 6) Hispanic. Initial blood draw at the receiving facilities showed K >5.0mEq/L in 22 (45.8%), K of 3.5-5.0mEq/L in 23 (47.9%), and K <3.5mEq/L in three patients (6.3%). Independent review of the EMS ECG found the presence of hyperkalemic-related change in 43 (89.6%) cases, and five (10.4%) patients did not meet criteria for treatment due to lack of either appropriate ECG findings or clinical suspicion. No episodes of unstable tachyarrhythmia or cardiac arrest occurred during EMS treatment or transport.
The study evaluated a novel protocol for detecting and managing HK in the prehospital setting. It is feasible for EMS crews to administer this protocol, although a larger study is needed to make the results generalizable.
Barrett’s oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case–control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20 000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990–1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007–2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile: OR = 0·59; CI: 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI: 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI: 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI: 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
This chapter offers lessons from engineering and other industries that promise developments in healthcare, and practical guidance for clinician-engineer partnerships. Section 1 provides guidance on how to establish a shared vocabulary and common understanding between engineers and clinicians of what terms such as AI and ML do and don’t mean. Section 2 identifies challenges clinician-engineering partnerships must overcome to deliver sustained value and ways to avoid common causes of failure. Section 3 provides specific advice on how to design projects to produce value at a series of stages rather than rely on the success of one, ambitious final model. Section 4 concludes by drawing on cautionary lessons from healthcare and other industries.
OBJECTIVES/GOALS: A functional precision medicine platform to identify therapeutic targets for a glioblastoma patient with Li Fraumeni syndrome was performed. Comparative transcriptomics identified druggable targets and patient derived organoids and a 3D-PREDICT drug screening assay was used to validate the pipeline and identify further therapeutic targets. METHODS/STUDY POPULATION: A comparative transcriptomics pipeline was used to identify druggable genes that are uniquely overexpressed in our patient of interest relative to a cancer compendium of 12,747 tumor RNA sequencing datasets including 200 GBMs. Mini-ring patient derived organoid-based drug viability assays were performed to validate the comparative transcriptomics data. Additionally, a spheroid-based drug screening assay (3D-PREDICT) was performed and used to identify further therapeutic targets. RESULTS/ANTICIPATED RESULTS: Using comparative transcriptomics STAT1 and STAT2 were found to be significantly overexpressed in our patient, indicating ruxolitinib, a Janus kinase 1 and 2 inhibitor, as a potential therapy. Druggable pathways predicted using comparative transcriptomics corresponded with ruxolitinib sensitivity in a panel of patient derived organoids screened with this compound. Cells from the LFS patient were among the most sensitive to ruxolitinib compared to patient-derived cells with lower STAT1 and STAT2 expression levels. Additionally, 3D-PREDICT screening identified the mTOR inhibitor everolimus as a potential candidate. These two targeted therapies were selected for our patient and resulted in radiographic disease stability. DISCUSSION/SIGNIFICANCE: This research illustrates the use of comparative transcriptomics to identify druggable pathways irrespective of actionable DNA mutations present. Our results are promising and serve to highlight the importance of functional precision medicine in tailoring treatment regimes to specific patients.
The present study reports the validity of multiple assessment methods for tracking changes in body composition over time and quantifies the influence of unstandardised pre-assessment procedures. Resistance-trained males underwent 6 weeks of structured resistance training alongside a hyperenergetic diet, with four total body composition evaluations. Pre-intervention, body composition was estimated in standardised (i.e. overnight fasted and rested) and unstandardised (i.e. no control over pre-assessment activities) conditions within a single day. The same assessments were repeated post-intervention, and body composition changes were estimated from all possible combinations of pre-intervention and post-intervention data. Assessment methods included dual-energy X-ray absorptiometry (DXA), air displacement plethysmography, three-dimensional optical imaging, single- and multi-frequency bioelectrical impedance analysis, bioimpedance spectroscopy and multi-component models. Data were analysed using equivalence testing, Bland–Altman analysis, Friedman tests and validity metrics. Most methods demonstrated meaningful errors when unstandardised conditions were present pre- and/or post-intervention, resulting in blunted or exaggerated changes relative to true body composition changes. However, some methods – particularly DXA and select digital anthropometry techniques – were more robust to a lack of standardisation. In standardised conditions, methods exhibiting the highest overall agreement with the four-component model were other multi-component models, select bioimpedance technologies, DXA and select digital anthropometry techniques. Although specific methods varied, the present study broadly demonstrates the importance of controlling and documenting standardisation procedures prior to body composition assessments across distinct assessment technologies, particularly for longitudinal investigations. Additionally, there are meaningful differences in the ability of common methods to track longitudinal body composition changes.
Prolonged survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces and personal protective equipment may lead to these surfaces transmitting this pathogen to others. We sought to determine the effectiveness of a pulsed-xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators.
Chamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and were exposed to different durations of PX-UV.
For hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 log10, >4.54 log10, and >4.12 log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in >4.79 log10 reduction in viral load. PX-UV significantly reduced SARS-CoV-2 on hard surfaces and N95 respirators.
With the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology to reduce environmental and personal protective equipment bioburden and to enhance both healthcare worker and patient safety by reducing the risk of exposure to SARS-CoV-2.
Behavioral and psychological symptoms of dementia (BPSD), constitute a major clinical component of Alzheimer’s disease (AD). There is a growing interest in BPSD as they are responsible for a large share of the suffering of patients and caregivers, and they strongly determine the patient’s lifestyle and management. Better detection and understanding of these symptoms is essential to provide appropriate management. This article is a consensus produced by the behavioral group of the European Alzheimer’s Disease Consortium (EADC). The aim of this article is to present clinical description and biological correlates of the major behavioral and psychological symptomatology in AD. BPSD is not a unitary concept. Instead, it should be divided into several symptoms or more likely: groups of symptoms, each possibly reflecting a different prevalence, course over time, biological correlate and psychosocial determinants. There is some clinical evidence for clusters within groups of BPSD. Biological studies indicate that patients with AD and BPSD are associated with variations in the pathological features (atrophy, brain perfusion/metabolism, histopathology) when compared to people with AD without BPSD. An individually tailored approach taking all these aspects into account is warranted as it may offer more, and better, pharmacological and non-pharmacological treatment opportunities.
The Beatles – which is to say John Lennon and Paul McCartney – dabbled in songwriting individually, prior to their joining forces in the Quarry Men in 1957. Paul had famously composed a ditty called “I Lost My Little Girl,” a skiffle-styled number that may have been influenced by the recent death of his mother when he was fourteen. John less famously wrote a song of which no record exists, titled “Calypso Rock.” In both instances, the two aspiring tunesmiths employed current styles as models for their compositions. (Calypso, embodied by Harry Belafonte, was a popular musical style in the USA and UK, coinciding with the nascent – and more popular – skiffle and rock ’n’ roll eras.) It was quite natural for aspiring songwriters to draw upon styles of the day that drew their interest, distinct from the prevailing pop and jazz sounds.
We introduce Hypercat, a large set of 2-d AGN torus images computed with the state-of-the-art clumpy radiative transfer code Clumpy. The images are provided as a 9-dimensional hypercube, in addition to a smaller hypercube of corresponding projected dust distribution maps. Hypercat also comprises a software suite for easy use of the hypercubes, quantification of image morphology, and simulation of synthetic observations with single-dish telescopes, interferometers, and Integral Field Units. We apply Hypercat to NGC 1068 and find that it can be spatially resolved in Near- and Mid-IR, for the first time with single-dish apertures, on the upcoming generation of 25–40m class telescopes. We also find that clumpy AGN torus models within a range of the parameter space can explain on scales of several parsec the recently reported polar elongation of MIR emission in several sources, while not upending basic assumptions about AGN unification.
Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos.
Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders.
In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02).
It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.
Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.
As the IAU heads towards its second century, many changes have simultaneously transformed Astronomy and the human condition world-wide. Amid the amazing recent discoveries of exoplanets, primeval galaxies, and gravitational radiation, the human condition on Earth has become blazingly interconnected, yet beset with ever-increasing problems of over-population, pollution, and never-ending wars. Fossil-fueled global climate change has begun to yield perilous consequences. And the displacement of people from war-torn nations has reached levels not seen since World War II.
The Astroinformatics Program is funded by the Chilean Economy Ministry’s (FIE Grant FIE-2016-V022, CORFO Grant 16IFI6626) with the mission to identify and initiate investments to foster Chilean Digital Economy, using Astronomy data-centric tools (known as astroinformatics). Over 2017 we worked with communities across sectors identifying opportunities to achieve the program mission, the Data Observatory vision emerged from that work and will guide design activities throughout 2018.
To compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypes
As part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.
The study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non–CTX-M ESBLs were detected.
Clinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.
Introduction: Each year about two thirds of U.S. smokers make a quit attempt. Yet, less than 5% remain abstinent three months post-quit date. One factor that may affect abstinence is negative feelings about the self-associated with being a smoker (disequilibrium), particularly if smoking is important to the sense of self and one is trying to quit.
Aims: We evaluated a multivariate structural equation model proposing that smoking's subjective importance to a smoker would influence carbon monoxide verified smoking abstinence at 24 weeks (post-quit date). Further, we assessed whether the relation would be moderated by the smoker's experience of disequilibrium.
Methods: Participants were 440 regular smokers taking part in a clinical trial assessing the effectiveness of different durations of nicotine replacement therapy use. Participants completed the subjective importance of smoking survey at baseline and were assessed for carbon monoxide verified seven-day point prevalence abstinence at 24 weeks
Results: Using exploratory structural equation modelling, the subjective importance of smoking was associated with point prevalence abstinence at 24 weeks, but only for smokers with high disequilibrium.
Conclusions: The results of this study suggest that experiencing negative feelings about being a smoker could motivate smokers to remain abstinent, despite the importance of smoking to the smoker's sense of self.
Protected areas have been established historically in residual places where the potential for extractive uses is low, implying that places at risk are usually under-protected. Argentina is no exception, with few protected areas established in productive regions that are prone to conversion. Here, using reptiles as a study group and considering the most important human threats in north-western Argentina, we estimated priority conservation areas where we expect species to persist in the face of climate change and land conversion. Protected areas cover no more than 9% of the study region, but represent less than 15% of reptile distributions. There are great opportunities for improving the conservation status in the region by protecting only 8% more of north-western Argentina, with the level of species protection inside the protected area network increasing almost four-fold, reaching 43% of species distributions on average and 59% of the distributions of threatened reptiles. Fortunately, the highest diversity of reptiles in the region does not match the places targeted for agriculture expansion. Our findings suggest that future prioritization schemes should embrace other groups that are especially diverse in the Chaco ecoregion, which overlaps with our study area.
Volumetric atrophy and microstructural alterations in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, no study to date has jointly investigated concomitant microstructural and volumetric changes of the hippocampus in dementia with Lewy bodies (DLB).
A total of 84 subjects (23 MCI, 17 DLB, 14 AD, and 30 healthy controls) were recruited for a multi-modal imaging (3T MRI and DTI) study that included neuropsychological evaluation. Freesurfer was used to segment the total hippocampus and delineate its subfields. The hippocampal segmentations were co-registered to the mean diffusivity (MD) and fractional anisotropy (FA) maps obtained from the DTI images.
Both AD and MCI groups showed significantly smaller hippocampal volumes compared to DLB and controls, predominantly in the CA1 and subiculum subfields. Compared to controls, hippocampal MD was elevated in AD, but not in MCI. DLB was characterized by both volumetric and microstructural preservation of the hippocampus. In MCI, higher hippocampal MD was associated with greater atrophy of the hippocampus and CA1 region. Hippocampal volume was a stronger predictor of memory scores compared to MD within the MCI group.
Through a multi-modal integration, we report novel evidence that the hippocampus in DLB is characterized by both macrostructural and microstructural preservation. Contrary to recent suggestions, our findings do not support the view that DTI measurements of the hippocampus are superior to volumetric changes in characterizing group differences, particularly between MCI and controls.
We studied neuroinflammation in individuals with late-life, depression, as a
risk factor for dementia, using [11C]PK11195 positron emission
tomography (PET). Five older participants with major depression and 13
controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),
with blood taken to measure C-reactive protein (CRP). We found significantly
higher CRP levels in those with late-life depression and raised
[11C]PK11195 binding compared with controls in brain regions
associated with depression, including subgenual anterior cingulate cortex,
and significant hippocampal subfield atrophy in cornu ammonis 1 and
subiculum. Our findings suggest neuroinflammation requires further
investigation in late-life depression, both as a possible aetiological
factor and a potential therapeutic target.
The San Francisco Fire Department’s (SFFD; San Francisco, California USA) Homeless Outreach and Medical Emergency (HOME) Team is the United States’ first Emergency Medical Services (EMS)-based outreach effort using a specially trained paramedic to redirect frequent users of EMS to other types of services. The effectiveness of this program at reducing repeat use of emergency services during the first seven months of the team’s existence was examined.
A retrospective analysis of EMS use frequency and demographic characteristics of frequent users was conducted. Clients that used emergency services at least four times per month from March 2004 through May 2005 were contacted for intervention. Patterns for each frequent user before and after intervention were analyzed. Changes in EMS use during the 15-month study interval was the primary outcome measurement.
A total of 59 clients were included. The target population had a median age of 55.1 years and was 68% male. Additionally, 38.0% of the target population was homeless, 43.4% had no primary care, 88.9% had a substance abuse disorder at time of contact, and 83.0% had a history of psychiatric disorder. The HOME Team undertook 320 distinct contacts with 65 frequent users during the study period. The average EMS use prior to HOME Team contact was 18.72 responses per month (SD=19.40), and after the first contact with the HOME Team, use dropped to 8.61 (SD=10.84), P<.001.
Frequent users of EMS suffer from disproportionate comorbidities, particularly substance abuse and psychiatric disorders. This population responds well to the intervention of a specially trained paramedic as measured by EMS usage.
TangherliniN, VillarJ, BrownJ, RodriguezRM, YehC, FriedmanBT, WadaP. The HOME Team: Evaluating the Effect of an EMS-based Outreach Team to Decrease the Frequency of 911 Use Among High Utilizers of EMS. Prehosp Disaster Med. 2016;31(6):603–607.