Evaluating the Economic Impact of Palliative and End-of-Life Care Interventions on Intensive Care Unit Utilization and Costs from the Hospital and Healthcare System Perspective.

Purpose of report: Understanding the impact of palliative care interventions on intensive care unit (ICU) costs and utilization is critical for demonstrating the value of palliative care. Performing these economic assessments, however, can be challenging. The purpose of this special report is to highlight and discuss important considerations when assessing ICU utilization and costs from the hospital perspective, with the goal of providing recommendations on methods to consider for future analyses. FINDINGS: ICU length of stay (LOS) and associated costs of care are common and important outcome measures, but must be analyzed properly to yield valid conclusions. There is significant variation in costs by day of stay in the ICU with only modest differences between an ICU day at the end of a stay and the first day on the acute care floor; this variation must be appropriately accounted for analytically. Furthermore, reporting direct variable costs, in addition to total ICU costs, is needed to understand short-term and long-term impact of a reduction in LOS. Importantly, incentives for the hospital to realize savings vary depending on reimbursement policies. SUMMARY: ICU utilization and costs are common outcomes in studies evaluating palliative care interventions. Accurate estimation and interpretation are key to understanding the economic implications of palliative care interventions

Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior.

Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially recruits mPFC D2R+ cells, but that this recruitment is attenuated in VPA-exposed mice. Stimulating mPFC D2R+ neurons disrupts normal social interaction. Conversely, inhibiting these cells enhances social behavior in VPA-exposed mice. Importantly, this effect was not reproduced by nonspecifically inhibiting mPFC neurons in VPA-exposed mice, or by inhibiting D2R+ neurons in wild-type mice. These findings suggest that multiple forms of autism may alter the physiology of specific deep-layer prefrontal neurons that project to subcortical targets. Furthermore, a highly overlapping population-prefrontal D2R+ neurons-plays an important role in both normal and abnormal social behavior, such that targeting these cells can elicit potentially therapeutic effects

Cyclotron line energy in Hercules X-1: stable after the decay

We summarize the results of a dedicated effort made between 2012 and 2019 to follow the evolution of the cyclotron line in Her X-1 through repeated NuSTAR observations. The previously observed nearly 20-year-long decay of the cyclotron line energy has ended in 2012: from then on, the pulse-phase-averaged flux-corrected cyclotron line energy has remained stable and constant at an average value of E_(cyc) = (37.44 ± 0.07) keV (normalized to a flux level of 6.8 RXTE/ASM-cts s⁻¹). The flux dependence of E_(cyc) discovered in 2007 is now measured with high precision, giving a slope of (0.675 ± 0.075) keV/(ASM-cts s⁻¹), corresponding to an increase of 6.5% of E_(cyc) for an increase in flux by a factor of two. We also find that all line parameters as well as the continuum parameters show a correlation with X-ray flux. While a correlation between E_(cyc) and X-ray flux (both positive and negative) is now known for several accreting binaries with various suggestions for the underlying physics, the phenomenon of a long-term decay has so far only been seen in Her X-1 and Vela X-1, with far less convincing explanations

Combining Adverse Pregnancy and Perinatal Outcomes for Women Exposed to Antiepileptic Drugs During Pregnancy, Using a Latent Trait Model

Background Application of latent variable models in medical research are becoming increasingly popular. A latent trait model is developed to combine rare birth defect outcomes in an index of infant morbidity. Methods This study employed four statewide, retrospective 10-year data sources (1999 to 2009). The study cohort consisted of all female Florida Medicaid enrollees who delivered a live singleton infant during study period. Drug exposure was defined as any exposure to Antiepileptic drugs (AEDs) during pregnancy. Mothers with no AED exposure served as the AED unexposed group for comparison. Four adverse outcomes, birth defect (BD), abnormal condition of new born (ACNB), low birth weight (LBW), and pregnancy and obstetrical complication (PCOC), were examined and combined using a latent trait model to generate an overall severity index. Unidimentionality, local independence, internal homogeneity, and construct validity were evaluated for the combined outcome. Results The study cohort consisted of 3183 mother-infant pairs in total AED group, 226 in the valproate only subgroup, and 43,956 in the AED unexposed group. Compared to AED unexposed group, the rate of BD was higher in both the total AED group (12.8% vs. 10.5%, P \u3c .0001), and the valproate only subgroup (19.6% vs. 10.5%, P  \u3c .0001). The combined outcome was significantly correlated with the length of hospital stay during delivery in both the total AED group (Rho = 0.24, P \u3c .0001) and the valproate only subgroup (Rho = 0.16, P = .01). The mean score for the combined outcome in the total AED group was significantly higher (2.04 ± 0.02 vs. 1.88 ± 0.01, P \u3c .0001) than AED unexposed group, whereas the valproate only subgroup was not. Conclusions Latent trait modeling can be an effective tool for combining adverse pregnancy and perinatal outcomes to assess prenatal exposure to AED, but evaluation of the selected components is essential to ensure the validity of the combined outcome

Revealing the spectral state transition of the Clocked Burster, GS 1826-238 with NuSTAR StrayCats

We present the long term analysis of GS 1826-238, a neutron star X-ray binary known as the "Clocked Burster", using data from NuSTAR StrayCats. StrayCats, a catalogue of NuSTAR stray light data, contains data from bright, off-axis X-ray sources that have not been focused by the NuSTAR optics. We obtained stray light observations of the source from 2014-2021, reduced and analyzed the data using nustar-gen-utils Python tools, demonstrating the transition of source from the "island" atoll state to a "banana" branch. We also present the lightcurve analysis of Type I X-Ray bursts from the Clocked Burster and show that the bursts from the banana/soft state are systematically shorter in durations than those from the island/hard state and have a higher burst fluence. From our analysis, we note an increase in mass accretion rate of the source, and a decrease in burst frequency with the transition

Theoretical Properties of Projection Based Multilayer Perceptrons with Functional Inputs

Many real world data are sampled functions. As shown by Functional Data Analysis (FDA) methods, spectra, time series, images, gesture recognition data, etc. can be processed more efficiently if their functional nature is taken into account during the data analysis process. This is done by extending standard data analysis methods so that they can apply to functional inputs. A general way to achieve this goal is to compute projections of the functional data onto a finite dimensional sub-space of the functional space. The coordinates of the data on a basis of this sub-space provide standard vector representations of the functions. The obtained vectors can be processed by any standard method. In our previous work, this general approach has been used to define projection based Multilayer Perceptrons (MLPs) with functional inputs. We study in this paper important theoretical properties of the proposed model. We show in particular that MLPs with functional inputs are universal approximators: they can approximate to arbitrary accuracy any continuous mapping from a compact sub-space of a functional space to R. Moreover, we provide a consistency result that shows that any mapping from a functional space to R can be learned thanks to examples by a projection based MLP: the generalization mean square error of the MLP decreases to the smallest possible mean square error on the data when the number of examples goes to infinity

Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors

Background: Sepsis survivors often develop chronic critical illness (CCI) and demonstrate the persistent inflammation, immunosuppression, and catabolism syndrome predisposing them to long-term functional limitations and higher mortality. There is a need to identify biomarkers that can predict long-term worsening of physical function to be able to act early and prevent mobility loss. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-accepted biomarker of cardiac overload, but it has also been shown to be associated with long-term physical function decline. We explored whether NT-proBNP blood levels in the acute phase of sepsis are associated with physical function and muscle strength impairment at 6 and 12 months after sepsis onset. Methods: This is a retrospective analysis conducted in 196 sepsis patients (aged 18-86 years old) as part of the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) who consented to participate in the 12-month follow-up study. NT-proBNP was measured at 24 h after sepsis onset. Patients were followed to determine physical function by short physical performance battery (SPPB) test score (scale 0 to12-higher score corresponds with better physical function) and upper limb muscle strength by hand grip strength test (kilograms) at 6 and 12 months. We used a multivariate linear regression model to test an association between NT-proBNP levels, SPPB, and hand grip strength scores. Missing follow-up data or absence due to death was accounted for by using inverse probability weighting based on concurrent health performance status scores. Statistical significance was set at p ≤ 0.05. Results: After adjusting for covariates (age, gender, race, Charlson comorbidity index, APACHE II score, and presence of CCI condition), higher levels of NT-proBNP at 24 h after sepsis onset were associated with lower SPPB scores at 12 months (p < 0.05) and lower hand grip strength at 6-month (p < 0.001) and 12-month follow-up (p < 0.05). Conclusions: NT-proBNP levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Human cardiac pericytes are susceptible to SARS-CoV-2 infection

COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19

Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is defined as the occurrence of multiple tumorous intraabdominal lesions, which are myomatous nodules. LPD is a rare disease with only about 100 cases reported. The usual course of LPD is benign with the majority of the patients being premenopausal females. Only two cases involving men have been reported, no syndrome or familial occurrence of LPD has been described. CASE PRESENTATION: We describe a Caucasian-American family in which six members (three men) are diagnosed with Leiomyomatosis peritonealis disseminata (LPD) and three deceased family members most likely had LPD (based on the autopsy reports). Furthermore we describe the association of LPD with Raynaud's syndrome and Prurigo nodularis. CONCLUSION: Familial clustering of Leiomyomatosis peritonealis disseminata (LPD) has not been reported so far. The etiology of LPD is unknown and no mode of inheritance is known. We discuss possible modes of inheritance in the presented case, taking into account the possibility of a genetic syndrome. Given the similarity to other genetic syndromes with leiomyomatosis and skin alterations, we describe possible similar genetic pathomechanisms