Hospital Costs Related to Early Extubation after Infant Cardiac Surgery

Background The Pediatric Heart Network Collaborative Learning Study (PHN CLS) increased early extubation rates after infant Tetralogy of Fallot (TOF) and coarctation (CoA) repair across participating sites by implementing a clinical practice guideline (CPG). The impact of the CPG on hospital costs has not been studied. Methods PHN CLS clinical data were linked to cost data from Children’s Hospital Association by matching on indirect identifiers. Hospital costs were evaluated across active and control sites in the pre- and post-CPG periods using generalized linear mixed effects models. A difference-in-difference approach was used to assess whether changes in cost observed in active sites were beyond secular trends in control sites. Results Data were successfully linked on 410/428 (96%) of eligible patients from 4 active and 4 control sites. Mean adjusted cost/case for TOF repair was significantly reduced in the post-CPG period at active sites ($42,833 vs.$56,304, p<0.01) and unchanged at control sites ($47,007 vs.$46,476, p=0.91), with an overall cost reduction of 27% in active vs. control sites (p=0.03). Specific categories of cost reduced in the TOF cohort included clinical (-66%, p<0.01), pharmacy (-46%, p=0.04), lab (-44%, p<0.01), and imaging (-32%, p<0.01). There was no change in costs for CoA repair at active or control sites. Conclusions The early extubation CPG was associated with a reduction in hospital costs for infants undergoing repair of TOF, but not CoA repair. This CPG represents an opportunity to both optimize clinical outcome and reduce costs for certain infant cardiac surgeries

GABA transporter function, oligomerization state, and anchoring: correlates with subcellularly resolved FRET

The mouse γ-aminobutyric acid (GABA) transporter mGAT1 was expressed in neuroblastoma 2a cells. 19 mGAT1 designs incorporating fluorescent proteins were functionally characterized by [^3H]GABA uptake in assays that responded to several experimental variables, including the mutations and pharmacological manipulation of the cytoskeleton. Oligomerization and subsequent trafficking of mGAT1 were studied in several subcellular regions of live cells using localized fluorescence, acceptor photobleach Förster resonance energy transfer (FRET), and pixel-by-pixel analysis of normalized FRET (NFRET) images. Nine constructs were functionally indistinguishable from wild-type mGAT1 and provided information about normal mGAT1 assembly and trafficking. The remainder had compromised [^3H]GABA uptake due to observable oligomerization and/or trafficking deficits; the data help to determine regions of mGAT1 sequence involved in these processes. Acceptor photobleach FRET detected mGAT1 oligomerization, but richer information was obtained from analyzing the distribution of all-pixel NFRET amplitudes. We also analyzed such distributions restricted to cellular subregions. Distributions were fit to either two or three Gaussian components. Two of the components, present for all mGAT1 constructs that oligomerized, may represent dimers and high-order oligomers (probably tetramers), respectively. Only wild-type functioning constructs displayed three components; the additional component apparently had the highest mean NFRET amplitude. Near the cell periphery, wild-type functioning constructs displayed the highest NFRET. In this subregion, the highest NFRET component represented ~30% of all pixels, similar to the percentage of mGAT1 from the acutely recycling pool resident in the plasma membrane in the basal state. Blocking the mGAT1 C terminus postsynaptic density 95/discs large/zona occludens 1 (PDZ)-interacting domain abolished the highest amplitude component from the NFRET distributions. Disrupting the actin cytoskeleton in cells expressing wild-type functioning transporters moved the highest amplitude component from the cell periphery to perinuclear regions. Thus, pixel-by-pixel NFRET analysis resolved three distinct forms of GAT1: dimers, high-order oligomers, and transporters associated via PDZ-mediated interactions with the actin cytoskeleton and/or with the exocyst

Salivary IgA and vimentin differentiate in vitro SARS-CoV-2 infection: a study of 290 convalescent COVID-19 patients

SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva. We collected 551 saliva samples from 290 healthcare workers who had tested positive for COVID-19, before vaccination, between June and December 2020. The samples were categorized based on their ability to block or enhance infection using in vitro assays. Mass spectrometry and ELISA experiments were used to identify and measure the abundance of proteins that specifically bind to SARS-CoV-2 antigens. IgA specific to SARS-CoV-2 antigens was detectable in over 83% of the convalescent saliva samples. We found that concentrations of anti-RBD IgA >500 pg/µg total protein in saliva correlates with reduced viral infectivity in vitro. However, there is a dissociation between the salivary IgA response to SARS-CoV-2, and systemic IgG titres in convalescent COVID19 patients. Then, using an innovative technique known as spike-baited mass spectrometry, we identified novel spike-binding proteins in saliva, most notably vimentin, which correlated with increased viral infectivity in vitro, could serve as a therapeutic target against COVID-19

Design and Rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial

The Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short-term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double blind, placebo controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co., Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From the International Kawasaki Disease Registry.

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CA

Mechanosensitivity during lower extremity neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and peripheral neuropathy: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Type 2 Diabetes Mellitus (T2DM) and diabetic symmetrical polyneuropathy (DSP) impact multiple modalities of sensation including light touch, temperature, position sense and vibration perception. No study to date has examined the mechanosensitivity of peripheral nerves during limb movement in this population. The objective was to determine the unique effects T2DM and DSP have on nerve mechanosensitivity in the lower extremity.</p> <p>Methods</p> <p>This cross-sectional study included 43 people with T2DM. Straight leg raise neurodynamic tests were performed with ankle plantar flexion (PF/SLR) and dorsiflexion (DF/SLR). Hip flexion range of motion (ROM), lower extremity muscle activity and symptom profile, intensity and location were measured at rest, first onset of symptoms (P1) and maximally tolerated symptoms (P2).</p> <p>Results</p> <p>The addition of ankle dorsiflexion during SLR testing reduced the hip flexion ROM by 4.3° ± 6.5° at P1 and by 5.4° ± 4.9° at P2. Individuals in the T2DM group with signs of severe DSP (n = 9) had no difference in hip flexion ROM between PF/SLR and DF/SLR at P1 (1.4° ± 4.2°; paired t-test p = 0.34) or P2 (0.9° ± 2.5°; paired t-test p = 0.31). Movement induced muscle activity was absent during SLR with the exception of the tibialis anterior during DF/SLR testing. Increases in symptom intensity during SLR testing were similar for both PF/SLR and DF/SLR. The addition of ankle dorsiflexion induced more frequent posterior leg symptoms when taken to P2.</p> <p>Conclusions</p> <p>Consistent with previous recommendations in the literature, P1 is an appropriate test end point for SLR neurodynamic testing in people with T2DM. However, our findings suggest that people with T2DM and severe DSP have limited responses to SLR neurodynamic testing, and thus may be at risk for harm from nerve overstretch and the information gathered will be of limited clinical value.</p

Detectable Clonal Mosaicism from Birth to Old Age and its Relationship to Cancer

Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18)

Addressing climate change with behavioral science:A global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.</p