Long-Term Care Facilities: Important Participants of the Acute Care Facility Social Network?

Background: Acute care facilities are connected via patient sharing, forming a network. However, patient sharing extends beyond this immediate network to include sharing with long-term care facilities. The extent of long-term care facility patient sharing on the acute care facility network is unknown. The objective of this study was to characterize and determine the extent and pattern of patient transfers to, from, and between long-term care facilities on the network of acute care facilities in a large metropolitan county. Methods/Principal Findings: We applied social network constructs principles, measures, and frameworks to all 2007 annual adult and pediatric patient transfers among the healthcare facilities in Orange County, California, using data from surveys and several datasets. We evaluated general network and centrality measures as well as individual ego measures and further constructed sociograms. Our results show that over the course of a year, 66 of 72 long-term care facilities directly sent and 67 directly received patients from other long-term care facilities. Long-term care facilities added 1,524 ties between the acute care facilities when ties represented at least one patient transfer. Geodesic distance did not closely correlate with the geographic distance among facilities. Conclusions/Significance: This study demonstrates the extent to which long-term care facilities are connected to the acute care facility patient sharing network. Many long-term care facilities were connected by patient transfers and further added many connections to the acute care facility network. This suggests that policy-makers and health officials should account for patient sharing with and among long-term care facilities as well as those among acute care facilities when evaluating policies and interventions. © 2011 Lee et al

Therapy development for the mucopolysaccharidoses : updated consensus recommendations for neuropsychological endpoints

Neurological dysfunction represents a significant clinical component of many of the mucopolysaccharidoses (also known as MPS disorders). The accurate and consistent assessment of neuropsychological function is essential to gain a greater understanding of the precise natural history of these conditions and to design effective clinical trials to evaluate the impact of therapies on the brain. In 2017, an International MPS Consensus Panel published recommendations for best practice in the design and conduct of clinical studies investigating the effects of therapies on cognitive function and adaptive behavior in patients with neuronopathic mucopolysaccharidoses. Based on an International MPS Consensus Conference held in February 2020, this article provides updated consensus recommendations and expands the objectives to include approaches for assessing behavioral and social-emotional state, caregiver burden and quality of life in patients with all mucopolysaccharidoses

Would school closure for the 2009 H1N1 influenza epidemic have been worth the cost?: a computational simulation of Pennsylvania

<p>Abstract</p> <p>Background</p> <p>During the 2009 H1N1 influenza epidemic, policy makers debated over whether, when, and how long to close schools. While closing schools could have reduced influenza transmission thereby preventing cases, deaths, and health care costs, it may also have incurred substantial costs from increased childcare needs and lost productivity by teachers and other school employees.</p> <p>Methods</p> <p>A combination of agent-based and Monte Carlo economic simulation modeling was used to determine the cost-benefit of closing schools (vs. not closing schools) for different durations (range: 1 to 8 weeks) and symptomatic case incidence triggers (range: 1 to 30) for the state of Pennsylvania during the 2009 H1N1 epidemic. Different scenarios varied the basic reproductive rate (R₀) from 1.2, 1.6, to 2.0 and used case-hospitalization and case-fatality rates from the 2009 epidemic. Additional analyses determined the cost per influenza case averted of implementing school closure.</p> <p>Results</p> <p>For all scenarios explored, closing schools resulted in substantially higher net costs than not closing schools. For R₀= 1.2, 1.6, and 2.0 epidemics, closing schools for 8 weeks would have resulted in median net costs of $21.0 billion (95$8.0 - $45.3 billion). The median cost per influenza case averted would have been$14,185 ($5,423 -$30,565) for R₀= 1.2, $25,253 ($9,501 - $53,461) for R₀= 1.6, and$23,483 ($8,870 -$50,926) for R₀= 2.0.</p> <p>Conclusions</p> <p>Our study suggests that closing schools during the 2009 H1N1 epidemic could have resulted in substantial costs to society as the potential costs of lost productivity and childcare could have far outweighed the cost savings in preventing influenza cases.</p

Exploring patterns in mental health treatment and interests of single adults in the United States: a secondary data analysis

ObjectiveThe objective of this study is to examine mental health treatment utilization and interest among the large and growing demographic of single adults in the United States, who face unique societal stressors and pressures that may contribute to their heightened need for mental healthcare.MethodWe analyzed data from 3,453 single adults, focusing on those with possible mental health treatment needs by excluding those with positive self-assessments. We assessed prevalence and sociodemographic correlates of mental health treatment, including psychotherapy and psychiatric medication use, and interest in attending psychotherapy among participants who had never attended.Results26% were in mental health treatment; 17% were attending psychotherapy, 16% were taking psychiatric medications, and 7% were doing both. Further, 64% had never attended psychotherapy, of which 35% expressed interest in future attendance. There were differences in current psychotherapy attendance and psychiatric medication use by gender and sexual orientation, with women and gay/lesbian individuals more likely to engage in both forms of mental health treatment. Additionally, interest in future psychotherapy among those who had never attended varied significantly by age, gender, and race. Younger individuals, women, and Black/African-American participants showed higher likelihoods of interest in psychotherapy.ConclusionOur research highlights a critical gap in mental health treatment utilization among single adults who may be experiencing a need for those services. Despite a seemingly higher likelihood of engagement in mental health treatment compared to the general population, only a minority of single adults in our sample were utilizing mental health treatment. This underutilization and the observed demographic disparities in mental health treatment underscore the need for targeted outreach, personalized treatment plans, enhanced provider training, and policy advocacy to ensure equitable access to mental healthcare for single adults across sociodemographic backgrounds

Exploiting Amino Acid Composition for Predicting Protein-Protein Interactions

Computational prediction of protein interactions typically use protein domains as classifier features because they capture conserved information of interaction surfaces. However, approaches relying on domains as features cannot be applied to proteins without any domain information. In this paper, we explore the contribution of pure amino acid composition (AAC) for protein interaction prediction. This simple feature, which is based on normalized counts of single or pairs of amino acids, is applicable to proteins from any sequenced organism and can be used to compensate for the lack of domain information.AAC performed at par with protein interaction prediction based on domains on three yeast protein interaction datasets. Similar behavior was obtained using different classifiers, indicating that our results are a function of features and not of classifiers. In addition to yeast datasets, AAC performed comparably on worm and fly datasets. Prediction of interactions for the entire yeast proteome identified a large number of novel interactions, the majority of which co-localized or participated in the same processes. Our high confidence interaction network included both well-studied and uncharacterized proteins. Proteins with known function were involved in actin assembly and cell budding. Uncharacterized proteins interacted with proteins involved in reproduction and cell budding, thus providing putative biological roles for the uncharacterized proteins.AAC is a simple, yet powerful feature for predicting protein interactions, and can be used alone or in conjunction with protein domains to predict new and validate existing interactions. More importantly, AAC alone performs at par with existing, but more complex, features indicating the presence of sequence-level information that is predictive of interaction, but which is not necessarily restricted to domains

The effect of glucocorticoids on tendon cell viability in human tendon explants

Background and purpose Previous studies on the culture of human tenocytes have shown that dexamethasone and triamcino-lone reduce cell viability, suppress cell proliferation, and reduce collagen synthesis. However, such cell cultures lack the extracellular matrix and three-dimensional structure of normal tendons, which affects their response to stimuli. We established a human tendon explant culture system and tested the effects of dexamethasone and triamcinolone on cell viability

Structure-Function Study of Mammalian Munc18-1 and C. elegans UNC-18 Implicates Domain 3b in the Regulation of Exocytosis

Munc18-1 is an essential synaptic protein functioning during multiple stages of the exocytotic process including vesicle recruitment, docking and fusion. These functions require a number of distinct syntaxin-dependent interactions; however, Munc18-1 also regulates vesicle fusion via syntaxin-independent interactions with other exocytotic proteins. Although the structural regions of the Munc18-1 protein involved in closed-conformation syntaxin binding have been thoroughly examined, regions of the protein involved in other interactions are poorly characterised. To investigate this we performed a random transposon mutagenesis, identifying domain 3b of Munc18-1 as a functionally important region of the protein. Transposon insertion in an exposed loop within this domain specifically disrupted Mint1 binding despite leaving affinity for closed conformation syntaxin and binding to the SNARE complex unaffected. The insertion mutation significantly reduced total amounts of exocytosis as measured by carbon fiber amperometry in chromaffin cells. Introduction of the equivalent mutation in UNC-18 in Caenorhabditis elegans also reduced neurotransmitter release as assessed by aldicarb sensitivity. Correlation between the two experimental methods for recording changes in the number of exocytotic events was verified using a previously identified gain of function Munc18-1 mutation E466K (increased exocytosis in chromaffin cells and aldicarb hypersensitivity of C. elegans). These data implicate a novel role for an exposed loop in domain 3b of Munc18-1 in transducing regulation of vesicle fusion independent of closed-conformation syntaxin binding

Disease Burden of Clostridium difficile Infections in Adults, Hong Kong, China, 2006-2014

Cross-sectional studies suggest an increasing trend in incidence and relatively low recurrence rates of Clostridium difficile infections in Asia than in Europe and North America. The temporal trend of C. difficile infection in Asia is not completely understood. We conducted a territory-wide population-based observational study to investigate the burden and clinical outcomes in Hong Kong, China, over a 9-year period. A total of 15,753 cases were identified, including 14,402 (91.4%) healthcare-associated cases and 817 (5.1%) community-associated cases. After adjustment for diagnostic test, we found that incidence increased from 15.41 cases/100,000 persons in 2006 to 36.31 cases/100,000 persons in 2014, an annual increase of 26%. This increase was associated with elderly patients, for whom incidence increased 3-fold over the period. Recurrence at 60 days increased from 5.7% in 2006 to 9.1% in 2014 (p<0.001). Our data suggest the need for further surveillance, especially in Asia, which contains ≈60% of the world’s population

PGF2α-F-prostanoid receptor signalling via ADAMTS1 modulates epithelial cell invasion and endothelial cell function in endometrial cancer

<p>Abstract</p> <p>Background</p> <p>An increase in cancer cell invasion and microvascular density is associated with a poorer prognosis for patients with endometrial cancer. In endometrial adenocarcinoma F-prostanoid (FP) receptor expression is elevated, along with its ligand prostaglandin (PG)F_2α, where it regulates expression and secretion of a host of growth factors and chemokines involved in tumorigenesis. This study investigates the expression, regulation and role of a disintegrin and metalloproteinase with thrombospondin repeat 1 (ADAMTS1) in endometrial adenocarcinoma cells by PGF_2αvia the FP receptor.</p> <p>Methods</p> <p>Human endometrium and adenocarcinoma tissues were obtained in accordance with Lothian Research Ethics Committee guidance with informed patient consent. Expression of ADAMTS1 mRNA and protein in tissues was determined by quantitative RT-PCR analysis and immunohistochemistry. Signal transduction pathways regulating ADAMTS1 expression in Ishikawa cells stably expressing the FP receptor to levels seen in endometrial cancer (FPS cells) were determined by quantitative RT-PCR analysis. In vitro invasion and proliferation assays were performed with FPS cells and human umbilical vein endothelial cells (HUVECs) using conditioned medium (CM) from PGF_2α-treated FPS cells from which ADAMTS1 was immunoneutralised and/or recombinant ADAMTS1. The role of endothelial ADAMTS1 in endothelial cell proliferation was confirmed with RNA interference. The data in this study were analysed by T-test or ANOVA.</p> <p>Results</p> <p>ADAMTS1 mRNA and protein expression is elevated in endometrial adenocarcinoma tissues compared with normal proliferative phase endometrium and is localised to the glandular and vascular cells. Using FPS cells, we show that PGF2α-FP signalling upregulates ADAMTS1 expression via a calmodulin-NFAT-dependent pathway and this promotes epithelial cell invasion through ECM and inhibits endothelial cell proliferation. Furthermore, we show that CM from FPS cells regulates endothelial cell ADAMTS1 expression in a rapid biphasic manner. Using RNA interference we show that endothelial cell ADAMTS1 also negatively regulates cellular proliferation.</p> <p>Conclusions</p> <p>These data demonstrate elevated ADAMTS1 expression in endometrial adenocarcinoma. Furthermore we have highlighted a mechanism whereby FP receptor signalling regulates epithelial cell invasion and endothelial cell function via the PGF_2α-FP receptor mediated induction of ADAMTS1.</p