Using Technology Solutions to Support Home Health, Safety, and Greater Independence and Quality of Life.

Supporting individuals with intellectual disability or related neurodevelopmental disabilities should access all available and types of supports that can enhance their personal independence, autonomy, health, safety, and overall quality of life. Herein we discuss the value of exploring the use of technology solutions as a under-utilized type of support used in our field. We briefly present the availability and benefits of using "smart home" technologies and remote support services technologies that can meet the support needs of this population and may also be a viable alternative to the heavy reliance on direct support professionals. This availability of this workforce has reach crisis levels in some counties, such as the United State. We briefly discuss how these technology solutions, may in some situations, be adequate substitutes to having the physical presence of direct support professionals.

Identification and early anticoagulation in patients with atrial fibrillation in the emergency department.

BACKGROUND: Emergency departments (ED) in the United States see more than half a million atrial fibrillation visits a year, however guideline recommended anticoagulation is prescribed in <55% of eligible patients. OBJECTIVE: The purpose of this study was to measure guideline recommended anticoagulation prescribing in patients with nonvalvular atrial fibrillation (NVAF) presenting to the ED, with the goal of closing any treatment gap established. METHODS: We conducted an observational, prospective cohort study in consecutive patients presenting to the ED with a diagnosis of NVAF. CHA2DS2-VASc and HAS-BLED scores were calculated and used as predefined criteria to establish guideline-based oral anticoagulation compliance in comparing routine care (baseline cohort) versus a multidisciplinary team approach. Transition of Care (TOC) services and follow-up were also provided in the multidisciplinary cohort. The primary endpoint was to compare the proportion of patients on guideline based oral anticoagulant (OAC) therapy at admission and discharge between the groups. RESULTS: In the Baseline Cohort (BC) (n = 99), 62.3% of patients with a moderate-high risk of stroke (CHA2DS2-VASc score ≥ 2) were discharged on guideline-based OAC therapy versus 87.8% in the Multidisciplinary Team Cohort (MTC) (n = 131), a 25.5% overall improvement for appropriate anticoagulation (p-value <.001, 95% CI (0.14-0.37)). CONCLUSIONS: A multidisciplinary team approach with TOC services for the identification and early intervention of NVAF patients at risk of stroke in the ED can significantly improve the percentage of moderate to high-risk patients that are discharged home with guideline based OAC.

Patient-reported outcomes as a prognostic marker of survival in patients with advanced nonsmall cell lung cancer treated with immunotherapy.

There has been minimal research on the prognostic value of patient-reported outcomes (PROs) for immune checkpoint inhibitors (ICIs). The relative performance of PROs compared to established markers such as Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and the Lung Immune Prognostic Index (LIPI) is unknown. In our study, data from the advanced nonsmall cell lung cancer (NSCLC) single-arm atezolizumab trials BIRCH, FIR and randomised-trials OAK, POPLAR (atezolizumab vs docetaxel) were pooled. The study included 1548 participants who initiated atezolizumab. The associations between pretreatment PROs and overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazards regression. Prediction performance was assessed using the C-statistic (c). PROs were recorded via the EORTC QLQ-C30 and QLQ-LC13. Patient-reported physical function, fatigue, global health, appetite, role function, pain, dyspnoea, social function, constipation, nausea-vomiting, emotional function and coughing were significantly associated with OS and PFS on univariable and adjusted analysis (P < .05). Physical function (c = 0.654), fatigue (c = 0.653) and global health (c = 0.650) were the most predictive variables for OS. Comparatively, the OS prediction performance of physical function (c = 0.65) was superior to ECOG-PS (c = .59) and LIPI (c = 0.63). On multivariable analysis physical function, ECOG-PS and LIPI were all significant (P < .001). In conclusion, PROs were identified as independent prognostic factors for OS and PFS in advanced NSCLC patients receiving ICI therapy. Further, patient-reported physical function was more predictive of OS than ECOG-PS and LIPI and contained independent information. This highlights the value of PROs as prognostic and stratification factors for clinical use and research trials of ICIs.

Using technology and remote support services to promote independent living of adults with intellectual disability and related developmental disabilities.

BACKGROUND: The use of remote support technologies is a newer form of service that can contribute to increased independence while giving adults with intellectual and developmental disabilities a sense of home safety. This research reviewed the use of remote support services, which is a waiver service that includes smart home technologies and remote support staff that can be called upon, when needed. METHOD: Using focus groups and telephone interviews, the present authors asked users of remote support services about their experience, including what they liked most and least about their experience with these technologies. RESULTS: Overall, increased independence and a sense of security and home safety were identified as the two principal benefits. Remote support technologies may be a part of the solution to addressing the lack of direct support professionals available to provide in-home care. CONCLUSIONS: The present authors discuss the benefits of remote support technologies and offer recommendations for future research regarding remote support technologies and the potential benefits of this newer form of support service.

Technology Tools: Increasing Our Reach in National Surveillance of Intellectual and Developmental Disabilities.

Challenges in collecting comprehensive health surveillance data on people with intellectual and developmental disabilities (IDD) are numerous. A number of important issues and strategies are discussed in the articles contained in this special issue of Intellectual and Developmental Disabilities. In this article, we focus on the advances and tools available in the area of technology. We explore a number of possible sources including accessing big data such as analyzing health information contained in Medicaid and Medicare health databases. We also discuss some of the possibilities afforded to us by complementing Medicaid/Medicare database information with health information available in the myriad of electronic health records. Lastly, we explore other technologies available that might yield valuable health supports and information, including wearable devices, remote supports and other smart home technologies, telehealth and telepsychiatry, as well as looking at ways to access other technologies that collect health information (e.g., glucometer, health apps, connected exercise devices, etc.).

Mechanisms of Mas1 Receptor-Mediated Signaling in the Vascular Endothelium.

OBJECTIVE: Angiotensin II (AngII) has been shown to regulate angiogenesis and at high pathophysiological doses to cause vasoconstriction through the AngII receptor type 1. Angiotensin 1 to 7 (Ang-(1-7)) acting through the Mas1 receptor can act antagonistically to high pathophysiological levels of AngII by inducing vasodilation, whereas the effects of Ang-(1-7) signaling on angiogenesis are less defined. To complicate the matter, there is growing evidence that a subpressor dose of AngII produces phenotypes similar to Ang-(1-7). APPROACH AND RESULTS: This study shows that low-dose Ang-(1-7), acting through the Mas1 receptor, promotes angiogenesis and vasodilation similar to a low, subpressor dose of AngII acting through AngII receptor type 1. In addition, we show through in vitro tube formation that Ang-(1-7) augments the angiogenic response in rat microvascular endothelial cells. Using proteomic and genomic analyses, downstream components of Mas1 receptor signaling were identified, including Rho family of GTPases, phosphatidylinositol 3-kinase, protein kinase D1, mitogen-activated protein kinase, and extracellular signal-related kinase signaling. Further experimental antagonism of extracellular signal-related kinases 1/2 and p38 mitogen-activated protein kinase signaling inhibited endothelial tube formation and vasodilation when stimulated with equimolar, low doses of either AngII or Ang-(1-7). CONCLUSIONS: These results significantly expand the known Ang-(1-7)/Mas1 receptor signaling pathway and demonstrate an important distinction between the pathological effects of elevated and suppressed AngII compared with the beneficial effects of AngII normalization and Ang-(1-7) administration. The observed convergence of Ang-(1-7)/Mas1 and AngII/AngII receptor type 1 signaling at low ligand concentrations suggests a nuanced regulation in vasculature. These data also reinforce the importance of mitogen-activated protein kinase/extracellular signal-related kinase signaling in maintaining vascular function.

Incidence, admission rates, and economic burden of pediatric emergency department visits for urinary tract infection: data from the nationwide emergency department sample, 2006 to 2011.

BACKGROUND: The Emergency Department (ED) is being increasingly utilized as a pathway for management of acute conditions such as the urinary tract infections (UTIs). OBJECTIVE: We sought to assess the contemporary trends in pediatric UTI associated ED visits, subsequent hospitalization, and corresponding financial expenditure, using a large nationally representative pediatric cohort. Further, we describe the predictors of admission following a UTI associated ED visit. METHODS: The Nationwide Emergency Department Sample (NEDS; 2006-2011) was queried to assess temporal-trends in pediatric (age ≤17 years) ED visits for a primary diagnosis of UTI (ICD9 CM code 590.X, 595.0, and 599.0), subsequent hospital admission, and total charges. These trends were examined using the estimated annual percent change (EAPC) method. Multivariable regression models fitted with generalized estimating equations (GEE) identified the predictors of hospital admission. RESULTS: Of the 1,904,379 children presenting to the ED for management of UTI, 86 042 (4.7%) underwent hospital admission. Female ED visits accounted for almost 90% of visits and increased significantly (EAPC 3.28%; p = 0.003) from 709 visits per 100 000 in 2006 to 844 visits per 100 000 in 2011. Male UTI incidence remained unchanged over the study-period (p = 0.292). The overall UTI associated ED visits also increased significantly during the study-period (EAPC 3.14%; p = 0.006) because of the increase in female UTI associated ED visits. Overall hospital admissions declined significantly over the study-period (EAPC -5.59%; p = 0.021). Total associated charges increased significantly at an annual rate of 18.26%, increasing from 254 million USD in 2006 to 464 million USD in 2011 (p < 0.001; Figure). This increase in expenditure was likely driven by increased utilization of diagnostic CT scanning in these patients (EAPC 22.86%; p < 0.001). Ultrasonography (p = 0.805), X-ray (p = 0.196), and urine analysis/culture use (p = 0.121) did not change over the study-period. In multivariable analysis, the independent predictors of admission included younger age (p < 0.001), male gender (OR = 2.05, p < 0.001), higher comorbidity status (OR = 14.81, p < 0.001), pyelonephritis (OR = 4.45, p < 0.001) and concurrent hydronephrosis (OR = 49.42, p < 0.001), stone disease (OR = 6.44, p < 0.001), or sepsis (OR = 18.83, p < 0.001). DISCUSSION: We show that the incidence of ED visits for pediatric UTI is on the rise. This rise in incidence could be due to several factors, including increasing prevalence of metabolic conditions such as obesity, diabetes and metabolic syndrome in children predisposing them to infections, or could be secondary to increasing sexual activity amongst adolescents and changing patterns of contraceptive use (increased use of OCP in place of condoms), or more simply might just be a reflection of changing practice patterns. Second, we demonstrate that total charges for management of UTI in the ED setting are increasing rapidly; the increase is primarily driven by increasing utilization of diagnostic imaging in the ED setting, as has been demonstrated in other ED based studies as well. CONCLUSIONS: In children presenting to the ED with a primary diagnosis of UTI, total ED charges are increasing at an alarming rate not commensurate with the increase in overall ED visits. While the preponderance of children presenting to the ED for UTI are treated and discharged, 4.7% of patients were admitted to the hospital for further management. The strongest predictors of inpatient admission were pyelonephritis, younger age, male gender, higher comorbidity status, and concurrent hydronephrosis, stone disease, or sepsis. Managing these at-risk patients more aggressively in the outpatient setting may prevent unnecessary ED visits and subsequent hospitalizations, and reduce associated healthcare costs.

From foe to friend: using animal toxins to investigate ion channel function.

Ion channels are vital contributors to cellular communication in a wide range of organisms, a distinct feature that renders this ubiquitous family of membrane-spanning proteins a prime target for toxins found in animal venom. For many years, the unique properties of these naturally occurring molecules have enabled researchers to probe the structural and functional features of ion channels and to define their physiological roles in normal and diseased tissues. To illustrate their considerable impact on the ion channel field, this review will highlight fundamental insights into toxin-channel interactions and recently developed toxin screening methods and practical applications of engineered toxins.

A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a.

ß-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1-S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.

Preventing diseases and outbreaks at child care centers using an education, evaluation, and inspection method.

From 2005 to 2008, Washoe County, Nevada, child care centers experienced an increase in illnesses from communicable disease outbreaks. The number of ill children and caregivers from these outbreaks went from 26 in 2005 to 266 in 2008, an increase of 923%. A clear need to reverse this trend existed. Therefore, in 2009 Washoe County strengthened its regulations for child care facilities by adding numerous communicable disease prevention standards. In addition, in 2009 a two-year education, evaluation, and inspection program was implemented at Washoe County child care centers. Following the implementation of this program, a decline occurred in the number of illnesses. The number of ill children and caregivers from outbreaks went from 266 in 2008 to 13 in 2011, a decrease of 95%.

Vascular endothelial growth factor-A signaling in bone marrow-derived endothelial progenitor cells exposed to hypoxic stress.

Bone marrow-derived endothelial progenitor cells (BM-EPCs) are stimulated by vascular endothelial growth factor-A (VEGF-A) and other potent proangiogenic factors. During angiogenesis, an increase in VEGF-A expression stimulates BM-EPCs to enhance endothelial tube formation and contribute to an increase in microvessel density. Hypoxia is known to produce an enhanced angiogenic response and heightened levels of VEGF-A have been seen in oxygen deprived epithelial and endothelial cells, yet the pathways for VEGF-A signaling in BM-EPCs have not been described. This study explores the influence of hypoxia on VEGF-A signaling in rat BM-EPCs utilizing a novel proteomic strategy to directly identify interacting downstream components of the combined VEGF receptor(s) signaling pathways, gene expression analysis, and functional phenotyping. VEGF-A signaling network analysis following liquid chromatographic separation and tandem mass spectrometry revealed proteins related to inositol/calcium signaling, nitric oxide signaling, cell survival, cell migration, and inflammatory responses. Alterations in BM-EPC expression of common angiogenic genes and tube formation in response to VEGF-A during hypoxia were measured and combined with the proteomic analysis to enhance and support the signaling pathways detected. BM-EPC tube formation assays in response to VEGF-A exhibited little tube formation; however, a cell projection/migratory phenotype supported the signaling data. Additionally, a novel assay measuring BM-EPC incorporation into preformed endothelial cell tubes indicated a significant increase of incorporated BM-EPCs after pretreatment with VEGF-A during hypoxia. This study verifies known VEGF-A pathway components and reveals several unidentified mechanisms of VEGF-A signaling in BM-EPCs during hypoxia that may be important for migration to sites of vascular regeneration.

Development and preclinical evaluation of an alphavirus replicon vaccine for influenza.

We used a propagation-defective, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the hemagglutinin (HA) and neuraminidase (NA) proteins from influenza A/Wyoming/03/2003 (H3N2). Efficient production methods were scaled to produce pilot lots of HA VRP and NA VRP and clinical lots of HA VRP. HA VRP-induced high-titered antibody responses in mice, rabbits and rhesus macaques, as measured by ELISA or hemagglutination inhibition (HI) assays, and robust cellular immune responses in mice and rhesus macaques, as measured by IFN-gamma ELISPOT. NA VRP also induced cellular immune responses in mice. A toxicology study with HA VRP and NA VRP in rabbits showed no adverse effects in any parameter. These studies support clinical testing of alphavirus replicon vaccines for influenza.