Effectiveness of Telehealth in Rural and Remote Emergency Departments: Systematic Review.

BACKGROUND: Emergency telehealth has been used to improve access of patients residing in rural and remote areas to specialist care in the hope of mitigating the significant health disparities that they experience. Patient disposition decisions in rural and remote emergency departments (EDs) can be complex and largely dependent on the expertise and experience available at local (receiving-end) hospitals. Although there has been some synthesis of evidence of the effectiveness of emergency telehealth in clinical practice in rural and remote EDs for nonacute presentations, there has been limited evaluation of the influence of contextual factors such as clinical area and acuity of presentation on these findings. OBJECTIVE: The aims of this systematic review are to examine the outcome measures used in studying the effectiveness of telehealth in rural and remote EDs and to analyze the clinical context in which these outcome measures were used and interpreted. METHODS: The search strategy used Medical Subject Headings and equivalent lists of subject descriptors to find articles covering 4 key domains: telehealth or telemedicine, EDs, effectiveness, and rural and remote. Studies were selected using the Population, Intervention, Comparator, Outcomes of Interest, and Study Design framework. This search strategy was applied to MEDLINE (Ovid), Cochrane Library, Scopus, CINAHL, ProQuest, and EconLit, as well as the Centre for Reviews and Dissemination databases (eg, National Health Service Economic Evaluation Database) for the search period from January 1, 1990, to May 23, 2020. Qualitative synthesis was performed on the outcome measures used in the included studies, in particular the clinical contexts within which they were interpreted. RESULTS: A total of 21 full-text articles were included for qualitative analysis. Telehealth use in rural and remote EDs demonstrated effectiveness in achieving improved or equivalent clinical effectiveness, appropriate care processes, and-depending on the context-improvement in speed of care, as well as favorable service use patterns. The definition of effectiveness varied across the clinical areas and contexts of the studies, and different measures have been used to affirm the safety and clinical effectiveness of telehealth in rural and remote EDs. The acuity of patient presentation emerged as a dominant consideration in the interpretation of interlinking time-sensitive clinical effectiveness and patient disposition measures such as transfer and discharge rates, local hospital admission, length of stay, and ED length of stay. These, together with clinical area and acuity of presentation, are the outcome determination criteria that emerged from this review. CONCLUSIONS: Emergency telehealth studies typically use multiple outcome measures to determine the effectiveness of the services. The outcome determination criteria that emerged from this analysis are useful when defining the favorable direction for each outcome measure of interest. The findings of this review have implications for emergency telehealth service design and policies. TRIAL REGISTRATION: PROSPERO CRD42019145903; https://tinyurl.com/ndmkr8ry.

Effectiveness and cost-effectiveness of TeleStroke consultations to support the care of patients who had a stroke presenting to regional emergency departments in Western Australia: an economic evaluation case study protocol.

INTRODUCTION: The Western Australia (WA) Acute TeleStroke Programme commenced incrementally across regional WA during 2016-2017. Since the introduction of the TeleStroke Programme, there has been monitoring of service outputs, including regional patient access to tertiary stroke specialist advice and reperfusion treatment; however, the impact of consultation with a stroke specialist via telehealth (videoconferencing or telephone) on the effectiveness and cost-effectiveness of stroke care and the drivers of cost-effectiveness has not been systematically evaluated. METHODS AND ANALYSIS: The aim of the case study was to examine the impact of consultation with a stroke specialist via telehealth on the effectiveness and cost-effectiveness of stroke and transient ischaemic attack care using a mixed methods approach. A categorical decision tree model will be constructed in collaboration with clinicians and programme managers. A before and after comparison using state-wide administrative datasets will be used to run the base model. If sample size and statistical power permits, the cases and comparators will be matched by stroke type and presence of CT scan at the initial site of presentation, age category and presenting hospital. The drivers of cost-effectiveness will be explored through stakeholder interviews. Data from the qualitative analysis will be cross-referenced with trends emerging from the quantitative dataset and used to guide the factors to be involved in subgroup and sensitivity analysis. ETHICS AND DISSEMINATION: Ethics approval for this case study has been granted from the Western Australian Country Health Service Human Research and Ethics Committee (RGS3076). Reciprocal approval has been granted from Curtin University Human Research Ethics Office (HRE2019-0740). Findings will be disseminated publicly through conference presentation and peer-review publications. Interim findings will be released as internal reports to inform the service development.

Effectiveness and cost-effectiveness of telehealth in rural and remote emergency departments: a systematic review protocol.

BACKGROUND: Emergency telehealth has been used to improve accessibility of rural and remote patients to specialist care. Evidence to date has demonstrated effectiveness and cost-effectiveness of telehealth in rural and remote emergency departments within a variety of contexts. However, systematic reviews to date have not focused on the rural and remote emergency departments. The purpose of this study is to review the outcome measures used in evaluations of emergency telehealth in rural and remote settings and assess evidence relating to their effectiveness and cost-effectiveness. METHODS: Randomised controlled trials, non-randomised controlled trials, and full and partial economic evaluations (e.g. cost-effectiveness, cost-benefit, and cost-utility analyses) of telehealth in rural and remote emergency departments will be included. Comprehensive literature searches will be conducted in multiple electronic databases (from 1990 onwards): MEDLINE (Ovid), Cochrane Library, Scopus, CINAHL, ProQuest, EconLit, CRD databases (e.g. NHS Economic Evaluation database), and Tufts Cost-Effectiveness Registry. Two authors will independently screen all citations, full-text articles, and abstract data. The methodological quality (or risk of bias) of individual studies will be appraised using an appropriate tool. A systematic narrative synthesis will be provided with information presented in the text and tables to summarise and explain the characteristics and findings of the studies. If feasible, we will conduct random effects meta-analysis. DISCUSSION: This review will identify gaps in the current body of evidence relating to the effectiveness and cost-effectiveness of rural and remote emergency telehealth services. By confining to articles written in the English language, this analysis may be subjected to publication bias and results need to be interpreted accordingly. We believe the results of this review could be valuable for the design of future economic evaluations of emergency telehealth services implemented in the rural and remote context. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019145903.

Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract.

Although majority of the genes linked to early-onset cataract exhibit lens fiber cell-enriched expression, our understanding of gene regulation in these cells is limited to function of just eight transcription factors and largely in the context of crystallins. We report on small Maf transcription factors Mafg and Mafk as regulators of several non-crystallin human cataract-associated genes in fiber cells and establish their significance to this disease. We applied a bioinformatics tool for cataract gene discovery iSyTE to identify Mafg and its co-regulators in the lens, and generated various null-allelic combinations of Mafg:Mafk mouse mutants for phenotypic and molecular analysis. By age 4 months, Mafg-/-:Mafk+/- mutants exhibit lens defects that progressively develop into cataract. High-resolution phenotypic characterization of Mafg-/-:Mafk+/- mouse lens reveals severely disorganized fiber cells, while microarray-based expression profiling identifies 97 differentially regulated genes (DRGs). Integrative analysis of Mafg-/-:Mafk+/- lens-DRGs with (1) binding motifs and genomic targets of small Mafs and their regulatory partners, (2) iSyTE lens expression data, and (3) interactions between DRGs in the String database, unravel a detailed small Maf regulatory network in the lens, several nodes of which are linked to cataract. This approach identifies 36 high-priority candidates from the original 97 DRGs. Significantly, 8/36 (22%) DRGs are associated with cataracts in human (GSTO1, MGST1, SC4MOL, UCHL1) or mouse (Aldh3a1, Crygf, Hspb1, Pcbd1), suggesting a multifactorial etiology that includes oxidative stress and misregulation of sterol synthesis. These data identify Mafg and Mafk as new cataract-associated candidates and define their function in regulating largely non-crystallin genes linked to human cataract.

Molecular characterization of mouse lens epithelial cell lines and their suitability to study RNA granules and cataract associated genes.

The discovery of cytosolic RNA granule (RG) component proteins associated with human cataract has initiated investigations on post-transcriptional mechanisms of gene expression control in the lens. Application of established mouse lens epithelial cell lines (LECs) can provide rapid insights on RG function in lens cells, especially because mouse mutants in several RG components are not available. However, although these LECs represent potential reagents for such analyses, they are uncharacterized for lens gene expression or RG formation. Therefore, a detailed molecular and cellular characterization of three permanent mouse LECs 17EM15, 21EM15 and αTN4 is performed in this study. Comparative analysis between microarray gene expression datasets on LEC 21EM15 and iSyTE lens tissue demonstrates that 30% of top 200 iSyTE identified lens-enriched genes are expressed in these cells. Majority of these candidates are independently validated to either have lens expression, function or linkage to cataract. Moreover, analysis of microarray data with genes described in Cat-Map, an online database of cataract associated genes and loci, demonstrates that 131 genes linked to cataract loci are expressed in 21EM15 cells. Furthermore, gene expression in LECs is compared to isolated lens epithelium or fiber cells by qRT-PCR and by comparative analyses with publically available epithelium or fiber-specific microarray and RNA-seq (sequencing) datasets. Expression of select candidate genes was validated by regular and real-time quantitative RT-PCR. Expression of lens epithelium-enriched genes Foxe3, Pax6, Anxa4 and Mcm4 is up-regulated in LEC lines, compared to isolated lens fiber cells. Moreover, similar to isolated lens epithelium, all three LECs exhibit down-regulation of fiber cell-expressed genes Crybb1, Mip and Prox1 when compared to fiber cells. These data indicate that the LEC lines exhibit greater similarity to lens epithelium than to fiber cells. Compared to non-lens cell line NIH3T3, LECs exhibit significantly enriched expression of transcription factors with important function in the lens, namely Pax6, Foxe3 and Prox1. In addition to these genes, all three LECs also express key lens- and cataract-associated genes, namely Dkk3, Epha2, Hsf4, Jag1, Mab21l1, Meis1, Pknox1, Pou2f1, Sfrp1, Sparc, Tdrd7 and Trpm3. Additionally, 21EM15 microarrays indicate expression of Chmp4b, Cryab and Tcfap2a among others important genes. Immunostaining with makers for Processing bodies (P-bodies) and Stress granules (SGs) demonstrates that these classes of RGs are robustly expressed in all three LECs. Moreover, under conditions of stress, 17EM15 and αTN4 exhibit significantly higher numbers of P-bodies and SGs compared to NIH3T3 cells. In sum, these data indicate that mouse LECs 21EM15, 17EM15 and αTN4 express key lens or cataract genes, are similar to lens epithelium than fiber cells, and exhibit high levels of P-bodies and SGs, indicating their suitability for investigating gene expression control and RG function in lens-derived cells.

Endocrine disruption screening by protein and gene expression of vitellogenin in freshly isolated and cryopreserved rainbow trout hepatocytes.

Xenobiotics may activate the estrogen receptor, resulting in alteration of normal endocrine functions in animals and humans. Consequently, this necessitates development of assay end points capable of identifying estrogenic xenobiotics. In the present study, we screened the potential estrogenicity of chemicals via their ability to induce vitellogenin (VTG) expression in cultured primary hepatocytes from male trout. A routine method for VTG detection measures the secretion of the protein by enzyme-linked immunosorbent assay (ELISA) in freshly isolated trout hepatocytes. However, this lengthy (6 days) culturing procedure requires that hepatocyte isolation is performed each time the assay is run. We optimized this methodology by investigating the utility of cryopreserved hepatocytes, shortening the incubation time, performing a quantitative real-time PCR (qPCR) method for VTG quantification, and verifying the model system with reference chemicals 17ß-estradiol, estrone, diethylstilbestrol, hexestrol, genistein, and a negative control, corticosterone. To test the performance of both freshly isolated and cryopreserved hepatocytes, mRNA was collected from hepatocytes following 24 h treatment for VTG gene expression analysis, whereas cell culture media was collected for a VTG ELISA 96 h post-treatment. EC50 values were obtained for each reference chemical except for corticosterone, which exhibited no induction of VTG gene or protein level. Our results show linear concordance between ELISA and qPCR detection methods. Although there was approximately 50% reduction in VTG inducibility following cryopreservation, linear concordance of EC50 values was found between freshly isolated and cryopreserved hepatocytes, indicating that cryopreservation does not alter the functional assessment of estrogen receptor activation and therefore VTG expression. These studies demonstrate that qPCR is a sensitive and specific method for detecting VTG gene expression that can be used together with cryopreserved trout hepatocytes for screening estrogenic chemicals, resulting in a reduction of the time required to perform the assay and enabling greater access to the model system through the approach of cryopreservation.

Sequence, cloning, and analysis of the fluvirucin B1 polyketide synthase from Actinomadura vulgaris.

Fluvirucin B1 , produced by Actinomadura vulgaris, is a 14-membered macrolactam active against a variety of infectious fungi as well as influenza A. Despite considerable interest from the synthetic community, very little information is available regarding the biosynthetic origins of the fluvirucins. Herein, we report the identification and initial characterization of the fluvirucin B1 polyketide synthase and related enzymes. The cluster consists of five extender modules flanked by an N-terminal acyl carrier protein and C-terminal thioesterase domain. All but one of the synthase modules contain the full complement of tailoring domains (ketoreductase, dehydratase, and enoyl reductase) as determined by sequence homology with known polyketide synthases. Acitve site analyses of several key components of the cluster are performed to further verify that this gene cluster is associated with production of fluvirucin B1 . This work will both open doors toward a better understanding of macrolactam formation and provide an avenue to genetics-based diversification of fluvirucin structure.

Murine macrophage inflammatory cytokine production and immune activation in response to Vibrio parahaemolyticus infection.

Vibrio parahaemolyticus is the most common cause of bacterial, seafood-related illness in the USA. Currently, there is a dearth of published reports regarding immunity to infection with this pathogen. Here, production of both pro- and anti-inflammatory cytokines by V. parahaemolyticus-infected RAW 264.7 murine macrophages was studied. It was determined that this infection results in increased concentrations of IL-1α, IL-6, TNF-α and IL-10. Additionally, decreases in cell surface TLR2 and TLR4 and increases in T-cell co-stimulatory molecules CD40 and CD86 were discovered. The data presented here begin to identify the immune variables required to eliminate V. parahaemolyticus from infected host tissues.

Castration anxiety and phobias.

Based on Freud's case study of "Little Hans," the authors tested the hypothesis that men with phobias would score higher on castration anxiety than men without phobias. College men with either average or high scores on the Fears Scale of the MMPI-2 (n = 10 men in each group) responded to the Thematic Apperception Test, which was scored for castration anxiety. Men with high scores on the Fears Scale had higher scores on castration anxiety than men with average scores on the Fears Scale. The findings are consistent with Freud's hypothesis about phobias.