58 research outputs found

    Application of biomedical informatics to chronic pediatric diseases: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>Chronic diseases affect millions of children worldwide leading to substantial disease burden to the children and their families as well as escalating health care costs. The increasing trend in the prevalence of complex pediatric chronic diseases requires innovative and optimal delivery of care. Biomedical informatics applications play an important role in improving health outcomes while being cost-effective. However, their utility in pediatric chronic diseases has not been studied in a comprehensive and systematic way. The objective of this study was to conduct a systematic review of the effects of biomedical informatics applications in pediatric chronic diseases.</p> <p>Methods</p> <p>A comprehensive literature search was conducted using MEDLINE, the Cochrane Library and EMBASE databases from inception of each database to September 2008. We included studies of any methodological type and any language that applied biomedical informatics to chronic conditions in children and adolescents 18 years of age or younger. Two independent reviewers carried out study selection and data extraction. Quality assessment was performed using a study design evaluation instrument to appraise the strength of the studies and their methodological adequacy. Because of heterogeneity in the conditions and outcomes we studied, a formal meta-analysis was not performed.</p> <p>Results</p> <p>Based on our search strategy, 655 titles and abstracts were reviewed. From this set we identified 27 relevant articles that met our inclusion criteria. The results from these studies indicated that biomedical informatics applications have favourable clinical and patient outcomes including, but not limited to, reduced number of emergency room visits, improved knowledge on disease management, and enhanced satisfaction. Seventy percent of reviewed papers were published after year 2000, 89% of users were patients and 11% were either providers or caregivers. The majority (96%) of the selected studies reported improved outcomes.</p> <p>Conclusion</p> <p>Published studies suggested positive impacts of informatics predominantly in pediatric asthma. As electronic tools become more widely adopted, there will be opportunities to improve patient care in a wide range of chronic illnesses through informatics solutions.</p

    The relevance of WHO injury surveillance guidelines for evaluation: learning from the aboriginal community-centered injury surveillance system (ACCISS) and two institution-based systems

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    <p>Abstract</p> <p>Background</p> <p>Over the past three decades, the capacity to develop and implement injury surveillance systems (ISS) has grown worldwide and is reflected by the diversity of data gathering environments in which ISS operate. The capacity to evaluate ISS, however, is less advanced and existing evaluation guidelines are ambiguous. Furthermore, the applied relevance of these guidelines to evaluate ISS operating in various settings is unclear. The aim of this paper was to examine how the World Health Organization (WHO) injury surveillance guidelines have been applied to evaluate systems operating in three different contexts.</p> <p>Methods</p> <p>The attributes of a good surveillance system as well as instructions for conducting evaluations, outlined in the WHO injury surveillance guidelines, were used to develop an analytical framework. Using this framework, a comparative analysis of the application of the guidelines was conducted using; the Aboriginal Community-Centered Injury Surveillance System (ACCISS) from Canada, the Shantou-Emergency Department Injury Surveillance Project (S-EDISP) from China, and the Yorkhill-Canadian Hospitals Injury Reporting and Prevention Program (Y-CHIRPP) imported from Canada and implemented in Scotland.</p> <p>Results</p> <p>The WHO guidelines provide only a basic platform for evaluation. The guidelines over emphasize epidemiologic attributes and methods and under emphasize public health and injury prevention perspectives requiring adaptation for context-based relevance. Evaluation elements related to the dissemination and use of knowledge, acceptability, and the sustainability of ISS are notably inadequate. From a public health perspective, alternative reference points are required for re-conceptualizing evaluation paradigms. This paper offers an ISS evaluation template that considers how the WHO guidelines could be adapted and applied.</p> <p>Conclusions</p> <p>Findings suggest that attributes of a good surveillance system, when used as evaluation metrics, cannot be weighted equally across ISS. In addition, the attribute of acceptability likely holds more relevance than previously recognized and should be viewed as a critical underpinning attribute of ISS. Context-oriented evaluations sensitive to distinct operational environments are more likely to address knowledge gaps related to; understanding links between the production of injury data and its use, and the effectiveness, impact, and sustainability of ISS. Current frameworks are predisposed to disassociating epidemiologic approaches from subjective factors and social processes.</p

    Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques

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    Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Oak root response to ectomycorrhizal symbiosis establishment: RNA-Seq derived transcript identification and expression profiling

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    Ectomycorrhizal symbiosis is essential for the life and health of trees in temperate and boreal forests where it plays a major role in nutrient cycling and in functioning of the forest ecosystem. Trees with ectomycorrhizal root tips are more tolerant to environmental stresses, such as drought, and biotic stresses such as root pathogens. Detailed information on these molecular processes is essential for the understanding of symbiotic tissue development in order to optimize the benefits of this natural phenomenon. Next generation sequencing tools allow the analysis of non model ectomycorrhizal plant-fungal interactions that can contribute to find the "symbiosis toolkits" and better define the role of each partner in the mutualistic interaction. By using 454 pyrosequencing we compared ectomycorrhizal cork oak roots with non-symbiotic roots. From the two cDNA libraries sequenced, over 2 million reads were obtained that generated 19,552 cork oak root unique transcripts. A total of 2238 transcripts were found to be differentially expressed when ECM roots were compared with non-symbiotic roots. Identification of up- and down-regulated gens in ectomycorrhizal roots lead to a number of insights into the molecular mechanisms governing this important symbiosis. In cork oak roots, ectomycorrhizal colonization resulted in extensive cell wall remodelling, activation of the secretory pathway, alterations in flavonoid biosynthesis, and expression of genes involved in the recognition of fungal effectors. In addition, we identified genes with putative roles in symbiotic processes such as nutrient exchange with the fungal partner, lateral root formation or root hair decay. These findings provide a global overview of the transcriptome of an ectomycorrhizal host root, and constitute a foundation for future studies on the molecular events controlling this important symbiosis.This work was funded by the Portuguese Foundation for Science and Technology (www.fct.pt) in the frame of the project Cork Oak EST Consortium SOBREIRO/0034/2009. Post-doc grant to MS was supported by the Portuguese Foundation for Science and Technology (SFRH/BPD/25661/2005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

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    This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

    Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

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    Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
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