Integrating Telemedicine Solutions with Electronic Health Records; Evaluation of Alternatives based on the Proposed Reference Architecture for Norway. Report 02-2016

This report studies the way forward for how a telemedicine solution can be integrated for exchange of data with an existing Electronic Health Record (EHR) system. The solution used an example for this report is based on a telemedicine solution for COPD patients (Chronic Obstructive Pulmonary Disease) developed in the project “Collaborative Point-of-Care Services Agder: Follow-up of COPD patients as part of the United4Health EU Project», with financial support from the Research Council of Norway. In addition, the EHR solution from DIPS ASA is used as an example of an existing system for integration. Important parameters for choosing way forward on how to are: urgency with regards to timeline level of structuring of the data. compliance with the reference architecture1proposed by the Norwegian Directorate of eHealth (NDE) Three alternative ways forward are discussed in this report, based on four different scenarios with their respectively defined use-cases. Possibilities of integration exists already today which may support one of the use cases in the simplest way, but may not be a futureproof solution regarding functionality and recommended standards. Such a solution is supported by DIPS Classic as well as DIPS Arena by using HL7 V3 interface in DIPS. The journal data may be stored in an unstructured way as a PDF document in a patients EHR. To send structured data from a Telemedicine System to an EHR will be the preferred way for the future, and will support several use cases in a more efficient way. This will require more work in total and is dependent on other parties (external storage, DIPS etc) for building infrastructure and new interfaces. Such solutions will still be of high interest in the future. This report describes two different scenarios for how such solutions can be implemented in the future using either external storage and XDS.b or using FHIR/OpenEHR. Which of these alternatives that will be the leading standard or best practice is hard to predict, since it will highly depend on how the user requirements from the health care market will request such solutions, and how the standardization requirements from National authorities evolves in the next years. In addition, it depends on how the developers/vendors of both telemedicine solutions and EHR-systems will responds to these requirements

Massive blow-out craters formed by hydrate-controlled methane expulsion from the Arctic seafloor

Widespread methane release from thawing Arctic gas hydrates is a major concern, yet the processes, sources, and fluxes involved remain unconstrained. We present geophysical data documenting a cluster of kilometer-wide craters and mounds from the Barents Sea floor associated with large-scale methane expulsion. Combined with ice sheet/gas hydrate modeling, our results indicate that during glaciation, natural gas migrated from underlying hydrocarbon reservoirs and was sequestered extensively as subglacial gas hydrates. Upon ice sheet retreat, methane from this hydrate reservoir concentrated in massive mounds before being abruptly released to form craters. We propose that these processes were likely widespread across past glaciated petroleum provinces and that they also provide an analog for the potential future destabilization of subglacial gas hydrate reservoirs beneath contemporary ice sheets.authorsversionPeer reviewe

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

The impact of caspase-12 on susceptibility to candidemia

Candida is one of the leading causes of sepsis, and an effective host immune response to Candida critically depends on the cytokines IL-1β and IL-18, which need caspase-1 cleavage to become bioactive. Caspase-12 has been suggested to inhibit caspase-1 activation and has been implicated as a susceptibility factor for bacterial sepsis. In populations of African descent, CASPASE-12 is either functional or non-functional. Here, we have assessed the frequencies of both CASPASE-12 alleles in an African-American Candida sepsis patients cohort compared to uninfected patients with similar predisposing factors. African-American Candida sepsis patients (n = 93) and non-infected African-American patients (n = 88) were genotyped for the CASPASE-12 genotype. Serum cytokine concentrations of IL-6, IL-8, and IFNγ were measured in the serum of infected patients. Statistical comparisons were performed in order to assess the effect of the CASPASE-12 genotype on susceptibility to candidemia and on serum cytokine concentrations. Our findings demonstrate that CASPASE-12 does not influence the susceptibility to Candida sepsis, nor has any effect on the serum cytokine concentrations in Candida sepsis patients during the course of infection. Although the functional CASPASE-12 allele has been suggested to increase susceptibility to bacterial sepsis, this could not be confirmed in our larger cohort of fungal sepsis patients

A cluster of Candida krusei infections in a haematological unit

<p>Abstract</p> <p>Background</p> <p><it>Candida krusei </it>infections are associated with high mortality. In order to explore ways to prevent these infections, we investigated potential routes for nosocomial spread and possible clonality of <it>C. krusei </it>in a haematological unit which had experienced an unusually high incidence of cases.</p> <p>Methods</p> <p>We searched for <it>C. krusei </it>contamination of the hospital environment and determined the level of colonization in patients and health care workers. We also analyzed the possible association between exposure to prophylactic antifungals or chemotherapeutic agents and occurrence of <it>C. krusei</it>. The <it>C. krusei </it>isolates found were genotyped by pulsed-field electrophoresis method in order to determine possible relatedness of the cases.</p> <p>Results</p> <p>Twelve patients with invasive <it>C. krusei </it>infection and ten patients with potentially significant infection or mucosal colonization were documented within nine months. We were unable to identify any exogenic source of infection or colonization. Genetic analysis of the isolates showed little evidence of clonal transmission of <it>C. krusei </it>strains between the patients. Instead, each patient was colonized or infected by several different closely related genotypes. No association between medications and occurrence of <it>C. krusei </it>was found.</p> <p>Conclusion</p> <p>Little evidence of nosocomial spread of a single <it>C. krusei </it>clone was found. The outbreak may have been controlled by cessation of prophylactic antifungals and by intensifying infection control measures, e.g. hand hygiene and cohorting of the patients, although no clear association with these factors was demonstrated.</p

p53 mutations in classic and pleomorphic invasive lobular carcinoma of the breast

Contains fulltext : 110338.pdf (publisher's version ) (Open Access)BACKGROUND: p53 is a tumor suppressor that is frequently mutated in human cancers. Although alterations in p53 are common in breast cancer, few studies have specifically investigated TP53 mutations in the breast cancer subtype invasive lobular carcinoma (ILC). Recently reported conditional mouse models have indicated that functional p53 inactivation may play a role in ILC development and progression. Since reports on the detection of TP53 mutations in the relatively favorable classic and more aggressive pleomorphic variants of ILC (PILC) are rare and ambiguous, we performed a comprehensive analysis to determine the mutation status of TP53 in these breast cancer subtypes. METHODS: To increase our understanding of p53-mediated pathways and the roles they may play in the etiology of classic ILC and PILC, we investigated TP53 mutations and p53 accumulation in a cohort of 22 cases of classic and 19 cases of PILC by direct DNA sequencing and immunohistochemistry. RESULTS: We observed 11 potentially pathogenic TP53 mutations, of which three were detected in classic ILC (13.6%) and 8 in PILC (42.1%; p = 0.04). While p53 protein accumulation was not significantly different between classic and pleomorphic ILC, mutations that affected structure and protein function were significantly associated with p53 protein levels. CONCLUSION: TP53 mutations occur more frequently in PILC than classic ILC.1 april 201

Control and Manipulation of Pathogens with an Optical Trap for Live Cell Imaging of Intercellular Interactions

The application of live cell imaging allows direct visualization of the dynamic interactions between cells of the immune system. Some preliminary observations challenge long-held beliefs about immune responses to microorganisms; however, the lack of spatial and temporal control between the phagocytic cell and microbe has rendered focused observations into the initial interactions of host response to pathogens difficult. This paper outlines a method that advances live cell imaging by integrating a spinning disk confocal microscope with an optical trap, also known as an optical tweezer, in order to provide exquisite spatial and temporal control of pathogenic organisms and place them in proximity to host cells, as determined by the operator. Polymeric beads and live, pathogenic organisms (Candida albicans and Aspergillus fumigatus) were optically trapped using non-destructive forces and moved adjacent to living cells, which subsequently phagocytosed the trapped particle. High resolution, transmitted light and fluorescence-based movies established the ability to observe early events of phagocytosis in living cells. To demonstrate the broad applicability of this method to immunological studies, anti-CD3 polymeric beads were also trapped and manipulated to form synapses with T cells in vivo, and time-lapse imaging of synapse formation was also obtained. By providing a method to exert fine control of live pathogens with respect to immune cells, cellular interactions can be captured by fluorescence microscopy with minimal perturbation to cells and can yield powerful insight into early responses of innate and adaptive immunity.National Institute of Biomedical Imaging and Bioengineering (U.S.) (grant T32EB006348)Massachusetts General Hospital (Department of Medicine Internal Funds)Center for Computational and Integrative Biology (Development fund)Center for Computational and Integrative Biology (AI062773)Center for Computational and Integrative Biology (grant AI062773)Center for Computational and Integrative Biology (grant DK83756)Center for Computational and Integrative Biology (grant DK 043351)National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health (U.S.) (grant AI057999

The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity

Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA+ plasma cells remain poorly understood. Here, we report that the B cell–expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37−/−) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA+ plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37–deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37−/− mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37−/− mice. To demonstrate the importance of CD37—which can associate with the pattern-recognition receptor dectin-1—in immunity to infection, CD37−/− mice were exposed to Candida albicans. We report that CD37−/− mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans–specific IgA antibodies. Importantly, adoptive transfer of CD37−/− serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response