A new health services platform for patient centred and personalised care

We fully support Bisognano and Schummers’s well presented and timely article. The 2002 Wanless report made us realise that without a change in approach the NHS would become financially challenged and that we needed a way to engage patients. We decided to use an evidence based, patient centred approach to enable patients with long term conditions to take control of their health through shared decision making. Patients with long term conditions were seen in care planning clinics where they could speak about their problems, including social, health, and economic ones. Patients set their goals and action plans—guided and coached by the clinician—and took home a print out of their care plans. Analysis showed a 40% reduction of service utilisation costs in these patients.3 4 This test of the care planning approach shows that “flipping healthcare” works. However, large scale deployment of this approach presented organisational challenges. Turning digital, we incorporated the innovation into an internet delivered service called VitruCare, a scalable and integrated digital health services platform that can present different service packages to suit the patient. Patients can set goals, action plans, and see real time changes in their health status while connected to and coached by their clinician. Early outcome data show improvements in weight, blood pressure, and glycosylated haemoglobin through lifestyle changes. This type of approach provides a route for individuals, families, and communities to engage and enables the cultural change in approach that the NHS desperately needs to be reinvigorated and to thrive. We believe that patient centred and personalised care will become the norm across the health service—engaging and activating patients, as well as enabling proactive management and immediacy to deliver improved outcomes in both health and healthcare

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

Background: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. Materials and methods: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. Results: Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). Conclusions: Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration: EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB

レーザースペックルフローグラフィーを用いて測定した硝子体手術の術前、術中、術後の眼血流

BACKGROUND AND OBJECTIVE: Vitrectomy markedly alters the intraocular milieu, which can then affect the physiology of the retina and choroid. This study investigates whether vitrectomy also alters ocular blood flow as determined by laser speckle flowgraphy (LSFG). PATIENTS AND METHODS: Twenty eyes of 20 patients that underwent vitrectomy for idiopathic macular hole or epiretinal membrane were studied. Standard 23-gauge microincision vitreous surgery was performed. Ocular blood flow of the optic nerve head, retinal vessels, and choroid was determined by LSGF before, during, and 2 weeks and 1 month after vitrectomy. RESULTS: Postoperative blood flow of the optic nerve head, retinal vessels, and choroid did not differ significantly from preoperative values. Intraoperative blood flow of the optic nerve head and retinal vessels decreased significantly from baseline with increasing infusion pressure from 20 mm Hg to 40 mm Hg (P < .01), and choroidal blood flow decreased significantly when the infusion pressure increased from 8 mm Hg to 20 mm Hg and from 20 mm Hg to 40 mm Hg (both P < .01). CONCLUSION: Blood flow did not differ significantly postoperatively versus preoperatively, but it was significantly reduced during vitrectomy with increasing infusion pressure. Careful attention should be paid to infusion pressure during vitrectomy.博士（医学）・乙第1368号・平成27年11月27日Copyright ©2014, SLACK Incorporated. All Rights Reserved.The definitive version is available at " http://dx.doi.org/10.3928/23258160-20140306-04

Population-based study of diagnostic assays for Borrelia infection: comparison of purified flagella antigen assay (Ideia™, Dako Cytomation) and recombinant antigen assay (Liaison®, DiaSorin)

<p>Abstract</p> <p>Background</p> <p>Testing for <it>Borrelia</it>-specific IgM and IgG-antibodies are often performed on a variety of poorly defined symptoms, and isolated IgM results are a frequent finding, which results in diagnostic uncertainty and further testing. We wanted to test the hypothesis that Borrelia-specific assays using recombinant antigens perform differently from assays based on purified flagella antigen.</p> <p>Methods</p> <p>We compared the use of recombinant antigens (LIAISON^®DiaSorin, Saluggia, Italy) and purified flagella antigen (IDEIA™ Borrelia, DakoCytomation, Glostrup, Denmark) in the assay for <it>Borrelia</it>-specific IgM and IgG-antibodies. The assays were tested on an unselected population of serum samples submitted from general practice. A total of 357 consecutive samples for analysis of <it>Borrelia </it>IgM and IgG antibodies. Furthermore, we analysed 540 samples for <it>Borrelia</it>-specific IgM or IgG antibodies first by the IDEIA™ and, if they were positive, the samples were further analysed using the LIAISON^®assay. To verify the correctness of the patient's serological status, discrepant samples were analysed by line blots (EcoLine, Virotech).</p> <p>Results</p> <p>In the consecutive series of 357 samples, the IgM assays detected 308 negative and 3 positive samples with concordant results. Compared with the line blot, the IDEIA™ system produced 21 false-positive IgM results, whereas the LIAISON^®system produced only one false-positive IgM result. The IgG assays showed 1 positive and 328 negative concordant results. The LIAISON^®system produced 9 true IgG-positive samples that were not detected by the IDEIA™ system, but the former produced 4 positive IgG results that were negative by line blot.</p> <p>Conclusion</p> <p>Diagnostic assays based on flagella antigen seem to show more false-positive IgM and false-negative IgG results than assays based on recombinant antigens. The latter may reduce the number of presumably false-positive IgM results and identify more IgG-positive subjects, but this system also produces more false-positive IgG results.</p

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I and MDA5) sense viral RNAs and activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing adaptor inducing interferon-β (TRIF), and mitochondrial antiviral signaling protein (MAVS), respectively. Previously, we demonstrated that hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 signaling by targeting MAVS for cleavage by 3ABC, a precursor of the sole HAV protease, 3Cpro, that is derived by auto-processing of the P3 (3ABCD) segment of the viral polyprotein. Here, we show that HAV also disrupts TLR3 signaling, inhibiting poly(I:C)-stimulated dimerization of IFN regulatory factor 3 (IRF-3), IRF-3 translocation to the nucleus, and IFN-β promoter activation, by targeting TRIF for degradation by a distinct 3ABCD processing intermediate, the 3CD protease-polymerase precursor. TRIF is proteolytically cleaved by 3CD, but not by the mature 3Cpro protease or the 3ABC precursor that degrades MAVS. 3CD-mediated degradation of TRIF depends on both the cysteine protease activity of 3Cpro and downstream 3Dpol sequence, but not 3Dpol polymerase activity. Cleavage occurs at two non-canonical 3Cpro recognition sequences in TRIF, and involves a hierarchical process in which primary cleavage at Gln-554 is a prerequisite for scission at Gln-190. The results of mutational studies indicate that 3Dpol sequence modulates the substrate specificity of the upstream 3Cpro protease when fused to it in cis in 3CD, allowing 3CD to target cleavage sites not normally recognized by 3Cpro. HAV thus disrupts both RIG-I/MDA5 and TLR3 signaling pathways through cleavage of essential adaptor proteins by two distinct protease precursors derived from the common 3ABCD polyprotein processing intermediate

Relationship between apolipoprotein(a) size polymorphism and coronary heart disease in overweight subjects

BACKGROUND: Overweight is associated with an increased cardiovascular risk which is only partially explained by conventional risk factors. The objective of this study was to evaluate lipoprotein(a) [Lp(a)] plasma levels and apolipoprotein(a) [apo(a)] phenotypes in relation to coronary heart disease (CHD) in overweight subjects. METHODS: A total of 275 overweight (BMI ≥ 27 kg/m(2)) subjects, of which 155 had experienced a CHD event, 337 normal weight subjects with prior CHD and 103 CHD-free normal weight subjects were enrolled in the study. Lp(a) levels were determined by an ELISA technique and apo(a) isoforms were detected by a high-resolution immunoblotting method. RESULTS: Lp(a) levels were similar in the three study groups. Overweight subjects with CHD had Lp(a) concentrations significantly higher than those without [median (interquartile range): 20 (5–50.3) versus 12.6 (2.6–38.6) mg/dl, P < 0.05]. Furthermore, overweight subjects with CHD showed a higher prevalence of low molecular weight apo(a) isoforms than those without (55.5% versus 40.8%, P < 0.05) and with respect to the control group (55.5% versus 39.8%, P < 0.05). Stepwise regression analysis showed that apo(a) phenotypes, but not Lp(a) levels, entered the model as significant independent predictors of CHD in overweight subjects. CONCLUSIONS: Our data indicate that small-sized apo(a) isoforms are associated with CHD in overweight subjects. The characterization of apo(a) phenotypes might serve as a reliable biomarker to better assess the overall CHD risk of each subject with elevated BMI, leading to more intensive treatment of modifiable cardiovascular risk factors

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

Investigating the Responses of Human Epithelial Cells to Predatory Bacteria

One beguiling alternative to antibiotics for treating multi-drug resistant infections are Bdellovibrio-and-like-organisms (BALOs), predatory bacteria known to attack human pathogens. Consequently, in this study, the responses from four cell lines (three human and one mouse) were characterized during an exposure to different predatory bacteria, Bdellovibrio bacteriovorus HD100, Bacteriovorus BY1 and Bacteriovorax stolpii EB1. TNF-alpha levels were induced in Raw 264.7 mouse macrophage cultures with each predator, but paled in comparison to those obtained with E. coli. This was true even though the latter strain was added at an 11.1-fold lower concentration (p &lt; 0.01). Likewise, E. coli led to a significant (54%) loss in the Raw 264.7 murine macrophage viability while the predatory strains had no impact. Tests with various epithelial cells, including NuLi-1 airway, Caco2, HT29 and T84 colorectal cells, gave similar results, with E. coli inducing IL-8 production. The viabilities of the NuLi-1 and Caco-2 cells were slightly reduced (8%) when exposed to the predators, while T84 viability remained steady. In no cases did the predatory bacteria induce actin rearrangement. These results clearly demonstrate the gentle natures of predatory bacteria and their impacts on human cells.ope