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Effective medication shipping and delivery by simply fresh cell-penetrating peptide produced from Midkine, along with two heparin joining sites braced with a length-specific helix.
BACKGROUND AND OBJECTIVES The glucagon-like peptide-1 receptor agonist liraglutide demonstrated cardiovascular and kidney benefits in the LEADER trial, particularly in participants with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This post hoc analysis evaluated the safety of liraglutide treatment in patients with CKD in LEADER. Overall, 9340 patients were randomized to liraglutide or placebo, both in addition to standard of care. Of those, 2158 patients had CKD versus 7182 without CKD (defined as eGFR 300 mg/g and ≥30 to ≤300 mg/g, respectively). At baseline, the mean eGFR in patients with CKD was 46±11 ml/min per 1.73 m2 versus 91±22 ml/min per 1.73 m2 in those without CKD. Time to first event within event groups was analyzed using Cox regression with treatment group, baseline eGFR group, or baseline albuminuria group as fixed factors. RESULTS Overall, serious adverse events were more frequently recorded in patients with CKD compared with those without CKD (59% versus 50%; interaction P=0.11); however, they occurred to the same extent in those on liraglutide versus placebo. GW3965 Similarly, no interaction of adverse events with randomized therapy was observed in patients with micro- or macro- versus normoalbuminuria (interaction P=0.11). Risk of severe hypoglycemia was significantly reduced with liraglutide versus placebo in patients with CKD or with micro- or macroalbuminuria (hazard ratio, 0.63 [95% CI, 0.43 to 0.91] and 0.57 [95% CI, 0.40 to 0.82], respectively). CONCLUSIONS In LEADER, the use of liraglutide in those with CKD was safe, with no difference between patients with and without CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER ClinicalTrials.gov; NCT01179048 (https//clinicaltrials.gov/ct2/show/NCT01179048). Copyright © 2020 by the American Society of Nephrology.OBJECTIVE To explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate-late preterm (MLPT). STUDY DESIGN A cohort of MLPT infants had brain MRI at approximately TEA (38-44 weeks' postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years' corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics. RESULTS 189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes. CONCLUSIONS Regional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Robotic-assisted technology has been used as a tool to enhance open and minimally invasive surgeries as well as percutaneous coronary and peripheral vascular interventions. It offers many potential benefits, including increased procedural and technical accuracy as well as reduced radiation dose during fluoroscopic procedures. It also offers the potential for truly "remote" procedures. Despite these benefits, robotic technology has not yet been used in the neuroendovascular field, aside from diagnostic cerebral angiography. Here, we report the first robotic-assisted, therapeutic, neuroendovascular intervention performed in a human. This was a stent-assisted coiling procedure to treat a large basilar aneurysm. All intracranial steps, including stent placement and coil deployment, were performed with assistance from the CorPath GRX Robotic System (Corindus, a Siemens Healthineers Company, Waltham, MA, USA). This represents a major milestone in the treatment of neurovascular disease and opens the doors for the development of remote robotic neuroendovascular procedures. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES To examine validity of prevalence-based models giving projections of prevalence of diabetes in adults, in England and the UK, and of Markov chain models giving estimates of economic impacts of interventions to prevent type 2 diabetes (T2D). METHODS Rapid reviews of both types of models. Estimation of the future prevalence of T2D in England by Markov chain models; and from the trend in the prevalence of diabetes, as reported in the Quality and Outcomes Framework (QOF), estimated by ordinary least squares regression analysis. SETTING Adult population in England and UK. MAIN OUTCOME MEASURE Prevalence of T2D in England and UK in 2025. RESULTS The prevalence-based models reviewed use sample estimates of past prevalence rates by age and sex and projected population changes. Three most recent models, including that of Public Health England (PHE), neither take account of increases in obesity, nor report Confidence Intervals (CIs). The Markov chain models reviewed use transition probabilities between states of risk and death, estimated from various sources. None of their accounts give the full matrix of transition probabilities, and only a minority report tests of validation. Their primary focus is on estimating the ratio of costs to benefits of preventive interventions in those with hyperglycaemia, only one reported estimates of those developing T2D in the absence of a preventive intervention in the general population.Projections of the prevalence of T2D in England in 2025 were (in millions) by PHE, 3.95; from the QOF trend, 4.91 and by two Markov chain models, based on our review, 5.64 and 9.07. CONCLUSIONS To inform national policies on preventing T2D, governments need validated models, designed to use available data, which estimate the scale of incidence of T2D and survival in the general population, with and without preventive interventions. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.INTRODUCTION Food insecurity is associated with increased risk for several health conditions and with poor chronic disease management. Key determinants for household food insecurity are income and food costs. Whereas short-term household incomes are likely to remain static, increased food prices would be a significant driver of food insecurity. OBJECTIVES To investigate food price drivers for household food security and its health consequences in the UK under scenarios of Deal and No-deal for Britain's exit from the European Union. To estimate the 5% and 95% quantiles of the projected price distributions. DESIGN Structured expert judgement elicitation, a well-established method for quantifying uncertainty, using experts. In July 2018, each expert estimated the median, 5% and 95% quantiles of changes in price for 10 food categories under Brexit Deal and No-deal to June 2020 assuming Brexit had taken place on 29 March 2019. These were aggregated based on the accuracy and informativeness of the experts on calibre permitted under CC BY. Published by BMJ.OBJECTIVE The prevalence of diabetes in Vietnam has increased from 2.5% in 2007 to 5.5% in 2017, but the burden of direct non-medical and indirect costs is unknown. The objective of this study was to estimate the direct non-medical costs and indirect costs due to type 2 diabetes mellitus (T2DM) and its associated complications among Vietnam Health Insurance System (VHIS) enrollees in Vietnam. DESIGN The first phase was a cross-sectional survey of patients with T2DM. In the second phase, data from the previous phase were used to predict direct non-medical costs and presenteeism costs of VHIS enrollees diagnosed with T2DM based on demographic and clinical characteristics in 2017. The human-capital approach was used for the calculation of indirect costs. SETTING AND PARTICIPANTS This study recruited 315 patients from a national hospital, a provincial hospital and a district hospital aged 18 or above, diagnosed with T2DM, enrolled in VHIS, and having at least one visit to hospitals between 1 June and 30 July 2018NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE We estimated the effect of an employer-sponsored health insurance (ESHI) scheme on healthcare utilisation of medically trained providers and reduction of out-of-pocket (OOP) expenditure among ready-made garment (RMG) workers. DESIGN We used a case-control study design with cross-sectional preintervention and postintervention surveys. SETTINGS The study was conducted among workers of seven purposively selected RMG factories in Shafipur, Gazipur in Bangladesh. PARTICIPANTS In total, 1924 RMG workers (480 from the insured and 482 from the uninsured, in each period) were surveyed from insured and uninsured RMG factories, respectively, in the preintervention (October 2013) and postintervention (April 2015) period. INTERVENTIONS We tested the effect of a pilot ESHI scheme which was implemented for 1 year. OUTCOME MEASURES The outcome measures were utilisation of medically trained providers and reduction of OOP expenditure among RMG workers. We estimated difference-in-difference (DiD) and applied two-part ional intervention be provided to RMG workers to improve their healthcare-seeking behaviours and increase their utilisation of ESHI-designated healthcare providers while keeping OOP payments low. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Free-fatty acid receptor-4 (FFA4), previously termed GPR120, is a G protein-coupled receptor (GPCR) for medium and long-chained fatty acids, agonism of which can regulate a myriad of metabolic, sensory, inflammatory, and proliferatory signals. Two alternative splice isoforms of FFA4 exist that differ by the presence of an additional 16 amino acids in the longer (FFA4-L) transcript, which has been suggested to be an intrinsically β-arrestin-biased GPCR. Although the shorter isoform (FFA4-S) has been studied more extensively, very little is known about mechanisms of regulation or signaling of the longer isoform. Because β-arrestin recruitment is dependent on receptor phosphorylation, in the current study, we used the endogenous agonist docosahexaenoic acid (DHA) to examine the mechanisms of FFA4-L phosphorylation, as well as DHA-dependent β-arrestin recruitment and DHA-dependent extracellular-signal regulated kinase-1/2 (ERK1/2) signaling in human embryonic kidney 293 cells. Our results reveal differences in basal phosphorylation of the two FFA4 isoforms, and we show that DHA-mediated phosphorylation of FFA4-L is primarily regulated by G protein-coupled receptor kinase 6, whereas protein kinase-C can also contribute to agonist-induced and heterologous phosphorylation.
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