88 research outputs found
Economic inequalities in burden of illness, diagnosis and treatment of five long-term conditions in England: panel study
We compared the distribution by wealth of self-reported illness burden (estimated from validated scales, biomarker and reported symptoms) for angina, cataract, depression, diabetes and osteoarthritis, with the distribution of self-reported medical diagnosis and treatment. We aimed to determine if the greater illness burden borne by poorer participants was matched by appropriately higher levels of diagnosis and treatment
Prior event rate ratio adjustment produced estimates consistent with randomized trial: a diabetes case study
Objectives: Electronic health records (EHR) provide a valuable resource for assessing drug side-effects, but treatments are not randomly allocated in routine care creating the potential for bias. We conduct a case study using the Prior Event Rate Ratio (PERR) Pairwise method to reduce unmeasured confounding bias in side-effect estimates for two second-line therapies for type 2 diabetes, thiazolidinediones, and sulfonylureas.
Study design and settings: Primary care data were extracted from the Clinical Practice Research Datalink (n = 41,871). We utilized outcomes from the period when patients took first-line metformin to adjust for unmeasured confounding. Estimates for known side-effects and a negative control outcome were compared with the A Diabetes Outcome Progression Trial (ADOPT) trial (n = 2,545).
Results: When on metformin, patients later prescribed thiazolidinediones had greater risks of edema, HR 95% CI 1.38 (1.13, 1.68) and gastrointestinal side-effects (GI) 1.47 (1.28, 1.68), suggesting the presence of unmeasured confounding. Conventional Cox regression overestimated the risk of edema on thiazolidinediones and identified a false association with GI. The PERR Pairwise estimates were consistent with ADOPT: 1.43 (1.10, 1.83) vs. 1.39 (1.04, 1.86), respectively, for edema, and 0.91 (0.79, 1.05) vs. 0.94 (0.80, 1.10) for GI.
Conclusion: The PERR Pairwise approach offers potential for enhancing postmarketing surveillance of side-effects from EHRs but requires careful consideration of assumptions.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The MASTERMIND (MRC APBI Stratification and
Extreme Response Mechanism IN Diabetes) consortium
is funded by the U.K Medical Research Council funded
study grant number MR/N00633X/1. The funder had no
role in study design, data collection, data analysis, data
interpretation, or writing of the report. IQVIA provided
some funding for this project.published version, accepted version (12 month embargo), submitted versio
Identifying Factors Leading to Harm in English General Practices
This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this record.Objective
The aim of the study was to identify the main factors leading to harm in primary care based on the experiences reported by patients.
Methods
We conducted a mixed-methods, cross-sectional study in 45 primary care centers in England. A random sample of 6736 patients was invited to complete the Patient-Reported Experiences and Outcomes of Safety in Primary Care questionnaire. We fitted structural equation modeling on the quantitative data (n = 1244 respondents) to identify contributory factors and primary incidents leading to harm. We conducted content analyses of responses to seven open-ended questions (n = 386) to obtain deeper insight into patient perceptions of the causes of harm experienced. Results from quantitative and qualitative analyses were triangulated.
Results
Patients reported harm related to physical health (13%), pain (11%), and mental health (19%) and harm that increased limitations in social activities (14%). Physical harm was associated with incidents affecting diagnosis (β = 0.43; delayed and wrong), and treatment (0.12; delayed, wrong treatment, or dose), which were in turn associated with incidents with patient-provider communication, coordination between providers, appointments, and laboratory tests. Pain was associated with laboratory tests (0.21; caused when collecting blood or tissue samples) and with problems booking an appointment when needed (0.13; delaying treatment for pain). Harm to mental health was associated with incidents related to the following: diagnosis (0.28), patient-provider communication (0.18), appointments (0.17), coordination between different providers (0.14), and laboratory tests (0.12). Harm increasing limitations in social activities was associated with incidents related to diagnosis (0.42) and diagnostic and monitoring procedures (0.20).
Conclusions
Our findings suggest the need for patient-centered strategies to reduce harm in primary care focusing on the improvement of the quality of diagnosis and patient-provider communication
Increased expression of axogenesis-related genes and mossy fibre length in dentate granule cells from adult HuD overexpressor mice
The neuronal RNA-binding protein HuD plays a critical role in the post-transcriptional regulation of short-lived mRNAs during the initial establishment and remodelling of neural connections. We have generated transgenic mice overexpressing this protein (HuD-Tg) in adult DGCs (dentate granule cells) and shown that their mossy fibres contain high levels of GAP-43 (growth-associated protein 43) and exhibit distinct morphological and electrophysiological properties. To investigate the basis for these changes and identify other molecular targets of HuD, DGCs from HuD-Tg and control mice were collected by LCM (laser capture microscopy) and RNAs analysed using DNA microarrays. Results show that 216 known mRNAs transcripts and 63 ESTs (expressed sequence tags) are significantly up-regulated in DGCs from these transgenic mice. Analyses of the 3â˛-UTRs (3â˛-untranslated regions) of these transcripts revealed an increased number of HuD-binding sites and the presence of several known instability-conferring sequences. Among these, the mRNA for TTR (transthyretin) shows the highest level of up-regulation, as confirmed by qRTâPCR (quantitative reverse transcriptionâPCR) and ISH (in situ hybridization). GO (gene ontology) analyses of up-regulated transcripts revealed a large over-representation of genes associated with neural development and axogenesis. In correlation with these gene expression changes, we found an increased length of the infrapyramidal mossy fibre bundle in HuD-Tg mice. These results support the notion that HuD stabilizes a number of developmentally regulated mRNAs in DGCs, resulting in increased axonal elongation
Magnetic Impurities in the Pnictide Superconductor BaKFeAs
NMR measurements have been performed on single crystals of
BaKFeAs (x = 0, 0.45) and CaFeAs grown from Sn
flux. The Ba-based pnictide crystals contain significant amounts of Sn in their
structure, %, giving rise to magnetic impurity effects evident in the
NMR spectrum and in the magnetization. Our experiments show that the large
impurity magnetization is broadly distributed on a microscopic scale,
generating substantial magnetic field gradients. There is a concomitant 20%
reduction in the transition temperature which is most likely due to magnetic
electron scattering. We suggest that the relative robustness of
superconductivity () in the presence of severe magnetic inhomogeneity
might be accounted for by strong spatial correlations between impurities on the
coherence length scale.Comment: 14 pages, 6 figures (submitted to New Journal of Physics
Charge Induced Vortex Lattice Instability
It has been predicted that superconducting vortices should be electrically
charged and that this effect is particularly enhanced for, high temperature
superconductors.\cite{kho95,bla96} Hall effect\cite{hag91} and nuclear magnetic
resonance (NMR) experiments\cite{kum01} suggest the existence of vortex
charging, but the effects are small and the interpretation controversial. Here
we show that the Abrikosov vortex lattice, characteristic of the mixed state of
superconductors, will become unstable at sufficiently high magnetic field if
there is charge trapped on the vortex core. Our NMR measurements of the
magnetic fields generated by vortices in BiSrCaCuO
single crystals\cite{che07} provide evidence for an electrostatically driven
vortex lattice reconstruction with the magnitude of charge on each vortex
pancake of x, depending on doping, in line
with theoretical estimates.\cite{kho95,kna05}Comment: to appear in Nature Physics; 6 pages, 7 figure
Integrated motor drives: state of the art and future trends
With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system.
This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented
Ensemble Decision Tree Models Using RUSBoost for Estimating Risk of Iron Failure in Drinking Water Distribution Systems
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