Health and economic impact of combining metformin with nateglinide to achieve glycemic control: Comparison of the lifetime costs of complications in the U.K

BACKGROUND: To reduce the likelihood of complications in persons with type 2 diabetes, it is critical to control hyperglycaemia. Monotherapy with metformin or insulin secretagogues may fail to sustain control after an initial reduction in glycemic levels. Thus, combining metformin with other agents is frequently necessary. These analyses model the potential long-term economic and health impact of using combination therapy to improve glycemic control. METHODS: An existing model that simulates the long-term course of type 2 diabetes in relation to glycosylated haemoglobin (HbA(1c)) and post-prandial glucose (PPG) was used to compare the combination of nateglinide with metformin to monotherapy with metformin. Complication rates were estimated for major diabetes-related complications (macrovascular and microvascular) based on existing epidemiologic studies and clinical trial data. Utilities and costs were estimated using data collected in the United Kingdom Prospective Diabetes Study (UKPDS). Survival, life years gained (LYG), quality-adjusted life years (QALY), complication rates and associated costs were estimated. Costs were discounted at 6% and benefits at 1.5% per year. RESULTS: Combination therapy was predicted to reduce complication rates and associated costs compared with metformin. Survival increased by 0.39 (0.32 discounted) and QALY by 0.46 years (0.37 discounted) implying costs of £6,772 per discounted LYG and £5,609 per discounted QALY. Sensitivity analyses showed the results to be consistent over broad ranges. CONCLUSION: Although drug treatment costs are increased by combination therapy, this cost is expected to be partially offset by a reduction in the costs of treating long-term diabetes complications

Full thickness epidermal burn from a heating pad on a cesarean incision with silver dressing: a case report

We present a case of a full thickness epidermal burn resulting from an all-natural clay-based heating pad over a cesarean incision silver dressing to bring awareness to the risks associated with nonpharmacologic management of post cesarean pain. There is limited guidance on nonpharmacological management of post cesarean pain. It is important that providers are able to advise their patients about their options, including to be wary of using heating pads on post-cesarean dressings, especially with pain in the early post-partum period

Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair

Microcephaly with early-onset, intractable seizures and developmental delay (MCSZ) is a hereditary disease caused by mutations in polynucleotide kinase/phosphatase (PNKP), a DNA strand break repair protein with DNA 5'-kinase and DNA 3'-phosphatase activity. To investigate the molecular basis of this disease, we examined the impact of MCSZ mutations on PNKP activity in vitro and in cells. Three of the four mutations currently associated with MCSZ greatly reduce or ablate DNA kinase activity of recombinant PNKP at 30°C (L176F, T424Gfs48X and exon15Δfs4X), but only one of these mutations reduces DNA phosphatase activity under the same conditions (L176F). The fourth mutation (E326K) has little impact on either DNA kinase or DNA phosphatase activity at 30°C, but is less stable than the wild-type enzyme at physiological temperature. Critically, all of the MCSZ mutations identified to date result in ∼10-fold reduced cellular levels of PNKP protein, and reduced rates of chromosomal DNA strand break repair. Together, these data suggest that all four known MCSZ mutations reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5'-kinase activity and all of the mutations greatly reducing cellular DNA 3'-phosphatase activity

Understanding factors associated with the translation of cardiovascular research: A multinational case study approach

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Funders of health research increasingly seek to understand how best to allocate resources in order to achieve maximum value from their funding. We built an international consortium and developed a multinational case study approach to assess benefits arising from health research. We used that to facilitate analysis of factors in the production of research that might be associated with translating research findings into wider impacts, and the complexities involved. Methods: We built on the Payback Framework and expanded its application through conducting co-ordinated case studies on the payback from cardiovascular and stroke research in Australia, Canada and the United Kingdom. We selected a stratified random sample of projects from leading medical research funders. We devised a series of innovative steps to: minimize the effect of researcher bias; rate the level of impacts identified in the case studies; and interrogate case study narratives to identify factors that correlated with achieving high or low levels of impact. Results: Twenty-nine detailed case studies produced many and diverse impacts. Over the 15 to 20 years examined, basic biomedical research has a greater impact than clinical research in terms of academic impacts such as knowledge production and research capacity building. Clinical research has greater levels of wider impact on health policies, practice, and generating health gains. There was no correlation between knowledge production and wider impacts. We identified various factors associated with high impact. Interaction between researchers and practitioners and the public is associated with achieving high academic impact and translation into wider impacts, as is basic research conducted with a clinical focus. Strategic thinking by clinical researchers, in terms of thinking through pathways by which research could potentially be translated into practice, is associated with high wider impact. Finally, we identified the complexity of factors behind research translation that can arise in a single case. Conclusions: We can systematically assess research impacts and use the findings to promote translation. Research funders can justify funding research of diverse types, but they should not assume academic impacts are proxies for wider impacts. They should encourage researchers to consider pathways towards impact and engage potential research users in research processes. © 2014 Wooding et al.; licensee BioMed Central Ltd.RAND Europe and HERG, with subsequent funding from the NHFA, the HSFC and the CIHR. This research was also partially supported by the Policy Research Programme in the English Department of Health

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children

Improving and Assessing Planet Sensitivity of the GPI Exoplanet Survey with a Forward Model Matched Filter

We present a new matched filter algorithm for direct detection of point sources in the immediate vicinity of bright stars. The stellar Point Spread Function (PSF) is first subtracted using a Karhunen-Lo\'eve Image Processing (KLIP) algorithm with Angular and Spectral Differential Imaging (ADI and SDI). The KLIP-induced distortion of the astrophysical signal is included in the matched filter template by computing a forward model of the PSF at every position in the image. To optimize the performance of the algorithm, we conduct extensive planet injection and recovery tests and tune the exoplanet spectra template and KLIP reduction aggressiveness to maximize the Signal-to-Noise Ratio (SNR) of the recovered planets. We show that only two spectral templates are necessary to recover any young Jovian exoplanets with minimal SNR loss. We also developed a complete pipeline for the automated detection of point source candidates, the calculation of Receiver Operating Characteristics (ROC), false positives based contrast curves, and completeness contours. We process in a uniform manner more than 330 datasets from the Gemini Planet Imager Exoplanet Survey (GPIES) and assess GPI typical sensitivity as a function of the star and the hypothetical companion spectral type. This work allows for the first time a comparison of different detection algorithms at a survey scale accounting for both planet completeness and false positive rate. We show that the new forward model matched filter allows the detection of $50\%$ fainter objects than a conventional cross-correlation technique with a Gaussian PSF template for the same false positive rate.Comment: ApJ accepte

Dynamical Mass Measurement of the Young Spectroscopic Binary V343 Normae AaAb Resolved With the Gemini Planet Imager

We present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the beta Pictoris moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10" M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components of M_Aa = 1.10 +/- 0.10 M_sun and M_Ab = 0.290 +/- 0.018 M_sun. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the beta Pic moving group. We derive a model-dependent age for the beta Pic moving group of 26 +/- 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.Comment: 12 pages, 7 figures. Accepted to A

The Peculiar Debris Disk of HD 111520 as Resolved by the Gemini Planet Imager

Using the Gemini Planet Imager (GPI), we have resolved the circumstellar debris disk around HD 111520 at a projected range of ~30-100 AU in both total and polarized $H$-band intensity. The disk is seen edge-on at a position angle of ~165$^{\circ}$ along the spine of emission. A slight inclination or asymmetric warping are covariant and alters the interpretation of the observed disk emission. We employ 3 point spread function (PSF) subtraction methods to reduce the stellar glare and instrumental artifacts to confirm that there is a roughly 2:1 brightness asymmetry between the NW and SE extension. This specific feature makes HD 111520 the most extreme examples of asymmetric debris disks observed in scattered light among similar highly inclined systems, such as HD 15115 and HD 106906. We further identify a tentative localized brightness enhancement and scale height enhancement associated with the disk at ~40 AU away from the star on the SE extension. We also find that the fractional polarization rises from 10 to 40% from 0.5" to 0.8" from the star. The combination of large brightness asymmetry and symmetric polarization fraction leads us to believe that an azimuthal dust density variation is causing the observed asymmetry.Comment: 9 pages, 8 Figures, 1 table, Accepted to Ap

GPI spectra of HR 8799 c, d, and e from 1.5 to 2.4μ\mum with KLIP Forward Modeling

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in H & K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same dataset. We also present a K band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H & K spectra, but do not find any conclusive differences between d and e or c and e, likely due to large error bars in the recovered spectrum of e. Compared to M, L, and T-type field brown dwarfs, all three planets are most consistent with mid and late L spectral types. All objects are consistent with low gravity but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets' near-IR flux and discuss how differences between the properties of these planets can be further explored.Comment: Accepted to AJ, 25 pages, 16 Figure