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  • Collins, P. W., et al. (författare)
  • Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A : influences of variance in pharmacokinetics and treatment regimens
  • 2010
  • Ingår i: Journal of Thrombosis and Haemostasis. - International Society on Thrombosis and Haemostasis. - 1538-7933 .- 1538-7836. ; 8:2, s. 269-275
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Prophylactic factor (F)VIII has been shown to reduce bleeds and arthropathy in patients with severe hemophilia A. OBJECTIVES: Assuming that the trough FVIII level is an important determinant of the efficacy of prophylaxis, this paper addresses the effect of the inter-patient variability in pharmacokinetics and different dosing regimens on trough levels. METHODS: Simulations used FVIII half-lives and in vivo recoveries (IVR), observed during clinical trials with Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method], and commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis. RESULTS AND CONCLUSIONS: Half-life and dose frequency had a larger effect on trough FVIII and time per week with FVIII&lt;1 IU dL(-1) than IVR and infused dose per kg. The combined effect of these parameters resulted in substantial inter-patient variability in the amount of FVIII required to sustain a desired trough level. Prophylactic regimens based on Monday, Wednesday, Friday dosing were less cost effective in maintaining a desired trough level throughout the week. Dose escalation on Friday to cover the weekend would require potentially harmful doses of FVIII in many patients, especially in young children where more than 50% would require a Friday dose of over 100 IU kg(-1) and some would require more than 400 IU kg(-1). Knowledge of individual patients' half-lives and alteration of frequency of infusions may allow the more cost-effective use of FVIII and potentially expand access to prophylaxis to a greater number of patients, especially in regions where healthcare resources are scarce.</p>
  • Elliott, J. A., et al. (författare)
  • Risk factors for loss of bone mineral density after curative esophagectomy
  • 2019
  • Ingår i: Archives of Osteoporosis. - 1862-3522. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • .Summary Micronutrient and fat malabsorption and altered enteroendocrine signaling occur after esophagectomy for cancer; however, the impact of malnutrition on bone health in this cohort has not been previously investigated. In this study, the prevalence of osteoporosis increased after curative surgery, associated with disease-specific, treatment-related, and population risk factors.PurposeImproved oncologic outcomes in esophageal cancer (EC) have resulted in increased survivorship and a focus on long-term quality of life. Malnutrition and micronutrient malabsorption are common among patients with EC, but the effect on bone metabolism is not known. The aim of this study was to characterize changes in bone mineral density (BMD) following curative esophagectomy.MethodsConsecutive disease-free patients who underwent esophagectomy with gastric conduit for pathologically node-negative disease from 2000 to 2014 were included. BMD was assessed at vertebral levels T12-L5 by computed tomography using a simple trabecular region-of-interest attenuation technique, and serum markers of nutritional status and bone metabolism were examined. Independent risk factors for osteoporosis were identified by multivariable logistic regression.ResultsSeventy-five consecutive patients were studied. Osteoporosis was present in 25% at diagnosis. BMD declined at 1 and 2years postoperatively (144.345.8 versus 128.6 +/- 46.2 and 122.7 +/- 43.5 Hounsfield Units (HU), P<0.0001), with increased osteoporosis prevalence to 38% and 44% (P=0.049), respectively. No significant postoperative change in vitamin D, calcium, or phosphate was observed, but alkaline phosphatase increased significantly (P<0.001). While female sex (P=0.004) and ASA grade (P=0.043) were independently associated with osteoporosis at diagnosis, age (P=0.050), female sex (P=0.023), smoking (P=0.024), and pathologic T stage (P=0.023) were independently predictive of osteoporosis at 1year postoperatively.Conclusions p id=Par5 Osteoporosis is prevalent among disease-free patients post-esophagectomy for EC, associated with disease-specific, treatment-related, and population risk factors. Strategies which minimize BMD decline should be considered to avoid fragility fractures in this cohort.
  • Hagander, Lars, et al. (författare)
  • Surgeon Migration Between Developing Countries and the United States: Train, Retain, and Gain from Brain Drain
  • 2013
  • Ingår i: World Journal of Surgery. - Springer. - 1432-2323. ; 37:1, s. 14-23
  • Tidskriftsartikel (refereegranskat)abstract
    • The critical shortage of surgeons in many low- and middle-income countries (LMICs) prevents adequate responses to surgical needs, but the factors that affect surgeon migration have remained incompletely understood. The goal of this study was to examine the importance of personal, professional, and infrastructural factors on surgeon migration from LMICs to the United States. We hypothesized that the main drivers of surgeon migration can be addressed by providing adequate domestic surgical infrastructure, surgical training programs, and viable surgical career paths. We conducted an internet-based nationwide survey of surgeons living in the US who originated from LMICs. 66 surgeons completed the survey. The most influential factors for primary migration were related to professional reasons (p a parts per thousand currency sign 0.001). Nonprofessional factors, such as concern for remuneration, family, and security were significantly less important for the initial migration decisions, but adopted a more substantial role in deciding whether or not to return after training in the United States. Migration to the United States was initially considered temporary (44 %), and a majority of the surveyed surgeons have returned to their source countries in some capacity (56 %), often on multiple occasions (80 %), to contribute to clinical work, research, and education. This study suggests that surgically oriented medical graduates from LMICs migrate primarily for professional reasons. Initiatives to improve specialist education and surgical infrastructure in LMICs have the potential to promote retention of the surgical workforce. There may be formal ways for LMICs to gain from the international pool of relocated surgeons.
  • Howes, L.~M., et al. (författare)
  • The EMBLA survey - metal-poor stars in the Galactic bulge
  • 2016
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - Oxford University Press. - 1365-2966. ; 460:1, s. 884-901
  • Tidskriftsartikel (refereegranskat)abstract
    • Cosmological models predict the oldest stars in the Galaxy should be found closest to the centre of the potential well, in the bulge. The Extremely Metal-poor BuLge stars with AAOmega survey (EMBLA) successfully searched for these old, metal-poor stars by making use of the distinctive SkyMapper photometric filters to discover candidate metal-poor stars in the bulge. Their metal-poor nature was then confirmed using the AAOmega spectrograph on the Anglo-Australian Telescope. Here we present an abundance analysis of 10 bulge stars with −2.8 < [Fe/H] < −1.7 from MIKE/Magellan observations, in total determining the abundances of 22 elements. Combining these results with our previous high-resolution data taken as part of the Gaia-ESO Survey, we have started to put together a picture of the chemical and kinematic nature of the most metal-poor stars in the bulge. The currently available kinematic data are consistent with the stars belonging to the bulge, although more accurate measurements are needed to constrain the stars’ orbits. The chemistry of these bulge stars deviates from that found in halo stars of the same metallicity. Two notable differences are the absence of carbon-enhanced metal-poor bulge stars, and the α element abundances exhibit a large intrinsic scatter and include stars which are underabundant in these typically enhanced elements.
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