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Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A paradigm shift in therapeutic approach 下载免费PDF全文
Mark D. Wilkie MRCS DO‐HNS Navdeep S. Upile MRCS DO‐HNS Andrew S. Lau MRCS DO‐HNS Stephen P. Williams MRCS Jon Sheard FRCPath Tim R. Helliwell FRCPath Max Robinson FRCPath Jennifer Rodrigues FRCA Krishna Beemireddy FRCA Huw Lewis–Jones FRCR Rebecca Hanlon FRCR David Husband FRCR Aditya Shenoy FRCR Nicholas J. Roland FRCS Shaun R. Jackson FRCS Fazilet Bekiroglu FRCS Sankalap Tandon FRCS Jeffrey Lancaster FRCS Terence M. Jones FRCS 《Head & neck》2016,38(8):1263-1270
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Umut Özbek Hui‐Min Lin Yan Lin Daniel E. Weeks Wei Chen John R. Shaffer Shaun M. Purcell Eleanor Feingold 《Genetic epidemiology》2018,42(6):539-550
In a genome‐wide association study (GWAS), association between genotype and phenotype at autosomal loci is generally tested by regression models. However, X‐chromosome data are often excluded from published analyses of autosomes because of the difference between males and females in number of X chromosomes. Failure to analyze X‐chromosome data at all is obviously less than ideal, and can lead to missed discoveries. Even when X‐chromosome data are included, they are often analyzed with suboptimal statistics. Several mathematically sensible statistics for X‐chromosome association have been proposed. The optimality of these statistics, however, is based on very specific simple genetic models. In addition, while previous simulation studies of these statistics have been informative, they have focused on single‐marker tests and have not considered the types of error that occur even under the null hypothesis when the entire X chromosome is scanned. In this study, we comprehensively tested several X‐chromosome association statistics using simulation studies that include the entire chromosome. We also considered a wide range of trait models for sex differences and phenotypic effects of X inactivation. We found that models that do not incorporate a sex effect can have large type I error in some cases. We also found that many of the best statistics perform well even when there are modest deviations, such as trait variance differences between the sexes or small sex differences in allele frequencies, from assumptions. 相似文献
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OBJECTIVES: To investigate patterns of patient preference for 3 formulations of zolmitriptan, in a primary care study utilizing a naturalistic longitudinal design. BACKGROUND: Although differences in efficacy between individual triptans tend to be small, migraine patients show clear preferences for individual triptans and formulations. The groups of patients suitable for the different triptan formulations, and the reasons underlying individual preferences, are not clearly understood. METHODS: Migraine patients entered a prospective, randomized, open, crossover, longitudinal design study, with patients receiving zolmitriptan formulations according to UK prescribing recommendations. Patients na?ve to zolmitriptan received zolmitriptan 2.5-mg film-coated tablets or 2.5-mg Orally Disintegrating Tablets (ODT) for 1 month, before being crossed over to receive the alternative formulation for Month 2. All patients then received zolmitriptan nasal spray 5 mg for Month 3. Patients could then choose the formulation(s) of their choice for a further 7 months. Patients recorded their preferences for individual formulations, the reasons for their preferences, and also the headache-related disability (measured by the Migraine Disability Assessment [MIDAS] score) at clinic visits. Primary endpoints were the individual preferences and changes in MIDAS scores. Adverse events were also recorded. RESULTS: Forty-eight patients took part in the study. At baseline, most patients expressed a preference for conventional tablets. After 4 months, 46.9% of patients preferred zolmitriptan ODT, 43.8% zolmitriptan nasal spray, and 6.3% the conventional tablet. The most common reasons given for preferring conventional tablets were personal reasons: for zolmitriptan ODT, convenience and, to a lesser extent, speed of onset: for zolmitriptan nasal spray, speed of onset, and overall efficacy. MIDAS scores decreased significantly following treatment with zolmitriptan. Zolmitriptan was well tolerated. CONCLUSIONS: Patient experience of newer zolmitriptan formulations influenced a change in preference away from conventional tablets. Speed and efficacy were the key drivers of preference for zolmitriptan nasal spray, while convenience mostly drove preference for the ODT formulation. Open, longitudinal, naturalistic studies may, allowing for biases, sometimes be an appropriate way of conducting migraine studies in primary care. 相似文献
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Background Atopic dermatitis (AD) is the most common form of eczema. As leukotriene mediators are involved in the inflammatory phase of atopic dermatitis, montelukast has been suggested as a possible therapy. Aim of the review To evaluate the safety and efficacy of montelukast off-label use for the treatment atopic dermatitis. Method A search was performed from database inception until March 2018 in six electronic databases for randomized-controlled-trials examining the use of montelukast for AD. Results Among 301 articles screened, 11 studies met the inclusion criteria and were included in the review. The study populations consist of paediatric and adult subjects with moderate-to-severe AD. Montelukast use was shown to improve symptoms such as pruritus in four studies. Another 2 studies reported that montelukast could improve symptoms similar to the standard regimen of topical steroid and oral antihistamine. However, five studies reported that montelukast had no effects in symptoms alleviation. The use of montelukast was associated with a similar safety profile to placebo and well-tolerated with minimal adverse effects. Conclusion There is limited evidence to suggest that the off-label use of montelukast is effective in treating moderate-to-severe AD. Further research with larger study populations employing standardized endpoint measuring instrument is warranted to further investigate the off-label use of montelukast in AD treatment. Until then, the use of conventional treatments including optimal daily skin hydration should remain the mainstay in the management of atopic dermatitis. In fact, for moderate-to-severe condition, steroid sparing immune-suppressants should still be used clinically until more effective and safer alternative is discovered. 相似文献
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Tanya Mokhateb-Rafii Martin Bialer Shaun Rodgers Christine Moore Todd Sweberg 《The Journal of emergency medicine》2019,56(1):e1-e4
Background
RIPPLY2-associated spondylocostal dysostosis is a rare disorder that leads to segmentation defects of the vertebrae. These vertebral defects can result in severe instability of the cervical spine, leading to cardiac arrest after only minor whiplash injury.Case Report
We present the case of a healthy 7-year-old child who experienced an out-of-hospital cardiac arrest. He was reported to have profound respiratory distress and collapsed after going down a slide, without trauma. He was resuscitated in the field, and presented to the emergency department, where return of spontaneous circulation was achieved. Imaging of his cervical spine revealed multiple abnormalities. It was determined that a whiplash injury led to hypoxia and bradycardia due to the anatomic abnormalities of his cervical spine, resulting in cardiovascular collapse. He recovered fully and was later diagnosed with SCDO6, an autosomal recessive inherited disorder caused by a mutation in the RIPPLY2 gene.Why Should an Emergency Physician Be Aware of This?
Unfamiliarity of providers with this mechanism of cardiac arrest, and the rarity of the syndrome itself, make early recognition very difficult. Late diagnosis and lack of preventative measures, including immediate cervical spine stabilization, can lead to catastrophic outcomes. In patients with cardiac arrest of unclear etiology, early consideration of cervical spine immobilization and evaluation can be lifesaving. 相似文献60.