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Medina Neergaard posted an update 6 months, 2 weeks ago
The need to test anticancer drugs in multiple indications has been addressed by basket trials, which are Phase I or II clinical trials involving multiple tumor subtypes and a single master protocol. Basket trials typically involve few patients per type, making it challenging to rigorously compare responses across types. We describe the use of permutation testing to test for differences among subgroups using empirical null distributions and the Benjamini-Hochberg procedure to control for false discovery. We apply the approach retrospectively to tumor-volume changes and progression-free survival in published basket trials for neratinib, larotrectinib, pembrolizumab, and imatinib and uncover examples of therapeutic benefit missed by conventional binomial testing. For example, we identify an overlooked opportunity for use of neratinib in lung cancers carrying ERBB2 Exon 20 mutations. Permutation testing can be used to design basket trials but is more conservatively introduced alongside established approaches to enrollment such as Simon’s two-stage design.
Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older.
In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participnds NIHR Clinical Research Network, and AstraZeneca.
UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.Rhinoplasty has become a detail-dependent surgery. With precise techniques better results have been achieved. We are continually searching for the ideal technique to offer predictable, accurate, and desired long-term results. Conservative rhinoplasty techniques have been described for more than 100 years as an alternative to dorsal resective surgeries and have reemerged as the new fashion among rhinoplasty surgeons. Selleckchem Pifithrin-μ This article presents our philosophy when approaching the nasal dorsum regarding its segments and their specific anatomic aspects and surgical demands. We describe our intermediate septal strip approach, the intermediate split and the Tetris concept, and discuss their advantages and limitations.Dorsal preservation rhinoplasty requires precise management of the osseocartilaginous vault. Ultrasonic piezo instruments offer several advantages compared with traditional tools such as hand saws, rasps, and osteotomes. As always, an understanding of the dynamics of manipulation of the vault, anatomy, and proper technique are paramount and are reviewed herein.Preservation rhinoplasty is a new term for an old technique. The authors have used the endonasal push-down and let-down techniques that are attributed to Dr Maurice Cottle throughout their careers on select patients with excellent success. The endonasal Cottle technique allows the authors to manage the nasal dorsum in a conservative fashion, reducing the need for routine restructuring of the middle third and nasal dorsum. The details of their approach are presented in this publication.Preservation rhinoplasty has been a trending topic in the rhinoplasty literature. There is no single technique that can correct all structures; therefore, patient analysis is paramount. This article focuses on the anatomy of the keystone area and the dynamics of the dorsum explained through the biotensegrity concept. Differences between push-down and let-down techniques are addressed from a nasal valve physiology point of view. The let-down technique maintains the tensegrity of the nasal pyramid. Preservation should be preferred, in most cases, over resection, as well as reposition over manipulation.This issue of Clinics explores the concept of “preservation” rhinoplasty. At present, this topic is gaining considerable attention. As proponents of preservation suggest, a great number of problems we encounter in rhinoplasty are problems that were not present before the surgery; therefore, they can often be attributable to the deconstruction and reconstruction that took place. Preservation rhinoplasty should be viewed generally as a mindset to limit deconstructive steps in rhinoplasty when possible, understanding that these steps and those to later reconstruct provide the potential to create new problems that did not previously exist.”Subperichondrial-subperiosteal dissection technique (SSDT) decreases soft tissue injury to a minimum by protecting soft tissues from dissection and retraction traumas. The fact remains that dissecting the perichondrium of the nasal tip cartilages is not effortless. Cartilages may be harmed if dissection is not initiated at the right location. The aforementioned surgeons have routinely used the SSDT between the years 2008 and 2019 in more than 4000 rhinoplasties. The number of the surgeons making use of the SSDT will increase with the understanding of the key points in dissection, their ordering, and use of correct instrumentation.”There has been particular recent interest in dorsal preservation rhinoplasty techniques because of claims of superior functional and aesthetic results relative to conventional hump reductions. The septum in dorsal preservation rhinoplasty is managed in a variety of ways with differences largely based on the location of septal excision (subdorsal resection, midseptal resection, and inferior septal resection). The technical considerations of a modified subdorsal strip method using a structural preservation technique are described. This technique maintains a subdorsal and caudal strut of cartilage. Patient-reported measures demonstrate significantly improved functional and aesthetic outcomes postoperatively with this procedure.
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