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Luke Boulter Rachel V. Guest Timothy J. Kendall David H. Wilson Davina Wojtacha Andrew J. Robson Rachel A. Ridgway Kay Samuel Nico Van Rooijen Simon T. Barry Stephen J. Wigmore Owen J. Sansom Stuart J. Forbes 《The Journal of clinical investigation》2015,125(3):1269-1285
Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC. 相似文献
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John Oppenheimer David J. Slade Beth A. Hahn Laurie Zografos Alicia Gilsenan David Richardson David McSorley Robson Lima Nestor A. Molfino Carlyne M. Averell 《Annals of allergy, asthma & immunology》2021,126(4):385-393.e2
BackgroundApproximately 30% to 50% of patients with moderate/severe asthma have inadequately controlled disease despite adherence to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy. Data on prevalence and burden of uncontrolled asthma in specialty settings are lacking.ObjectiveTo evaluate the prevalence and burden of uncontrolled asthma in respiratory specialist clinics in the United States.MethodsAdults with physician-diagnosed asthma attending pulmonary and allergy clinics with self-reported ICS use in the previous 4 weeks completed an electronic questionnaire including the Asthma Control Test and St George’s Respiratory Questionnaire. Additional information was collected using an electronic case report form.ResultsOf 774 patients attending 12 pulmonary and 12 allergy clinics, 53% were not well controlled (mean [SD] Asthma Control Test, 14.3 [3.6] vs 22.4 [1.6] in well-controlled patients). Among ICS/LABA users, 56% were not well controlled, which increased with increasing ICS dose (low-dose 45.7%; high-dose 59.7%). The not well-controlled group reported more respiratory illnesses, more comorbidities, and poorer health-related quality of life (mean [SD] St George’s Respiratory Questionnaire, 46.1 [18.9] vs 19.8 [12.9] in the well-controlled group). These patients also had more asthma exacerbations (≥1 exacerbation, 68.9% vs 43.1%) and increased health care resource utilization (≥1 asthma-related hospitalization, 10.7% vs 2.7%); 27.3% were also receiving systemic corticosteroids. Approximately 40% of the population were eligible for step-up to ICS/LABA/long-acting muscarinic antagonist triple therapy, and 20% were eligible for biologic therapy.ConclusionSubstantial unmet needs exist among patients with inadequately controlled asthma managed in United States specialist settings, which may be addressed by improved patient and physician education, better guideline implementation, and improved adherence. 相似文献
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Kate M. O’Brien Johanna M. van Dongen Amanda Williams Steven J. Kamper John Wiggers Rebecca K. Hodder Elizabeth Campbell Emma K. Robson Robin Haskins Chris Rissel Christopher M. Williams 《BMC public health》2018,18(1):1408
Background
The prevalence of knee osteoarthritis is increasing worldwide. Obesity is an important modifiable risk factor for both the incidence and progression of knee osteoarthritis. Consequently, international guidelines recommend all patients with knee osteoarthritis who are overweight receive support to lose weight. However, few overweight patients with this condition receive care to support weight loss. Telephone-based interventions are one potential solution to provide scalable care to the many patients with knee osteoarthritis. The objective of this study is to evaluate, from a societal perspective, the cost-utility and cost-effectiveness of a telephone-based weight management and healthy lifestyle service for patients with knee osteoarthritis, who are overweight or obese.Methods
An economic evaluation was undertaken alongside a pragmatic randomised controlled trial. Between May 19 and June 30, 2015, 120 patients with knee osteoarthritis were randomly assigned to an intervention or usual care control group in a 1:1 ratio. Participants in the intervention group received a referral to an existing non-disease specific 6-month telephone-based weight management and healthy lifestyle service. Quality-adjusted life years (QALYs) was the utility measure and knee pain intensity, disability, weight, and body mass index (BMI) were the clinical measures of effect. Costs included intervention costs, healthcare utilisation costs (healthcare services and medication use) and absenteeism costs due to knee pain. Data was collected at baseline, 6?weeks and 26?weeks. The primary cost-effectiveness analysis was performed from the societal perspective.Results
Mean cost differences between groups (intervention minus control) were $493 (95%CI: -3513 to 5363) for healthcare costs, $-32 (95%CI: -73 to 13) for medication costs, and $125 (95%CI: -151 to 486) for absenteeism costs. The total mean difference in societal costs was $1197 (95%CI: -2887 to 6106). For QALYs and all clinical measures of effect, the probability of the intervention being cost-effective compared with usual care was less than 0.36 at all willingness-to-pay values.Conclusions
From a societal perspective, telephone-based weight loss support, provided using an existing non-disease specific 6-month weight management and healthy lifestyle service was not cost-effective in comparison with usual care for overweight and obese patients with knee osteoarthritis.Trial registration number
ACTRN12615000490572, registered 18th May 20157.
Robson Frederico Cunha Alberto Carlos Botazzo Delbem Adriana Sales Cunha Correia Renata Zoccal Novais 《Dental traumatology》2008,24(6):e81-e84
Abstract – This article reports a longitudinal follow‐up of a 15‐month‐old child with dental trauma resulting from an attack by a dog. The injury consisted of laceration of the facial tissues and loss of the upper central deciduous incisors, in addition to loss of bone tissue in the same area. A malformation of the crown of the right central permanent incisor and complete change of the shape of the left central permanent incisor were observed. The etiological factors of childhood injuries as well as the importance of dental emergency care are discussed and the 14‐year clinical and radiographic follow up of the case is presented. 相似文献
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Bertrand Vabres Yan Chérel David Minault Jérémy Hervouet Yvette Ducournau Anne Moreau Véronique Daguin Flora Coulon Annaïck Pallier Sophie Brouard Simon C. Robson Mark B. Nottle Peter J. Cowan Eric Venturi Pascal Mermillod Philippe Brachet Cesare Galli Irina Lagutina Roberto Duchi Jean‐Marie Bach Bernard Vanhove 《Xenotransplantation》2014,21(5):431-443