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- Bengtsson, Daniel, 1975-, et al.
(författare)
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Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide
- 2015
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 100:4, s. 1689-1698
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Tidskriftsartikel (refereegranskat)abstract
- Context/Objective: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use in pituitary tumors is limited. Design and Setting: We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-50% in LAPTs, and 5-80% in carcinomas. Main Outcome: Response to TMZ and the association with tumor expression of O6-methylguanine DNA methyltransferase (MGMT), MLH1, MSH2, and MSH6, examined by immunohistochemistry. Results: Complete tumor regression occurred in two carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35% to 80% occurred in 5 LAPTs and 2 carcinomas. Another patient with LAPT had a 71% decrease in prolactin levels without change in tumor volume. Three LAPTs could not be evaluated. Median MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ. Conclusions: This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
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- Petersson, M., et al.
(författare)
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Natural history and surgical outcome of Rathke's cleft cysts-A study from the Swedish Pituitary Registry
- 2022
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 96:1, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- Objective Rathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathke's cleft cysts vary since data on the natural history are sparse. Patients and Design Data at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts <= 3 mm in diameter were excluded from the study. Measurements Data included demographics, cyst size, pituitary function, visual defects and surgery. Results The mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of >= 10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 930 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). Conclusions Rathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.
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- Björnsson Hallgren, Hanna C, et al.
(författare)
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Specific exercises for subacromial pain : Good results maintained for 5 years
- 2017
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Ingår i: Acta Orthopaedica. - : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 88:6, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — We have previously shown that specific exercises reduced the need for surgery in subacromial painpatients at 1-year follow-up. We have now investigated whetherthis result was maintained after 5 years and compared the outcomesof surgery and non-surgical treatment.Patients and methods — 97 patients were included in the previouslyreported randomized study of patients on a waiting list forsurgery. These patients were randomized to specifi c or unspecifi cexercises. After 3 months of exercises the patients were asked ifthey still wanted surgery and this was also assessed at the present5-year follow-up. The 1-year assessment included Constant–Murley score, DASH, VAS at night, rest and activity, EQ-5D, andEQ-VAS. All these outcome assessments were repeated after 5years in 91 of the patients.Results — At the 5-year follow-up more patients in the specifi cexercise group had declined surgery, 33 of 47 as compared with16 of 44 (p = 0.001) in the unspecifi c exercise group. The meanConstant–Murley score continued to improve between the 1- and5-year follow-ups in both surgically and non-surgically treatedgroups. On a group level there was no clinically relevant changebetween 1 and 5 years in any of the other outcome measuresregardless of treatment.Interpretation — This 5-year follow-up of a previously publishedrandomized controlled trial found that specifi c exercisesreduced the need for surgery in patients with subacromial pain.Patients not responding to specifi c exercises may achieve similargood results with surgery. These fi ndings emphasize that a specifi cexercise program may serve as a selection tool for surgery.
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| 8. |
- Evgrafov, A., et al.
(författare)
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Stochastic structural topology optimization : Existence of solutions and sensitivity analyses
- 2003
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Ingår i: Zeitschrift für angewandte Mathematik und Mechanik. - : Wiley. - 0044-2267 .- 1521-4001. ; 83:7, s. 479-492
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Tidskriftsartikel (refereegranskat)abstract
- We consider structural topology optimization problems including unilateral constraints arising from, for example, non-penetration conditions in contact mechanics or non-compression conditions for elastic ropes. To construct more realistic models and to hedge off possible failures or an inefficient behaviour of optimal structures, we allow parameters (for example, loads) defining the problem to be stochastic. The resulting nonsmooth stochastic optimization problem is an instance of stochastic mathematical programs with equilibrium constraints (SMPEC), or stochastic bilevel programs. The existence as well as the continuity of optimal solutions with respect to the lower bounds on the design variables are established. The question of continuity of the optimal solutions with respect to small changes in the probability measure is analysed. For a subclass of the problems considered the answer is affirmative, thus establishing the robustness of optimal solutions. © 2003 WILEY-VCH Verlag GmbH & Co. KGaA.
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- Nilsen, Per, 1960-, et al.
(författare)
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A Framework to Guide Implementation of AI in Health Care : Protocol for a Cocreation Research Project
- 2023
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Ingår i: JMIR Research Protocols. - Toronto : JMIR Publications. - 1929-0748. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artificial intelligence (AI) has the potential in health care to transform patient care and administrative processes, yet health care has been slow to adopt AI due to many types of barriers. Implementation science has shown the importance of structured implementation processes to overcome implementation barriers. However, there is a lack of knowledge and tools to guide such processes when implementing AI-based applications in health care.Objective: The aim of this protocol is to describe the development, testing, and evaluation of a framework, “Artificial Intelligence-Quality Implementation Framework” (AI-QIF), intended to guide decisions and activities related to the implementation of various AI-based applications in health care.Methods: The paper outlines the development of an AI implementation framework for broad use in health care based on the Quality Implementation Framework (QIF). QIF is a process model developed in implementation science. The model guides the user to consider implementation-related issues in a step-by-step design and plan and perform activities that support implementation. This framework was chosen for its adaptability, usability, broad scope, and detailed guidance concerning important activities and considerations for successful implementation. The development will proceed in 5 phases with primarily qualitative methods being used. The process starts with phase I, in which an AI-adapted version of QIF is created (AI-QIF). Phase II will produce a digital mockup of the AI-QIF. Phase III will involve the development of a prototype of the AI-QIF with an intuitive user interface. Phase IV is dedicated to usability testing of the prototype in health care environments. Phase V will focus on evaluating the usability and effectiveness of the AI-QIF. Cocreation is a guiding principle for the project and is an important aspect in 4 of the 5 development phases. The cocreation process will enable the use of both on research-based and practice-based knowledge.Results: The project is being conducted within the frame of a larger research program, with the overall objective of developing theoretically and empirically informed frameworks to support AI implementation in routine health care. The program was launched in 2021 and has carried out numerous research activities. The development of AI-QIF as a tool to guide the implementation of AI-based applications in health care will draw on knowledge and experience acquired from these activities. The framework is being developed over 2 years, from January 2023 to December 2024. It is under continuous development and refinement.Conclusions: The development of the AI implementation framework, AI-QIF, described in this study protocol aims to facilitate the implementation of AI-based applications in health care based on the premise that implementation processes benefit from being well-prepared and structured. The framework will be coproduced to enhance its relevance, validity, usefulness, and potential value for application in practice. © 2023 The Author(s).
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| 10. |
- Nilsson, S., et al.
(författare)
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Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study
- 2007
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Ingår i: Lancet Oncol. - 1470-2045 .- 1474-5488. ; 8:7, s. 587-594
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra. METHODS: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. FINDINGS: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.
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