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Background
To date, targeted tyrosine kinase inhibitors have been approved for FGFR2 and FGFR3 fusions (pemigatinib and erdafitinib, respectively), but the importance of FGFR2 mutations for transformation activity and as a druggable gene variant with response to different FGFR inhibitors is poorly understood. FGFR2 inhibitors present a mainstay of treatment for locally advanced or metastatic intrahepatic cholangiocellular carcinoma (iCCA).
Methods
A 74-year-old male was diagnosed with iCCA in liver segments seven and eight with infiltration of the hepatic veins and inferior vena cava revealed a C382R mutation of the intramembrane domain of FGRR2 receptor. We performed an in-silico study to understand the potential mode-of-action of the mutant FGFR2 targets. Based on experimentally determined structures we then used a structure generated by AlphaFold2 as the variation in question is located at a position not determined well in the experiments. This revealed that the C382R mutation is located in the trans-membranal domain at a position crucial for signal transduction, both for activation and inhibition of downstream-signaling. The Molecular Tumor Board decided to start the treatment with 13.5 mg pemigatinib once daily for 14 days, followed by 7 days of free therapy interval resulting in a sustained partial response. The patient continues to be treated of 13.5 mg as described above.
Results
In our case report, we were able to show that the patient in whom an C382R mutation was detected responded to the therapy with pemigatinib. This shows that real-world scenarios differ from the data of the approval studies, thereby illustrating how complex data on patients with FGFR mutations is. One of the main problems of large approval studies is that the functionality of the respective alterations is often disregarded.
Conclusions
Our results suggest that respective mutation may be successfully targeted by FGFR-selective tyrosine-kinase inhibitors, demonstrating the importance of the functional characterization of mutations.
no conflicts of interest.
Purpose: This study aimed to gain knowledge about environmental factors (EFs) that impact work and social life participation of people with multiple sclerosis (MS) in Austria and Switzerland to extend the knowledge of participation and to identify key areas for measuring participation.
Method: A three-round Delphi study was conducted defining patients as experts. In the 1st round, qualitative data was gathered through questionnaires, analyzed with content analysis, and factors were assigned to EFs as classified in the ICF. In the 2nd and 3rd round, experts judged EFs according to its relevance to obtain consensus (cut-off 75%). Categories were ranked on a scale from mostly important to important.
Results: One hundred and twelve Austrian and 109 Swiss experts were recruited. The content analysis revealed 768 EFs. The study resulted in a list of 176 consensus factors for Austria and 177 Switzerland. Five categories revealed to be highly important, 12 moderately important, 6 fairly important, and 10 important.
Conclusions: This study indicates that participation in work or social life is influenced by physical, social, attitudinal, and policy factors. Consensus factors afford insights into areas for consideration in the development of participation outcome measurements and support a comprehensive and inclusive rehabilitation approach.
Point mutations of the fibroblast growth factor receptor (FGFR)2 receptor in intrahepatic cholangiocarcinoma (iCC) are mainly of unknown functional significance compared to FGFR2 fusions. Pemigatinib, a tyrosine kinase inhibitor, is approved for the treatment of cholangiocarcinoma with FGFR2 fusion/rearrangement. Although it is hypothesized that FGFR2 mutations may cause uncontrolled activation of the signaling pathway, the data for targeted therapies for FGFR2 mutations remain unclear. In vitro analyses demonstrated the importance of the p.C382R mutation for ligand-independent constitutive activation of FGFR2 with transforming potential. The following report describes the clinical case of a patient diagnosed with an iCC carrying a FGFR2 p.C382R point mutation which was detected in liquid, as well as in tissue-based biopsies. The patient was treated with pemigatinib, resulting in a sustained complete functional remission in fluorodeoxyglucose-positron emission tomography/computed tomography over 10 months to date. The reported case is the first description of a complete functional remission under the treatment with pemigatinib in a patient with p.C383R mutation.
Predictive Modeling (PM) techniques are gaining importance in the worldwide health insurance business. Modern PM methods are used for customer relationship management, risk evaluation or medical management. This article illustrates a PM approach that enables the economic potential of (cost-)effective disease management programs (DMPs) to be fully exploited by optimized candidate selection as an example of successful data-driven business management. The approach is based on a Generalized Linear Model (GLM) that is easy to apply for health insurance companies. By means of a small portfolio from an emerging country, we show that our GLM approach is stable compared to more sophisticated regression techniques in spite of the difficult data environment. Additionally, we demonstrate for this example of a setting that our model can compete with the expensive solutions offered by professional PM vendors and outperforms non-predictive standard approaches for DMP selection commonly used in the market.
The International Spinal Cord Injury (InSCI) community survey has been developed to collect internationally comparable data on the lived experience of persons with spinal cord injury (SCI) in all 6 WHO regions.
The InSCI survey provides a crucial first step to generate evidence on functioning, health maintenance, and subjective well-being in persons with SCI globally.
A major challenge in setting up the InSCI community survey was to develop a data model and questionnaire that comprehensively captures what matters to people and, at the same time, is feasible and parsimonious in terms of participant’s burden.
This paper outlines the components of the InSCI data model and presents the question selection to operationalize the data model along the 4 guiding principles of efficiency, feasibility, comparability, and truth and discrimination.
The data model consists of 6 components operationalized with 125 questions including functioning (n = 28 body functions and structures; n = 42 activities and participation), contextual factors (n = 26 environmental; n = 19 personal factors), lesion characteristics (n = 2), and appraisal of health and well-being (n = 8).
The InSCI questionnaire presents an efficient and feasible solution with satisfying comparability to other populations; however, its validity and reliability still needs to be confirmed.
This study investigates the impact of generative AI systems like ChatGPT on semi-structured decision-making, specifically in evaluating undergraduate dissertations. We propose using Davis’ technology acceptance model (TAM) and Schulz von Thun’s four-sides communication model to understand human–AI interaction and necessary adaptations for acceptance in dissertation grading. Utilizing an inductive research design, we conducted ten interviews with respondents having varying levels of AI and management expertise, employing four escalating-consequence scenarios mirroring higher education dissertation grading. In all scenarios, the AI functioned as a sender, based on the four-sides model. Findings reveal that technology acceptance for human–AI interaction is adaptive but requires modifications, particularly regarding AI’s transparency. Testing the four-sides model showed support for three sides, with the appeal side receiving negative feedback for AI acceptance as a sender. Respondents struggled to accept the idea of AI, suggesting a grading decision through an appeal. Consequently, transparency about AI’s role emerged as vital. When AI supports instructors transparently, acceptance levels are higher. These results encourage further research on AI as a receiver and the impartiality of AI decision-making without instructor influence. This study emphasizes communication modes in learning-ecosystems, especially in semi-structured decision-making situations with AI as a sender, while highlighting the potential to enhance AI-based decision-making acceptance.
Functioning information constitutes a relevant component for determining patients’ service needs and respective resource use. Diagnosis-Related Group (DRG) systems can be optimized by integrating functioning information.
First steps toward accounting for functioning information in the German DRG (G-DRG) system have been made; yet, there is no systematic integration of functioning information. The G-DRG system is part of the health system; it is embedded in and as such dependent on various stakeholders and vested interests.
This study explores the stakeholder’s perspective on integrating functioning information in the G-DRG system. A qualitative interview study was conducted with national stakeholders in 4 groups of the G-DRG system (health policy, administration, development, and consultations).
Interviews were analyzed using inductive thematic analysis. In total, 14 interviews were conducted (4 administration and 10 consultation group). Three main themes were identified: (1) functioning information in the G-DRG system: opportunities and obstacles, (2) general aspects concerning optimizing G-DRG systems by integrating additional information, and (3) ideas and requirements on how to proceed.
The study offers insights into the opportunities and obstacles of integrating functioning information in the G-DRG system. The relevance of functioning information was evident. However, the value of functioning information for the G-DRG system was seen critically. Integrating functioning information alone does not seem to be sufficient and a systems approach is needed.
Objectives
To examine which professionals administered which assessment instruments in which patient in clinical practice during first rehabilitation after newly acquired spinal cord injury (SCI) and the differences in the frequencies of different assessments between patient groups.
Setting
Specialized SCI acute care and rehabilitation clinic.
Methods
Patients after SCI, aged 18 years and above, admitted for first rehabilitation between December 2014 and December 2015 were analyzed. Descriptive statistics of 54 selected assessments. p values based on the χ 2 test were calculated for assessments used in both paraplegic and tetraplegic patients.
Results
One hundred and nineteen patients were screened. Forty-one assessments were administered, of which 10 on average more than once per patient. The most frequently used assessments were Spinal Cord Independence Measure III (7.7 times per patient), Skin Assessment (3.6 times), and Manual Muscle Test (3.2 times for Lower Extremities; 2.5 times for Upper Extremities). The American Spinal Injury Association Impairment Scale was administered on average 1.9 times per patient. More variation in the number of assessments per patient was observed in patients with complete and incomplete lesions compared to patients with paraplegia and tetraplegia.
Conclusion
Assessments covering neurological functioning, mobility, and self-care are used in clinical practice during first rehabilitation of patients with SCI, while others covering autonomic functioning, pain, participation, or quality of life are still missing. Based on these observations and national and international requirements, a meaningful standard for an assessment toolkit, applicable in general and in specific subgroups, needs to be defined and implemented.
Objective: Many studies published in the journal WORK in the recent decades have discussed work and employment trends. However, the dimensions of these contributions over time have not been reviewed. The main objective of this study was to investigate the knowledge development in regard to work-related rehabilitation in WORK over the last two decades.
Methods: A scoping review was conducted using the following five stages: (i) identifying research question, (ii) identifying relevant studies, (iii) study selection, (iv) charting, summarizing, and collating the data, and (v) reporting the results. Studies were selected from the WORK Article Database.
Results: Seventy-five relevant studies were identified. The findings reflect that WORK has published papers from across the world, with most of the studies from the United States, Sweden, Canada, and Hong Kong. The complexity and multi-factorial nature of work-related rehabilitation was reflected in the application of quantitative, qualitative, and mixed method research approaches, as well as case studies. Study participants were characterized by work, and non-work related injuries, systematic diseases/chronic illness, fulfilled certain socio-demographic characteristic, and represented various stakeholders. Fewer studies drew on secondary resources. In the findings one re-occurring theme has been noted: 'maintaining/obtaining/returning to secure and stable employment/work'.
Conclusions: Four key-reflections evolved from this scoping review that provide potential avenues for future research. These key-reflections include (i) the national, transnational and international dimension of the reviewed studies, (ii) the various societal levels informing work-related rehabilitation practices, (iii) the diversity of methodologies applied in current research, and (iv) the variability of terminology used within the reviewed studies. The journal WORK has published a variety of research over the last two decades and contributed significantly to our current understanding of work-related rehabilitation. However, further research in these reflective areas would expand the current knowledge base.