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  • Danielsson, D., et al. (författare)
  • Brachytherapy and osteoradionecrosis in patients with base of tongue cancer
  • 2023
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 143:1, s. 77-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. Aims: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. Material and Methods: We used data from the Swedish Head and Neck Cancer Register between 2008–2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. Results: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p =.012), whereas overall survival did not differ (HR = 0.95, p =.782). Conclusions and Significance: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.
  • Hellstrand Tang, Ulla, et al. (författare)
  • Exploring the Role of Complexity in Health Care Technology Bottom-Up Innovations : Multiple-Case Study Using the Nonadoption, Abandonment, Scale-Up, Spread, and Sustainability Complexity Assessment Tool
  • 2024
  • Ingår i: JMIR Human Factors. - : JMIR Publications. - 2292-9495. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: New digital technology presents new challenges to health care on multiple levels. There are calls for further research that considers the complex factors related to digital innovations in complex health care settings to bridge the gap when moving from linear, logistic research to embracing and testing the concept of complexity. The nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework was developed to help study complexity in digital innovations.OBJECTIVE: This study aims to investigate the role of complexity in the development and deployment of innovations by retrospectively assessing challenges to 4 digital health care innovations initiated from the bottom up.METHODS: A multicase retrospective, deductive, and explorative analysis using the NASSS complexity assessment tool LONG was conducted. In total, 4 bottom-up innovations developed in Region Västra Götaland in Sweden were explored and compared to identify unique and shared complexity-related challenges.RESULTS: The analysis resulted in joint insights and individual learning. Overall, the complexity was mostly found outside the actual innovation; more specifically, it related to the organization's readiness to integrate new innovations, how to manage and maintain innovations, and how to finance them. The NASSS framework sheds light on various perspectives that can either facilitate or hinder the adoption, scale-up, and spread of technological innovations. In the domain of condition or diagnosis, a well-informed understanding of the complexity related to the condition or illness (diabetes, cancer, bipolar disorders, and schizophrenia disorders) is of great importance for the innovation. The value proposition needs to be clearly described early to enable an understanding of costs and outcomes. The questions in the NASSS complexity assessment tool LONG were sometimes difficult to comprehend, not only from a language perspective but also due to a lack of understanding of the surrounding organization's system and its setting.CONCLUSIONS: Even when bottom-up innovations arise within the same support organization, the complexity can vary based on the developmental phase and the unique characteristics of each project. Identifying, defining, and understanding complexity may not solve the issues but substantially improves the prospects for successful deployment. Successful innovation within complex organizations necessitates an adaptive leadership and structures to surmount cultural resistance and organizational impediments. A rigid, linear, and stepwise approach risks disregarding interconnected variables and dependencies, leading to suboptimal outcomes. Success lies in embracing the complexity with its uncertainty, nurturing creativity, and adopting a nonlinear methodology that accommodates the iterative nature of innovation processes within complex organizations.
  • Li, Xiangyu, et al. (författare)
  • Classification of clear cell renal cell carcinoma based on PKM alternative splicing
  • 2020
  • Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
  • Liedberg, Fredrik, et al. (författare)
  • Cumulative incidence of midline incisional hernia and its surgical treatment after radical cystectomy and urinary diversion for bladder cancer: A nation-wide population-based study
  • 2021
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective To study the cumulative incidence and surgical treatment of midline incisional hernia (MIH) after cystectomy for bladder cancer. Methods In the nationwide Bladder Cancer Data Base Sweden (BladderBaSe), cystectomy was performed in 5646 individuals. Cumulative incidence MIH and surgery for MIH were investigated in relation to age, gender, comorbidity, previous laparotomy and/or inguinal hernia repair, operative technique, primary/secondary cystectomy, postoperative wound dehiscence, year of surgery, and period-specific mean annual hospital cystectomy volume (PSMAV). Results Three years after cystectomy the cumulative incidence of MIH and surgery for MIH was 8% and 4%, respectively. The cumulative incidence MIH was 12%, 9% and 7% in patients having urinary diversion with continent cutaneous pouch, orthotopic neobladder and ileal conduit. Patients with postoperative wound dehiscence had a higher three-year cumulative incidence MIH (20%) compared to 8% without. The corresponding cumulative incidence surgery for MIH three years after cystectomy was 9%, 6%, and 4% for continent cutaneous, neobladder, and conduit diversion, respectively, and 11% for individuals with postoperative wound dehiscence (vs 4% without). Using multivariable Cox regression, secondary cystectomy (HR 1.3 (1.0-1.7)), continent cutaneous diversion (HR 1.9 (1.1-2.4)), robot-assisted cystectomy (HR 1.8 (1-3.2)), wound dehiscence (HR 3.0 (2.0-4.7)), cystectomy in hospitals with PSMAV 10-25 (HR 1.4 (1.0-1.9)), as well as cystectomy during later years (HRs 2.5-3.1) were all independently associated with increased risk of MIH. Conclusions The cumulative incidence of MIH was 8% three years postoperatively, and increase over time. Avoiding postoperative wound dehiscence after midline closure is important to decrease the risk of MIH.
  • Steineck, Gunnar, 1952, et al. (författare)
  • Contouring pudendal nerves.
  • 2018
  • Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 57:4, s. 438-439
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  • Wallander, Marit, et al. (författare)
  • Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures : a study from the fractures and fall injuries in the elderly cohort (FRAILCO)
  • 2019
  • Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 30:1, s. 115-125
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary: Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures. Introduction: Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer. Methods: We included 179,744 men (79.1 ± 7.9 years (mean ± SD)) from the Swedish registry to which national directories were linked in order to study associations regarding fractures, fall injuries, morbidity, mortality and medications. We identified 159,662 men without prostate cancer, 6954 with prostate cancer and current ADT and 13,128 men with prostate cancer without ADT. During a follow-up of approximately 270,300 patient-years, we identified 10,916 incident fractures including 4860 hip fractures. Results: In multivariable Cox regression analyses and compared to men without prostate cancer, those with prostate cancer and ADT had increased risk of any fracture (HR 95% CI 1.40 (1.28–1.53)), hip fracture (1.38 (1.20–1.58)) and MOF (1.44 (1.28–1.61)) but not of non-skeletal fall injury (1.01 (0.90–1.13)). Patients with prostate cancer without ADT did not have increased risk of any fracture (0.97 (0.90–1.05)), hip fracture (0.95 (0.84–1.07)), MOF (1.01 (0.92–1.12)) and had decreased risk of non-skeletal fall injury (0.84 (0.77–0.92)). Conclusions: Patients with prostate cancer and ADT is a fragile patient group with substantially increased risk of osteoporotic fractures both compared to patients without prostate cancer and compared to those with prostate cancer without ADT. We believe that this must be taken in consideration in all patients with prostate cancer already at the initiation of ADT. 
  • Gulyas, Miklos, et al. (författare)
  • COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer.
  • 2018
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 244-250
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.Methods: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.Results: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81–1.27 and HR 1.12; 95% CI 0.78–1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60–1.54; and HR =1.51; 95% CI 0.86–2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).Conclusions: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.
  • Ali, Muhaddisa Barat, 1986, et al. (författare)
  • A novel federated deep learning scheme for glioma and its subtype classification
  • 2023
  • Ingår i: Frontiers in Neuroscience. - 1662-4548 .- 1662-453X. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Deep learning (DL) has shown promising results in molecular-based classification of glioma subtypes from MR images. DL requires a large number of training data for achieving good generalization performance. Since brain tumor datasets are usually small in size, combination of such datasets from different hospitals are needed. Data privacy issue from hospitals often poses a constraint on such a practice. Federated learning (FL) has gained much attention lately as it trains a central DL model without requiring data sharing from different hospitals. Method: We propose a novel 3D FL scheme for glioma and its molecular subtype classification. In the scheme, a slice-based DL classifier, EtFedDyn, is exploited which is an extension of FedDyn, with the key differences on using focal loss cost function to tackle severe class imbalances in the datasets, and on multi-stream network to exploit MRIs in different modalities. By combining EtFedDyn with domain mapping as the pre-processing and 3D scan-based post-processing, the proposed scheme makes 3D brain scan-based classification on datasets from different dataset owners. To examine whether the FL scheme could replace the central learning (CL) one, we then compare the classification performance between the proposed FL and the corresponding CL schemes. Furthermore, detailed empirical-based analysis were also conducted to exam the effect of using domain mapping, 3D scan-based post-processing, different cost functions and different FL schemes. Results: Experiments were done on two case studies: classification of glioma subtypes (IDH mutation and wild-type on TCGA and US datasets in case A) and glioma grades (high/low grade glioma HGG and LGG on MICCAI dataset in case B). The proposed FL scheme has obtained good performance on the test sets (85.46%, 75.56%) for IDH subtypes and (89.28%, 90.72%) for glioma LGG/HGG all averaged on five runs. Comparing with the corresponding CL scheme, the drop in test accuracy from the proposed FL scheme is small (−1.17%, −0.83%), indicating its good potential to replace the CL scheme. Furthermore, the empirically tests have shown that an increased classification test accuracy by applying: domain mapping (0.4%, 1.85%) in case A; focal loss function (1.66%, 3.25%) in case A and (1.19%, 1.85%) in case B; 3D post-processing (2.11%, 2.23%) in case A and (1.81%, 2.39%) in case B and EtFedDyn over FedAvg classifier (1.05%, 1.55%) in case A and (1.23%, 1.81%) in case B with fast convergence, which all contributed to the improvement of overall performance in the proposed FL scheme. Conclusion: The proposed FL scheme is shown to be effective in predicting glioma and its subtypes by using MR images from test sets, with great potential of replacing the conventional CL approaches for training deep networks. This could help hospitals to maintain their data privacy, while using a federated trained classifier with nearly similar performance as that from a centrally trained one. Further detailed experiments have shown that different parts in the proposed 3D FL scheme, such as domain mapping (make datasets more uniform) and post-processing (scan-based classification), are essential.
  • Andersson, John, 1978, et al. (författare)
  • Developing a multivariable prediction model of global health-related quality of life in patients treated for rectal cancer : a prospective study in five countries
  • 2024
  • Ingår i: International Journal of Colorectal Disease. - : Springer Nature. - 0179-1958 .- 1432-1262. ; 39
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Rectal cancer and its treatment have a negative impact on health-related quality of life (HRQoL). If risk factors for sustained low HRQoL could be identified early, ideally before the start of treatment, individualised interventions could be identified and implemented to maintain or improve HRQoL. The study aimed to develop a multivariable prediction model for global HRQoL 12 months after rectal cancer treatment.Methods Within COLOR II, a randomised, multicentre, international trial of laparoscopic and open surgery for rectal cancer, a sub-study on HRQoL included 385 patients in 12 hospitals and five countries. The HRQoL study was optional for hospitals in the COLOR II trial. EORTC QLQ-C30 and EORTC QLQ-CR38 were analysed preoperatively and at 1 and 12 months postoperatively. In exploratory analyses, correlations between age, sex, fatigue, pain, ASA classification, complications, and symptoms after surgery to HRQoL were studied. Bivariate initial analyses were followed by multivariate regression models.Results Patient characteristics and clinical factors explained 4–10% of the variation in global HRQoL. The patient-reported outcomes from EORTC QLQ-C30 explained 55–65% of the variation in global HRQoL. The predominant predictors were fatigue and pain, which significantly impacted global HRQoL at all time points measured.Conclusion We found that fatigue and pain were two significant factors associated with posttreatment global HRQoL in patients treated for rectal cancer T1-T3 Nx. Interventions to reduce fatigue and pain could enhance global HRQoL after rectal cancer treatment.
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