1,807 research outputs found

    Dose-volume relationships of planned versus estimated delivered radiation doses to pelvic organs at risk and side effects in patients treated with salvage radiotherapy for recurrent prostate cancer

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    Purpose: To investigate estimated delivered dose distributions using weekly cone-beam computed tomography (CBCT) scans for pelvic organs at risk (OARs) in salvage radiotherapy (SRT) after radical prostatectomy. Furthermore, to compare them with the originally planned dose distributions and analyse associations with gastrointestinal (GI) and genitourinary (GU) side effects. Methods: This study is part of a phase II trial involving SRT for recurrent prostate cancer. Treatment was personalised based on PSA response during SRT, classifying patients as PSA responders or non-responders. Estimated radiation dose distributions were obtained using deformable image registration from weekly CBCT scans. GI and GU toxicities were assessed using the RTOG toxicity scale, while patient-reported symptoms were monitored through self-assessment questionnaires. Results: The study included 100 patients, with similar treatment-related side effects observed in both responders and non-responders. Differences in dose-volume metrics between the planned and estimated delivered doses for the examined OARs were mostly modest, although generally statistically significant. We identified statistically significant associations between QUANTEC-recommended dose-volume constraints and acute bowel toxicity, as well as late urinary patient-reported symptoms, for both the estimated delivered and planned dose distributions. Conclusion: We found small but statistically significant differences between estimated delivered and planned doses to OARs. These differences showed trends toward improved associations for estimated delivered dose distributions with side effects. Enhanced registration methods and imaging techniques could potentially further enhance the assessment of truly delivered doses and yield more reliable dose-volume constraints for future therapies

    Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases – an open, multicentre, randomised non-inferiority phase 3 trial

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    Introduction Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.Methods and analysis In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I–III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.Ethics and dissemination The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.Trial registration number NCT05634889

    Echocardiographic estimation of pulmonary artery wedge pressure : invasive derivation, validation, and prognostic association beyond diastolic dysfunction grading

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    Background and aims: Grading of diastolic function can be useful, but indeterminate classifications are common. Objectives: We aimed to invasively derive and validate a quantitative echocardiographic estimation of pulmonary artery wedge pressure (PAWP), and to compare its prognostic performance to diastolic dysfunction grading. Methods: Echocardiographic measures were used to derive an estimated PAWP (ePAWP) using multivariable linear regression in patients undergoing right heart catheterization (RHC). Prognostic associations were analyzed in the National Echocardiography Database of Australia (NEDA). Results: In patients who had undergone both RHC and echocardiography within two hours (n=90), ePAWP was derived using left atrial volume index, mitral peak early velocity (E), and pulmonary vein systolic velocity (S). In a separate external validation cohort (n=53, simultaneous echocardiography and RHC), ePAWP showed good agreement with invasive PAWP (mean±SD difference 0.5±5.0 mmHg) and good diagnostic accuracy for estimating PAWP>15mmHg (area under the curve [95% confidence interval] 0.94 [0.88-1.00]). Among patients in NEDA (n=38,856, median [interquartile range] follow-up 4.8 [2.3-8.0] years, 2,756 cardiovascular deaths), ePAWP was associated with cardiovascular death even after adjustment for age, sex, and diastolic dysfunction grading (hazard ratio (HR) 1.08 [1.07-1.09] per mmHg) and provided incremental prognostic information to diastolic dysfunction grading (improved C-statistic from 0.65 to 0.68, p<0.001). Increased ePAWP was associated with worse prognosis across all grades of diastolic function (HR normal: 1.07 [1.06-1.09]; indeterminate: 1.08 [1.07-1.09]; abnormal: 1.08 [1.07-1.09], p<0.001 for all). Conclusions: Echocardiographic ePAWP is an easily acquired continuous variable with good accuracy that associates with prognosis beyond diastolic dysfunction grading

    AllmÀnhetens riskuppfattning för tjock- och Àndtarmscancer kopplat till levnadsvanor : En kvalitativ studie för att utveckla riskkommunikationen

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    Bakgrund: Tjock- och Àndtarmscancer Àr en av de vanligaste cancerdiagnoserna i Sverige dÀr mer Àn hÀlften av fallen skulle kunna förebyggas genom Àndrade levnadsvanor. Att undersöka hur mÀnniskor resonerar kring sin risk att drabbas av tjock- och Àndtarmscancer Àr av betydelse för cancerprevention och utformandet av riskinformation. Syfte: Syftet med studien var att undersöka allmÀnhetens riskuppfattning för tjock- och Àndtarmscancer kopplat till levnadsvanor för att öka förstÄelsen om hur riskkommunikation kan utvecklas. Metod: Studien var en kvalitativ intervjustudie med strukturerade, öppna frÄgor. Deltagare rekryterades genom ett strategiskt urval kombinerat med snöbollsurval. Deltagarna (N=19) varierande i kön, Älder och utbildningsnivÄ. Data analyserades induktivt med innehÄllsanalys. Resultat: Kategorierna: Förkunskap och uppfattningar om tjock- och Àndtarmscancer och dess riskfaktorer; Tankar om egen risk; AvvÀgningar och motivation till beteendeförÀndring; SamhÀllets ansvar för riskkommunikation och preventiva insatser. Deltagare upplevde generellt en lÄg risk att drabbas av tjock- och Àndtarmscancer. Brist pÄ kunskap, tidigare misslyckade försök och sociala aspekter identifierades som hinder för beteendeförÀndring. Mer kunskap efterfrÄgades samtidigt som majoriteten upplevde nuvarande riskkommunikationen som överflödig och förvirrande.  Slutsats: Studien indikerade att om kunskapen om tjock- och Àndtarmscancer ökade skulle viljan för beteendeförÀndring kunna frÀmjas eftersom kunskapsbrist upplevdes som ett av hindren. Deltagarna uttryckte Àven att sociala aspekter spelade roll för viljan och möjligheten till beteendeförÀndring. Noga övervÀgningar bör göras om nÀr riskinformation ska kommuniceras. Vidare studier bör fokusera pÄ vilka andra faktorer som kan pÄverka individers vilja och motivation till beteendeförÀndring och hur riskinformation kan spridas för att nÄ sÄ mÄnga som möjligt.Background: Colorectal cancer is one of the most prevalent cancer diagnoses in Sweden. More than 50% of the cases could potentially be prevented through lifestyle changes. To improve the preventive work and develop risk information, it is of interest to understand how people perceive their risk.  Objective: The objective was to investigate people's risk perception for colorectal cancer linked to lifestyle factors to increase the understanding of how risk communication can be developed. Method: A qualitative interview study was performed. Through a strategic selection combined with snowball sampling, participants (N=19) were recruited varying in age, gender, and education level. The data were analyzed inductively with content analysis. Results: The categories: Prior knowledge and perception of colorectal cancer and its risk factors; Thoughts about personal risk; Consideration and motivation for behavior change; Society's responsibility for risk communication and preventive measures. Participants generally perceived low risk for colorectal cancer. Lack of knowledge, previous failed attempts, and social aspects were identified as barriers to behavior change. More knowledge was requested even though the majority experienced the current risk communication as redundant and confusing. Conclusion: The study indicates that if knowledge about colorectal cancer increased, the desire for behavioral change could increase too. Social aspects play a role in the willingness and possibility of behavioral change. Careful considerations should be made about when to communicate risk information. Future studies should focus on which other factors can influence individuals' willingness and motivation for behavior change and how risk information can reach broader

    Research ethics committee members’ perspectives on paediatric research: a qualitative interview study

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    Research ethics committees (RECs) have a crucial role in protecting children in research. However, studies on REC members’ perspectives on paediatric research are scarce. We conducted a qualitative study to explore Swedish scientific REC members’ perspectives on ethical aspects in applications involving children with severe health conditions. The REC members considered promoting participation, protecting children and regulatory adherence to be central aspects. The results underscored the importance of not neglecting ill children’s rights to adapted information and participation. REC members supported a contextual and holistic approach to vulnerability and risk, which considers the child’s and parents’ psychological wellbeing and the child’s integrity, both short and long term. The ethical complexity of paediatric research requires continuous ethical competence development within RECs

    Turning points as a tool in narrative research

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    This article focuses on how the concept of “turning points” can be used innarrative research when studying people’s (professional) identities and identity formation. By examining various understandings of turning points, we aim to show how they can be identified and used as analytical tools indifferent ways when conducting narrative analyses of (professional) identityf ormation. A case study from a research project on police identity is used to illustrate the application of various perspectives on turning points. The article offers guidance for researchers on choosing a context and focus for analysing turning points, as well as on the theoretical perspectives that come with these choices, and thereby suggests directions for analytical attention. The article shows how different perspectives on turning points have consequences for the understanding of professional identities. Open Access publication of this article was funded through a Transformative Agreement with Linköping University.</p

    Health Care Disparities in Patients Undergoing Hysterectomy for Benign Indications: A Systematic Review

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    OBJECTIVE: To explore how markers of health care disparity are associated with access to care and outcomes among patients seeking and undergoing hysterectomy for benign indications. DATA SOURCES: PubMed, EMBASE, and ClinicalTrials.gov were searched through January 23, 2022. METHODS OF STUDY SELECTION: The population of interest included patients in the United States who sought or underwent hysterectomy by any approach for benign indications. Health care disparity markers included race, ethnicity, geographic location, insurance status, and others. Outcomes included access to surgery, patient level outcomes, and surgical outcomes. Eligible studies reported multivariable regression analyses that described the independent association between at least one health care disparity risk marker and an outcome. We evaluated direction and strengths of association within studies and consistency across studies. TABULATION, INTEGRATION, AND RESULTS: Of 6,499 abstracts screened, 39 studies with a total of 46 multivariable analyses were included. Having a Black racial identity was consistently associated with decreased access to minimally invasive, laparoscopic, robotic, and vaginal hysterectomy. Being of Hispanic ethnicity and having Asian or Pacific Islander racial identities were associated with decreased access to laparoscopic and vaginal hysterectomy. Black patients were the only racial or ethnic group with an increased association with hysterectomy complications. Medicare insurance was associated with decreased access to laparoscopic hysterectomy, and both Medicaid and Medicare insurance were associated with increased likelihood of hysterectomy complications. Living in the South or Midwest or having less than a college degree education was associated with likelihood of prior hysterectomy. CONCLUSION: Studies suggest that various health care disparity markers are associated with poorer access to less invasive hysterectomy procedures and with poorer outcomes for patients who are undergoing hysterectomy for benign indications. Further research is needed to understand and identify the causes of these disparities, and immediate changes to our health care system are needed to improve access and opportunities for patients facing health care disparities. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021234511

    AllmÀnhetens riskuppfattning för tjock- och Àndtarmscancer kopplat till levnadsvanor : En kvalitativ studie för att utveckla riskkommunikationen

    No full text
    Bakgrund: Tjock- och Àndtarmscancer Àr en av de vanligaste cancerdiagnoserna i Sverige dÀr mer Àn hÀlften av fallen skulle kunna förebyggas genom Àndrade levnadsvanor. Att undersöka hur mÀnniskor resonerar kring sin risk att drabbas av tjock- och Àndtarmscancer Àr av betydelse för cancerprevention och utformandet av riskinformation. Syfte: Syftet med studien var att undersöka allmÀnhetens riskuppfattning för tjock- och Àndtarmscancer kopplat till levnadsvanor för att öka förstÄelsen om hur riskkommunikation kan utvecklas. Metod: Studien var en kvalitativ intervjustudie med strukturerade, öppna frÄgor. Deltagare rekryterades genom ett strategiskt urval kombinerat med snöbollsurval. Deltagarna (N=19) varierande i kön, Älder och utbildningsnivÄ. Data analyserades induktivt med innehÄllsanalys. Resultat: Kategorierna: Förkunskap och uppfattningar om tjock- och Àndtarmscancer och dess riskfaktorer; Tankar om egen risk; AvvÀgningar och motivation till beteendeförÀndring; SamhÀllets ansvar för riskkommunikation och preventiva insatser. Deltagare upplevde generellt en lÄg risk att drabbas av tjock- och Àndtarmscancer. Brist pÄ kunskap, tidigare misslyckade försök och sociala aspekter identifierades som hinder för beteendeförÀndring. Mer kunskap efterfrÄgades samtidigt som majoriteten upplevde nuvarande riskkommunikationen som överflödig och förvirrande.  Slutsats: Studien indikerade att om kunskapen om tjock- och Àndtarmscancer ökade skulle viljan för beteendeförÀndring kunna frÀmjas eftersom kunskapsbrist upplevdes som ett av hindren. Deltagarna uttryckte Àven att sociala aspekter spelade roll för viljan och möjligheten till beteendeförÀndring. Noga övervÀgningar bör göras om nÀr riskinformation ska kommuniceras. Vidare studier bör fokusera pÄ vilka andra faktorer som kan pÄverka individers vilja och motivation till beteendeförÀndring och hur riskinformation kan spridas för att nÄ sÄ mÄnga som möjligt.Background: Colorectal cancer is one of the most prevalent cancer diagnoses in Sweden. More than 50% of the cases could potentially be prevented through lifestyle changes. To improve the preventive work and develop risk information, it is of interest to understand how people perceive their risk.  Objective: The objective was to investigate people's risk perception for colorectal cancer linked to lifestyle factors to increase the understanding of how risk communication can be developed. Method: A qualitative interview study was performed. Through a strategic selection combined with snowball sampling, participants (N=19) were recruited varying in age, gender, and education level. The data were analyzed inductively with content analysis. Results: The categories: Prior knowledge and perception of colorectal cancer and its risk factors; Thoughts about personal risk; Consideration and motivation for behavior change; Society's responsibility for risk communication and preventive measures. Participants generally perceived low risk for colorectal cancer. Lack of knowledge, previous failed attempts, and social aspects were identified as barriers to behavior change. More knowledge was requested even though the majority experienced the current risk communication as redundant and confusing. Conclusion: The study indicates that if knowledge about colorectal cancer increased, the desire for behavioral change could increase too. Social aspects play a role in the willingness and possibility of behavioral change. Careful considerations should be made about when to communicate risk information. Future studies should focus on which other factors can influence individuals' willingness and motivation for behavior change and how risk information can reach broader

    Evaluating the utility of brightfield image data for mechanism of action prediction

    No full text
    Fluorescence staining techniques, such as Cell Painting, together with fluorescence microscopy have proven invaluable for visualizing and quantifying the effects that drugs and other perturbations have on cultured cells. However, fluorescence microscopy is expensive, time-consuming, labor-intensive, and the stains applied can be cytotoxic, interfering with the activity under study. The simplest form of microscopy, brightfield microscopy, lacks these downsides, but the images produced have low contrast and the cellular compartments are difficult to discern. Nevertheless, by harnessing deep learning, these brightfield images may still be sufficient for various predictive purposes. In this study, we compared the predictive performance of models trained on fluorescence images to those trained on brightfield images for predicting the mechanism of action (MoA) of different drugs. We also extracted CellProfiler features from the fluorescence images and used them to benchmark the performance. Overall, we found comparable and largely correlated predictive performance for the two imaging modalities. This is promising for future studies of MoAs in time-lapse experiments for which using fluorescence images is problematic. Explorations based on explainable AI techniques also provided valuable insights regarding compounds that were better predicted by one modality over the other.De tvÄ första författarna delar förstaförfattarskapetDe tvÄ sista författarna delar sistaförfattarskapet</p

    A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and 68Ga-PSMA-PET for biochemical relapse after radical prostatectomy - The PROPER 1 trial

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    Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET).Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still ≄ 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy.Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders.Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.Clinical trial registration numbers: NCT02699424&ISRCTN45905321
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