Treatment Decisions Research Articles

Applications of artificial intelligence for imaging-driven diagnosis and treatment of bone and soft tissue tumors

Bone and soft tissue tumors occur in the musculoskeletal system, and malignant bone tumors of bone and soft tissue account for 0.2% of all human malignant tumors, and if not diagnosed and treated in a timely manner, patients may be at risk of a poor prognosis. Image interpretation plays an increasingly important role in the diagnosis of bone and soft tissue tumors. Artificial intelligence (AI) can be applied in clinical treatment to integrate large amounts of multidimensional data, derive models, predict outcomes, and improve treatment decisions. Among these methods, deep learning is a widely employed technique in AI that predominantly utilizes convolutional neural networks (CNN). The network is implemented through repeated training of datasets and iterative parameter adjustments. Deep learning-based AI models have successfully been applied to various aspects of bone and soft tissue tumors, encompassing but not limiting in image segmentation, tumor detection, classification, grading and staging, chemotherapy effect evaluation, recurrence and prognosis prediction. This paper provides a comprehensive review of the principles and current state of AI in the medical image diagnosis and treatment of bone and soft tissue tumors. Additionally, it explores the present challenges and future prospects in this field.

Abstract C074: Patient-provider communication and receipt of definitive prostate cancer treatment by race and rurality

Abstract Background: Patient-provider communication (PPC) is critical in treatment decisions for cancer care, and it is unknown if improved communication may mitigate disparities in prostate cancer (PCa) outcomes by race and rurality. We examined associations between PPC and treatment receipt among Black and White patients diagnosed with incident PCa in the North Carolina Louisiana Prostate Cancer Project. Methods: Near-equal numbers of Black (n=1130) and White (n=1128) participants were recruited by rapid case ascertainment from 2004-2009. PPC was assessed from the baseline survey, where participants rated their cancer provider using three subscales adapted from the Primary Care Assessment Survey for contextual knowledge of the patient (CK: knowledge of patient’s medical history, home/work responsibilities, their worries, and the patient as a person), and communication content (CMN: doctor’s thoroughness of questions, attention, explanations of health problems, instructions about symptoms, and advice/help in making care decisions), and interpersonal treatment (IT: amount of time spent, patience, friendliness, caring, concern, and respect for patient). First-course treatment was ascertained from medical records and defined as definitive (surgery or radiation) compared to non-definitive treatment (all other). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for receipt of definitive treatment with logistic regression, adjusted for age at diagnosis, cancer aggressiveness, educational attainment, and marital status. Results: Black participants were diagnosed at younger ages (mean 62 vs. 64 years) with more aggressive disease (21% vs. 15%) and received surgery or radiation less often than White participants (73% vs. 77%). Median PPC subscales differed between Black and White participants (CK: 16 vs 15; CMN: 23 vs 24; IT: 22 vs 23), and between rural and urban participants (CK: 16 vs 16; CMN: 22 vs 24; IT: 21 vs 23). The odds of receiving definitive treatment was associated with positive communication content (1.12, 1.06-1.18), and interpersonal treatment (1.08, 1.02-1.14) among Black and White participants. Among urban participants, communication content (1.09, 1.05-1.15), and interpersonal treatment (1.09, 1.04-1.14) were associated with higher odds of definitive treatment. Among rural participants, higher communication content was associated with increased odds of receiving definitive treatment (OR 1.15, 95%CI: 1.04-1.28). We did not observe associations for contextual knowledge with the odds of receipt for definitive treatment subgroups. Conclusions: Positive patient-provider communication was associated with higher odds of receiving surgery/radiation in a historical cohort of PCa patients diagnosed between 2004-2009. Higher communication content and interpersonal treatment could promote uptake of contemporary guideline-based treatment recommendations for PCa. Future research will assess the validity and reliability of the communication subscales via annual follow-up questionnaires and associations with cancer-specific survival. Citation Format: Jeanny H Wang, Bria Carmichael, Shaun Jones, Hung-Jiu Tan, Deshira D. Wallace, Jennifer L. Lund, Lixin Song, Jeannette T. Bensen, Eboneé N. Butler. Patient-provider communication and receipt of definitive prostate cancer treatment by race and rurality [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C074.

EMERGENCY ESOPHAGECTOMY FOR ESOPHAGEAL PERFORATION FOLLOWING BALLOON DILATION DUE TO STENOSIS POST-ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGEAL CANCER: A CASE REPORT

Introduction and importance: Esophageal perforation from endoscopic dilation is rare (0.53% to 0.6% incidence) but serious, with mortality rates of 12.5% to 20%. Optimal treatment is debated and depends on the medical facility’s capabilities, patient’s symptoms, extent of perforation, and severity of associated lesions. Treatment options include medical management (fasting, antibiotics), esophageal stenting, surgical closure, or emergency esophagectomy. Early diagnosis and treatment are crucial to reduce mortality and hospital stay. Case presentation: A 49-year-old male with lower third esophageal cancer (stage cT1aN0M0) underwent endoscopic submucosal dissection (ESD) and developed esophageal stenosis. Dilation attempts led to esophageal perforation, necessitating emergency esophagectomy with gastric conduit reconstruction. The patient improved and was discharged on day 10 post-operation without complications. Clinical discussion: Managing esophageal perforation post-endoscopic dilation is complex. This case highlights the importance of rapid recognition and intervention. Esophageal dilation, while effective for stenosis, carries a perforation risk. Treatment decisions must be tailored to individual patients, considering perforation severity, patient’s health, and facility resources. Here, severe perforation and clinical condition warranted emergency esophagectomy. The successful outcome underscores the efficacy of this surgical intervention when performed timely at specialized centers. Conclusion: Emergency esophagectomy with gastric conduit reconstruction for treating esophageal perforation due to stenosis post endoscopic submucosal dissection for esophageal cancer is considered a safe procedure and can be performed at an experienced esophageal surgery center.

Analytical and Clinical Validation of the Oncomine Dx Target Test to Assess HER2 Mutation Status in Tumor Tissue Samples From Patients With Non–Small Cell Lung Cancer Treated With Trastuzumab Deruxtecan in the DESTINY-Lung01 and DESTINY-Lung02 Studies

Context.— Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)–targeted therapy, has demonstrated durable anticancer activity in patients with advanced, metastatic HER2 (also known as ERBB2)–mutant (HER2m) non–small cell lung cancer (NSCLC) who have limited treatment options and poor prognosis. Objective.— To analytically validate and assess the clinical utility of the Oncomine Dx Target (ODxT) Test as a companion diagnostic to identify patients with HER2m NSCLC. Design.— Tumor samples from patients in DESTINY-Lung01 and DESTINY-Lung02 were retrospectively analyzed alongside commercially procured samples using the ODxT test and compared to the assays used for screening in these clinical trials. Results.— Positive percent agreement (PPA) and negative percent agreement (NPA) between the ODxT Test and TruSight Tumor 170 assay when testing DESTINY-Lung01 and commercially procured samples met prespecified thresholds (PPA and NPA ≥90%) for analytical accuracy (100% and 99.1%). The ODxT Test results were highly concordant with clinical trial assays (CTAs) used in DESTINY-Lung01 (PPA and NPA, 98.0% and 100%) and DESTINY-Lung02 (PPA and NPA, 96.7% and 100%) to identify activating HER2 mutations in tumor samples. Confirmed objective response rates were similar between patients with HER2m tumors identified by the ODxT Test and by CTAs in DESTINY-Lung01 (58.3% and 54.9%) and DESTINY-Lung02 (53.6% and 53.8%). Response duration was 12.0 and 9.3 months for patients identified by the ODxT Test and CTAs, respectively, in DESTINY-Lung01. Conclusions.— The ODxT Test detected HER2 mutations in NSCLC with high analytical and clinical accuracy and identified HER2m populations with response rates similar to populations identified by CTAs, supporting clinical utility of the ODxT Test to inform treatment decisions for HER2m NSCLC.

Developing an Individualized Patient Decision Aid for Chronic Coronary Disease Based on the ISCHEMIA Trial: A Mixed-Methods Study

BACKGROUND: Pursuing initial invasive or conservative management of chronic coronary disease (CCD) is a preference-sensitive decision that should include shared decision-making. Communicating the benefits of either approach is challenging, as individual patients rarely achieve the population-averaged outcomes reported in clinical trials. Our objective was to develop a patient decision aid (PDA) with patient-specific estimates of outcomes for initial invasive versus conservative management of CCD, based on the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches). METHODS: This was a multiphase mixed-methods study using focus groups of outpatients with CCD, caregivers, clinicians, and researchers. Focus groups were held in Kansas City, MO and New York City, NY between September 2021 and June 2022. Patients with CCD were included if they had a positive stress test within 1 year. Phase 1 focused on patient priorities for outcomes to guide treatment decisions. Phase 2 involved PDA development and refinement. Phase 3 involved further refinement and member checking. Key themes involving shared decision-making and treatment preferences were elicited from focus groups using a deductive approach to develop a PDA representing the outcomes most important to patients. RESULTS: Of 46 patient and caregiver participants, the mean age was 63.5 years, 53% were female, 61% were White, 24% were Black, and 9% were Hispanic. When deciding between treatments, participants valued shared decision-making but generally deferred decisions to clinicians. The outcomes most important to participants were survival and quality of life, followed by physical functioning and symptoms. To represent these outcomes, participants favored simple visualizations, such as a speedometer or health meter. When deciding between treatment options, participants preferred to use the PDA collaboratively with a clinician instead of as a stand-alone tool. CONCLUSIONS: Our novel, patient-centered approach to developing a PDA for CCD with patient-specific outcomes has the potential to rapidly translate clinical trial results to individual patients and support shared decision-making.

Miniaturized protein profiling permits targeted signaling pathway analysis in individual circulating tumor cells to improve personalized treatment

BackgroundTraditional genomic profiling and mutation analysis of single cells like Circulating Tumor Cells (CTCs) fails to capture post-translational and functional alterations of proteins, often leading to limited treatment efficacy. To overcome this gap, we developed a miniaturized ‘protein analysis on the single cell level’ workflow—baptized ZeptoCTC. It integrates established technologies for single-cell isolation with sensitive Reverse Phase Protein Array (RPPA) analysis, thus enabling the comprehensive assessment of multiple protein expression and activation in individual CTCs.MethodsThe ZeptoCTC workflow involves several critical steps. Firstly, individual cells are labeled and isolated. This is followed by cell lysis and the printing of true single cell lysate preparations onto a ZeptoChip using a modified micromanipulator, CellCelector™. The printed lysates then undergo fluorescence immunoassay RPPA protein detection using a ZeptoReader. Finally, signal quantification is carried out with Image J software, ensuring precise measurement of multiple protein levels.ResultsThe efficacy of ZeptoCTC was demonstrated through various applications. Initially, it was used for measuring EpCAM protein expression, a standard marker for CTC detection, revealing higher levels in single MCF-7 over MDA-MB-231 tumor cells. Furthermore, in Capivasertib (Akt-inhibitor)-treated MCF-7 single cells, ZeptoCTC detected a 2-fold increase in the pAkt/Akt ratio compared to control cells, and confirmed co-performed bulk-cell western blot analysis results. Notably, when applied to individual CTCs from metastasized breast cancer patients, ZeptoCTC revealed significant differences in protein activation levels, particularly in measured pAkt and pErk levels, compared to patient-matched WBCs. Moreover, it successfully differentiated between CTCs from patients with different Akt1 genotypes, highlighting its potential to determine the activation status of druggable cancer driving proteins for individual and targeted treatment decision making.ConclusionsThe ZeptoCTC workflow represents a valuable tool in single cell cancer research, crucial for personalized medicine. It permits detailed analysis of key proteins and their activation status of targeted, cancer-driven signaling pathways in single cell samples, aiding in understanding tumor response, progression, and treatment efficacy beyond bulk analysis. The method significantly advances clinical investigations in cancer, improving treatment precision and effectiveness. The workflow will be applicable to protein analysis on other types of single cells like relevant in stem cell, neuropathology and hemopoietic cell research.

Interpretation of SD-OCT imaging data in real-life conditions versus standardized reading centre analysis in eyes with diabetic macular oedema or macular oedema secondary to retinal vein occlusion: 24-month follow-up of the ORCA study.

As part of the prospective, non-interventional OCEAN study, the ORCA module evaluated physicians' spectral domain optical coherence tomography (SD-OCT) image interpretations in the treatment of diabetic macular oedema (DME) or macular oedema (ME) secondary to retinal vein occlusion (RVO). Presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) was evaluated independently by physicians and reading centres (RCs) on 1612 SD-OCT scans of 133 patients diagnosed with either DME or ME secondary to RVO. Agreement between physicians and RCs was calculated for both cohorts individually and as a combined ME cohort. Physicians' treatment decisions were analysed related to the results of the OCT-evaluations. For the combined ME cohort, presence of IRF/SRF was recorded by RCs in 792/1612 (49.1%) visits and by physicians in 852/1612 (52.9%) visits, with an agreement regarding presence or absence of foveal fluid in 70.4% of cases. In 64.4% (510/792) of visits with RC-detected foveal IRF and/or SRF no injection was given. In 30.3% of these visits with foveal fluid no reason was identified for a 'watch and wait' approach indicating possible undertreatment. BCVA deterioration was seen in a quarter of these eyes at the following visit. Despite good agreement between physicians and RCs to recognize SRF and IRF, our data indicate that omitting injections despite foveal involvement of fluid is frequent in routine clinical practice. This may put patients at risk of undertreatment, which may negatively impact real-life BCVA outcomes. www. gov , identifier NCT02194803.

Intravitreal Dexamethasone Implant in Anti-Vascular Endothelial Growth Factor Pretreated Diabetic Macular Edema—A Swiss Cohort Study

Background/Objectives: Diabetic macular edema (DME) is a significant cause of visual impairment, often treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond adequately to this treatment. This study aims to evaluate the contribution of the intravitreal dexamethasone (DEX) implant as a second-line treatment in DME patients with insufficient response to anti-VEGF therapy or with high treatment burden. Methods: This retrospective multicenter cohort study was conducted across seven clinical sites in Switzerland. The study included eyes with active DME that had been pretreated with anti-VEGF for at least six months before receiving DEX therapy. Data were extracted from electronic patient records, focusing on best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection frequency. Results: A total of 95 eyes from 89 patients (38.8% females, mean age 65.6 ± 9.1 years, follow-up time 80.6 ± 38.5 [13.5–166.7] months) were analyzed. Prior to the first DEX implant, eyes had undergone an average of 16.0 ± 13.3 anti-VEGF injections over 32.5 ± 22.4 months. Post-DEX treatment, 22.1% of eyes received DEX monotherapy, 44.2% received a combination of DEX and anti-VEGF, 25.3% continued with anti-VEGF monotherapy, and 8.4% received no further treatment. The number of anti-VEGF injections decreased significantly from 6.4 ± 3.1 in the year before DEX to 1.6 ± 2.4 in the year after DEX (p < 0.001). BCVA remained stable (0.4 ± 0.3 logMAR at baseline, 0.4 ± 0.5 logMAR at 24 months, p = 0.2), while CST improved from 477.7 ± 141.0 to 320.4 ± 125.5 μm (p < 0.001), and the presence of retinal fluid decreased from 98.0% to 61.1% (p = 0.021). During follow-up, 26.3% of eyes required glaucoma medication, 4.2% underwent glaucoma surgery, and 1.1% needed cataract surgery. Conclusions: In real-world clinical settings, the addition of DEX to anti-VEGF therapy in DME patients significantly reduces treatment burden and retinal fluid while maintaining visual function. Treatment decisions should balance anatomical and functional outcomes, considering individual patient needs.

Investigating the Salience of Clinical Meaningfulness and Clinically Meaningful Outcomes in Metastatic Breast Cancer Care Delivery

PURPOSE As metastatic breast cancer (mBC) treatment evolves, there is a need to understand how clinical meaningfulness, or a meaningful change in a patient's daily life, and clinically meaningful outcomes inform patient-centered care. Partnering with key stakeholders ensures patient-centered research incorporates the knowledge and expertise of advisors with lived experience. We describe a multistakeholder engagement approach to examine how people living with mBC (PLWmBC), caregivers, and health care providers interpret clinical meaningfulness and clinically meaningful outcomes and their influence on mBC treatment decision making and care. METHODS Qualitative focus groups with PLWmBC, caregivers, and health care providers were conducted and analyzed along three overarching themes: interpretations of clinical meaningfulness and clinically meaningful outcomes; treatment recommendations, preferences, and decisions; and implications for clinical practice. Patient-led and professional organizations served as research partners in study design, implementation, and interpretation of findings. RESULTS Partnerships were established with four patient-led and three professional organizations representing diverse constituencies throughout the United States. Twenty-two focus groups were conducted with 50 PLWmBC, 24 caregivers, and 41 health care providers (oncologists, n = 11; advanced practice providers, n = 13; oncology nurses, n = 17) between March and June 2023. PLWmBC and caregivers were unfamiliar with the concepts of clinical meaningfulness and clinically meaningful outcomes. Although health care providers were familiar, they did not use the terms when discussing treatment with PLWmBC. Across groups, participants emphasized the importance of meaningful outcomes beyond overall survival, including quality of life and improvement in symptoms and functioning. Participants noted that outcomes considered meaningful are individualized and dynamic. CONCLUSION This study offers insight into how partnering with patient advocacy and professional organizations can enhance research quality and aid translation of findings to clinical practice, thereby supporting patient-centered care.

Endoscopic Submucosal Dissection for Early Gastric Cancer Exceeding Expanded Criteria—Long-Term Outcomes from the German ESD Registry

Background and aims: Endoscopic submucosal dissection (ESD) has become a standard treatment for early gastric cancer (EGC), often fulfilling guideline criteria (GC) or expanded criteria (EC). When lesions exceed the EC, surgical resection is recommended. However, a subgroup of these patients are not treated surgically. The aim of this study was to investigate the long-term follow-up of patients after ESD for EGC outside the EC (out of indication; OI). Methods: Patients who were included in the prospective German ESD registry were analyzed when ESD was performed for EGC. Patients were stratified in three groups according to histopathological features (GC, EC and OI). The results were evaluated in terms of patient characteristics, procedure characteristics and follow-up data. Results: Over a 48-month period, 195 patients from 14 German centers were included. In total, 71 lesions (36.4%) met the guideline criteria, 70 lesions (35.9%) corresponded to the expanded criteria and 54 lesions (27.7%) turned out to be OI. The R0 resection rate was significantly higher for the GC and EC groups than for the OI group (94.4% vs. 84.3% vs. 55.6%, p < 0.001). Additional surgery was not performed in 72% (39/54) of patients in the OI group. During a mean follow-up of 37 months, overall survival showed no significant difference between the EC and OI groups when endoscopic follow-up was performed without additional surgery (p = 0.064). Conclusions: The results show that a good long-term survival can be achieved after ESD for patients with OI lesions without additional surgery. The treatment decision has to be made on an individual basis, taking the patient’s comorbidities and the risk of surgical resection into account.

Risk of recurrent venous thromboembolism in patients with cancer: an individual patient data meta-analysis and development of a prediction model

Background About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions. Aim To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT. Methods For this individual patient data (IPD) meta-analysis, we used data from four randomized controlled trials evaluating low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) for CAT (Hokusai VTE Cancer, SELECT-D, CLOT, and CATCH). The primary outcome was adjudicated on-treatment recurrent CAT during 6-month follow-up. A clinical prediction model was developed using multivariable logistic regression analysis with backward selection. This model was validated using internal-external cross validation. Performance was assessed by the c-statistic and a calibration plot. Results After excluding patients using vitamin K antagonists, the combined dataset comprised 2,245 patients with cancer and acute CAT who were treated with edoxaban (23%), rivaroxaban (9%), dalteparin (47%), or tinzaparin (20%). Recurrent on-treatment CAT during 6-month follow-up occurred in 150 (6.7%) patients. Predictors included in the final model were age (restricted cubic spline), breast cancer (OR 0.42; 95%-CI 0.20-0.87), metastatic disease (OR 1.44; 95%-CI 1.01-2.05), treatment with DOAC (OR 0.66; 95%-CI 0.44-0.98), and deep vein thrombosis only as index event (OR 1.72; 95%-CI 1.31-2.27). The c-statistic of the model was 0.63 (95%-CI 0.54-0.72) after internal-external cross validation. Calibration varied across studies. Conclusions The prediction model for recurrent CAT included five clinical predictors and has only modest discrimination. Prediction of recurrent CAT at the initiation of anticoagulation remains challenging.

On the Need for Better Information from Randomized Clinical Trials in Oncology

Cancer patients frequently seek information from their oncologists regarding the anticipated outcomes of their treatment. They commonly inquire about the potential for a cure and the likelihood of achieving it, as well as whether the treatment will prolong their life and, if so, by how much. In oncology, randomized controlled trials play a pivotal role in informing treatment decisions. It is essential that published randomized controlled trials provide comprehensive data to enable clinicians to deliver precise and reliable information to patients. The concept of the Hazard Ratio (HR) can be challenging for many oncologists and is often misunderstood in terms of its implications for risk. Thus, incorporating both relative and absolute risk metrics in addition to hazard ratios could substantially enhance patient care. This consideration is crucial not only for patients and oncologists but also for policymakers within public health systems.

Decisional Conflicts in Patients With Low-Risk Papillary Thyroid Microcarcinomas Considering Active Surveillance

ImportanceInternationally, active surveillance has been shown to be beneficial and safe in the management of low-risk papillary thyroid microcarcinomas. However, choosing active surveillance is a difficult treatment decision for patients with low-risk papillary thyroid microcarcinomas.ObjectiveTo identify and analyze the antecedents and mediating processes of decisional conflicts when patients consider active surveillance as an alternative to surgery.Design, Setting, and ParticipantsIn this qualitative study, semistructured interviews were conducted between April 2023 and December 2023 at 3 tertiary hospitals in China. Thirty-one participants who were diagnosed with low-risk papillary thyroid microcarcinomas, who had experienced considering active surveillance as an alternative to surgery and who scored above 25 on the decision conflict scale were purposively recruited. Inductive content analysis led to emergent themes. Data analysis was performed from April 2023 to February 2024. Methods used to protect the trustworthiness of the study results included audit trails and member checks.Main outcomes and MeasuresPatients’ experience of decisional conflicts and the antecedents and mediating processes relating to these decisional conflicts.ResultsAmong 31 participants (median [range] age, 39.2 [22-63] years; 22 [71%] were female and 9 [29%] were male), 3 themes were classified: (1) decisional conflicts in decision preparation, (2) decisional conflicts in decision-making, and (3) decisional conflicts in decision implementation. The patient’s experiences of decisional conflicts were diverse and occurred throughout the entire decision-making process. The antecedents of the decisional conflicts included personal influencing factors, system-level influencing factors, and the relational-situational context. Patients with low-risk papillary thyroid microcarcinomas interacted with these antecedents in the process of decision-making and eventually failed to mediate, leading to decisional conflicts.Conclusions and relevanceThis qualitative study found that patients with low-risk papillary thyroid microcarcinomas experienced clinically significant decisional conflicts and experienced considerable challenges and psychological problems in decision-making. The antecedents of decisional conflicts and accompanying mediating processes can provide guidance for individuals, health care professionals, and health care systems to provide decision support for patients with low-risk papillary thyroid microcarcinomas.

User-Centered Design and Usability of Voxe as a Pediatric Electronic Patient-Reported Outcome Measure Platform: Mixed Methods Evaluation Study

Background Electronic patient-reported outcome measures (ePROMs) are standardized digital instruments integrated into clinical care to collect subjective data regarding patients’ health-related quality of life, functional status, and symptoms. In documenting patient-reported progress, ePROMs can guide treatment decisions and encourage measurement-based care practices. Voxe is a pediatric and user-centered ePROM platform for patients with chronic health conditions. Objective We aimed to describe the user-centered design approach involving feedback from end users and usability testing of Voxe’s platform features to support implementation in a pediatric health care setting. Methods Purposive sampling was used to recruit patients aged 8-17 years from 2 chronic illness populations in 2 pediatric hospitals in Canada. Patients’ health care team members were also purposively recruited. One-on-one iterative testing sessions were conducted digitally by research team members with participants to obtain feedback on the appearance and functionalities of the Voxe platform prototype. Patients and health care providers (HCPs) completed Voxe-related task-based activities. International Organization for Standardization key performance indicators were tracked during HCP task-based activities. HCPs also completed the System Usability Scale. To test platform usability, the think-aloud technique was used by participants during the completion of structured tasks. After completing all task-based activities, patient participants selected 5 words from the Microsoft Desirability Toolkit to describe their overall impression and experience with the Voxe platform. Qualitative data about likes, dislikes, and ease of use were collected through semistructured interviews. Feedback testing sessions were conducted with patients and HCPs until Voxe was acceptable to participating end users, with no further refinements identified. Quantitative and qualitative data analysis were completed using descriptive statistics and content analysis. Results A total of 49 patients and 38 HCPs were recruited. Patients were positive about Voxe’s child-centered design characteristics and notification settings. HCPs rated Voxe as user-friendly and efficient, with the time to complete tasks decreasing over time. HCPs were satisfied with the Voxe platform functionalities and identified the value of Voxe’s system notifications, summarized display of ePROM results, and its capacity to integrate with electronic medical records. Patients’ and HCPs’ high satisfaction rates with the Voxe prototype highlight the importance of being responsive to user suggestions from the inception of eHealth platform developments to ensure their efficient and effective design. Conclusions This paper describes the user-centered creation and usability testing of Voxe as an ePROM platform for implementation into clinical care for pediatric patients with chronic health conditions. As a patient-facing platform that can be integrated into electronic medical records, Voxe aligns with measurement-based care practices to foster quality patient-centered approaches to care. End users’ positive feedback and evaluation of the platform’s user-friendliness and efficiency suggest that Voxe represents a valuable and promising solution to systematically integrate patient-related outcome (PRO) data into complex and dynamic clinical health care settings. International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2021-053119

Evaluation of the diagnostic ability of the Fränkel manoeuvre to detect the contributing jaw in angle class II division 1 malocclusion

BackgroundA correct diagnosis of patients with an Angle Class II malocclusion is needed to guide treatment decisions toward the contributing jaw and to achieve better treatment outcomes. The aim of the study is to evaluate the diagnostic potential of the Fränkel manoeuvre (FM) for detecting the components determining sagittal discrepancy in Angle Class II division 1.Materials and methodsAnonymous questionnaires containing photographs were distributed totwo groups: general practitioner (GP) dentists and orthodontists. The level of the patient’s profile aesthetics before (T0) and after (T1) the manoeuvre was determined using a 100 mm visual analog scale, and the ‘profile improvement’ score was defined as T1 minus T0. The diagnostic ability of the FM was calculated by comparison with lateral cephalometry as a reference standard using receiver operating characteristic (ROC) curve analysis.ResultsA total of 102 respondents participated in the survey; 40 were orthodontists, and 62 were GP dentists. According to the post-FM images, the “profile improvement” score (T1-T0) was significantly greater in patients with mandibular retrusion than in those with maxillary protrusion (p < 0.05). The predictive power of FM, coinciding with the area under the ROC curve, was 0.62 for GPs and 0.78 for orthodontists.ConclusionsThe FM method is a useful and accurate tool for diagnosing skeletal Angle Class II malocclusion etiology (mandibular retrusion or maxillary protrusion), especially when used by orthodontists.

Reduced anthelmintic use on 13 New Zealand sheep farms: farmer motivations and practical implementation

ABSTRACT Aims: To describe the personal drivers, sources of information and gastro-intestinal parasite control methods used by a group of New Zealand sheep farmers identified as low users of anthelmintic (AHC), and their perception of the efficacy and impacts of this approach. Methods: A convenience sample of 13 sheep farmers farming with a policy of reduced AHC use (no pre-determined routine treatments of ewes >19 months old and/or lambs not routinely treated at pre-determined intervals from weaning through to late autumn) were identified. Semi-structured interviews were conducted regarding their farming philosophy, motivations for reducing AHC use, perceptions of the impacts of farming with reduced AHC use, and parasite control practices. Semi-quantitative data were analysed using descriptive statistics for demographic data and categorising participants’ use of AHC and non-chemical control methods. Qualitative data regarding participants’ motivations, approaches and rationale were analysed by systematic analysis of the transcripts and distillation of key concepts. Results: Participants had been operating with reduced AHC use for 3 to ≥20 years. Key motivators for reducing AHC use were a diagnosis of anthelmintic resistance (AR) or concerns about AR developing. Parasite management information came from a wide range of sources. All respondents expressed overall positive views regarding the impacts of reduced AHC use but detailed information was not available. All identified that regular monitoring, based primarily on subjective animal and non-animal factors was important for their parasite control strategy. Most used faecal egg counts (FEC), often in an ad hoc manner. Five never treated adult ewes, two routinely treated ewes prior to lambing with short-acting AHC and the remainder occasionally treated a small number in low body condition. Four routinely treated some or all lambs at 28–30-day intervals from weaning to late autumn while the remainder based their treatment decisions for lambs on monitored information. All placed heavy emphasis on feeding sheep well, ensuring high post-grazing residuals, and cross-grazing. Conclusions: AR was a key motivator for participants to reduce AHC use, and a range of information sources and decision-making processes were used. Key parasite management practices were monitoring, primarily using subjective assessments, emphasis on feeding stock well and cross-grazing. Clinical relevance: The rising prevalence of AR will likely result in increasing the motivation for sheep farmers to reduce their AHC use. Veterinarians will play a key role in providing advice and assistance to facilitate changes in parasite management.

A Pharmacological Overview of Degarelix and Relugolix in Advanced Prostate Cancer

Prostate cancer (PCa) ranks the second most diagnosed cancers among men globally and the sixth leading cause of cancer-related deaths. Advanced prostate cancer can be defined as the recurrence after definitive therapies (radical prostatectomy or external beam radiotherapy) and de novo metastasis (metastasis without prior treatment). Advanced PCa can be categorized as metastatic hormone sensitive prostate cancer (mHSPC), non-metastatic castration resistant prostate cancer (nmCRPC), and metastatic castration resistant prostate cancer (mCRPC). Management of advanced PCa often involves castration to reduce testosterone levels, which can be achieved by gonadotropin releasing hormone antagonists such as degarelix and relugolix. Degarelix is injectable while relugolix is an orally administered form of GnRH antagonist. This review aims to explore the latest pharmacological aspects of these drugs to inform treatment decisions for advanced PCa.

The ATOM-Seq sequence capture panel can accurately predict microsatellite instability status in formalin-fixed tumour samples, alongside routine gene mutation testing

Microsatellite instability (MSI) occurs across a number of cancers and is associated with different clinical characteristics when compared to microsatellite stable (MSS) cancers. As MSI cancers have different characteristics, routine MSI testing is now recommended for a number of cancer types including colorectal cancer (CRC). Using gene panels for sequencing of known cancer mutations is routinely performed to guide treatment decisions. By adding a number of MSI regions to a small gene panel, the efficacy of simultaneous MSI detection in a series of CRCs was tested. Tumour DNA from formalin-fixed, paraffin-embedded (FFPE) tumours was sequenced using a 23-gene panel kit (ATOM-Seq) provided by GeneFirst. The mismatch repair (MMR) status was obtained for each patient from their routine pathology reports, and compared to MSI predictions from the sequencing data. By testing 29 microsatellite regions in 335 samples the MSI status was correctly classified in 314/319 samples (98.4% concordance), with sixteen failures. By reducing the number of regions in silico, comparable performance could be reached with as few as eight MSI marker positions. This test represents a quick, and accurate means of determining MSI status in FFPE CRC samples, as part of a routine gene mutation assay, and can easily be incorporated into a research or diagnostic setting. This could replace separate mutation and MSI tests with no loss of accuracy, thus improving testing efficiency.

Exploring How Values of Colorectal Cancer Patients and their Caregivers Influence Treatment Decision-Making.

As we adopt value models to inform drug reimbursement, coverage, clinical trials, and treatment choices, aligning these models to reflect patient values and preferences becomes increasingly relevant. In this study, we focus on colorectal cancer (CRC), which is highly prevalent and a leading cause of death in Canada, and new drug treatment options are costly. The aim of this study was to understand how the values and experiences of people with CRC and their caregivers inform their perspectives about new and emerging colorectal cancer drug treatments. We applied qualitative methods to identify key personal, social, and system factors about how the values of people with CRC and their caregivers' values influence their treatment decision-making in a more holistic manner. Canadian adults (>18 years) living with non-metastatic or metastatic CRC and caregivers were recruited from oncology clinics and Colorectal Cancer Canada (CCC) using purposive sampling. Participants engaged in structured interviews by telephone. Interviews were transcribed verbatim and analyzed thematically guided by a qualitative phenomenological approach and Sherwin's ethical theory of relational autonomy using NVivo software. We conducted structured interviews with 12 people with CRC and six of their caregivers, and elicited patient and caregiver values and their influence on treatment decision-making context of key personal, social, and system factors. Thematic analysis of transcripts led to the development of four overarching and intersecting themes that were identified as influencing people with CRC and their caregivers' treatment decision-making: treatment outcomes and effectiveness, intrapersonal and interpersonal factors, quality of life, and survivorship and prognosis. Our findings suggest intersecting influences of patient-, community-, and social network-, and systemic-level factors that influence patients' decisions on treatment. Perceived clinical benefit, requirements of treatment, available information, the impact of treatment on social relationships and daily life, and the impact of social support were key factors described by participants. To our knowledge, this is the first study to utilize the theory of relational autonomy to understand patient and caregiver values in the context of treatment decisions in CRC. Using these findings, a continued exploration of people with CRC's values in treatment decision-making and how much patients value or weight the different aspects of treatment would help further advance patient care and guide healthcare system decision-making.

Prognostic Significance of Human Papillomavirus Genotypes in Oropharyngeal Squamous Cell Carcinoma.

The prognostic significance of human papillomavirus (HPV) genotypes in oropharyngeal squamous cell carcinoma (OPSCC) has garnered considerable attention due to the increasing reliance on HPV status for clinical decision-making. This study aimed to compare the survival outcomes associated with different HPV genotypes in patients with OPSCC relative to HPV-negative tumors, providing insights into the potential implications for treatment de-intensification strategies. Patients diagnosed with invasive OPSCC were included from the National Cancer Database (NCDB). Patients were stratified based on HPV status and genotype, with HPV-negative tumors serving as the reference group. Multivariable Cox regression analysis was performed to assess the independent prognostic value of different HPV genotypes. Th majority of patient were classified as HPV-positive (N = 17,358, 70.0%), with HPV 16 being the most common genotype (N = 15410/17358, 88.8%) compared with other high-risk (N = 1217/17,358, 7.0%) and low-risk (N = 731/17,358, 4.2%) HPV genotypes. A significantly lower risk of death was measured for all HPV-positive compared with HPV-negative tumors (HPV 16: adjusted HR 0.51; 95% CI: 0.49-0.54; other high-risk HPV: adjusted HR 0.56; 95% CI: 0.49-0.63; low-risk HPV: adjusted HR 0.59; 95% CI: 0.50-0.68; p < 0.001). This study highlights the significant prognostic value of HPV genotypes in OPSCC, underscoring the superior survival outcomes of HPV-positive tumors across all genotypes compared with HPV-negative tumors. Detailed HPV subtype analysis can inform better treatment decisions and support de-intensification strategies for patients with low-risk genotypes. 3 Laryngoscope, 2024.