Is there scope to do better? Clinical communication with adolescents and young adults with cancer-A scoping review.

INTRODUCTION: How to communicate effectively with adolescent and young adults with cancer (AYACs) is a research priority. In a UK-wide survey of young people with cancer's research priorities, communication was a striking cross-cutting theme. It is increasingly recognised that AYACs have experiences and communication needs that differ significantly from those of younger children and older adults. The purpose of this review is to explore the features of effective clinical communication with AYACs. METHODS: A literature search was undertaken to identify and map the available evidence using a broad scope to get an overview of the pertinent literature, identify knowledge gaps and clarify concepts. The searches yielded 5825 records, generating 4040 unique articles. These were screened and 71 full articles were read by four researchers with disagreements resolved by discussion leaving 29 included articles. Narrative synthesis was undertaken in relation to each of the research questions. RESULTS: Three key themes were identified: being an adolescent/young adult, supporters, and healthcare professionals (HCPs). AYACs need to feel that HCPs understand their unique perspective. They want to be involved, this changes over time and in different contexts. Supporters are a central tenet, are most often parents and undertake several roles which are not always universally supportive. HCPs enable involvement of AYACs, and this needs to be actively promoted. AYACs preference for their level of involvement requires continual assessment. The three themes are interlinked and exist within the wider scope of the triadic encounter and cancer experience. CONCLUSION: Supporters, most often parents were a key feature across the data and were seemingly paradoxical in nature. Triadic communication, the presence of a third person, is a central tenet of communication with AYACs and we propose a conceptual model to represent the nuances, components, and facets of this complex communication.

Prognostic modeling in early rheumatoid arthritis: reconsidering the predictive role of disease activity scores.

OBJECTIVE: In this prospective cohort study, we provide several prognostic models to predict functional status as measured by the modified Health Assessment Questionnaire (mHAQ). The early adoption of the treat-to-target strategy in this cohort offered a unique opportunity to identify predictive factors using longitudinal data across 20 years. METHODS: A cohort of 397 patients with early RA was used to develop statistical models to predict mHAQ score measured at baseline, 12 months, and 18 months post diagnosis, as well as serially measured mHAQ. Demographic data, clinical measures, autoantibodies, medication use, comorbid conditions, and baseline mHAQ were considered as predictors. RESULTS: The discriminative performance of models was comparable to previous work, with an area under the receiver operator curve ranging from 0.64 to 0.88. The most consistent predictive variable was baseline mHAQ. Patient-reported outcomes including early morning stiffness, tender joint count (TJC), fatigue, pain, and patient global assessment were positively predictive of a higher mHAQ at baseline and longitudinally, as was the physician global assessment and C-reactive protein. When considering future function, a higher TJC predicted persistent disability while a higher swollen joint count predicted functional improvements with treatment. CONCLUSION: In our study of mHAQ prediction in RA patients receiving treat-to-target therapy, patient-reported outcomes were most consistently predictive of function. Patients with high disease activity due predominantly to tenderness scores rather than swelling may benefit from less aggressive treatment escalation and an emphasis on non-pharmacological therapies, allowing for a more personalized approach to treatment. Key Points • Long-term use of the treat-to-target strategy in this patient cohort offers a unique opportunity to develop prognostic models for functional outcomes using extensive longitudinal data. • Patient reported outcomes were more consistent predictors of function than traditional prognostic markers. • Tender joint count and swollen joint count had discordant relationships with future function, adding weight to the possibility that disease activity may better guide treatment when the components are considered separately.

Triadic communication with teenagers and young adults with cancer: a systematic literature review - 'make me feel like I'm not the third person'.

OBJECTIVES: Clinical communication needs of teenagers and young adults with cancer (TYACs) are increasingly recognised to differ significantly from younger children and older adults. We sought to understand who is present with TYACs, TYACs' experiences of triadic communication and its impact. We generated three research questions to focus this review: (1) Who is present with TYACs in healthcare consultations/communication?, (2) What are TYACs' experiences of communication with the supporter present? and (3) What is the impact of a TYAC's supporter being present in the communication? DESIGN: Systematic review with narrative synthesis. DATA SOURCES: The search was conducted across six databases: Medline, CINAHL, Embase, PsycINFO, Web of Science and AMED for all publications up to December 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Included papers were empirical research published after 2005; participants had malignant disease, diagnosed aged 13-24 years (for over 50% of participants); the research addressed any area of clinical communication. DATA EXTRACTION AND SYNTHESIS: Three independent reviewers undertook full-text screening. A review-specific data extraction form was used to record participant characteristics and methods from each included paper and results relevant to the three review questions. RESULTS: A total of 8480 studies were identified in the search, of which 36 fulfilled the inclusion criteria. We found that mothers were the most common supporter present in clinical communication encounters. TYACs' experiences of triadic communication are paradoxical in nature-the supporter can help or hinder the involvement of the young person in care-related communication. Overall, young people are not included in clinical communication and decisions at their preferred level. CONCLUSION: Triadic communication in TYACs' care is common, complex and dynamic. Due to the degree of challenge and nuances raised, healthcare professionals need further training on effective triadic communication. PROSPERO REGISTRATION NUMBER: CRD42022374528.

Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2.

SHIP1, an inositol 5-phosphatase, plays a central role in cellular signaling. As such, it has been implicated in many conditions. Exploiting SHIP1 as a drug target will require structural knowledge and the design of selective small molecules. We have determined apo, and magnesium and phosphate-bound structures of the phosphatase and C2 domains of SHIP1. The C2 domains of SHIP1 and the related SHIP2 modulate the activity of the phosphatase domain. To understand the mechanism, we performed activity assays, hydrogen-deuterium exchange mass spectrometry, and molecular dynamics on SHIP1 and SHIP2. Our findings demonstrate that the influence of the C2 domain is more pronounced for SHIP2 than SHIP1. We determined 91 structures of SHIP1 with fragments bound, with some near the interface between the two domains. We performed a mass spectrometry screen and determined four structures with covalent fragments. These structures could act as starting points for the development of potent, selective probes.

Up and away with cervical cancer: IL-29 is a promising cytokine for immunotherapy of cervical cancer due to its powerful upregulation of p18, p27, and TRAILR1.

Cervical cancer is one of the most common types of female cancers worldwide. IL-29 is an interesting cytokine in the IFNλ family. Its role in the pathogenesis of neoplasia is complicated and has been studied in other cancers, such as lung cancer, gastric cancer, and colorectal cancer. IL-29 has been previously reported to promote the growth of pancreatic cancer. However, the direct role of IL-29 in cervical cancer has not been studied yet. This study was performed to investigate the direct effect on cervical cancer cell growth. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects of IL-29 on cell survival, proliferation, and apoptosis of a well-studied cervical cancer cell line, SiHa. We further investigated the potential molecular mechanisms by using RT-PCR and IHC. We found that the percentage of colonies of SiHa cells was decreased in the presence of IL-29. This was consistent with a decreased OD value of cancer cells. Furthermore, the relative caspase-3 activity in cancer cells increased in the presence of IL-29. The anti-proliferative effect of IL-29 on cancer cells correlated with increased expression of the anti-proliferative molecules p18 and p27. The pro-apoptotic effect of IL-29 on cancer cells correlated with increased expression of the pro-apoptotic molecule TRAILR1. IL-29 inhibits cervical cancer cell growth by inhibiting cell proliferation and promoting cell apoptosis. Thus, IL-29 might be a promising cytokine for immunotherapy of cervical cancer.

Investigation of the mechanisms for wireless nerve stimulation without active electrodes.

Electric-field stimulation of neuronal activity can be used to improve the speed of regeneration for severed and damaged nerves. Most techniques, however, require invasive electronic circuitry which can be uncomfortable for the patient and can damage surrounding tissue. A recently suggested technique uses a graft-antenna-a metal ring wrapped around the damaged nerve-powered by an external magnetic stimulation device. This technique requires no electrodes and internal circuitry with leads across the skin boundary or internal power, since all power is provided wirelessly. This paper examines the microscopic basic mechanisms that allow the magnetic stimulation device to cause neural activation via the graft-antenna. A computational model of the system was created and used to find that under magnetic stimulation, diverging electric fields appear at the metal ring's edges. If the magnetic stimulation is sufficient, the gradients of these fields can trigger neural activation in the nerve. In-vivo measurements were also performed on rat sciatic nerves to support the modeling finding that direct contact between the antenna and the nerve ensures neural activation given sufficient magnetic stimulation. Simulations also showed that the presence of a thin gap between the graft-antenna and the nerve does not preclude neural activation but does reduce its efficacy.

Machine learning and deep learning predictive models for long-term prognosis in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Machine learning and deep learning models have been increasingly used to predict long-term disease progression in patients with chronic obstructive pulmonary disease (COPD). We aimed to summarise the performance of such prognostic models for COPD, compare their relative performances, and identify key research gaps. METHODS: We conducted a systematic review and meta-analysis to compare the performance of machine learning and deep learning prognostic models and identify pathways for future research. We searched PubMed, Embase, the Cochrane Library, ProQuest, Scopus, and Web of Science from database inception to April 6, 2023, for studies in English using machine learning or deep learning to predict patient outcomes at least 6 months after initial clinical presentation in those with COPD. We included studies comprising human adults aged 18-90 years and allowed for any input modalities. We reported area under the receiver operator characteristic curve (AUC) with 95% CI for predictions of mortality, exacerbation, and decline in forced expiratory volume in 1 s (FEV1). We reported the degree of interstudy heterogeneity using Cochran's Q test (significant heterogeneity was defined as p≤0·10 or I2>50%). Reporting quality was assessed using the TRIPOD checklist and a risk-of-bias assessment was done using the PROBAST checklist. This study was registered with PROSPERO (CRD42022323052). FINDINGS: We identified 3620 studies in the initial search. 18 studies were eligible, and, of these, 12 used conventional machine learning and six used deep learning models. Seven models analysed exacerbation risk, with only six reporting AUC and 95% CI on internal validation datasets (pooled AUC 0·77 [95% CI 0·69-0·85]) and there was significant heterogeneity (I2 97%, p<0·0001). 11 models analysed mortality risk, with only six reporting AUC and 95% CI on internal validation datasets (pooled AUC 0·77 [95% CI 0·74-0·80]) with significant degrees of heterogeneity (I2 60%, p=0·027). Two studies assessed decline in lung function and were unable to be pooled. Machine learning and deep learning models did not show significant improvement over pre-existing disease severity scores in predicting exacerbations (p=0·24). Three studies directly compared machine learning models against pre-existing severity scores for predicting mortality and pooled performance did not differ (p=0·57). Of the five studies that performed external validation, performance was worse than or equal to regression models. Incorrect handling of missing data, not reporting model uncertainty, and use of datasets that were too small relative to the number of predictive features included provided the largest risks of bias. INTERPRETATION: There is limited evidence that conventional machine learning and deep learning prognostic models demonstrate superior performance to pre-existing disease severity scores. More rigorous adherence to reporting guidelines would reduce the risk of bias in future studies and aid study reproducibility. FUNDING: None.

The past, present, and future of immunotherapy for endometrial adenocarcinoma.

Incidences of endometrial adenocarcinoma are increasing in the USA with poor prognosis for patients with advanced disease. The current treatment standard is surgery including total hysterectomy and bilateral oophorectomy with surgical staging and adjunct treatment, such as chemotherapy or radiation. However, these methods do not present as an effective treatment option for poorly differentiated advanced cancers. Advancements in immunotherapy now offer a new approach for various types of cancer and specifically show promise in the treatment of endometrial adenocarcinoma. This review summarizes immunotherapeutic treatment options relevant to endometrial adenocarcinoma, such as immune checkpoint blockades, bispecific T-cell engager antibodies, vaccinations, and adoptive cell transfer. This study could be helpful for clinicians to identify treatment options more suitable for women with late-stage endometrial adenocarcinoma.

The Novel Use of IL-28 as an Effective Radiosensitizer in Pancreatic Cancer.

BACKGROUND/AIM: Pancreatic cancer is the second most common gastrointestinal cancer in the world, yet the five-year survival outcome rate of less than 5% urges for improvement in medical interventions of pancreatic cancer. Currently, high dose radiation therapy (RT) is used as an adjuvant treatment; however, the high level of RT required to treat advanced neoplasms leads to high incidence rates of side effects. In recent years, the utilization of cytokines as radiosensitizing agents has been studied, in order to reduce the amount of radiation required. However, few studies have examined IL-28 regarding its potential as a radiosensitizer. This study is the first to utilize IL-28 as a radiosensitizing agent in pancreatic cancer. MATERIALS AND METHODS: MiaPaCa-2, a widely used pancreatic cancer cell line was used in this study. Clonogenic survival and cell proliferation assays were used to evaluate growth and proliferation of MiaPaCa-2 cells. Caspase-3 activity assay was used to evaluate apoptosis of MiaPaCa-2 cells and RT-PCR was used to study the possible molecular mechanisms. RESULTS: Our results showed that IL-28/RT enhanced RT-induced inhibition of cell proliferation and promoted apoptosis of MiaPaCa-2 cells. Furthermore, compared to RT alone, we found that IL-28/RT up-regulated the mRNA expression of TRAILR1 and P21, while down-regulating mRNA expression of P18 and survivin in MiaPaCa-2 cells. CONCLUSION: IL-28 has the potential to be used as a radiosensitizer for pancreatic cancer and warrants further investigation.

Artificial intelligence and the future of radiographic scoring in rheumatoid arthritis: a viewpoint.

Rheumatoid arthritis is an autoimmune condition that predominantly affects the synovial joints, causing joint destruction, pain, and disability. Historically, the standard for measuring the long-term efficacy of disease-modifying antirheumatic drugs has been the assessment of plain radiographs with scoring techniques that quantify joint damage. However, with significant improvements in therapy, current radiographic scoring systems may no longer be fit for purpose for the milder spectrum of disease seen today. We argue that artificial intelligence is an apt solution to further improve upon radiographic scoring, as it can readily learn to recognize subtle patterns in imaging data to not only improve efficiency, but can also increase the sensitivity to variation in mild disease. Current work in the area demonstrates the feasibility of automating scoring but is yet to take full advantage of the strengths of artificial intelligence. By fully leveraging the power of artificial intelligence, faster and more sensitive scoring could enable the ongoing development of effective treatments for patients with rheumatoid arthritis.

Adolescent and Young Adult Cancer Placements: Developing Complex Clinical Communication Skills of Medical Students.

Purpose: Following implementation of a student selected module in adolescent and young adult cancer care for medical students, we sought to explore their experiences of the specialty. Methods: We undertook a focus group of five medical students all in their fourth to sixth year of study. Transcripts were transcribed verbatim and analyzed thematically. Results: We identified six key themes repeatedly elicited during the focus group; these were specialized and holistic care, patient's perspective, connectedness and professional boundaries, triadic communication, emotional impacts, and professional development and support. Conclusion: Early exposure to this specialty is positive for students and the model could be replicated elsewhere.

"A Different Person Entirely": Adolescent and Young Adults' Experiences Returning to Education after Cancer Treatment.

Purpose: Adolescent and young adults (AYAs) establish their independent, adult identities as part of their psychosocial development, a process that is largely informed by educational experiences. Not only is a cancer diagnosis disruptive to this process but also AYA cancer survivors (AYACs) face barriers as they attempt to reintegrate into educational systems. This study explores the experiences of AYACs as they return to education, to identify these obstacles and the implications for care teams. Methods: In-depth semistructured interviews were conducted with AYACs (n = 8), 16-19 years of age at diagnosis and 18-27 years of age at time of interview. Interviews were transcribed verbatim and analyzed using the principles of Giorgi's phenomenological analysis. Results: Four major themes were identified: AYACs suffer from debilitating late effects (theme 1) post-treatment as they adjust to a loss of normality and other fundamental losses (theme 2) associated with a cancer diagnosis, such as irrecoverable future plans. The educational systems (theme 3) to which they return can be both accommodating, capable of making allowances, and uncompromising, unable to adapt to AYAC survivors' needs. Appropriate mechanisms to facilitate resilience (theme 4) among AYACs are vital for successful return to education. Conclusion: This study supports previous findings that late effects and systemic barriers can hinder return to education, but further research focused on this age group is required. We believe that treating clinicians and specialist services can facilitate the return of AYACs to education by providing warning and comprehensive information about late effects, as early as possible before treatment completion, as well as effective information sharing with educational institutions.

How Can Health Care Professionals Communicate Effectively with Adolescent and Young Adults Who Have Completed Cancer Treatment? A Systematic Review.

Communication with teenage and young adult or adolescent and young adult (AYA) patients with cancer is critically important and not consistently taught in health care education. We have developed a local training for medical students to experience and join AYA cancer consultations to improve clinicians' abilities in the future. We have undertaken a systematic review of the literature, to provide a comprehensive overview of studies evaluating communication in this specific patient group, to guide clinical practice and future research. We searched MEDLINE, EMBASE, PsycINFO, Web of Science, and CINAHL databases for literature containing data relating to communication in AYAs previously treated for malignant disease. To ensure as comprehensive a review as possible, the researchers defined the AYA age range using the extremes used globally: 13-39 years. Two thousand eight hundred and thirty-seven articles were identified, which were reduced to 1517 after duplicates were removed. After handsearching references and citation tracking, 1556 abstracts were screened of which 40 full-text articles were assessed for eligibility. Only 12 met all inclusion criteria and were included in the final analysis. Young people want to be heard and have trust in their health care professionals (HCPs). They want to be involved in decisions about their care, and HCPs must establish who else the AYA wants to be involved in the decision-making process. AYAs want information to be given in an amount they can control and at a time preferred by them. Further education of communication skills, especially triadic communication, is essential for professionals involved in AYA care.