Can the Use of Telemedicine in the Management of Continuous Positive Airway Pressure for the Treatment of Obstructive Sleep Apnea Reduce Clinical Time and Additional Appointments: A Randomized Controlled Trial.

Introduction: Obstructive sleep apnea (OSA) is a common sleep breathing disorder and is associated with increased cardiovascular risk and daytime sleepiness. Continuous positive airway pressure (CPAP) is a treatment for OSA, which splints the airway open. The introduction of telemedicine in CPAP devices offers clinical staff an alternative method of reviewing patients, monitoring treatment, and reducing clinical time. Materials and Methods: A randomized control trial was conducted with patients randomized to one of three arms: Arm 1 (standard care), Arm 2 (modem and a virtual appointment), and Arm 3 (modem, smart device application DreamMapper™, and a virtual appointment). Ninety participants requiring treatment with CPAP following a diagnosis of OSA were recruited and data collected at baseline, 14 days, and 180 days. Additional contacts or appointments were also recorded. Results: Ninety participants (n = 90) were recruited (68% males and 32% females) with an average age of 52.0 ± 13.13 years and apnea/hypopnea index (AHI) 43.5 ± 21.92 (events/h). There was a statistically significant difference between the three arms in the average clinical time taken for the first follow-up appointment (p = 0.001). There was a statistically significant difference between the three arms in the number of additional appointments or contacts required (p = 0.03). Discussion and Conclusion: Telemedicine reduced clinical time at first follow-up, and in patients who received standard care or a smart device application to monitor their own CPAP treatment, there were significantly less additional appointments required when compared with telemedicine support in the form of a modem alone.

Nursing students' knowledge of and attitudes towards pain management: An integrative review.

OBJECTIVES: The objectives of this review were to appraise the available literature regarding nursing students' knowledge of and attitudes towards pain management; and secondly, to examine the instruments currently used to measure students' knowledge of and attitudes towards pain management. DESIGN: This review was conducted using Whittemore and Knafl's five-stage framework for integrative reviews. DATA SOURCES: A comprehensive search to retrieve relevant studies published in English between 1978 and 2022 was conducted using the databases: CINAHL, MEDLINE, Embase and Scopus databases. An updated search of the same databases was performed to identify studies published in 2023-2024. REVIEW METHODS: The initial search located 558 articles. One more relevant article was identified from an updated search test. Total of 244 duplicated records were removed. The remaining 315 studies were eligible for screening. After screening and checking for eligibility, 29 included articles were critically appraised using the Joanna Briggs Institute critical appraisal tools. RESULTS: Synthesis of the findings of the 29 included studies indicated that, internationally, nursing students have limited knowledge and often hold negative attitudes towards pain. Various instruments have been used to measure students' knowledge and attitudes towards pain. Most studies used true/false or multiple-choice questions and Likert-type scales. The validity and reliability of most of the tools were reported to be acceptable. The most commonly used instrument was the Knowledge and Attitudes Survey Regarding Pain. CONCLUSION: The findings from this review suggest the need for refinement of pain education programs to improve nursing students' knowledge of and attitudes towards pain management. Future research should focus on understanding the personal and environmental factors that impact students' level of knowledge and attitudes so as to inform curriculum development and ultimately the quality of the care graduates provide.

Overexpression of Fibroblast Activation Protein (FAP) in stroma of proliferative inflammatory atrophy (PIA) and primary adenocarcinoma of the prostate.

Fibroblast activation protein (FAP) is a serine protease upregulated at sites of tissue remodeling and cancer that represents a promising therapeutic and molecular imaging target. In prostate cancer, studies of FAP expression using tissue microarrays are conflicting, such that its clinical potential is unclear. Furthermore, little is known regarding FAP expression in benign prostatic tissues. Here we demonstrated, using a novel iterative multiplex IHC assay in standard tissue sections, that FAP was nearly absent in normal regions, but was increased consistently in regions of proliferative inflammatory atrophy (PIA). In carcinoma, FAP was expressed in all cases, but was highly heterogeneous. High FAP levels were associated with increased pathological stage and cribriform morphology. We verified that FAP levels in cancer correlated with CD163+ M2 macrophage density. In this first report to quantify FAP protein in benign prostate and primary tumors, using standard large tissue sections, we clarify that FAP is present in all primary prostatic carcinomas, supporting its potential clinical relevance. The finding of high levels of FAP within PIA supports the injury/regeneration model for its pathogenesis and suggests that it harbors a protumorigenic stroma. Yet, high levels of FAP in benign regions could lead to false positive FAP-based molecular imaging results in clinically localized prostate cancer.

Chaplaincy and spiritual care in Australian ambulance services: an exploratory cross-sectional study.

Ambulance staff wellbeing programs aim to support the bio-psycho-social and sometimes spiritual needs of paramedics. While evidence demonstrates strong connections between spirituality and/or religion to wellbeing outcomes, little is known about spiritual care in ambulance services or its impact. The aim of this study was to investigate paramedics' perspectives on the role and value of Australian ambulance chaplains. A cross-sectional online study of registered paramedics in Australia was conducted between November and December 2022. Analysis of the 150 responses identified that paramedics viewed the chaplain's role as one built on professional caring relationships that provided proactive and reactive care in paramedic workplaces. Chaplains were perceived to promote wellbeing by incorporating emotional, psychological, social and spiritual care, and assisting paramedics to access additional support. Perceived religiousness of chaplains and organisational factors were barriers to paramedics accessing chaplains, while pre-existing relationships and shared experiences positively influenced paramedics decision to seek chaplain support.

Upskill training and preparedness of non-critical-care registered nurses deployed to intensive care units during the COVID-19 pandemic: A scoping review.

BACKGROUND: The increase in intensive care unit (ICU) capacity compelled by the COVID-19 pandemic required the rapid deployment of non-critical-care registered nurses to the ICU setting. The upskill training needed to prepare these registered nurses for deployment was rapidly assembled due to the limited timeframe associated with the escalating pandemic. Scoping the literature to identify the content, structure, and effectiveness of the upskill education provided is necessary to identify lessons learnt during the COVID-19 pandemic response so that they may guide workforce preparation for future surge planning. AIM: The aim of this scoping review was to map the literature to identify the available information regarding upskill training and preparedness of non-critical-care registered nurses deployed to the ICU during the COVID-19 pandemic. METHODS: This scoping review was conducted in accordance with JBI methodology. A protocol outlined the review questions and used the participants, concept, and context framework to define the inclusion and exclusion criteria. A search of healthcare databases MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), Cochrane, and Scopus was supplemented with a grey literature search via Google. RESULTS: Screening and review found 32 manuscripts that met the inclusion criterion for examination. Analysis revealed variation in duration of programs, theoretical versus practical content, face-to-face or online mode of delivery, and duration of preparation time at the bedside in the ICU setting. Data on contributors to preparedness for deployment were sparse but included training, support, peer education, buddy time, and clarity around responsibilities and communication. DISCUSSION: Evaluation of upskill education was mostly limited to post-training surveys. Few studies explored the preparedness of deployed registered nurses as an outcome of their upskill training or described measures of effectiveness of ICU deployment. CONCLUSION: There is limited evidence describing preparedness of non-critical-care registered nurses on deployment to the ICU. Further research is needed to identify what elements of upskill education led to preparedness and effective deployment to the ICU setting.

Celebrating Australian nurses who are pioneering the response to climate change: a compilation of case studies.

BACKGROUND: Nurses, the largest healthcare workforce, are well placed to provide leadership in initiatives that promote planetary health. Yet, few practical examples of nurse leadership in the health sector's response to climate change are evident in the scholarly literature. AIM: The aim of this discussion paper is to profile Australian nurses who are leading initiatives designed to champion planetary health and promote sustainable practice. METHODS: The paper presents a series of case studies derived from interviews conducted in October and November 2023. FINDINGS: The nurses' experiences and insights, along with the challenges they have encountered, are presented as evidence of Kouzes and Posner's five practices of exemplary leadership. CONCLUSION: The case studies demonstrate that appointment of more nurses with climate and sustainability expertise will accelerate the implementation of responsive strategies that target waste management, emissions reduction and climate resilience across healthcare organisations.

Use and effectiveness of the arts for enhancing healthcare students' empathy skills: A mixed methods systematic review.

OBJECTIVE: To identify, critically appraise and synthesise evidence of the use and effectiveness of the arts for enhancing pre-registration/prelicensure healthcare students' empathy skills. DESIGN: A systematic review of mixed methods literature. DATA SOURCES: A search of six electronic databases was conducted. REVIEW METHODS: Articles describing English language, peer-reviewed, primary research studies reporting empathy as an outcome of an arts-based intervention with pre-registration/prelicensure healthcare students (years 1-7) and published between 2000 and 2024 were eligible for inclusion. The JBI Manual for Evidence Synthesis guided the review and a convergent segregated methodology was used to synthesise the results. Methodological rigour of included studies was examined using the Mixed Methods Appraisal Tool. RESULTS: Twenty studies from 12 countries described the use of the arts to develop empathy, with visual arts being the most common approach (n = 8). Other modalities included film, drama, digital stories, literature, creative writing, music, poetry, photography and dance. Studies included nursing, medicine and dental, pharmacy and/or health sciences students. Ten studies used quantitative methods, three qualitative, and seven used mixed methods designs. Of the studies that presented pre-post outcome measures, nine reported significant gains in empathy scores at post-test and two reported non-significant gains in empathy. In eight studies, empathy scores demonstrated a significant intervention effect with effect sizes ranging from moderate (d = 0.52) to large (d = 1.19). Findings from qualitative studies revealed that arts pedagogies support students to better understand the perspectives of people with a lived experience of suffering but that these approaches are sometimes perceived negatively by students. CONCLUSIONS: Arts interventions generally have a positive effect on healthcare students' empathy levels and enable a nuanced conceptual understanding of empathy. Arts modalities used as a stimulus for active learning and supported with facilitated group-based discussion and/or reflection, tend to be most effective.

Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: the COMBAT phase II trial.

Cyclic high-dose testosterone administration, known as bipolar androgen therapy (BAT), is a treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report the results of a multicenter, single arm Phase 2 study (NCT03554317) enrolling 45 patients with heavily pretreated mCRPC who received BAT (testosterone cypionate, 400 mg intramuscularly every 28 days) with the addition of nivolumab (480 mg intravenously every 28 days) following three cycles of BAT monotherapy. The primary endpoint of a confirmed PSA50 response rate was met and estimated at 40% (N = 18/45, 95% CI: 25.7-55.7%, P = 0.02 one-sided against the 25% null hypothesis). Sixteen of the PSA50 responses were achieved before the addition of nivolumab. Secondary endpoints included objective response rate (ORR), median PSA progression-free survival, radiographic progression-free survival (rPFS), overall survival (OS), and safety/tolerability. The ORR was 24% (N = 10/42). Three of the objective responses occurred following the addition of nivolumab. After a median follow-up of 17.9 months, the median rPFS was 5.6 (95% CI: 5.4-6.8) months, and median OS was 24.4 (95% CI: 17.6-31.1) months. BAT/nivolumab was well tolerated, resulting in only five (11%) drug related, grade-3 adverse events. In a predefined exploratory analysis, clinical response rates correlated with increased baseline levels of intratumoral PD-1 + T cells. In paired metastatic tumor biopsies, BAT induced pro-inflammatory gene expression changes that were restricted to patients achieving a clinical response. These data suggest that BAT may augment antitumor immune responses that are further potentiated by immune checkpoint blockade.

The measured impact of the COVID-19 pandemic on nursing students' wellbeing, clinical placement and learning experiences: a cross sectional study.

Background: The epidemiological patterns of COVID-19 varied across Australia and differed from most other countries. Few studies describe the impact that the pandemic had on nursing student wellbeing, education and career.Aim: This study aimed to investigate how the COVID-19 pandemic impacted on nursing students' well-being, clinical placement and learning.Design: Cross-sectional survey.Setting: Sydney, Australia.Participants: Second- and third-year nursing students.Methods: Second- and third-year nursing degree students were asked to participate in an ethically approved study during March to May 2021. The de-identified on-line survey consisted of 63 closed end question and one open ended question. On completion, the dataset was exported from Redcap and imported into SPSS for analysis. Open ended text data were analysed by two researchers.Results: Of the 105 participating nursing students, a third (n = 26/83, 31%) thought about changing their degree to a non-nursing degree. The acknowledged risk of caring for a COVID-19 patient incrementally increased stress (ß-coefficient = 0.6, p value = 0.009, 95% CI 0.2-0.9). Conversely students who intended to complete their degree were less likely to report stress. Students who had prior nursing experience were three times more likely to report an increased generalised anxiety level (OR 3.8, p-value = 0.02, 95% CI 1.2-12.2), yet they were less likely to experience personal accomplishment burnout compared to other students. Nursing students who contemplated a change of degree to a non-nursing degree were 15.7 times more likely to experience emotional exhaustion and were 3.5 times more likely to be report a risk of depersonalisation (p = 0.03, 95% CI, 1.3-11.5).Conclusion: The COVID-19 pandemic compromised nursing student well-being, and theoretical and practical learning. Findings have implications for healthcare and academic staff who teach nursing students. Implementation of student-centred evidence-based strategies to manage stress, burnout and anxiety, and to sustain a healthy student cohort is essential to retain the future nursing workforce.

Promoting sustainability in nursing and midwifery clinical laboratories: Strategies for resource reduction, reuse, and recycling.

BACKGROUND: The impacts of climate change on planetary health are multifaceted and threaten public health gains made since World War II. Healthcare is the fifth largest global emitter of greenhouse gas emissions, demanding significant efforts to transition to an environmentally sustainable future. Addressing these issues will require collective societal action. In this regard, universities have a dual responsibility - (1) to tackle complex social, economic, and environmental challenges by championing sustainability initiatives designed to positively impact planetary health; and (2) to ensure that graduates are equipped with the knowledge, attitudes and skills needed to steward planetary health towards a more sustainable future. The future nursing and midwifery workforce must be educated to mitigate the health sector's impact on the environment, advocate for action on climate change, prepare for ongoing health impacts of unpredictable climate and environmental changes, and help communities and healthcare systems become more climate resilient. WHAT THIS PAPER CONTRIBUTES: To help increase nursing and midwifery educators' and students' capacity to support planetary-health related interventions, the overarching purpose of this paper is to provide a series of exemplars that illustrate sustainability initiatives used in four university-based clinical skills laboratories. These initiatives each demonstrate a commitment to the United Nation's Sustainable Development Goals and can be used to help embed the importance of planetary health in student learning.

Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate.

BACKGROUND: Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. METHODS: A robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). RESULTS: This new assay (telomere chromogenic in situ hybridization ["Telo-CISH"]) produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. CONCLUSIONS: In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.

The Use of Telemedicine in the Management of Continuous Positive Airway Pressure for the Treatment of Obstructive Sleep Apnoea: A Randomised Controlled Trial.

Introduction: Obstructive sleep apnea (OSA) is a condition whereby the airway gets partially or totally obstructed during sleep. Gold standard treatment for moderate to severe OSA is continuous positive airway pressure (CPAP). However, compliance with treatment is often poor, with low hours of usage and patients stopping treatment. Methods: A nonblinded, single-center, randomized controlled trial was conducted with patients randomized to 1 of 3 arms (arm 1, standard care; arm 2, modem; and arm 3, modem and DreamMapper™ app). Ninety patients diagnosed with OSA requiring CPAP were recruited. Data, including CPAP compliance, apnea/hypopnea index (AHI), and Epworth sleepiness score (ESS), were collected at baseline and 14 and 180 days post-CPAP initiation. Results: Of the group participants (N = 90), 68% were male and 32% female with a mean age of 52.0 ± 13.13 years, mean body-mass index of 36.4 ± 7.91 (kg/m2), mean ESS of 10.19 ± 5.75, and mean AHI of 43.5 ± 21.92 (events/hour). There was no statistically significant difference between the three arms in mean hours of CPAP usage in 24 hours at 14 days: arm 1, 6.22 ± 2.15; arm 2, 5.47 ± 2.25; and arm 3, 6.44 ± 1.54 (p = 0.256). There were also no statistically significant differences between the three arms in mean hours of CPAP usage in 24 hours at 180 days: arm 1, 6.20 ± 1.27; arm 2, 5.57 ± 1.49; and arm 3, 6.26 ± 1.29 (p = 0.479). Discussion and Conclusion: Compliance with CPAP treatment showed no significant differences between the three arms, with high compliance observed in all arms.

Pre-assessment judgement framework for judging nursing students' performance in clinical placements: A qualitative case study.

AIM: This study aims to better understand and articulate the pre-assessment judgement processes commonly used by experienced clinical facilitators when assessing nursing students undertaking clinical placement. BACKGROUND: In the Australian context, clinical facilitators are registered nurses who primarily educate, monitor, support and assess groups of nursing students on clinical placements without carrying a patient load. The duties and scope of clinical facilitators may differ across international and institutional contexts. However, the core concepts of this paper will be relevant despite these differences as the importance of facilitators' confidence in making pre-assessment judgements of individual nursing student performance while on placement is universally acknowledged. Nursing students are often assessed on their provision of safe practice, patient task-orientated outcomes and professional behaviour. Clearly articulating performance judgements prior to formal assessment is vital to ensure progressive learning of students. Literature reports that many clinical facilitators lack confidence in the art of making performance judgements and call for targeted professional training and support in the clinical assessment of nursing students. To better understand and address this problem, clinical facilitators need a shared understanding of how individual nursing students' pre-assessment performance judgements are reached during placement experiences. DESIGN: A qualitative case study was used, with data collected via semi-structured interviews. Fifteen Australian clinical facilitators participated, each with over six months of experience. METHODS: Interview transcripts were analysed through an interpretive-constructivist paradigm. Thematic analysis revealed themes that were then deductively described through the application of the Cognitive Continuum Theory. RESULTS: Six modes of pre-assessment judgement emerged from the data synthesis process: 1) Recognising patterns, 2) Acknowledging uncertainty, 3) Understanding key players, 4) Verifying or refuting the information, 5) Benchmarking performance and 6) Contextualising information. Each mode is validated through the deductive application of the Cognitive Continuum theory. CONCLUSIONS: Understanding how experienced clinical facilitators make pre-assessment performance judgements has the potential to increase confidence in performance judgement decisions. In turn, confidence in judgements will increase clinical facilitator's capacity to give nursing students feedback that can be explained and justified. The pre-assessment judgement framework also provides a preliminary model for teaching the art of reaching accurate performance judgements to clinical educators in disciplines beyond nursing.

Modifying the clinical reasoning cycle to enhance forensic mental health nursing utility.

Forensic mental health nursing is a specialty area of practice requiring specific knowledge and skills to work collaboratively with consumers. The Clinical Reasoning Cycle has been recognised as a potential framework to support nursing practice; however, it has been identified that adaptations are required to enhance utility in a forensic mental health services. The aim of this study was to explore and finalise a version of the cycle for forensic mental health nursing practice. Focus groups and interviews were used to explore adaptations with staff from a state-wide forensic service and forensic mental health nursing academics. Data were thematically analysed. Four main themes were interpreted: (1) allegiance to the Nursing Process, (2) moving the cycle from page to practice, (3) working as a team, or not, and (4) implementation will be a marathon and not a sprint. While nursing academics were more in favour of updating the Nursing Process to ensure contemporary practice is captured, staff from the service were supportive of the adapted cycle but emphasised the need to ensure collaboration with the consumer and their supporters. The adapted cycle was seen to articulate the contribution of forensic mental health nursing care, and support for a nursing-specific cycle was embraced by other disciplines, despite some hesitation from nurses. Prior to implementation there is a need to ensure the merits of the cycle are clearly articulated, along with a range of resources and specific contextual information to ensure the cycle can be successfully applied to enhance nursing practice and consumer care.

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression.

Increased mitochondrial function may render some cancers vulnerable to mitochondrial inhibitors. Since mitochondrial function is regulated partly by mitochondrial DNA copy number (mtDNAcn), accurate measurements of mtDNAcn could help reveal which cancers are driven by increased mitochondrial function and may be candidates for mitochondrial inhibition. However, prior studies have employed bulk macrodissections that fail to account for cell type-specific or tumor cell heterogeneity in mtDNAcn. These studies have often produced unclear results, particularly in prostate cancer. Herein, we developed a multiplex in situ method to spatially quantify cell type-specific mtDNAcn. We show that mtDNAcn is increased in luminal cells of high-grade prostatic intraepithelial neoplasia (HGPIN), is increased in prostatic adenocarcinomas (PCa), and is further elevated in metastatic castration-resistant prostate cancer. Increased PCa mtDNAcn was validated by 2 orthogonal methods and is accompanied by increases in mtRNAs and enzymatic activity. Mechanistically, MYC inhibition in prostate cancer cells decreases mtDNA replication and expression of several mtDNA replication genes, and MYC activation in the mouse prostate leads to increased mtDNA levels in the neoplastic prostate cells. Our in situ approach also revealed elevated mtDNAcn in precancerous lesions of the pancreas and colon/rectum, demonstrating generalization across cancer types using clinical tissue samples.

Patient's views of empathic and compassionate healthcare interactions: A scoping review.

BACKGROUND: Compassion and empathy are integral to safe and effective patient care. However, to date, most studies have focused on exploring, defining, measuring and analysing empathy and compassion from the perspective of researchers or clinicians. There has been limited attention to the perspectives of patients. OBJECTIVE: The objective of this scoping review was to map the literature to identify patients' views of healthcare provider behaviours that exemplify empathic and compassionate interactions. METHOD: This review used the Joanna Briggs Institute scoping review methodology. A comprehensive search of eight electronic databases was conducted with English language studies published in the last 10 years considered for inclusion. RESULTS: Database searching resulted in 459 records for initial screening. After de-duplication and conducting a title and abstract review, 32 full-text articles were screened for eligibility. A total of 14 studies met the inclusion criteria and were critically reviewed using the Mixed Methods Appraisal Tool. The included papers profiled studies that had been conducted in clinical settings across seven countries. The healthcare encounters described in the papers were with a range of healthcare providers. Two overarching and interconnected categories of behaviours were identified as indicative of empathic/compassionate encounters: (1) communication skills such as listening, touch, body language, eye contact and positive demeanour; and (2) helping behaviours demonstrated by small acts of kindness that go beyond routine healthcare. CONCLUSION: Given the breadth of studies describing the positive impact of empathy/compassion on people's physical and psychosocial wellbeing, the results from this review are valuable and shed new light on patients' views and experiences. The results provide a deeper understanding of healthcare provider behaviours that exemplify empathic and compassionate healthcare interactions and can be used to inform the education and training of healthcare providers from all disciplines.

Healthcare professionals' experiences of interprofessional collaboration in patient education: A systematic review.

OBJECTIVES: This study explores interprofessional collaboration amongst healthcare professionals in patient education. METHODS: A systematic review was conducted. A search in seven databases was conducted from 2011 to 2022 and screened against the inclusion criteria. Quality appraisal was done independently by two reviewers. Studies were extracted and synthesised using the data-based convergent synthesis design. RESULTS: Twenty-one studies were included. Five themes on factors affecting interprofessional collaboration in patient education emerged: 1) role clarification, 2) communication infrastructure, 3) shared space for collaboration, 4) interprofessional trust, and 5) organisational support. CONCLUSION: Findings highlighted the importance of developing trustful relationships within the multidisciplinary team in delivering patient education. Channels for additional infrastructural support, guidelines and training in patient education delivery is required. Future research could explore patients' perspectives on how their learning needs in patient education may be optimised through a multidisciplinary approach. PRACTICE IMPLICATIONS: Healthcare leaders could promote shared goals within the team by facilitating a common space and time for interprofessional team rounding, and by developing shared patient education resources and documentation processes. Interprofessional education focusing on the delivery of team-based patient education could be implemented to foster understanding of the interdependent role of multidisciplinary healthcare professionals.

Predicting Prostate Cancer Molecular Subtype With Deep Learning on Histopathologic Images.

Microscopic examination of prostate cancer has failed to reveal a reproducible association between molecular and morphologic features. However, deep-learning algorithms trained on hematoxylin and eosin (H&E)-stained whole slide images (WSI) may outperform the human eye and help to screen for clinically-relevant genomic alterations. We created deep-learning algorithms to identify prostate tumors with underlying ETS-related gene (ERG) fusions or PTEN deletions using the following 4 stages: (1) automated tumor identification, (2) feature representation learning, (3) classification, and (4) explainability map generation. A novel transformer-based hierarchical architecture was trained on a single representative WSI of the dominant tumor nodule from a radical prostatectomy (RP) cohort with known ERG/PTEN status (n = 224 and n = 205, respectively). Two distinct vision transformer-based networks were used for feature extraction, and a distinct transformer-based model was used for classification. The ERG algorithm performance was validated across 3 RP cohorts, including 64 WSI from the pretraining cohort (AUC, 0.91) and 248 and 375 WSI from 2 independent RP cohorts (AUC, 0.86 and 0.89, respectively). In addition, we tested the ERG algorithm performance in 2 needle biopsy cohorts comprised of 179 and 148 WSI (AUC, 0.78 and 0.80, respectively). Focusing on cases with homogeneous (clonal) PTEN status, PTEN algorithm performance was assessed using 50 WSI reserved from the pretraining cohort (AUC, 0.81), 201 and 337 WSI from 2 independent RP cohorts (AUC, 0.72 and 0.80, respectively), and 151 WSI from a needle biopsy cohort (AUC, 0.75). For explainability, the PTEN algorithm was also applied to 19 WSI with heterogeneous (subclonal) PTEN loss, where the percentage tumor area with predicted PTEN loss correlated with that based on immunohistochemistry (r = 0.58, P = .0097). These deep-learning algorithms to predict ERG/PTEN status prove that H&E images can be used to screen for underlying genomic alterations in prostate cancer.

Progressive Spreading of DNA Methylation in the GSTP1 Promoter CpG Island across Transitions from Precursors to Invasive Prostate Cancer.

Glutathione S-transferase pi 1 (GSTP1) is lowly expressed in normal prostate luminal cells and becomes induced in most proliferative inflammatory atrophy (PIA) lesions. GSTP1 becomes silenced in prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma (CaP) via cytosine-phospho-guanine (CpG) island promoter hypermethylation. However, GSTP1 methylation patterns in PIA and PIN, and their relationship to patterns in CaP are poorly understood. We used bisulfite genomic sequencing to examine patterns of GSTP1 promoter CpG island methylation in laser capture microdissected benign, PIA, PIN, and CaP regions from 32 subjects that underwent radical prostatectomy. We analyzed 908 sequence clones across 24 normal epithelium, 37 PIA, 18 PIN, and 23 CaP regions, allowing assessment of 34,863 CpG sites with allelic phasing. Normal and PIA lesions were mostly unmethylated with 0.52 and 1.3% of total CpG sites methylated, respectively. PIN and CaP lesions had greater methylation with 24% and 51% of total CpG sites methylated, respectively. The degree of GSTP1 methylation showed progression from PIA << PIN < CaP. PIN lesions showed more partial methylation compared with CaP lesions. Partially methylated lesions were enriched for methylation changes at AP1 and SP1 transcription factor binding sites. These results demonstrate that methylation density in the GSTP1 CpG island in PIN was intermediate relative to that in normal prostate epithelium/PIA and CaP lesions. These results are consistent with gradual spreading of DNA methylation centered at the SP1/AP1 transcription factor binding sites in precursor lesions, with subsequent spreading of methylation across the entire CpG island in transition to CaP. PREVENTION RELEVANCE: DNA hypermethylation at the GSTP1 promoter progressively spreads from being unmethylated in normal prostate to intermediate levels in precursor lesions to extensive methylation in cancer. This molecular progression of GSTP1 promoter methylation patterns in early prostate carcinogenesis could be useful for identification and interception of prostate cancer precursors.

Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate.

Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. Here, a robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). This new assay ("Telo-CISH") produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.