Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial.

BACKGROUND: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [177Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [68Ga]Ga-PSMA-11 and 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET-CT. METHODS: TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [68Ga]Ga-PSMA-11 and 2-[18F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[18F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [177Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete. FINDINGS: 291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [177Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [177Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [177Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [177Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference -0·5 months [95% CI -3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [68Ga]Ga-PSMA-11 and 2-[18F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1). INTERPRETATION: These results support the use of [177Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[18F]FDG-discordant disease. FUNDING: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It's a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman's Ride.

[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages.

We assessed gene expression in tissue macrophages from various mouse organs. The diversity in gene expression among different populations of macrophages was considerable. Only a few hundred mRNA transcripts were selectively expressed by macrophages rather than dendritic cells, and many of these were not present in all macrophages. Nonetheless, well-characterized surface markers, including MerTK and FcγR1 (CD64), along with a cluster of previously unidentified transcripts, were distinctly and universally associated with mature tissue macrophages. TCEF3, C/EBP-α, Bach1 and CREG-1 were among the transcriptional regulators predicted to regulate these core macrophage-associated genes. The mRNA encoding other transcription factors, such as Gata6, was associated with single macrophage populations. We further identified how these transcripts and the proteins they encode facilitated distinguishing macrophages from dendritic cells.

Utility of multigene panel next-generation sequencing in routine clinical practice for identifying genomic alterations in newly diagnosed metastatic nonsmall cell lung cancer.

BACKGROUND: The standard of care in newly diagnosed metastatic non-small cell lung cancer (NSCLC) is to test for aberrations in three genes for driver mutations - ALK, ROS1 and epidermal growth factor receptor (EGFR) - and also for immunohistochemistry to be performed for programmed death-ligand 1 expression level. Next-generation sequencing (NGS), with or without RNA fusion testing, is increasingly used in standard clinical practice to identify patients with potentially actionable mutations. Stratification of NGS mutation tiers is currently based on the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) Tiers I-V and X. AIM: Our aim was to analyse NSCLC tumour samples for the prevalence of Tiers I-V mutations to establish guidance for current and novel treatments in patients with metastatic disease. METHODS: NGS was performed employing the Oncomine Precision Assay (without RNA fusion testing) that interrogates DNA hotspot variants across 45 genes to screen 210 NSCLC tissue samples obtained across six Sydney hospitals between June 2021 and March 2022. RESULTS: In our cohort, 161 of 210 (77%) had at least one gene mutation identified, with 41 of 210 (20%) having two or more concurrent mutations. Tier I mutations included 42 of 210 (20%) EGFR mutations (EIA) and five of 210 (3%) MET exon 14 skipping mutations (EIB). Non-Tier I variants included 22 of 210 (11%) KRAS G12C hotspot mutations (EIIB), with a further 47 of 210 (22%) having non-G12C KRAS (EX) mutations. NGS testing revealed an additional 15% of cases with Tier II ESCAT mutations in NSCLC. Forty-six percent of patients also demonstrated potential Tier III and IV mutations that are currently under investigation in early-phase clinical trials. CONCLUSIONS: In addition to identifying patients with genomic alterations suitable for clinically proven standard-of-care therapeutic options, the 45-gene NGS panel has significant potential in identifying potentially actionable non-Tier 1 mutations that may become future standard clinical practice in NSCLC.

Early warning scores for sepsis identification and prediction of in-hospital mortality in adults with sepsis: A systematic review and meta-analysis.

AIM: The early warning scores (EWS), quick Sequential Organ Failure Assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria have been proposed as sepsis screening tools. This review aims to summarise and compare the performance of EWS with the qSOFA and SIRS criteria for predicting sepsis diagnosis and in-hospital mortality in patients with sepsis. DESIGN: A systematic review with meta-analysis. REVIEW METHODS: Seven databases were searched from January 1, 2016 until March 10, 2022. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, likelihood ratios and diagnostic odd ratios were pooled by using the bivariate random effects model. Overall performance was summarised by using the hierarchical summary receiver-operating characteristics curve. This paper adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. RESULTS: Ten studies involving 52,474 subjects were included in the review. For predicting sepsis diagnosis, the pooled sensitivity of EWS (65%, 95% CI: 55, 75) was similar to SIRS ≥2 (70%, 95% CI: 49, 85) and higher than qSOFA ≥2 (37%, 95% CI: 20, 59). The pooled specificity of EWS (77%, 95% CI: 64, 86) was higher than SIRS ≥2 (62%, 95% CI: 41, 80) but lower than qSOFA ≥2 (94%, 95% CI: 86, 98). Results were similar for the secondary outcome of in-hospital mortality. CONCLUSIONS: Although no one scoring system had both high sensitivity and specificity, the EWS had at least equivalent values in most measures of diagnostic accuracy compared with SIRS or qSOFA. IMPLICATIONS FOR THE PROFESSION: Healthcare systems in which EWS is already in place should consider whether there is any clinical benefit in adopting qSOFA or SIRS. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review did not directly involve patient or public contribution to the manuscript.

p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients.

The cell cycle plays a key and complex role in the development of human cancers. p21 is a potent cyclin-dependent kinase inhibitor (CDKI) involved in the promotion of cell cycle arrest and the regulation of cellular senescence. Altered p21 expression in rectal cancer cells may affect tumor cells' behavior and resistance to neoadjuvant and adjuvant therapy. Our study aimed to ascertain the relationship between the differential expression of p21 in rectal cancer and patient survival outcomes. Using tissue microarrays, 266 rectal cancer specimens were immunohistochemically stained for p21. The expression patterns were scored separately in cancer cells retrieved from the center and the periphery of the tumor; compared with clinicopathological data, tumor regression grade (TRG), disease-free, and overall survival. Negative p21 expression in tumor periphery cells was significantly associated with longer overall survival upon the univariate (p = 0.001) and multivariable analysis (p = 0.003, HR = 2.068). Negative p21 expression in tumor periphery cells was also associated with longer disease-free survival in the multivariable analysis (p = 0.040, HR = 1.769). Longer overall survival times also correlated with lower tumor grades (p= 0.011), the absence of vascular and perineural invasion (p = 0.001; p < 0.005), the absence of metastases (p < 0.005), and adjuvant treatment (p = 0.009). p21 expression is a potential predictive and prognostic biomarker for clinical outcomes in rectal cancer patients. Negative p21 expression in tumor periphery cells demonstrated significant association with longer overall survival and disease-free survival. Larger prospective studies are warranted to investigate the ability of p21 to identify rectal cancer patients who will benefit from neoadjuvant and adjuvant therapy.

A Significant Association between Type 1 Diabetes and Helicobacter pylori Infection: A Meta-Analysis Study.

Background and Objectives: Type 1 diabetes mellitus (T1DM) is a chronic and serious condition that is characterized by inadequate pancreatic-ß-cells' insulin production. The connection between T1DM and Helicobacter pylori infection remains uncertain. This study aimed to conduct a systematic meta-analysis to examine the association between H. pylori infection, hemoglobin A1c levels, and the development of T1DM. Materials and Methods: The initial search identified 451 articles on the association between H. pylori infection and T1DM. Among them, 12 articles had 2797 participants who met the inclusion criteria for an advanced meta-analysis. Results: A significant association was observed between H. pylori infection and T1DM (OR 1.77, 95% CI 1.47-2.12, p < 0.0001), with heterogeneity: Tau2 = 0.47; Chi2 = 57.07, df = 11 (p < 0.0001); I2 = 81%. Subgroup analysis showed that H. pylori infection was significantly associated with a longer duration of T1DM and higher hemoglobin A1c levels (p < 0.001 for both) but not with age at T1DM diagnosis (p = 0.306). Conclusions: These findings contribute to the understanding of the association between H. pylori infection and T1DM and highlight the potential role of H. pylori in influencing the duration and glycemic control of diabetes. Therefore, pediatric patients who have longstanding T1DM and poor glycemic control should be screened for H. pylori infection.

Desktop Virtual Reality Versus Face-to-Face Simulation for Team-Training on Stress Levels and Performance in Clinical Deterioration: a Randomised Controlled Trial.

BACKGROUND: Simulation-based education can equip healthcare providers with the ability to respond to and manage stressors associated with rapidly deteriorating patient situations. However, little is known about the benefits of using virtual reality (VR) for this purpose. OBJECTIVE: To compare between desktop VR and face-to-face simulation in stress responses and performance outcomes of a team-based simulation training in managing clinical deterioration. DESIGN: A randomised controlled study METHOD: The study was conducted on 120 medical and nursing students working in interprofessional teams. The teams were randomly assigned to participate in a 2-h simulation using either the desktop VR or face-to-face simulation with simulated patient (SP). Biophysiological stress response, psychological stress, and confidence levels were measured before and after the simulation. Performance outcomes were evaluated after the simulation using a deteriorating patient scenario. RESULTS: The systolic blood pressure and psychological stress response were significantly increased among participants in VR and SP groups; however, no significant differences were found between the groups. There was also no significant difference in confidence and performance outcomes between participants in the VR and SP groups for both medical and  nursing students. Although the psychological stress response was negatively correlated (r = -0.43; p < 0.01) with confidence levels, there was no association between stress response and performance score. CONCLUSION: Despite being less immersive, the desktop VR was capable of inducing psychological and physiological stress responses by placing emotional, social, and cognitive demands on learners. Additionally, by ensuring close alignment between the simulation tasks and the clinical tasks (i.e. functional fidelity), the desktop VR may provide similar performance outcomes as conventional simulation training. This evidence is timely given the rise in the use of virtual learning platforms to facilitate training during the COVID-19 pandemic where face-to-face training may not be feasible. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov NCT04330924.

Artificial Intelligence Versus Human-Controlled Doctor in Virtual Reality Simulation for Sepsis Team Training: Randomized Controlled Study.

BACKGROUND: Interprofessional communication is needed to enhance the early recognition and management of patients with sepsis. Preparing medical and nursing students using virtual reality simulation has been shown to be an effective learning approach for sepsis team training. However, its scalability is constrained by unequal cohort sizes between medical and nursing students. An artificial intelligence (AI) medical team member can be implemented in a virtual reality simulation to engage nursing students in sepsis team training. OBJECTIVE: This study aimed to evaluate the effectiveness of an AI-powered doctor versus a human-controlled doctor in training nursing students for sepsis care and interprofessional communication. METHODS: A randomized controlled trial study was conducted with 64 nursing students who were randomly assigned to undertake sepsis team training with an AI-powered doctor (AI-powered group) or with medical students using virtual reality simulation (human-controlled group). Participants from both groups were tested on their sepsis and communication performance through simulation-based assessments (posttest). Participants' sepsis knowledge and self-efficacy in interprofessional communication were also evaluated before and after the study interventions. RESULTS: A total of 32 nursing students from each group completed the simulation-based assessment, sepsis and communication knowledge test, and self-efficacy questionnaire. Compared with the baseline scores, both the AI-powered and human-controlled groups demonstrated significant improvements in communication knowledge (P=.001) and self-efficacy in interprofessional communication (P<.001) in posttest scores. For sepsis care knowledge, a significant improvement in sepsis care knowledge from the baseline was observed in the AI-powered group (P<.001) but not in the human-controlled group (P=.16). Although no significant differences were found in sepsis care performance between the groups (AI-powered group: mean 13.63, SD 4.23, vs human-controlled group: mean 12.75, SD 3.85, P=.39), the AI-powered group (mean 9.06, SD 1.78) had statistically significantly higher sepsis posttest knowledge scores (P=.009) than the human-controlled group (mean 7.75, SD 2.08). No significant differences were found in interprofessional communication performance between the 2 groups (AI-powered group: mean 29.34, SD 8.37, vs human-controlled group: mean 27.06, SD 5.69, P=.21). However, the human-controlled group (mean 69.6, SD 14.4) reported a significantly higher level of self-efficacy in interprofessional communication (P=.008) than the AI-powered group (mean 60.1, SD 13.3). CONCLUSIONS: Our study suggested that AI-powered doctors are not inferior to human-controlled virtual reality simulations with respect to sepsis care and interprofessional communication performance, which supports the viability of implementing AI-powered doctors to achieve scalability in sepsis team training. Our findings also suggested that future innovations should focus on the sociability of AI-powered doctors to enhance users' interprofessional communication training. Perhaps in the nearer term, future studies should examine how to best blend AI-powered training with human-controlled virtual reality simulation to optimize clinical performance in sepsis care and interprofessional communication. TRIAL REGISTRATION: ClinicalTrials.gov NCT05953441; https://clinicaltrials.gov/study/NCT05953441.

Interprofessional collaboration in telemedicine for long-term care: An exploratory qualitative study.

BACKGROUND: Widespread and sustained adoption of telemedicine in long-term residential care is emerging. Nursing home (NH) nurses play a key role in collaborating with remote physicians to manage residents' medical conditions through videoconferencing. Therefore, understanding of interprofessional collaboration and effective communication between nurses and physicians is critical to ensure quality of care and safety during teleconsultations. AIMS: To explore NH nurses' and physicians' experiences of interprofessional collaboration and communication during teleconsultations. METHODS: A qualitative descriptive design was adopted. Purposive sampling was conducted to recruit 22 physicians and nurses involved in NH teleconsultations. Semi-structured online interviews were conducted, and data were thematically analyzed. RESULTS: Three themes were identified: (1) Manner of communication in telemedicine, (2) sociocultural influences in collaborative practice, and (3) role expectations in telemedicine. Both nurses and physicians recognized the importance of building and maintaining trust as physicians heavily depended on nurses for provision of objective information for clinical decision-making. However, practice differences were observed between nurses and physicians during teleconsultations. Sociocultural influences such as power relations and language barriers also affected the nurse-physician relationship and interpersonal communication. Additionally, different performance expectations were identified between nurses and physicians. CONCLUSION: Interprofessional collaboration in teleconsultations is challenging because of lack of in-person assessment and dependence on nurses for clinical information. In addition, expectations and communication styles differ among healthcare professionals. This study called for interprofessional telemedicine training with incorporation of shared mental models to improve role clarity and communication. Given the international-dominated healthcare workforce in long-term care, the development of cultural competency could also be considered in telemedicine training to enhance nurse-physician collaborative practice. CLINICAL RELEVANCE: Telemedicine is increasingly adopted in long-term care settings, where multidisciplinary healthcare professionals from different health institutions are involved in resident care. Interprofessional collaboration should be incorporated into telehealth education for enhanced clinical practice in this care delivery model.

Nurses' knowledge and confidence in recognizing and managing patients with sepsis: A multi-site cross-sectional study.

AIMS: (1) To examine registered nurses' knowledge and confidence in recognizing and managing to patients with sepsis and (2) identify nurse and workplace factors that influence their knowledge on sepsis. DESIGN: A multi-site, cross-sectional survey. METHODS: An online survey was developed and content validated. Data was collected from registered nurses working in the inpatient wards and emergency departments of three hospitals of a single healthcare cluster in Singapore during August 2021. Statistical analyses of closed-ended responses and content analysis of open-ended responses were undertaken. RESULTS: A total of 709 nurses completed the survey. Nurses possessed moderate levels of knowledge about sepsis (mean score = 10.56/15; SD = 2.01) and confidence in recognizing and responding to patients with sepsis (mean score = 18.46/25; SD = 2.79). However, only 369 (52.0%) could correctly define sepsis. Nurses' job grade, nursing education level and clinical work area were significant predictors of nurses' sepsis knowledge. Specifically, nurses with higher job grade, higher nursing education level or those working in acute care areas (i.e. emergency department, high dependency units or intensive care units) were more likely to obtain higher total sepsis knowledge scores. A weak positive correlation was observed between sepsis knowledge test scores and self-confidence (r = .184). Open comments revealed that participants desired for more sepsis education and training opportunities and the implementation of sepsis screening tool and sepsis care protocol. CONCLUSION: A stronger foundation in sepsis education and training programs and the implementation of sepsis screening tools and care bundles are needed to enhance nurses' knowledge and confidence in recognizing and managing patients with sepsis. IMPACT: The findings of this study are beneficial to administrators, educators and researchers in designing interventions to support nurses in their role in recognizing and responding to sepsis.

A hybrid systematic narrative review of instruments measuring home-based care nurses' competency.

AIM: The aim of the study was to identify and synthesize the contents and the psychometric properties of the existing instruments measuring home-based care (HBC) nurses' competencies. DESIGN: A hybrid systematic narrative review was performed. REVIEW METHODS: The eligible studies were reviewed to identify the competencies measured by the instruments for HBC nurses. The psychometric properties of instruments in development and psychometric testing design studies were also examined. The methodological quality of the studies was evaluated using the Medical Education Research Study Quality Instrument and COSMIN checklist accordingly. DATA SOURCES: Relevant studies were searched on CINAHL, MEDLINE (via PubMed), EMBASE, PsychINFO and Scopus from 2000 to 2022. The search was limited to full-text items in the English language. RESULTS: A total of 23 studies reporting 24 instruments were included. 12 instruments were adopted or modified by the studies while the other 12 were developed and psychometrically tested by the studies. None of the instruments encompassed all of the 10 home-based nursing care competencies identified in an earlier study. The two most frequently measured competencies were the management of health conditions, and critical thinking and problem-solving skills, while the two least measured competencies were quality and safety, and technological literacy. The content and structural validity of most instruments were inadequate since the adopted instruments were not initially designed or tested among HBC nurses. CONCLUSION: This review provides a consolidation of existing instruments that were used to assess HBC nurses' competencies. The instruments were generally not comprehensive, and the content and structural validity were limited. Nonetheless, the domains, items and approaches to instrument development could be adopted to develop and test a comprehensive competency instrument for home-based nursing care practice in the future. IMPACT: This review consolidated instruments used to measure home-based care nurses' competency. The instruments were often designed for ward-based care nurses hence a comprehensive and validated home-based nursing care competency instrument is needed. Nurses, researchers and nursing leaders could consider the competency instruments identified in this review to measure nurses' competencies, while a home-based nursing care competency scale is being developed. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was required in this review.

Development and psychometric evaluation of the Attitudes Towards Recognising Early and Noticeable Deterioration (ATREND) scale.

AIMS AND OBJECTIVES: To develop and evaluate the psychometric properties of an instrument that measures nurses' Attitudes Towards Recognising Early and Noticeable Deterioration (ATREND). BACKGROUND: General ward nurses play an important role in recognising patient deterioration. However, their attitudes towards early recognition of clinical deterioration have not been adequately explored due to the lack of a valid and reliable scale. DESIGN: An instrument development and validation study. METHODS: A three-phase structure that followed the STROBE checklist was used: (1) item generation, (2) content and face validity assessment and (3) psychometric properties evaluation. The scale items were developed based on a comprehensive literature review and content validity assessment by 15 international experts from five countries. The psychometric properties of the ATREND scale were tested on 434 registered nurses, with retest evaluations (n = 100) at two hospitals. Exploratory and confirmatory factor analyses were used to examine the factor structure of the scale. The scale was also evaluated for its internal consistency, test-retest reliability and convergent validity. RESULTS: The scale's content validity was 0.95. A 3-factor solution was identified from the final 11 items: (1) beliefs about importance of patient observation, (2) use of broader patient assessment skills and (3) confidence in recognising clinical deterioration. The internal consistency reliability of the scale was supported with an acceptable Cronbach's alpha value of 0.745. Test-retest reliability of the scale was excellent, with an intraclass correlation coefficient of 0.825. The ATREND scale shows evidence of good convergent validity. CONCLUSION: The final 11-item ATREND scale demonstrates adequate initial evidence of reliability and validity for use in acute ward settings. RELEVANCE TO CLINICAL PRACTICE: Nursing educators and clinicians may use this scale to assess ward nurses' attitudes and practices towards early recognition of clinical deterioration and then enhance their competencies and behaviours in the recognition of clinical deterioration.

Collaborative practice among general ward staff on escalating care in clinical deterioration: A systematic review.

AIM: To understand the issues surrounding collaborative practice and collaboration experiences among general ward staff in the escalation of care for clinically deteriorating patients. DESIGN: A systematic synthesis without meta-analysis. REVIEW METHODS: Seven electronic databases (CINAHL, Cochrane, Embase, PsycINFO, PubMed, Scopus and ProQuest Theses and Dissertations) were searched from their inception to 30 April 2022. Two reviewers independently screened titles, abstracts and full text for eligibility. The critical appraisal skill programme, Joanna Briggs Institute checklist for analytical cross-sectional studies and mixed methods appraisal tool were used to appraise the quality of the included studies. Both quantitative and qualitative research data were extracted, analysed and then synthesised using the data-based convergent qualitative synthesis approach. This review adhered to the Synthesis without meta-analysis (SWiM) reporting guidelines. RESULTS: A total of 17 studies were included. Two themes and six sub-themes were generated: (1) intraprofessional factors-inadequate handover, workload and mutual support, raising and acting on concerns, and seeking help from seniors and (2) interprofessional factors-differences in communication styles, and hierarchical approach versus interpersonal relationships. CONCLUSIONS: This systematic review highlights the need to address the intra- and interprofessional issues surrounding collaborative practice in escalation of care among general ward staff. IMPLICATIONS FOR THE PROFESSION: Findings from this review will inform healthcare leaders and educators on the development of relevant strategies and multi-disciplinary training to foster effective teamwork among nurses and doctors, with the goal of improving the escalation of care for patients with clinical deterioration. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review did not directly involve patient or public contribution to the manuscript.

Automated rapid response system activation-Impact on nurses' attitudes and perceptions towards recognising and responding to clinical deterioration: Mixed-methods study.

AIM: To explore general ward nurses' attitudes and perceptions towards recognising and responding to clinical deterioration in a hospital with automated rapid response system activation. BACKGROUND: There is growing interest in deploying automated clinical deterioration notification systems to reduce delayed or failed recognition and response to clinical deterioration of ward patients. However, little is known about its impact on ward nurses' perspectives and work patterns. DESIGN: A mixed-methods study. METHODS: Online survey of 168 registered nurses and individual interviews with 10 registered nurses in one acute hospital in Singapore. The study adhered to the STROBE checklist for cross-sectional studies and the COREQ guidelines for qualitative studies. RESULTS: Many nurses (38.1%) rarely performed patient assessments or observations other than vital signs assessment to assess for early signs of clinical deterioration. About 30% were worried about being criticised for calling the primary team doctors. Four themes emerged from the qualitative analysis: automated rapid response system activation as a safety net, being more cautious with vital signs monitoring, the NEWS2 alone is inadequate, and ward nurses as the 'middleman' between the intensive care unit outreach nurse and primary team doctors. CONCLUSIONS: Although nurses value the automated rapid response system activation as a safety net to minimise delays in accessing urgent critical care resources, it does not address the sociocultural barriers inherent in escalation of care. Although the automated system led nurses to be more cautious with vital signs monitoring, it does not encourage them to perform comprehensive patient assessments to detect early signs of deterioration. RELEVANCE TO CLINICAL PRACTICE: Nurse education on assessing for clinical deterioration should focus on the use of broader patient assessment skills other than vital signs. Sociocultural barriers to escalation of care remain a key issue that needs to be addressed by hospital management. NO PATIENT OR PUBLIC CONTRIBUTION: No patients, service users, care-givers or members of the public were involved in the study.

Adherence to Iron Chelation Therapy Among Children with Beta Thalassemia Major: A Multicenter Cross-Sectional Study.

BACKGROUND: Adherence to iron chelation therapy (ICT) remains an issue among thalassemia patients. This study aimed to determine the prevalence of non-adherence to ICT among children with beta thalassemia major in Malaysia and the factors associated with it. METHODS: This was a cross-sectional study conducted between November 2019 and November 2021 at seven tertiary hospitals in Malaysia. Participants registered with Malaysian Thalassemia Registry were recruited by convenience sampling. Adherence was measured via pill count and self-reported adherence. Knowledge about thalassemia and ICT was measured using a questionnaire from Modul Thalassemia by Ministry of Health of Malaysia. A decision tree was used to identify predictors of non-adherence. RESULTS: A total of 135 patients were recruited. The prevalence of non-adherence to ICT in those who took subcutaneous ± oral medications was 47.5% (95% CI: 31.5%, 63.9%) and the prevalence of non-adherence to ICT in those who took oral medications only was 21.1% (95% CI: 13.4%, 30.6%). The median knowledge score was 67.5% (IQR 15%). A decision tree has identified two factors associated with non-adherence. They were ICT's route of administration and knowledge score. Out of 100 patients who were on oral medications only, 79 were expected to adhere. Out of 100 patients who were on subcutaneous ± oral medications and scored less than 56.25% in knowledge questionnaire, 86 were expected to non-adhere. Based on the logistic regression, the odds of non-adherence in patients who took oral medications only was 71% lower than the odds of non-adherence in patients who took subcutaneous ± oral medications (OR = 0.29; 95% CI = 0.13, 0.65; p = .002). CONCLUSION: The prevalence of non-adherence to ICT among children with beta thalassemia major in Malaysia was 20/95 (21.1%) in those who took oral medications only and the prevalence of non-adherence was 19/40 (47.5%) in those who took subcutaneous ± oral medications. The factors associated with non-adherence were ICT's route of administration and knowledge score.

KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort.

KRAS and BRAF mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the KRAS/BRAF mutation rates and survival outcomes in CRC between ethnic groups at a single institution. We also investigate the contributions of genetic, environmental, and laboratory factors to the variations in KRAS/BRAF mutation rates reported from different countries. Clinicopathological data from 453 ethnically diverse patients with CRC were retrospectively analyzed at Liverpool Hospital, NSW Australia (2014-2016). KRAS/BRAF mutations were detected using real-time PCR (Therascreen kits from Qiagen). Mismatch repair (MMR) status was determined using immunohistochemical staining. Four ethnic groups were analyzed: Caucasian, Middle Eastern, Asian, and South American. Overall survival data were available for 406 patients. There was no significant difference in KRAS mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (p = 0.34). BRAF mutation rates differed significantly between races (p = 0.025), with Caucasians having the highest rates (13.5%) and Middle Easterners the lowest (0%). A secondary analysis in which Caucasians were divided into three subgroups showed that ethnic grouping correlated significantly with KRAS mutation rate (p = 0.009), with central and eastern Europeans having the highest rates (58.3%). There were no significant differences in overall survival (OS) or disease-free survival (DFS) between the four races. The similarity in KRAS mutation rates across races raises the possibility that the differences in KRAS mutation rates reported from various countries may either not be statistically significant or may be due to environmental and/or laboratory factors rather than underlying racial genetic differences. In contrast, we verified that BRAF mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant BRAF mutation rates reported from different countries.

Nursing Students' Perceptions Toward Recovery in Mental Health: A Descriptive Qualitative Study.

BACKGROUND: Recovery in mental health remains inconclusive where the two most prevailing definitions "clinical" and "personal" remain. In nursing schools, students are predominantly taught straightforward concepts of clinical recovery, which result in only a perfunctory and rudimentary understanding of recovery among the undergraduates. AIMS: To explore the perceptions of nursing undergraduates on recovery for people experiencing mental health conditions. METHOD: A descriptive qualitative study was conducted on 14 nursing undergraduates from Years 1 to 4 of the study. Participants were recruited through convenience sampling, and the required sample size was determined by data saturation. Semistructured questions were used during the individual face-to-face interviews from October and December 2019. Recordings were transcribed verbatim; the transcripts were then subjected to thematic analysis. RESULTS: Three themes were identified to support the research questions: (1) semantics of major terms used in mental health care-where participants provided the description of terminologies used; (2) the meaning of recovery-where participants explained their views on "recovery"; and (3) sources of conceptualization-where participants explained their conceptual understanding on mental health conditions and recovery. CONCLUSION: The findings suggest that the need for a more holistic approach encompassing personal recovery should be included in the nursing curriculum. This is necessary to promote enabling support in the recovery of people experiencing mental health conditions beyond medical interventions.

[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial.

BACKGROUND: Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers ß radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer. METHODS: We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428. FINDINGS: Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9-37]; p=0·0016). Grade 3-4 adverse events occurred in 32 (33%) of 98 men in the [177Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [177Lu]Lu-PSMA-617. INTERPRETATION: [177Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [177Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel. FUNDING: Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.

Enablers and barriers to nurse-facilitated geriatric teleconsultations in nursing homes: a qualitative descriptive multi-site study.

BACKGROUND: Nurses play a major role in facilitating teleconsultations in nursing homes with remote physicians. Currently, evidence explicating their role in teleconsultations is lacking. As telemedicine usage grows, understanding the factors that enable or impede nurses' role in teleconsultations allows for more support in the provision of patient care through this modality. OBJECTIVE: This study sought to explore enablers and barriers nurses faced in facilitating geriatric teleconsultations in nursing homes. METHODS: A qualitative descriptive study using semi-structured interviews was conducted in Singapore, from July to November 2021. Purposive sampling of nursing home nurses was undertaken. Data were inductively analysed using Braun and Clarke's thematic analysis approach. RESULTS: Twenty-two nursing home nurses participated in the study. Six key themes were identified as enablers and barriers in nurse-facilitated geriatrics teleconsultations. Enablers included nurses' acknowledgement of teleconsultations as needs-orientated service, close partnership with the hospital-based geriatric service for training and workflow support and nurses' sense of empowerment in teleconsultation involvement. Barriers that existed were the nurses' lack of confidence in physical assessment and communication competencies, role conflict due to nurses' perceived inability to meet physicians' expectations and limited scope of practice in performing teleconsultation-related tasks and the presence of technology-related challenges. CONCLUSION: The identification of enablers and barriers in teleconsultations for nursing home residents provides insights for future research and development in telemedicine-related implementation and educational interventions in long-term care. Developing strong partnerships between telemedicine providers and nursing homes, further enhancement of nurses' telemedicine competencies and optimising digital infrastructure are warranted.