Insulator-based dielectrophoresis-assisted separation of insulin secretory vesicles.

Organelle heterogeneity and inter-organelle contacts within a single cell contribute to the limited sensitivity of current organelle separation techniques, thus hindering organelle subpopulation characterization. Here, we use direct current insulator-based dielectrophoresis (DC-iDEP) as an unbiased separation method and demonstrate its capability by identifying distinct distribution patterns of insulin vesicles from INS-1E insulinoma cells. A multiple voltage DC-iDEP strategy with increased range and sensitivity has been applied, and a differentiation factor (ratio of electrokinetic to dielectrophoretic mobility) has been used to characterize features of insulin vesicle distribution patterns. We observed a significant difference in the distribution pattern of insulin vesicles isolated from glucose-stimulated cells relative to unstimulated cells, in accordance with maturation of vesicles upon glucose stimulation. We interpret the difference in distribution pattern to be indicative of high-resolution separation of vesicle subpopulations. DC-iDEP provides a path for future characterization of subtle biochemical differences of organelle subpopulations within any biological system.

Patients' experience of incontinence and incontinence-associated dermatitis in hospital settings: a qualitative study.

OBJECTIVE: To explore the experience of patients with incontinence and incontinence-associated dermatitis (IAD) in acute care hospitals and their family caregivers, including their perceptions and management, as well as the impact on their wellbeing. METHOD: A qualitative exploratory study design was employed in 18 wards across six acute/subacute hospitals in New South Wales, Australia. Patients with incontinence (with or without IAD) were invited to participate. Where interviews were not possible with the patient, their family caregiver was invited to participate. Semi-structured interviews were conducted. RESULTS: There were 45 interviewees in the study; 41 were patients with incontinence (11 of whom had IAD) and four were family caregivers. The experience of incontinence was captured by three themes: 'incontinence interrupts every aspect of my life'; 'actively concealing and cloaking'; and 'perceived as irreversible'. Incontinence was expected by the patients at their age and did not come as a surprise. It was normalised and approached with stoicism. As such, patients self-managed their incontinence by developing strategies to ensure they avoided episodes of incontinence during their stay. Incontinence left patients feeling anxious, embarrassed and with a sense of shame, and they did not communicate these feelings, or engage with health professionals about their incontinence, nor did health professionals discuss their incontinence with them. There was a strong sense of resignation that incontinence was irreversible and nothing could be done to improve it. All participants displayed little knowledge of IAD. The experience of having IAD was characterised by the theme 'debilitating and desperate for relief' and was experienced as a particularly painful, itching and burning condition that left patients distressed and irritable. CONCLUSION: Patients with incontinence in acute settings required further education from health professionals to reduce the stigma of incontinence, and provide further support to manage their incontinence. Health professionals can also play a key role in educating patients about the risks of developing IAD and how it can be prevented.

Multiple myeloma incidence, mortality, and prevalence estimates and projections, Australia, 1982-2043: a statistical modelling study.

OBJECTIVES: To examine changes in multiple myeloma incidence and mortality rates during 1982-2018, and to estimate its incidence, mortality, and prevalence for 2019-2043. STUDY DESIGN: Population-based statistical modelling study; analysis of and projections based on Australian Institute of Health and Welfare multiple myeloma incidence, mortality, and survival data. SETTING: Australia, 1982-2018 (historical data) and projections to 2043. MAIN OUTCOME MEASURES: Changes in multiple myeloma incidence and mortality rates, 1982-2018, determined by joinpoint regression analysis (age-standardised to 2021 Australian population); projection of rates to 2043 based on age-period-cohort models; estimated 5- and 30-year prevalence of multiple myeloma (modified counting method). RESULTS: The incidence of multiple myeloma increased during 1982-2018 (eg, annual percentage change [APC], 2006-2018, 1.9%; 95% confidence interval [CI], 1.7-2.2%), but the mortality rate declined during 1990-2018 (APC, -0.4%; 95% CI, -0.5% to -0.2%). The age-standardised incidence rate was projected to increase by 14.9% during 2018-2043, from 8.7 in 2018 to 10.0 (95% CI, 9.4-10.7) new cases per 100 000 population in 2043; the mortality rate was projected to decline by 27.5%, from 4.0 to 2.9 (95% CI, 2.6-3.3) deaths per 100 000 population. The annual number of people newly diagnosed with multiple myeloma was estimated to increase by 89.2%, from 2120 in 2018 to 4012 in 2043; the number of deaths from multiple myeloma was projected to increase by 31.7%, from 979 to 1289. The number of people living with multiple myeloma up to 30 years after initial diagnosis was projected to increase by 163%, from 10 288 in 2018 to 27 093 in 2043, including 13 019 people (48.1%) diagnosed during the preceding five years. CONCLUSION: Although the decline in the mortality rate was projected to continue, the projected increases in the incidence and prevalence of multiple myeloma in Australia over the next 25 years indicate that investment in prevention and early detection research, and planning for prolonged treatment and care, are needed.

Impact of an evidence-based bundle on incontinence-associated dermatitis prevalence in hospital patients: A quasi-experimental translational study.

The study aimed to evaluate the effect of an intervention on the prevalence and severity of incontinence-associated dermatitis (IAD) in six hospitals in one state in Australia. This quasi-experimental pre-and post-study, conducted in 18 wards, was part of a larger implementation science study on incontinence-associated dermatitis. Skin and incontinence assessments were conducted on patients during February and March 2020 (pre-intervention) and July and August 2021 (post-intervention). The intervention comprised continence assessment and management, an education brochure for patients, family and caregivers on IAD, the Ghent Global IAD Categorisation Tool (GLOBIAD) and a skin care regime with patient skin protection measures (three-in-one barrier cream cloths, minimisation of bed protection layers, use of appropriate continence aid). A total of 1897 patients were assessed (pre-intervention = 964, post-intervention = 933). A total of 343 (35.6%) pre-intervention patients and 351 (37.6%) post-intervention patients had incontinence. The prevalence of hospital-acquired IAD was 6.71% in the pre-intervention group and 4.27% in the post-intervention group; a reduction of 36.3% (p = 0.159) despite higher patient acuity, prevalence of double incontinence and the COVID-19 pandemic in the post-intervention group compared with the pre-intervention group. Our multisite best practice IAD prevention and treatment intervention was able to reduce the prevalence and severity of hospital-acquired IAD, suggesting enduring effectiveness of the intervention.

Subcellular Feature-Based Classification of α and ß Cells Using Soft X-ray Tomography.

The dysfunction of α and ß cells in pancreatic islets can lead to diabetes. Many questions remain on the subcellular organization of islet cells during the progression of disease. Existing three-dimensional cellular mapping approaches face challenges such as time-intensive sample sectioning and subjective cellular identification. To address these challenges, we have developed a subcellular feature-based classification approach, which allows us to identify α and ß cells and quantify their subcellular structural characteristics using soft X-ray tomography (SXT). We observed significant differences in whole-cell morphological and organelle statistics between the two cell types. Additionally, we characterize subtle biophysical differences between individual insulin and glucagon vesicles by analyzing vesicle size and molecular density distributions, which were not previously possible using other methods. These sub-vesicular parameters enable us to predict cell types systematically using supervised machine learning. We also visualize distinct vesicle and cell subtypes using Uniform Manifold Approximation and Projection (UMAP) embeddings, which provides us with an innovative approach to explore structural heterogeneity in islet cells. This methodology presents an innovative approach for tracking biologically meaningful heterogeneity in cells that can be applied to any cellular system.

An online intervention to improve oncology health professional self-efficacy in communicating with carers: Hybrid effectiveness-implementation evaluation of the eTRIO program.

OBJECTIVES: Many oncology health professionals (HPs) report communicating with carers as complex; and receive limited carer-relevant training. We developed an online HP education program for supporting and managing carer involvement (eTRIO). We aimed to assess whether HPs' self-efficacy in carer communication, knowledge, and decision-making preferences improve following eTRIO. Satisfaction and implementation potential were assessed. METHODS: This type 1 hybrid effectiveness-implementation study used a pre-post single arm intervention design. HPs completed baseline measures, the eTRIO online module, and measures at 1- and 12-weeks post-intervention. Measures included: self-efficacy in carer communication (13-items), applied knowledge (7-items), preference for carer involvement in decisions (1-item). Fifteen of participants completed feedback interviews which underwent thematic analysis. User analytics were collected and analysed. RESULTS: Fifty-six HPs completed baseline measures, 42 completed post- and follow-up measures. At baseline mean self-efficacy score was 88. HPs showed a statistically significant increase in self-efficacy post-intervention (mean = 105.8, CI [12.99, 20.47]), maintained at 12-weeks (mean = 101.1, CI [8.00, 15.72]). There were no changes in knowledge or decision-making preferences. Program engagement and satisfaction were high, 86.7% participants rated eTRIO as very/extremely helpful. CONCLUSIONS AND PRACTICE IMPLICATIONS: eTRIO provided HPs with confidence to effectively engage with carers and manage complex situations such as family dominance. These gains are noteworthy, as conflict with families/carers contributes to HP burnout.

Development of Web-Based Education Modules to Improve Carer Engagement in Cancer Care: Design and User Experience Evaluation of the e-Triadic Oncology (eTRIO) Modules for Clinicians, Patients, and Carers.

BACKGROUND: Carers often assume key roles in cancer care. However, many carers report feeling disempowered and ill-equipped to support patients. Our group published evidence-based guidelines (the Triadic Oncology [TRIO] Guidelines) to improve oncology clinician engagement with carers and the management of challenging situations involving carers. OBJECTIVE: To facilitate implementation of the TRIO Guidelines in clinical practice, we aimed to develop, iteratively refine, and conduct user testing of a suite of evidence-based and interactive web-based education modules for oncology clinicians (e-Triadic Oncology [eTRIO]), patients with cancer, and carers (eTRIO for Patients and Carers [eTRIO-pc]). These were designed to improve carer involvement, communication, and shared decision-making in the cancer management setting. METHODS: The eTRIO education modules were based on extensive research, including systematic reviews, qualitative interviews, and consultation analyses. Guided by the person-based approach, module content and design were reviewed by an expert advisory group comprising academic and clinical experts (n=13) and consumers (n=5); content and design were continuously and iteratively refined. User experience testing (including "think-aloud" interviews and administration of the System Usability Scale [SUS]) of the modules was completed by additional clinicians (n=5), patients (n=3), and carers (n=3). RESULTS: The final clinician module comprises 14 sections, requires approximately 1.5 to 2 hours to complete, and covers topics such as carer-inclusive communication and practices; supporting carer needs; and managing carer dominance, anger, and conflicting patient-carer wishes. The usability of the module was rated by 5 clinicians, with a mean SUS score of 75 (SD 5.3), which is interpreted as good. Clinicians often desired information in a concise format, divided into small "snackable" sections that could be easily recommenced if they were interrupted. The carer module features 11 sections; requires approximately 1.5 hours to complete; and includes topics such as the importance of carers, carer roles during consultations, and advocating for the patient. The patient module is an adaptation of the relevant carer module sections, comprising 7 sections and requiring 1 hour to complete. The average SUS score as rated by 6 patients and carers was 78 (SD 16.2), which is interpreted as good. Interactive activities, clinical vignette videos, and reflective learning exercises are incorporated into all modules. Patient and carer consumer advisers advocated for empathetic content and tone throughout their modules, with an easy-to-read and navigable module interface. CONCLUSIONS: The eTRIO suite of modules were rigorously developed using a person-based design methodology to meet the unique information needs and learning requirements of clinicians, patients, and carers, with the goal of improving effective and supportive carer involvement in cancer consultations and cancer care.

Supportive Communication Between Emerging Adults With Cancer and Nurses During Diagnosis and Cancer Treatment: An Exploratory Qualitative Study Using Interviews.

BACKGROUND: Having a cancer diagnosis during early adulthood can be a significant challenge for an individual. Nurses' supportive communication plays a vital role during the diagnosis and treatment period to lessen psychological distress and promote coping. OBJECTIVE: This exploratory study aimed to examine (1) the experiences of emerging adults with cancer (EAs) aged between 18 and 25 years in communicating with nurses during diagnosis and treatment and (2) nurses' experiences of providing supportive communication with this patient group. METHODS: Semistructured interviews were conducted with EAs and nurses with experience caring for this patient group. Thematic analysis was conducted, guided by interpretive hermeneutic perspectives. RESULTS: Eight EA participants and 7 nurse participants participated in interviews. Five themes emerged: (1) having casual conversations with nurses helped EAs cope during cancer treatment and (2) helped EAs fulfill the need for social connectedness, (3) nurses as a different form of peer-like support, (4) nurses used themselves as a therapeutic tool to foster trust and emotional safety of EAs, and (5) nurses needed to maintain professional boundaries while being compassionate. CONCLUSIONS: This study highlighted a rather underdocumented aspect of supportive communication: meeting psychosocial needs through casual, day-to-day conversations. IMPLICATIONS FOR PRACTICE: Having casual conversations with nurses appeared to help EAs' psychological coping during cancer treatment. These casual conversations, which on the surface seemed clinically insignificant, fulfilled their psychosocial needs. Considering the valuable interpersonal engagement that led to emotional benefits for EAs, communication training for cancer nurses needs to build their capacity to maintain both relational and emotional boundaries.

Experiences and perspectives of colorectal cancer survivors and general practitioners on the delivery of survivorship care in general practice: a mixed methods study.

BACKGROUND: Many colorectal cancer (CRC) survivors experience ongoing sequelae from their cancer treatment. Limited evidence exists regarding how CRC survivors and general practitioners (GPs) manage these sequelae in the community. This study aimed to explore the experiences and perspectives of CRC survivors and GPs on current approaches to monitoring and managing sequelae of CRC treatment. METHODS: We conducted a mixed-methods study using cross-sectional national surveys and qualitative interviews with CRC survivors and GPs to explore: (1) treatment sequelae experienced by CRC survivors, (2) how these were monitored and managed by general practitioners, and (3) suggestions to improve ongoing management of the treatment sequelae. Survey responses were reported descriptively. Qualitative data were thematically analysed using an interpretive descriptive approach. RESULTS: Seventy participants completed surveys: 51 CRC survivors and 19 GPs, and four interviews were conducted with GPs. CRC survivors experienced a range of treatment sequelae, but often did not discuss these with their GPs (experienced vs discussed: 86% vs 47% for fatigue/lack of energy, 78% vs 27% for psychological/emotional concern, 63% vs 22% for impaired sleep, 69% vs 29% for weight loss/gain, 59% vs 16% for sexual and intimacy concerns). GPs reported inadequate information transfer from cancer services and workload as major barriers to optimal care. CONCLUSIONS: System-level changes that facilitate adequate information transfer from cancer services to GPs upon CRC treatment completion, as well as addressing time constraint issues essential for comprehensive monitoring and management of CRC treatment sequelae, could enhance the care of CRC survivors in the community setting.

In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography.

Actin mediates insulin secretion in pancreatic ß-cells through remodeling. Hampered by limited resolution, previous studies have offered an ambiguous depiction as depolymerization and repolymerization. We report the in situ structure of actin remodeling in INS-1E ß-cells during glucose-stimulated insulin secretion at nanoscale resolution. After remodeling, the actin filament network at the cell periphery exhibits three marked differences: 12% of actin filaments reorient quasi-orthogonally to the ventral membrane; the filament network mainly remains as cell-stabilizing bundles but partially reconfigures into a less compact arrangement; actin filaments anchored to the ventral membrane reorganize from a "netlike" to a "blooming" architecture. Furthermore, the density of actin filaments and microtubules around insulin secretory granules decreases, while actin filaments and microtubules become more densely packed. The actin filament network after remodeling potentially precedes the transport and release of insulin secretory granules. These findings advance our understanding of actin remodeling and its role in glucose-stimulated insulin secretion.

Evaluating a shared care pathway intervention for people receiving chemotherapy to reduce post-treatment unplanned hospital presentations: a randomised controlled trial.

PURPOSE: The aim of this randomised controlled trial (RCT) was to explore whether a community nursing intervention for outpatients receiving systemic therapy reduced unplanned hospital presentations and improved physical and psychosocial health outcomes over the first three cycles of treatment compared to a control group receiving standard care. METHODS: The number of and reasons for unplanned presentations were obtained for 170 intervention and 176 control group adult patients with solid tumours starting outpatient chemotherapy. Poisson regression was used to compare the number of presentations between the intervention and control groups. Patients self-completed the Hospital Anxiety and Depression Scale, the Cancer Behavior Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) at the start of the first four cycles. Linear regression techniques were used to compare quality of life outcomes. RESULTS: The reduction in unplanned presentations in the intervention group relative to the control group was 12% (95% CI, - 25%, 37%; P = 0.48). At the start of cycle 4, there was no difference in anxiety (difference = 0.47 (95% CI, - 0.28, 1.22; P = 0.22)), depression (difference = 0.57 (95% CI, - 0.18, 1.31; P = 0.13)) or EORTC QLQ-C30 summary score (difference = 0.16 (95% CI, - 2.67, 3.00; P = 0.91)). Scores for self-efficacy as measured by the Cancer Behavior Inventory were higher in the intervention group (difference = 4.3 (95% CI, 0.7, 7.9; P = 0.02)). CONCLUSION: This RCT did not demonstrate a benefit in reducing unplanned presentations to hospital. The trial identified improved cancer-based self-efficacy in patients receiving the intervention. TRIAL REGISTRATION: Registered at Australian and New Zealand Clinical Trials Registry: ACTRN12614001113640, registered 21/10/2014.

The Viability and Acceptability of a Virtual Wound Care Command Centre in Australia.

The objective of this study was to assess the viability and acceptability of an innovative Virtual Wound Care Command Centre where patients in the community, and their treating clinicians, have access to an expert wound specialist service that comprises a digital wound application (app) for wound analysis, decision-making, remote consultation, and monitoring. Fifty-one patients with chronic (42.6%) wounds were healed, with a median time to healing of 66 (95% CI: 56-88) days. All patients reported high satisfaction with their wound care, 86.4% of patients recommended the Virtual Wound Care Command Centre with 84.1% of patients reporting the app as easy to use. The data revealed that the Virtual Wound Care Command Centre was a viable and acceptable patient-centred expert wound consultation service for chronic wound patients in the community.

Ethical challenges experienced by veterinary practitioners in relation to adverse events: Insights from a qualitative study.

BACKGROUND: Understanding ethical challenges experienced in relation to adverse events is necessary to inform strategies that optimise patient safety and practitioner wellbeing. METHODS: A qualitative exploration of UK veterinary practitioners' experiences of adverse events was conducted. Data were collected via 12 focus groups and 20 interviews and analysed using an inductive coding technique. RESULTS: Questions surrounding acceptable boundaries of care, decision-making autonomy, personal scope of practice, use of evidence and speaking up about patient safety concerns were identified as ethically challenging to practitioners when endeavouring to prevent adverse events. Issues of appropriate accountability, interaction and communication with animal owners and the prioritisation of emotional and technical support for themselves and others were identified as ethically challenging in the aftermath of adverse events. LIMITATIONS: The qualitative nature of this study limits the generalisability of the findings. CONCLUSIONS: Ethical challenges are experienced by veterinary practitioners in relation to both preventing and responding in the aftermath of adverse events. Strategies that facilitate ethical decision making and reflection and encourage openness and learning from adverse events would likely improve patient safety and enhance practitioner wellbeing. Further research is needed to develop and implement support for practitioners who experience ethical challenges in relation to adverse events.

Development and implementation barriers of a new patient-reported measure: The Radiation therapy-related Inconvenience Questionnaire (RIQ).

INTRODUCTION: Radiation therapy (RT) can benefit approximately 50% of cancer patients and contribute to 40% of all cancer cures, yet its utilisation in cancer is low globally. Several factors contribute to this including perceived inconvenience related to accessing and utilising RT. To quantitatively assess the latter, a new tool - the Radiation therapy-related Inconvenience Questionnaire (RIQ) - was developed. This study aimed to pre-test the RIQ and explore barriers and facilitators to implementing it in routine clinical practice and clinical trials. METHODS: Semi-structured cognitive interviews were conducted with patients undertaking RT, recruited via three hospitals to examine content validity, acceptability, and comprehensibility of the RIQ. Interviews identified inconsistencies, relevance, and clarity of items. Semi-structured interviews with healthcare professionals involved in the delivery of care to individuals undertaking RT explored barriers and facilitators to routine usage. Thematic analysis was used to identify themes. RESULTS: Patients (N = 15) identified problems in content, instructions, layout, length, and response options; consequently, 25 items were revised and eight removed, resulting in a final 29-item questionnaire. Clinicians identified staff- and patient-specific barriers to implementing RIQ in clinical practice. Perceived facilitators included the following: (a) workplace factors, (b) mode of administration, and (c) imparting knowledge. CONCLUSION: This study demonstrated acceptability and comprehensibility of the 29-item RIQ amongst cancer patients undertaking RT and treating clinicians. The next phase will evaluate the RIQ's measurement properties in a larger clinical study. The barriers and facilitators identified can guide future implementation of RIQ in clinical practice and clinical trials.

Development of a risk prediction tool for patients with locally advanced and recurrent rectal cancer undergoing pelvic exenteration: protocol for a mixed-methods study.

INTRODUCTION: Pelvic exenteration (PE) surgery represents the only potentially curative treatment option for patients with locally advanced or recurrent rectal cancer (LARRC). Given the potential morbidity, whether or not PE should be recommended for an individual patient presents a major decisional conflict. This study aims to identify the outcomes of PE for which there is consensus among patients, carers and clinicians regarding their importance in guiding treatment decision-making, and to develop a risk prediction tool which predicts these outcomes. METHODS AND ANALYSIS: This study will be conducted at a specialist PE centre, and employ a mixed-methods study design, divided into three distinct phases. In phase 1, outcomes of PE will be identified through a comprehensive systematic review of the literature (phase 1a), followed by exploration of the experiences of individuals who have undergone PE for LARRC and their carers (phase 1b, target sample size 10-20 patients and 5-10 carers). In phase 2, a survey of patients, their carers and clinicians will be conducted using Delphi methodology to explore consensus around the outcomes of highest priority and the level of influence each outcome should have on treatment decision-making. In phase 3 a, risk prediction tool will be developed using data from a single PE referral centre (estimated sample size 500 patients) to predict priority outcomes using multivariate modelling, and externally validated using data from an international PE collaboration. ETHICS AND DISSEMINATION: Ethical approval has been granted for phases 1 and 2 (X22-0422 and 2022/ETH02659) and for maintenance of the database used in phase 3 (X13-0283 and HREC/13/RPAH/504). Informed consent will be obtained from participants in phases 1b and 2; a waiver of consent for secondary use of data in phase 3 will be sought. Study results will be submitted for publication in international and/or national peer reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42022351909.

Robenacoxib versus meloxicam following ovariohysterectomy in cats: A randomised, prospective clinical trial involving owner-based assessment of pain.

BACKGROUND: Injectable non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to queens undergoing ovariohysterectomy (OVH), but the requirement for postoperative administration is unclear and practices vary. Existing studies assessing efficacy rely on pain scoring by experienced clinicians. However, following OVH, most cats are discharged within hours of recovery. METHODS: Cats undergoing OVH were randomly assigned to two treatment groups: MEL and ROB. Cats in the MEL group (n = 76) received meloxicam (0.2 mg/kg) and those in the ROB group (n = 65) received robenacoxib (2 mg/kg). Owners were contacted by a blinded assessor 3 days postoperatively and asked to identify physical or behavioural changes and to assign pain scores using a numerical rating scale. RESULTS: More cats in the ROB group displayed abnormal behaviours than cats in the MEL group (p = 0.03). Most owners assigned a pain score of 0 (72%) (n = 101), but pain scores were significantly higher in the ROB group than in the MEL group (p = 0.005). LIMITATION: Methods of owner assessment of pain in cats have not been validated. CONCLUSIONS: Both meloxicam and robenacoxib are effective in controlling postoperative pain. Meloxicam may have improved efficacy in certain patient populations. Applying a blanket approach to prescribing NSAIDs to cats undergoing OVH postoperatively may not be necessary. This has safety, environmental and cost implications.