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Objective This study aimed to qualitatively explore the experiences of healthcare professionals implementing changes (as change initiators) and operationalizing interdisciplinary teamwork in a rehabilitation service within the Irish healthcare system. Data sources Data for this study were collected through focus group discussions with change initiators involved in interdisciplinary team initiatives at a rehabilitation service in Ireland. Review methods A reflexive thematic analysis was employed to analyse the focus group data, which involved identifying patterns and themes within the narratives provided by participants. Results Three overarching themes emerged from the analysis: 1. \"Nature of the Battle for Change\", 2. \"Characteristics of the 'Status Quo' and Contradictions to IDT Working,\" and 3. \"Power and Identity: Threats to Hierarchy and Status\". These themes shed light on the challenges faced in implementing interdisciplinary teamwork, particularly the perceived threats to individual power and professional identity within hierarchical healthcare structures. Conclusion Implementing healthcare changes, especially in historically hierarchical healthcare systems is complex. Interdisciplinary team rehabilitation can challenge the status quo, posing adoption barriers. A nuanced, bottom-up approach is recommended, emphasizing long-term coalition building, continuous professional development, and early discussions about hierarchy and status. These recommendations offer practical guidance for stakeholders seeking to implement interdisciplinary, person-oriented approaches in rehabilitation practices, facilitating better anticipation and resolution of challenges, and ultimately improving care delivery and patient outcomes.

Learning Health System (LHS) aims to continuously integrate clinical data and patient outcomes to enhance care quality, efficiency, and patient experience by leveraging real-time data and fostering a culture of shared learning. Following its relocation to a state-of-the-art facility in 2020, the National Rehabilitation Hospital (NRH) presents a unique opportunity to embed LHS concepts into its rehabilitation services. This transition also provides a critical moment to explore interdisciplinary team (IDT) dynamics, decision-making practices, and collaborative frameworks, all aimed at improving team effectiveness and patient outcomes.  LHS principles promote the integration of research, clinical practice, and data analytics to create a feedback loop for continuous care improvement. In rehabilitation settings, the adoption of LHS can lead to more personalised, patient-centred care by facilitating collaboration within IDTs. NRH has embraced this approach, aligning with the LHS model to deliver holistic, adaptive, and data-driven care.  Research team conducted a scoping review, and four themes were identified for implementing an LHS in rehabilitation settings as, 1) Creating a functioning data infrastructure, 2) Ensuring data quality, 3) Assembling a multidisciplinary team, and 4) Addressing institutional characteristics such as communication and organisational learning. To make our LHS framework more actionable, research team presented the results of this scoping review and asked over 40 healthcare professionals and researchers to prioritise them during a workshop at ICIC 24.  Current presentation initiates three work packages (WPs) for exploring the implementation of LHS concepts at NRH. WP1 involves consultation with staff through a World Café process, gathering insights from healthcare staff to develop the roadmap of LHS. WP2 focuses on co-design workshops with working groups to define LHS goals, integrate patient-centred care, and establish an implementation strategy. WP3 will continuously evaluate the impact of LHS on rehabilitation services at NRH, ensuring iterative refinement and learning across the hospital.  The LINK project will contribute valuable insights into how LHS principles can transform rehabilitation care, fostering a culture of continuous improvement, patient engagement, and interdisciplinary collaboration.

Background: Implementing a patient-centred, interdisciplinary approach to shared decision-making in goal setting is essential in rehabilitation, aligning care with patient needs, fostering safer environments, and boosting motivation. At the National Rehabilitation Hospital, Ireland (NRH), a new goal-setting process was introduced to improve care in specialised rehabilitation services, supported by a framework of system-wide governance and leadership. This study aimed to examine managers’ perspectives on the process one year post-implementation, specifically focusing on how their support and leadership strategies, within a broader organisational governance context, facilitated or impeded the integration of the process into routine rehabilitation patient care. Approach: Semi-structured interviews with managers across units and disciplines provided insights into challenges faced, as well as the leadership’s role in aligning staff with this new, patient-centred rehabilitation goal setting process. Thematic analysis was used to identify how governance structures and leadership strategies influenced both engagement and barriers to the implementation. Results: Nine managers participated, with an average age of 43.38 years (SD = 6.91) and 17.17 years (SD = 8.75) of experience at NRH. Both managers and staff demonstrated willingness to adopt the new process, yet described barriers to full implementation into daily rehabilitation routine care. Managers often expressed a sense of isolation, positioned between clinical staff and the interdisciplinary team advocating for the process. They highlighted the lack of clear authority or organisational support to enforce new goals, which limited their leadership capacity and created a passive role in implementation. While staff supported the patient-centred focus, they raised concerns over unrealistic patient expectations and time constraints, which managers were unable to address effectively due to limited systemic mechanisms. Despite these obstacles, managers valued the long-term potential of this patient-centred goal setting process, recognising the importance of sustained governance support to fully embed the process. Implications: This study examined the role of leadership and governance in embedding patient-centred process within healthcare settings, with a particular focus on rehabilitation. Findings suggest that while managers recognise the benefits of interdisciplinary, patient-focused approaches, the long-term success of these initiatives depends on supportive governance structures, clear authority, and continuous leadership development. Insights from this study will inform ongoing quality improvement strategies at the NRH, supporting the development of governance frameworks that foster interdisciplinary teamwork in rehabilitation settings. These findings are also valuable for other rehabilitation providers, offering the strategies toward enhancing patient-centred quality improvements in other rehabilitation settings.

Background: Research has demonstrated the importance of a patient-centred, interdisciplinary approach to shared decision-making in goal setting within rehabilitation, enhancing personalised care, reducing risks, and aligning treatment with patients’ needs. This approach promotes safer healthcare environments, increases patient motivation, and improves rehabilitation outcomes. The National Rehabilitation Hospital implemented a new goal-setting process to optimise patient care in specialised rehabilitation services in 2023. This study aimed to examine staff perceptions of the process, comparing differences between its initiation (T1) and one year post-implementation (T2), to assess its impact on care delivery and outcomes.  Approach: This study employed a mixed methods approach to explore staff experiences and perspectives on the implementation of a new patient-centred goal-setting process at its initiation (T1) and one year post-implementation (T2). Quantitative data were collected to assess staff attitudes, interdisciplinary collaboration, and evaluate the integration of the new process into routine practice. In addition, in-depth interviews were conducted to gain further insights into staff-perceived enablers, barriers, and the impact of the goal-setting process on patient care and teamwork across various rehabilitation specialties. Quantitative data were analysed using t-tests, while qualitative data were analysed using thematic analysis. Results: In T1, 56 staff completed the survey, with 61 participating in T2. Results showed a slight increase in staff confidence and optimism between T1 and T2, alongside a significant decrease in team inclusion (from 87.5% to 75.4%, p < .05). Staff considered the process sustainable at both time points, with sense-making scores rising from 3.40 to 3.73. For the qualitative study, 15 staff members were interviewed in both T1 and T2, revealing mixed findings: at T1, staff viewed the process as positive and collaborative, though some felt it added to their workload and pressure. By T2, staff remained motivated, recognising the process’s benefits for patient care, though concerns about resources and team adaptation persisted. Implications: Implementing quality improvement activity in a healthcare organisation, even though the participants see its value, is a difficult undertaking. The study identified staff experience of the implementation journey of this new goal setting process. Results illuminate challenges and strategies to implementing changes to goal setting within rehabilitation context. Findings will be used to inform implementation of other quality improvement activities within the hospital and further contribute to knowledge for rehabilitation practice. 

Background Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targetable proteins for treatment. PARP inhibitors (PARPi) are effective in BRCA -mutated cancers but have limited utility in non-germline BRCA-mutated (non-g BRCA m) TNBC. We hypothesized that inducing BRCAness by targeting RAD51, a key homologous recombination protein, could sensitize non-g BRCA m TNBC to PARPi. Methods EGFP-tagged RAD51 was generated and EGFP signal was monitored for identifying agents that affected RAD51 protein expression and stability. Cell viability was assayed using cell counting kit-8. Synergism of ivabradine and olaparib was determined using SynergyFinder 3.0. DR-GFP, EJ5-GFP and comet assays were employed to evaluate the degree of DNA repair and damage, respectively. Protein and mRNA levels were determined by western blot and qPCR, respectively. ChIP was used to determine the binding to ATF6 to the promoter of FBXO24. CoIP was employed to determine the interaction between RAD51 and FBXO24. Xenografts on nude mice and PDTX were in vivo models for validating the combined effect of ivabradine and olaparib. Results Using an EGFP-RAD51 reporter, we identified ivabradine as a RAD51-reducing agent. In vitro studies with TNBC cell lines demonstrated that ivabradine synergized with PARPi to reduce cell viability (ZIP score > 10), induce apoptosis, and impair HR-mediated DNA repair. This synergy was confirmed in vivo using xenografts and patient-derived tumor xenografts, where co-treatment with clinical grade ivabradine (Coralan) and PARPi olaparib (Lynparza) led to substantial tumor growth inhibition without notable toxicity. Mechanistically, ivabradine triggered ER stress, activating ATF6 to upregulate FBXO24-dependent ubiquitination, leading to RAD51 degradation, resulting in the condition of BRCAness. Chromatin immunoprecipitation and co-immunoprecipitation confirmed the ATF6-FBXO24-RAD51 cascade. These findings reveal a novel mechanism by which ivabradine, an FDA-approved cardiac drug, induces BRCAness, by degrading RAD51 via the ATF6-FBXO24 axis, thus, by mimicking HR deficiency hypersensitizes BRCA-proficient TNBC to olaparib. Conclusion This study highlights the translational potential of repurposing ivabradine as a therapeutic strategy for non-g BRCA m TNBC. By addressing a critical unmet need of this aggressive breast cancer subtype, it can potentially expand the utility of PARPi. Graphical abstract Schematic diagram illustrates the synergistic effect of IVA and OLA. IVA treatment results in enhanced ER stress, leading to the activation of ATF6. The activated ATF6 translocates to the nucleus and binds to the promoter of FBXO24 to induce its expression. FBXO24 mediates RAD51 protein degradation via the ubiquitin-proteasome system. The reduction of RAD51 expression contributes to the feature of BRCAness. Adding PARP inhibitor OLA can prevent single-strand DNA damage from repairing, subsequently becoming DNA double-strand breakage (DSB). The low expression of RAD51 mediated by IVA compromises the mechanism for repairing DSB via HR, leading to the accumulation of DSB. Eventually, cell death is induced.

The cytotoxicity of several important antitumor drugs depends on formation of the covalent topoisomerase-DNA cleavage complex. However, cellular processes such as DNA replication are necessary to convert the cleavage complex into a cytotoxic lesion, but the molecular mechanism of this conversion and the precise nature of the cytotoxic lesion are unknown. Using a bacteriophage T4 model system, we have previously shown that antitumor drug-induced cleavage complexes block replication forks in vivo. In this report, we show that these blocked forks can be cleaved by T4 endonuclease VII to create overt DNA breaks. The accumulation of blocked forks increased in endonuclease VII-deficient infections, suggesting that endonuclease cleavage contributes to fork processing in vivo. Furthermore, purified endonuclease VII cleaved the blocked forks in vitro close to the branch points. These results suggest that an indirect pathway of branched-DNA cleavage contributes to the cytotoxicity of antitumor drugs that target DNA topoisomerases.

Abstract Objectives: The purpose of the study was to compare the performance of GloCyte (Advanced Instruments, Norwood, MA), a new semiautomated instrument for cerebrospinal fluid cell counting, with the manual hemocytometer method and the automated Sysmex XN (Sysmex, Kobe, Japan) body fluid mode. The clinical impact of replacing the manual method with either automated method was determined. Methods: Fifty-seven samples from 38 patients were analyzed by all three methods. Pearson correlation and Passing-Bablok regression were used to compare methods. Cytospin smears were reviewed on all samples, and clinical histories were obtained. Results: There was a strong linear relationship between the manual and automated methods for WBC counts (R = 0.988 for GloCyte; R = 0.980 for Sysmex XN). Positive bias was absent or negligible for WBC counts less than 30/μL. GloCyte and manual RBC counts were equivalent. There were no samples for which replacement of manual WBC counts by automated counts would have changed the diagnosis. Both automated methods showed improved precision for WBC counts compared with the manual method. Conclusions: Replacing manual WBC counts by GloCyte or Sysmex XN WBC counts would improve consistency of results without compromising diagnostic accuracy.