Palliative care interventional research in general practice: a narrative review of factors affecting research conduct

BACKGROUND AND OBJECTIVE: The majority of palliative care provision occurs in general practice, yet only 9% of palliative care clinical trials were conducted in this setting. Evidence from hospital and specialist settings is not readily transferable to general practice, as the population, context and care processes are vastly different. Conducting interventional palliative care research in general practice settings is subject to many challenges and barriers. This narrative review aims to describe the factors influencing the conduct of interventional research in general practice settings for patients with palliative care needs. METHODS: A narrative review was performed to identify factors affecting the conduct of palliative care interventional studies in general practice. A literature search of MEDLINE was conducted on 26 September 2023, and data were synthesised utilising a narrative approach. KEY CONTENT AND FINDINGS: Sixteen articles were identified. Five thematic groupings were identified from the literature that affected the interventions: factors related to health care professionals (HCPs), patients and carers, general practices, health systems, and research design. HCPs and practices were focused on providing clinical care and struggled to incorporate research into their workload. Staff and patients often had negative perceptions in palliative care combined with limited research experience, often resulting in unwillingness to engage in interventions and gatekeeping. Engaging with general practice staff to design, participate and champion research were key facilitators of successful interventions. CONCLUSIONS: Palliative care interventions in general practice are invariably complex and challenging, yet acutely needed to address the care needs of patients in the community setting. Working together with patients, carers and clinicians to design and implement interventions appropriate for general practice settings is fundamental to their success

Factors influencing deprescribing in primary care for those towards the end of life:A qualitative interview study with patients and healthcare practitioners

Background: For people with limited lifetime expectancy, the benefit of many medications may be outweighed by their potential harms. Despite the relevance of reducing unnecessary medication use, deprescribing is poorly enacted in primary care practice. Aim: This study aims to describe factors, as identified by primary care professionals and patients, that influence deprescribing in the last phase of life. Design: Semi-structured interviews were conducted and analysed using a thematic approach. Setting/participants: This study was performed in primary care settings, including general practices, hospices and community care teams in The Netherlands. Purposefully identified primary care professionals (general practitioners, pharmacists, nurses) and patients with limited lifetime expectancy due to advanced chronic illness or cancer and their caretakers were interviewed. Results: Three themes emerged detailing factors influencing deprescribing in the last phase of life in primary care: (1) non-maleficence, the wish to avoid additional psychological or physical distress; (2) reactive care, the lack of priority and awareness of eligible patients; and (3) discontinuity of care within primary care and between primary care and specialty care. Conclusions: Deprescribing is an incremental process, complicated by the unpredictability of life expectancy and attitudes of patients and health care professionals that associate continued medication use with clinical stability. Opportunities to facilitate the deprescribing process and its acceptance include the routinely systematic identification of patients with limited life expectancy and potentially inappropriate medications, and normalisation of deprescribing as component of regular primary care, occurring for all patients and continuing into end-of-life care.</p

Factors influencing deprescribing in primary care for those towards the end of life: A qualitative interview study with patients and healthcare practitioners

BACKGROUND: For people with limited lifetime expectancy, the benefit of many medications may be outweighed by their potential harms. Despite the relevance of reducing unnecessary medication use, deprescribing is poorly enacted in primary care practice. AIM: This study aims to describe factors, as identified by primary care professionals and patients, that influence deprescribing in the last phase of life. DESIGN: Semi-structured interviews were conducted and analysed using a thematic approach. SETTING/PARTICIPANTS: This study was performed in primary care settings, including general practices, hospices and community care teams in The Netherlands. Purposefully identified primary care professionals (general practitioners, pharmacists, nurses) and patients with limited lifetime expectancy due to advanced chronic illness or cancer and their caretakers were interviewed. RESULTS: Three themes emerged detailing factors influencing deprescribing in the last phase of life in primary care: (1) non-maleficence, the wish to avoid additional psychological or physical distress; (2) reactive care, the lack of priority and awareness of eligible patients; and (3) discontinuity of care within primary care and between primary care and specialty care. CONCLUSIONS: Deprescribing is an incremental process, complicated by the unpredictability of life expectancy and attitudes of patients and health care professionals that associate continued medication use with clinical stability. Opportunities to facilitate the deprescribing process and its acceptance include the routinely systematic identification of patients with limited life expectancy and potentially inappropriate medications, and normalisation of deprescribing as component of regular primary care, occurring for all patients and continuing into end-of-life care

Inter-domain Cooperation in INCENP Promotes Aurora B Relocation from Centromeres to Microtubules

The chromosomal passenger complex is essential for error-free chromosome segregation and proper execution of cytokinesis. To coordinate nuclear division with cytoplasmic division, its enzymatic subunit, Aurora B, relocalizes from centromeres in metaphase to the spindle midzone in anaphase. In budding yeast, this requires dephosphorylation of the microtubule-binding (MTB) domain of the INCENP analog Sli15. The mechanistic basis for this relocalization in metazoans is incompletely understood. We demonstrate that the putative coiled-coil domain within INCENP drives midzone localization of Aurora B via a direct, electrostatic interaction with microtubules. Furthermore, we provide evidence that the CPC multimerizes via INCENP's centromere-targeting domain (CEN box), which increases the MTB affinity of INCENP. In (pro)metaphase, the MTB affinity of INCENP is outcompeted by the affinity of its CEN box for centromeres, while at anaphase onset—when the histone mark H2AT120 is dephosphorylated—INCENP and Aurora B switch from centromere to microtubule localization

Mps1 promotes rapid centromere accumulation of Aurora B

Aurora B localization to mitotic centromeres, which is required for proper chromosome alignment during mitosis, relies on Haspin-dependent histone H3 phosphorylation and on Bub1-dependent histone H2A phosphorylation—which interacts with Borealin through a Shugoshin (Sgo) intermediate. We demonstrate that Mps1 stimulates the latter recruitment axis. Mps1 activity enhances H2A-T120ph and is critical for Sgo1 recruitment to centromeres, thereby promoting Aurora B centromere recruitment in early mitosis. Importantly, chromosome biorientation defects caused by Mps1 inhibition are improved by restoring Aurora B centromere recruitment. As Mps1 kinetochore localization reciprocally depends on Aurora B, we propose that this Aurora B-Mps1 recruitment circuitry cooperates with the Aurora B-Haspin feedback loop to ensure rapid centromere accumulation of Aurora B at the onset of mitosis