'If It Was Easy Somebody Would Have Fixed It': An Exploration of Loneliness and Social Isolation Amongst People Who Frequently Call Ambulance Services.

INTRODUCTION: The aim of the study was to explore social isolation and loneliness in those who frequently contacted the ambulance service, what factors contributed to this and how unmet needs could be addressed. METHODS: Semi-structured interviews with staff from the ambulance service and service users who were identified as frequently contacting the ambulance service. Service users also completed the UCLA loneliness scale and personal community maps. Data were analysed thematically before triangulation with the UCLA loneliness scale and personal community maps. RESULTS: The final analysis was drawn from 15 staff and seven service user participants. The relationship between social isolation and loneliness and contacting the ambulance service was a contributing, but not the driving, factor in contacting the ambulance service. For service users, we identified three key themes: (1) impact on activities of daily living and loneliness and/or isolation as a result of a health condition; (2) accessing appropriate health and social care services to meet needs; (3) the link between social isolation and/or loneliness and contact with the ambulance service. The analysis of staff data also highlighted three key themes: (1) social isolation and/or loneliness in their role; (2) access to other appropriate health and social care services; (3) the impact of austerity and Covid-19 on social isolation and/or loneliness. CONCLUSIONS: Our research emphasises the complex nature of social isolation and loneliness, including the cyclic nature of poor health and social isolation and loneliness, and how this contributes to contact with the ambulance service. PATIENT OR PUBLIC CONTRIBUTION: The advisory group for the study was supported by a public and patient representative who contributed to the design of the study documentation, data analysis and authorship.

The Physician Quality Improvement Initiative: Engaging Physicians in Quality Improvement, Patient Safety, Accountability and their Provision of High-Quality Patient Care.

University Health Network has been working to become a high-reliability organization, with a focus on safe, quality patient care. In response, the Medical Affairs Department has implemented several strategic initiatives to drive accountability, quality improvement and engagement with our physician population. One of these initiatives, the Physician Quality Improvement Initiative (PQII) is a physician-led project designed to provide active medical staff, in collaboration with their physician department chiefs, a comprehensive approach to focused and practical quality improvement in their practice. In this document, we outline the project, including its implementation strategy, logic model and outcomes, and provide discussion on how it fits into UHN's global strategy to provide safe, quality patient care.

Cost-effectiveness of ribociclib versus palbociclib in combination with an aromatase inhibitor as first-line treatment of postmenopausal women with HR+/HER2- advanced breast cancer: analysis based on final OS results of MONALEESA-2 and PALOMA-2.

BACKGROUND AND AIMS: Combination of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor and an aromatase inhibitor is the standard of care first-line (1L) treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Updated clinical data have become available from the MONALEESA-2 and PALOMA-2 trials for ribociclib and palbociclib, respectively. This analysis with updated data assessed the cost-effectiveness of ribociclib versus palbociclib, both in combination with letrozole, in the setting of 1L therapy of postmenopausal women with HR+/HER2- ABC, from a United Kingdom (UK) National Health Service perspective. METHODS: A three state (progression-free, progressed disease, and death) partitioned survival model with a 1-month cycle was developed. Clinical data were derived from MONALEESA-2 (NCT01958021) and PALOMA-2 (NCT01740427). The treatment effect was modeled using hazard ratios (HRs) for progression-free survival and overall survival derived through a matched-adjusted indirect comparison. Trial data and published literature were used to derive utility values. Cost inputs included drug acquisition, disease monitoring, subsequent therapies, and adverse events. Costs and outcomes were discounted by 3.5%, over a 40-year lifetime horizon. One-way and probabilistic sensitivity analyses were performed. RESULTS: Ribociclib dominated palbociclib, and was both overall cost saving (-£3,273) and more effective (+1.251 quality-adjusted life years [QALYs]). Ribociclib total drug costs were £17,156 lower than palbociclib. At a £30,000 per QALY willingness-to-pay threshold, the probability of ribociclib being cost-effective was almost 100%. Ribociclib remained cost-effective when varying HRs, utilities, drug cost, and health state costs. CONCLUSIONS: Ribociclib is both cost-saving and cost-effective compared with palbociclib for the 1L treatment of postmenopausal women with HR+/HER2- ABC in the UK.

Can Occupational Therapy Address the Occupational Implications of Hoarding?

Hoarding is often described as a medical disorder, defined by a persistent difficulty in discarding possessions and associated high levels of emotional distress when forced to part with these. This article will discuss how having a different view of hoarding, seeing hoarding as a daily occupation which provides value, purpose, and meaning and with a relationship to self-identity and life purpose, could offer alternate interventions to support an individual who hoards. The article will consider the components of hoarding activity and how these relate to health and wellbeing and doing, being, belonging, and becoming as understood by occupational therapists. The article will consider what occupational therapy, a profession which considers a person's daily occupations, the things that occupy their time and which give meaning to their existence, could offer as an alternative to current hoarding interventions. Proposals for occupational therapy interventions will be suggested which would support occupational choice, support engagement in activities which have more positive outcomes on a person's health, and seek to address barriers which limit engagement and occupational performance in activities within the person's home environment.

Histone deacetylase inhibitors: overview and perspectives.

Histone deacetylase inhibitors (HDACi) comprise structurally diverse compounds that are a group of targeted anticancer agents. The first of these new HDACi, vorinostat (suberoylanilide hydroxamic acid), has received Food and Drug Administration approval for treating patients with cutaneous T-cell lymphoma. This review focuses on the activities of the 11 zinc-containing HDACs, their histone and nonhistone protein substrates, and the different pathways by which HDACi induce transformed cell death. A hypothesis is presented to explain the relative resistance of normal cells to HDACi-induced cell death.

Histone deacetylase inhibitors selectively suppress expression of HDAC7.

There are 18 histone deacetylases (HDAC) generally divided into four classes based on homology to yeast HDACs. HDACs have many protein substrates in addition to histones that are involved in regulation of gene expression, cell proliferation, and cell death. Inhibition of HDACs can cause accumulation of acetylated forms of these proteins, thus altering their function. HDAC inhibitors (HDACi), such as the hydroxamic acid-based vorinostat (suberoylanilide hydroxamic acid), inhibit the zinc-containing classes I, II, and IV, but not the NAD(+)-dependent class III, enzymes. HDACis are a group of novel anticancer agents. Vorinostat is the first HDACi approved for clinical use in the treatment of the cancer cutaneous T-cell lymphoma. Factors affecting expression of HDACs are not well understood. This study focuses on the effect of the HDACi vorinostat on the expression of class I and class II HDACs. We found that vorinostat selectively down-regulates HDAC7 with little or no effect on the expression of other class I or class II HDACs. Fourteen cell lines were examined, including normal, immortalized, genetically transformed, and human cancer-derived cell lines. Down-regulation of HDAC7 by vorinostat is more pronounced in transformed cells sensitive to inhibitor-induced cell death than in normal cells or cancer cells resistant to induced cell death. Modulation of HDAC7 levels by small interfering RNA-mediated knockdown or by HDAC7 overexpression is associated with growth arrest but without detectable changes in acetylation of histones or p21 gene expression. Selective down-regulation of HDAC7 protein may serve as a marker of response of tumors to HDACi.

Working together to build a respectful workplace: transforming OR culture.

Respect is important in the creation of a positive perioperative work environment and effective OR teams. Low scores for respect in the OR on an employee opinion survey and responses on a more customized survey that examined issues associated with respect prompted leaders at the University Health Network to undertake a multiyear organizational strategy to address respect and quality of worklife initiatives. An interprofessional quality of worklife task force convened to create an action plan to address the outcomes of the surveys. The work of the task force included developing and implementing a code of conduct team charter for the OR, empowering leaders to better manage conflict through education and coaching, creating a collaborative, consistent approach to conflict resolution, and designing an education strategy for staff members to enhance communication and conflict resolution. Results of recent employee opinion surveys have reflected positive outcomes. Efforts to sustain the effects of the project include quarterly recognition awards and ongoing education focused on wellness and communication skills.