Potential overtreatment during life-limiting illness and end of life in older adults

Sammanfattning: Background. A growing body of evidence suggests that older patients are subject to potential overtreatment at the end of life, characterised by disease modifying therapies, preventive medications, and frequent care transitions. This occurs even though many older patients express a preference for symptom management and tend to avoid curative therapies near death. Nowadays age-related chronic diseases and neurodegenerative conditions are the top causes of death leading to a more foreseeable trajectory of decline at the end of life compared to compared to those who die suddenly or prematurely due to global pandemics. However, drugs and procedures, with longer time-to-benefit than the seriously ill older patients’ life expectancy, are still administered causing potential adverse events, deteriorated quality of life and higher dependency. Aim. The present doctoral thesis aimed to evaluate the quality of end-of-life care in older adults, with a focus on potential overtreatment and life-limiting illness. The four individual studies of the thesis contributed to this aim from different, yet complimentary aspects. Study I. We identified overtreatment indicators in the existing literature and discovered that nearly half of them cannot be appropriately measured in administrative and healthcare data in Sweden. However, based on the 15 unique indicators that we could measure, we estimated that one third (36.9%) of patients with solid cancer received care in their last month of life deemed as potential overtreatment. Cancer-specific treatments were the most common form of potential overtreatment (27.0%), followed-by potentially futile non-cancer specific treatments (12.3%), and hospital transitions (9.4%). Study II. We found that older decedents had an average 1.7 unplanned hospitalisations during their last year of life, which corresponded to an incidence rate of 175 per 100 person-years. Those with a cancer trajectory had the highest incidence rate at 231 per 100 patient-years, whereas individuals on a trajectory of prolonged dwindling had the lowest rate at 99 per 100 patient-years. Unplanned hospitalisations were unevenly distributed throughout the last year of life. From the third month before death, the incidence rate started to increase, which is the point where the different patterns of hospitalisation between illness trajectories became evident. Study III. We reported that endocrine treatment, which is a systemic disease modifying treatment, was initiated by 5% in the last three months of life and continued by 39% of the older decedents with hormone receptor-positive metastatic breast cancer. We found several factors linked to continuation of treatment, for example, higher age (RR85+ years: 1.25 [1.12-1.41]), higher education (RRtertiary education: 0.89 [0.81-0.98]), and multi-dose drug dispensing (RR: 1.22 [1.13-1.32]). Initiation of treatment was associated with, for instance, number of hospitalised days (RR1-14 inpatient days: 1.81 [1.12-2.91]) and CDK4/6 use (3.16 [2.25- 4.44]). Study IV. Based on a self-controlled case series analysis, we discovered that the concomitant dispensation of cholinesterase inhibitors (ChEIs) and non-steroidal anti- inflammatory drugs (NSAIDs) resulted in a heightened risk of peptic ulcer disease (adjusted IRR: 9.0, 95% confidence interval: 6.8-11.8, E-value: 17.5) compared to periods without treatment. This risk was over and beyond the risks observed for NSAIDs alone (IRR 5.2, 4.4-6.0, E-value: 9.8). We found no evidence of increased risks associated with the use of ChEIs alone (IRR 1.0, 0.9-1.2, E-value: 1.2). Conclusions. Our findings suggest that older adults and seriously ill individuals are potentially exposed to various types of treatment near the end of life that may be deemed as overtreatment, which warrants further attention from policy makers, healthcare professionals, researchers, and the society as a whole. Overly intensive care, fuelled by disease modifying treatments, preventive therapies and frequent transitions close to death is generally against the preferences of older people. Important to note that reducing or eliminating these types of treatments is not about rationing healthcare or denying treatment, but rather about ensuring that patients spend their last months in good quality care, characterised by symptom management and avoidance of unnecessary and preventable risks factors and adverse effects.