Understanding the symptom experience in chronic conditions

Background: The World Health Organization defines chronic conditions as those having a long duration, generally slow progression, and requiring some level of health care management across time. In 2019, on average, more than 30% of adults across OECD (Organisation for Economic Co-operation and Development) countries had a chronic condition. Due to the aging of the populations, this number is projected to continuously increase and cause disability and premature death, making it an important global health concern. Chronically ill people are burdened by several symptoms, which often occur simultaneously. High symptom burden is associated with higher health-care utilization and hospitalization rates, higher health-care costs, and lower quality of life. People with chronic conditions may improve their clinical outcomes, including symptoms, if they perform adequate self-care to maintain their health, monitor their symptoms, and manage symptoms when they occur. However, patients often find it difficult to perform self-care and, in these cases, caregivers could help. In addition, there is accumulating evidence suggesting that people with a chronic condition experience difficulties in perceiving their symptoms, which, in turn, is associated with distorted or exaggerated symptom burden. This might be related to illness-induced interoceptive impairments. Interoception refers to the processes through with the brain perceive, elaborates, and responds to signals originating from within the body, including symptoms. In chronic conditions, some studies have shown that some brain structures, such as the insular cortex, are damaged and this leads to interoceptive alterations, which, in turn, results in symptom-processing deficits. Objectives: This PhD project aimed to a) cluster patients based on their physical and psychological symptoms and predict symptom cluster membership based on variables other than symptoms; b) assess the influence of caregiver contribution to self-care on symptom burden and the mediating role of patient self-care; c) explore the role of interoception in the symptom experience of people with a chronic condition. Methods: In the first study, we clustered 510 Italian patients with heart failure, previously recruited for the MOTIVATE-HF trial, based on their symptoms. The cluster analysis was performed using two scores of the Hospital Anxiety-Depression scale and two scores of the Heart-Failure Somatic Perception 6 Scale. ANOVA and chi-square test were used to compare patients’ characteristics among clusters. For the predictive analysis, we split the data into a training set and a test set and trained three classification models on the former to predict patients’ symptom-cluster membership based on 11 clinical/sociodemographic variables. Permutation analysis investigated which variables best predicted cluster-membership. In the second study, we analysed baseline and 3-month data from the MOTIVATEHF trial and performed multigroup confirmatory factor analysis to test measurement invariance, and autoregressive longitudinal path analysis with contemporaneous mediation to test the study hypotheses. In the third study, we conducted a systematic review. We searched five databases and included all primary research published between 2013-2021 in which at least one dimension of interoception was measured. Any chronic condition and any symptom were included. Only the adult population was considered. Results: In the first study we identified four clusters of HF patients based on the intensity and combination of psychological and physical symptoms: mixed distress (high psychological, low physical symptoms), high distress, low distress, moderate distress. NYHA-class and sleep quality were the most important variables in predicting symptom cluster membership. In the second study, we found that higher caregiver contribution to self-care maintenance was associated with higher patient self-care maintenance (β=0.280, p<0.001), which, in turn, was associated with lower symptom burden (β=-0.280, p<0.001). Patient self-care maintenance mediated the effect of caregiver contribution to self-care maintenance on symptom burden (β=-0.06, 95% BC bootstrapped CI: -0.13; -0.03). In the third study, we included 18 quantitative studies investigating the relationship between three interoceptive dimensions (i.e., accuracy, sensibility, awareness) and condition-specific symptoms in eight chronic conditions. We found that people with chronic conditions had lower interoceptive accuracy than healthy controls. Higher interoceptive sensibility was associated with lower symptom severity/frequency. Only one study explored interoceptive awareness. Conclusion: This PhD project offers new insights into the science of symptoms experienced by adults with a chronic condition, emphasizes the underling the role of caregivers in symptom management, and promotes further understanding of the role of interoceptive mechanisms in symptom perception. By doing so, this PhD project can better support clinicians and researchers in identifying tailored symptom- management strategies and in investigating the effect of clusters of symptoms on patient outcomes, even when direct access to symptoms-related data is absent.