Patient participation : what it is and what it is not

In general, patient participation is regarded as being informed and partaking in decision making regarding one’s care and treatment. This interpretation is common in legislation throughout the Western world and corresponding documents guiding health care professionals, as well as in scientific studies. Even though this understanding of the word participation can be traced to a growing emphasis on individuals’ autonomy in society and to certain dictionary defi nitions, there are other ways of understanding participation from a semantic point of view, and no trace of patients’ descriptions of what it is to participate can be found in these definitions. Hence, the aim of this dissertation was to understand patients’ experience of the phenomenon of patient participation. An additional aim was to understand patients’ experience of non-participation and to describe the conditions for patient participation and non-participation, in order to understand the prerequisites for patient participation. The dissertation comprises four papers. The philosophical ideas of Ricoeur provided a basis for the studies: how communication can present ways to understand and explain experiences of phenomena through phenomenological hermeneutics. The first and second studies involved a group of patients living with chronic heart failure. For the fi rst study, 10 patients were interviewed, with a narrative approach, about their experience of participation and non-participation, as defi ned by the participants. For the second study, 11 visits by three patients at a nurse-led outpatient clinic were observed, and consecutive interviews were performed with the patients and the nurses, investigating what they experience as patient participation and non-participation. A triangulation of data was performed to analyse the occurrence of the phenomena in the observed visits. For paper 3 and 4, a questionnaire was developed and distributed among a diverse group of people who had recent experience of being patients. The questionnaire comprised respondent’s description of what patient participation is, using items based on findings in Study 1, along with open-ended questions for additional aspects and general issues regarding situations in which the respondent had experienced patient participation and/or non-participation. The findings show additional aspects to patient participation: patient participation is being provided with information and knowledge in order for one to comprehend one’s body, disease, and treatment and to be able to take self-care actions based on the context and one’s values. Participation was also found to include providing the information and knowledge one has about the experience of illness and symptoms and of one’s situation. Participation occurs when being listened to and being recognised as an individual and a partner in the health care team. Non-participation, on the other hand, occurs when one is regarded as a symptom, a problem to be solved. To avoid non-participation, the information provided needs to be based on the individual’s need and with recognition of the patient’s knowledge and context. In conclusion, patient participation needs to be reconsidered in health care regulations and in clinical settings: patients’ defi nitions of participation, found to be close to the dictionaries’ description of sharing, should be recognised and opportunities provided for sharing knowledge and experience in two-way-communication.

Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.    The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.    This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.    In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.    Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease

Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.