The role of health literacy in the onset and accumulation of multimorbidity and its related outcomes: a mediation model

Multimorbidity: a challenge for patients, healthcare organizations and society 
Multimorbidity is associated with a negative impact on the quality of life, worse health outcomes, higher use of healthcare, and higher mortality rates(1-5). Multimorbidity is defined as the presence of two or more co-occurring chronic diseases(6). In a high-income country such as the Netherlands the prevalence of multimorbidity is estimated to be 13% to 35% of the population(7), with the higher end corresponding to elderly populations. In particular, older people, people with lower levels of educational attainment, people with lower socioeconomic status, and people with a migration background or from minority communities are at risk of developing multimorbidity (8-11). The most prevalent combination of diseases among patients living with multimorbidity are diabetes mellitus and heart diseases (e.g. hypertension, heart failure, coronary heart disease) (7, 12). Hypertension with a global prevalence of around 32%, (1) is one of the main risk factors for the onset of multimorbidity (2, 3). Despite the increase in hypertension early detection and adequate medical and lifestyle treatment, a decrease in efficient illness control continues to be a relevant public health problem. Large differences in illness outcomes among some patients are still observed, for example earlier onset or accumulation of multimorbidity (13, 14).  
Multimorbidity represent a great challenge because of the complex care needs patients with multimorbidity experience. On one hand, at individual-level, patients with LHL face difficulties dealing with the complexity and the demands of healthcare systems (15, 16). Specially, patients with LHL and multimorbidity may perceive a high treatment burden with a detrimental effect on their quality of life. Patients with multimorbidity and LHL may have to deal with different treatments and recommendations their diseases require. For example, these can all be prescribed by different healthcare providers in different settings. In addition, this kind of situation can lead to some of the most common problems with polypharmacy, such as adverse effects due to interactions between medications that were not taken into account by all the different professionals, and non-adherence to treatment (17). On the other hand, multimorbidity consequences at health system-level are broad and vary in severity, going from a higher number of medical specialties visits, frequent hospital admissions and longer hospital stays and premature mortality, which ultimately means higher costs for the healthcare organization (13, 18-20). Furthermore, reported societal consequences of patients with multimorbidity include less ability to work, leading to either a decrease in productivity, and potentially an increase in loss of employment, or an increased difficulty to get employment (21-23). Thus, leaving patients living with multimorbidity without the ability to be self-sufficient.
Health literacy and multimorbidity
A shared characteristic or problem of patients with multimorbidity is limited health literacy. Limited health literacy can be understood as inadequate abilities to access, understand and use of medical information to stay healthy (24). According to the European Health literacy survey, almost 30% of the population in The Netherlands has limited health literacy (25). Limited Health Literacy (LHL) is strongly associated with multiple negative health outcomes for patients. These include earlier onset of disease, faster progression of diseases and multimorbidity, all of which can lead to higher rates of hospitalization, higher mortality rates, and higher health care costs (26-29). LHL has been recognized as a strong contributor to health inequalities (28). Patients with LHL and at higher risk for multimorbidity, as patients with hypertension, may experience less effective skills and adequate health behaviors to deal with their illness, resulting in the onset and accumulation of multimorbidity and adverse multimorbidity related outcomes. Therefore, insights in mediating factors in different contexts are warranted to serve as input for a future health literacy-specific intervention that contribute to better health outcomes for patients at risk of multimorbidity.
Insight in mediating factors to inform health literacy-specific interventions 
Healthcare organizations strive to provide better tailored care and treatment for patients living with multimorbidity. This has become an essential objective and a priority from the perspectives of patients, clinicians, and policy makers (2, 5, 21, 30). However, to our knowledge, there is a lack of robust evidence in the mediators of the relation between multimorbidity and health literacy, which can be considered potential targets for interventions to improve the health outcomes of patients with limited health literacy. These potential mediating factors consist of patient related factors and healthcare organizations related factors (31). 
First, individual factors include lifestyle and health behaviors like alcohol and tobacco consumption, physical activity, adherence to treatment, nutritional status and diet (1, 8, 9).  As well as, psychosocial factors as depression, anxiety and social support. Furthermore, it has hypothesized that patients with LHL may experience less effective self-management skills to develop and maintain these lifestyle changes, thus self-management might also be a key underlying mediating mechanism (32-34). Different models of self-management in patients with chronic illness have been described, including the common-sense model, the social cognitive model and the theory of planned behavior. Such models stablish that self-management skills include components such as motivation, problem solving (or self-regulation), self-efficacy beliefs and disease-related knowledge. Motivation and problem solving refers to the overall will, initiative and capacity to carry out a treatment plan, whereas self-efficacy beliefs, to the self-confidence to implement and control them (10). Second, healthcare organizational factors such as number of visits for medical attention, perceived time of consultation, perceived complexity of the information given by healthcare professionals and the organization, perceived navigation problems, perceived communication barriers might play a role (19, 22, 30) (see figure 1).