Box 1.

Take home messages on MNA

MNA is associated with increased risk of rejection, allograft loss, patients’ death and higher healthcare costs.

The degree of MNA, which can influence the clinical outcomes and that requires a specific treatment strategy, is not defined

MNA risk factors are associated with patients, therapy, disease characteristics, healthcare organization, and socioeconomic and cultural characteristics. Some of these factors can be modifiable and represent the corner of treatment strategies.

Because MNA can appear/worsen during extremely stressful moments or anytime, it must be constantly monitored. Since risk factors can vary at any moment, different strategies may need to be adopted in the same patient.

Intentional MNA, which is characterized by a—usually unrecognized—deliberate refusal to comply with the prescribed therapy, is hard to diagnose and treat. These patients are hardly included in clinical trials. Constant motivational-behavioural interventions may represent the only viable resource to prevent and treat intentional MNA.

Unintentional MNA is characterized by non-deliberate reduced adherence to the prescribed therapy. It is easier to diagnose and to treat. Unintentional MNA diagnostic tools might occasionally be oversensitive.

Strategies that have been assessed for the prevention and treatment of MNA include: - the commitment of healthcare personnel involved in drug distribution (i.e. pharmacist, nurses) - the use of electronic reminders (i.e. alarmed drug container, phone alarms and Apps) - therapy simplification - multidisciplinary approaches (i.e. nurses, psychologists, medical doctors and trained therapy coaches) to maximize the correction of individual risk factors.

Overall, they were shown to improve MNA, but the effect generally vanished thereafter. Moreover, no trial published so far has shown any improvement in clinical outcomes. Lack of benefit may be related to failure to include MNA patients because of the ‘streetlight effect’