Introduction

Noncommunicable diseases (NCDs) are the most frequent pathologies affecting the older population and are associated with high morbidity and disease burden [1]. In the last decades, clinical management of NCDs has made significant advancements. As a consequence, the prevalence of NCDs has increased, and older people are more and more likely to use multiple medications for the long-term management of NCDs and to have complex drug regimens [2]. In the real clinical world, this scenario may negatively affect medication adherence that, in older and multimorbid adults, has been estimated to be only around 50% [3,4]. According to the definition by the World Health Organization, medication adherence is “the extent to which a person’s behavior—taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider” [5]. Medication non-adherence can be intentional when the patient voluntarily decides not to follow medical recommendations or unintentional if it results from forgetfulness or not fully understanding medical instructions [6]. Medication non-adherence can also be classified based on the timing of medical prescriptions. In particular, primary medication non-adherence concerns newly prescribed treatments that have never been initiated, while secondary non-adherence includes behaviors leading to not correctly taking the medications when prescriptions are filled [7].

Medication adherence is a crucial issue after hospital discharge since changes in medication regimes or therapeutic requirements may represent new at-home challenges for patients and caregivers. Previous evidence showed that 56% of individuals aged 70 years or older reported discrepancies between the instructions received and their actual home medication just after 48 hours from discharge [8].

Scarce medication adherence represents a substantial risk factor for morbidity, mortality, and poor quality of life and is associated with high healthcare costs due to the lack of disease control and the need for hospitalizations [9–12]. There are different factors affecting medication adherence in the geriatric population: among patient-related factors, cognitive and psychological disturbances, poor health literacy, lack of medication knowledge, and misunderstanding of verbal instructions; among physician-related factors, poor communication; and, among system-based factors, lack of patient’s education [13]. An evidence-based review of randomized controlled studies found that behavioral/educational, pharmacist-led or reminder/simplification interventions can improve medication adherence in older adults [14]. Moreover, reports from different medical settings have shown that appropriate physician-patient communication on the diagnosis and treatment plan and shared decision-making could positively influence medication adherence and health-related outcomes [15].

To explore these issues in the older population, we designed a project to primarily test the effectiveness of a multidisciplinary intervention (vs. usual care) on adherence to medical recommendations in older inpatients after hospital discharge. Secondary aims were 1) to evaluate whether a multidisciplinary intervention could reduce the risk of incident falls, emergency department accesses, rehospitalizations, and mortality within the first three months after hospital discharge; 2) to assess the comprehension of medical recommendations of older patients (or their caregivers) at hospital discharge; and, 3) to identify the factors influencing poor comprehension and adherence to medical recommendations in older people.

Materials and methods

Study design and participants

In this randomized controlled clinical trial (RCT), participants will be recruited according to the following inclusion criteria:

• Patients (≥60 years old) admitted to the Geriatric Units of the University Hospitals of Padua (Italy) and Ferrara (Italy);
• Patients who will be discharged home;
• Patients for whom the expected survival is >7 days (considering that the study outcomes are assessed at 7, 30, and 90 days from hospital discharge and that patients with very short expected survival who are discharged at home usually are under palliative care, managed by a specialized team);
• Acquisition of informed consent to participate in the study.

Patients transferred to other medical wards or discharged to long-term care facilities will be excluded.

For all those patients who are unable to manage therapy themselves at home, caregivers will be involved. Participants giving their consent will receive a detailed explanation of the project, its phases, and the purposes of the study. After hospital discharge, the total observation period for each study participant will be 90 days, as illustrated in Fig 1.

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Fig 1. Flow-chart of the study.

https://doi.org/10.1371/journal.pone.0297238.g001

The APPROACH study protocol was approved by the Ethical Committee of the Padua Province for the coordinating center (Geriatric Unit, Department of Medicine, University of Padua, n. 5037/AO/21) and the Ethical Committee of the Area Vasta Emilia Centro della Regione Emilia-Romagna (CE-AVEC) for the collaborating center (Geriatric Unit, Department of Medical Sciences, University of Ferrara, n. 947/2021/Sper/AOUFe). All participants and, when applicable, their caregivers signed a written informed consent for participating in the study. The project complies with the principles of the Declaration of Helsinki.

Study assessments

Participants will undergo the following assessments (for a graphic summary, please see Fig 2):

1. Phase 1: data from the comprehensive geriatric assessment and additional information about the patient stay, prescribed therapies, health literacy, and sociodemographic characteristics of the caregiver (when applicable) will be collected at hospital discharge by trained researchers.
2. Phase 2: patients’ (or the caregivers, when applicable) understanding of medical recommendations before and after the explanation by the attending physician will be assessed at hospital discharge.
3. Phase 3: Participants will be randomly assigned to an intervention or control group.
4. Phase 4: After 7 days, adherence to medical recommendations at hospital discharge will be assessed through phone interviews with patients (or their caregivers, when applicable).
5. Phase 5: After 30 and 90 days, data on accidental falls, emergency department visits, rehospitalizations, and vital status will be collected both by accessing medical records and through phone interviews. During these interviews, the psychosocial impact of assistive technology will also be assessed.

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Fig 2. Timeline of the intervention and study assessments.

Abbreviations: CGA, Comprehensive Geriatric Assessment.

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Data collection

Trained researchers at the Geriatric Units of the University Hospitals of Padua (Italy) and Ferrara (Italy) will collect data through the administration of structured interviews and standardized scales and questionnaires (for the complete list of the assessed variables, please see Table 1). For each scale or questionnaire, we will use the corresponding Italian version validated or used in previous studies.

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Table 1. List of the domains evaluated and the used instruments.

https://doi.org/10.1371/journal.pone.0297238.t001

Participants’ characteristics.

At hospital discharge (Phase 1), participants will be assessed about sociodemographic data (age, sex, educational level, previous work, marital status, number of living children, living arrangement) and current (cause and duration of the hospitalization) and anamnestic clinical status (Cumulative Illness Rating Scale [16] [CIRS], number and type of medications used before the hospital admission). Moreover, data from the routine multidimensional geriatric assessment will be recorded, including the evaluation of cognitive function (Short Portable Mental Status Questionnaire [17] [SPMSQ]), nutritional status (Mini Nutritional Assessment—Short form [18] [MNA-SF] and anthropometric data, such as body weight and height, waist, mid-arm, and calf circumference), risk of developing pressure ulcers (Exton-Smith Scale [19] [ESS]) and functional ability (Activity of Daily Living (ADL) [20] and Instrumental ADL [21] [IADL]). In addition, participants will be evaluated concerning frailty (FRAIL questionnaire [22]), sarcopenia (SARC-F questionnaire, handigrip [23]), medication adherence before the hospitalization (4-item validated Morisky, Green, Levine scale [24], and Medication adherence report scale [25] [MARS-5]), health literacy [26] (Brief health literacy questionnaire), and the psychosocial impact of assistive technology on participants who will be using any device (Psychosocial Impact of Assistive Devices Scale [27] [PIADS]).

Primary and secondary outcomes.

At hospital discharge (Phase 2), researchers will interview the patients (or their caregivers, when applicable) about the comprehension of the medical recommendations reported in the discharge summary. In particular, before and after the explanation of the medical recommendations by the physician, possible mistakes in the understanding of prescriptions will be recorded and classified based on the fact they concern the identification (e.g. do not spell the drug correctly or do not know the role of the medication), dosage, number of administrations, and time of administration of each drug.

After 7, 30, and 90 days from hospital discharge (Phase 4 and 5), patients will undergo a phone interview lasting approximately 30 minutes to obtain information on the ongoing treatments (recording name, dose, and administration time of the therapies taken). In particular, for each medical recommendation included in the discharge summary, we will assess whether the patient follows that prescription by taking the correct drug at the correct dosage and administration time. From the ratio between the number of medications taken with full adherence and the total number of prescriptions included in the discharge summary, we will derive the proportion to which the patient adheres to the given medical recommendations (primary outcome). As an additional measure of medication adherence, we will consider the results at the 4-item validated Morisky, Green, Levine scale [24] and MARS-5 [25].

Moreover, data on incident falls, hospitalizations and vital status will be recorded from phone interviews and medical records at the local hospitals. These outcomes were selected in light of the current literature supporting the impact of poor medication adherence on the risk of accidental falls and the need for medical attention [26,27]. At the 30- and 90-day follow-up, the psychosocial impact of assistive devices will be evaluated with the PIADS instrument.

Discussion

This project aims to underline the importance of a comprehensive evaluation and communication with older people that may help clinicians plan personalized interventions, better control chronic conditions, and support capacity-enhancing behaviors [29]. Overall, this should facilitate the recovery of older adults after hospital discharge by improving their medication adherence and functional abilities at home.

It is common for older patients at hospital discharge to be unable to recall their diagnoses and the names, roles, and adverse effects of the prescribed medications [14,15]. In particular, written discharge instructions alone have emerged as poorly understood by approximately 45% of patients [17]. To address this issue and in light of the gaps arising from some reviews on this topic [14,15], we have proposed a project that may be novel and relevant for clinical practice.

First, different from previous studies that focused on the effectiveness of a single domain investigation (behavioural/educational, pharmacist-led, reminder/simplification [14]), the project will test the potential benefits of a multidimensional approach in improving medication adherence. This approach is more likely to identify the multiple factors influencing patients’ adherence to medical recommendations, including not only sociodemographic and health characteristics but also cognitive or functional deficits [13]. As suggested by a recent consensus, tackling the complexity of non-adherence would require a multi-stakeholder, patient-centered approach that should involve different players and services [15]. Training health professionals on communication skills will facilitate achieving the goals in these first steps and may increase physician and patient satisfaction, reduce burnout, and support therapeutic alliance [30,31]. Moreover, this multidisciplinary intervention of the study participants may positively influence patients’ in different health domains and allow us to identify factors that, interacting with medication adherence, could influence health-related outcomes in such individuals. Indeed, by improving adherence to medical recommendations, we expect to find also a lower risk of adverse health-related outcomes (i.e., falls, hospitalizations, and mortality).

Second, in addition to its multidisciplinary nature, the proposed intervention is characterized by low costs, low technologic requirements −which, to date, may still be a factor that hampers the adherence of patients in the oldest classes of age in Italy− and easy implementation. These features strengthen the feasibility of this intervention in a real-life setting.

Third, another strength of this project is the use of different methods to comprehensively capture the level of the patient’s adherence to medical instructions at hospital discharge since studies on the topic have shown a wide heterogeneity in this assessment. As suggested by current guidelines [32], patients’ adherence will be estimated using multiple assessment methods based on structured face-to-face interviews and validated scales.

On the other hand, among the possible obstacles to the project implementation are difficulties in participants’ enrolment and attrition. In particular, the enrolment of the study participants and the project’s activities could be slowed down by the COVID-19 pandemic, whose related restrictions could hamper the interactions between different health professionals and the communication with patients’ caregivers. Moreover, randomization is not performed by the enrollment site, and this cannot completely rule out that part of the trained team may explain the medical recommendations to the control group more extensively than usual during the routine discharge meeting. This issue could eventually lead to an underestimation of the effectiveness of the intervention. However, the components of further explanation and recall of the medical recommendations solely characterize the intervention and represent a decisive addition to the routine practice that could positively influence patients’ adherence.

Overall, the study will benefit our primary audience, namely the patients involved, and may also offer helpful information and support to caregivers of clinically complex individuals. It could also provide useful insights for implementing this integrated care model in different settings. For instance, a possible project extension will be integrating this multidisciplinary intervention at hospital discharge with a closer involvement and collaboration of general practitioners. In that way, patients’ functional recovery after hospital discharge will be further promoted by strengthening the continuum between secondary and primary care.

As regards the dissemination activities, the results of this project will lead to the production of scientific papers that will be submitted for publication in international biomedical journals. The participation of study team members in national and international conferences will offer a further opportunity to disseminate the results of our project and their potential implications. Physicians working at the local hospital will be updated over the study period on the ongoing project and, after its end, will be invited to a dedicated seminar to show the study results and to increase awareness of the importance of adequate communication and education of the patient at hospital discharge by experts in communication and skilled pharmacologists. Moreover, the team will organize educational events to present the study findings and stress the importance of full adherence to medical recommendations to promote healthy ageing.

Conclusions

In conclusion, the APPROACH trial will test the effectiveness of a multidomain intervention with an integrated care approach to improve the comprehension and adherence to medical recommendations of older people at hospital discharge, compared with usual care. This intervention is expected to facilitate the returning home and functional recovery of older patients after hospital discharge and influence other health-related outcomes, reducing the risk of accidental falls, hospital readmissions, and mortality.

Supporting information

Acknowledgments

we are grateful to the APPROACH working group: Viviana Bagalà (University Hospital of Ferrara, Ferrara, Italy), Simone Balanzoni (University Hospital of Ferrara, Ferrara, Italy), Elena Barbieri (University Hospital of Ferrara, Ferrara, Italy), Valentina Bernardi (University of Padua, Padua, Italy), Anna Bertocco (University of Padua, Padua, Italy), Francesca Bizzotto (University of Padua, Padua, Italy), Marianna Boccafogli (University Hospital of Ferrara, Ferrara, Italy), Carlotta Bortoluzzi (University of Padua, Padua, Italy), Alessandra Cannata (University of Ferrara, Ferrara, Italy), Fabio Celi (University of Padua, Padua, Italy), Francesca Cera (University of Padua, Padua, Italy), Andrea Cignarella (University of Padua, Padua, Italy), Chiara Curreri (University Hospital of Padua, Padua, Italy), Francesca Curri (University of Padua, Padua, Italy), Laura Dal Gesso (University of Padua, Padua, Italy), Marina De Rui (University Hospital of Padua, Padua, Italy), Maria Devita (University of Padua, Padua, Italy), Benedetta Di Marzio (University of Padua, Padua, Italy), Nicolò Gentili (University of Padua, Padua, Italy), Andrea Grandieri (University Hospital of Ferrara, Ferrara, Italy), Alessandro Lazzarin (University of Padua, Padua, Italy), Maria Leonardo (University Hospital of Ferrara, Ferrara, Italy), Federica Limongi (Institute of Neuroscience, National Research Council, Padua, Italy), Serena Lorenzo (University of Padua, Padua, Italy), Lisa Marzano (University Hospital of Ferrara, Ferrara, Italy), Eleonora Mizzon (University of Padua, Padua, Italy), Marianna Noale (Institute of Neuroscience, National Research Council, Padua, Italy), Giulia Pampolini (University Hospital of Ferrara, Ferrara, Italy), Federica Piccione (University of Padua, Padua, Italy), Nicola Rampon (University of Padua, Padua, Italy), Francesca Remelli (University of Ferrara, Ferrara, Italy), Alberto Rossi (University of Padua, Padua, Italy), Arianna Sala (University Hospital of Ferrara), Sara Sambo (University of Padua, Padua, Italy), Claudia Sartori (University of Padua, Padua, Italy), Giuseppe Sergi (University of Padua, Padua, Italy), Paola Siviero (Institute of Neuroscience, National Research Council, Padua, Italy), Silvia Sturani (University of Padua, Padua, Italy), Sara Tamascelli (University of Ferrara, Ferrara, Italy), Giulia Tasso (University of Padua, Padua, Italy), Marta Tinazzo (University of Padua, Padua, Italy), Caterina Trevisan (University of Ferrara, Ferrara, Italy; University of Padua, Padua, Italy), Jessica Vanin (University of Padua), Federico Vezzali (University Hospital of Ferrara, Ferrara, Italy), Stefano Volpato (University of Ferrara, Ferrara, Italy), Bruno Micael Zanforlini (University Hospital of Padua, Padua, Italy).