Individualized Medication Review in Older People: Differences Due To Place of Residence Being Their Own Home or A Nursing Home

Background: Ageing is associated with complex and dynamic changes leading to multimorbidity and, therefore, polypharmacy. A periodic medication review in frail older people lead to optimize medication use. The aims of the study were to identify inappropriate prescription and to assess the results of a medication review in older people, according to their place of residence. Methods: This was a study with paired pre- and post-medication review data based on person-centered prescription, with a follow-up assessment at three months. We recruited patients who lived in the community, either in their own home or in a nursing home. We select patients of 65 years or more with multimorbidity whom his General Practitioner identied diculties with the prescription management and the need of a medication review. Finally, a medication review was carried out through the application of the Patient-Centered Prescription model. Data collected were: age, sex, place of residence, morbidities, functional and cognitive status, frailty index, number of medications, therapeutical complexity, anticholinergic and/or sedative burden and monthly medication expenditure. The Chi-square test or Fisher's exact test were used to evaluate the relationship between qualitative variables and the patients’ place of residence. Student’s t-test was used to analyze the relationship between quantitative variables and the patients’ place of residence. Results: 428 patients. 90% of people presented at least one inappropriate prescription in both settings. In nursing homes, a higher number of implemented optimization proposals was detected (81.6% versus 65.7% (p<0.001)). Post-medication review, nursing-home patients had a greater decrease in their mean number of medications, polypharmacy prevalence, therapeutic complexity and in monthly medication expenditure (p<0.001). Conclusions: Patient-Centered Prescription model detected a high number of inappropriate prescriptions in both settings. However, once medication was reviewed and optimization proposals implemented, nursing-home patients presented


Background
In recent decades, the increasingly ageing population has brought with it a high prevalence of chronic diseases. As chronic diseases are associated with functional impairment and disability, a large number of older adults require daily assistance and are often placed in nursing homes [1].
When two or more chronic conditions coexist, it is known as multimorbidity. Elderly patients with multimorbidity often present frailty criteria, which is a common clinical syndrome that carries an increased risk of poor health outcomes [2]. Consequently, they usually require greater medical care and, as a result, polypharmacy (the concurrent use of ve or more medications [3]) is common among them.
Multimorbidity and polypharmacy are associated with an increased use of inappropriate prescriptions (IP), and, consequently, with a higher risk of suffering adverse drug reactions (ADR) [3].
Given the marked vulnerability of frail patients, there is concern and evidence they may not bene t from intensive management of chronic conditions in the same way as study populations do. Therefore, it becomes essential to ensure that the bene t of treatment outweighs the harm it may do to very vulnerable patients, in whom the risk of side effects may be particularly high [3].
Therefore, it becomes necessary to establish a periodic Medication Review (MR) for frail elderly patients, which is a structured evaluation of patient's medicines with the aim of optimizing medication use and improving health outcomes. This entails detecting medication-related problems and recommending interventions [4].

Study objectives:
To study the frailty characteristics of the analyzed population To identify inappropriate prescriptions in older patients and to assess the results of a medication review based on a patient-centered prescription model, in terms of polypharmacy, therapeutical complexity and anticholinergic and sedative burden and, monthly medication expenditure.
To study the implementation of proposals to optimize medications, differences according to their place of residence.

Design
It was a study with paired pre-and post-MR data, with a follow-up assessment at three months. We recruited patients who lived in the community, either in their own home or in nursing home, from a semiurban area in Catalonia (Spain).

Participants
Patients were consecutively considered for inclusion if they met the following eligibility criteria: older people (≥ 65 years) with multimorbidity (two or more morbidities) to whom his General Practitioner identi ed di culties with the prescription management and the need of a MR from a consultant team (make up from a geriatrician and a clinical pharmacist). Patients in their probable last hours or days of life were excluded.
From June 2019 to October 2020, potential participants were enrolled in the study of informed consent was provided by them, or their main caregiver in case of them being unable to provide consent, as approved by ethics committee. To identify the cohort, it was called Community Elderly Patients cohort (CEP cohort).

Data Collection
Personal data: Age, gender, and place of residence.
Functional data: Dependence/independence for medication management. Dependence/independence for basic activities of daily living (Barthel Index (BI) [5]).
Medical data: the morbidities (from the expanded diagnostic clusters within the Johns Hopkins University ACG system [6]) and age-adjusted Charlson Index [7]. Dementia diagnosis, as stated in the medical records, and the degree of deterioration was established in accordance with GDS (Global Deterioration Scale) [8]; Blood pressure levels available in the last year. Geriatric syndromes.
Analytical data: Full blood count, ionogram, urea and electrolytes. Also, glycosylated haemoglobin (HbA1c) available in the last year.
Identi cation of end-of-life patients (EOL patients) (NECPAL CCOMS-ICO© [11]): these were patients considered to be in the nal months or year of their life. The criteria used to identify them a were: i) identi cation as such by their primary care physician, ii) advanced illness criteria [11] or iii) frail-VIG index > 0.50.
Individual main therapeutic goal: According to their baseline situation, a therapeutic aim was established: i) survival, in patients with a t baseline situation; ii) maintaining functionality, in patients with an intermediate baseline situation; and iii) symptomatic control in the most vulnerable patients (patients in EOL situation should be included).
Monthly medication expenditure: overall expenditure for public health care insurance was taken into consideration (without patient contribution).

Medication review:
Each patient's treatment was analyzed by applying the Patient-Centered-Prescription (PCP) model [14]. This is a systematic 4-stage process, carried out by a multi-disciplinary team formed by patient's General Practitioner and the nurse with a consultant team (a geriatrician and a clinical pharmacist). The model centers therapeutic decisions on the patient's global assessment (comprehensive geriatric assessment (CGA), the calculation of the FI) and the resulting individual main therapeutic goal. These decisions were taken in conjunction with the patient or with the main caregiver in cases of incapacity according to the baseline situation (Fig. 1).
Criteria used to determine IP: the following recommendations were used to identify IP in the most prevalent chronic conditions [14]: Patients at the end of life (according to NECPAL CCOMS-ICO© [11]): the indication of medications aimed at prolonging survival was reassessed. Medications for primary prevention were evaluated for potential discontinuation and those for secondary prevention were individualized in accordance with patient goals [15].  (Table 1). ii) Qualitative criteria regarding drug prescription to consider inappropriate prescription: The prescription of sulphonylureas (SU) was considered inappropriate due to their high risk of hypoglycemia [17,18]. Patients with doses of metformin not adjusted for renal failure [17]. And the use of insulins associated with the highest risk of hypoglycemic episodes (short-acting insulins, mixtures and postprandial use) was considered inappropriate, except in justi ed cases [17]. Hypertension and cardiovascular therapy: it is recommended less intensive control in people with multimorbidity, especially in cases of dementia or limited life expectancy [19]. We proposed measures for pharmacological adjustment in end-of-life patients whose mean systolic blood pressure (SBP) was under 130 mmHg in the last year [15].
Dyslipidemia: statins are not recommended in end-of-life patients [15], regardless of the indication, especially for primary prevention. In addition, withdrawal of lipid-lowering medication was suggested for people who had total cholesterol (TC) lower than 150mg/dl, given that it is a malnutrition marker [20].
Mental health and Dementia: the recommendations of the European Association of Palliative Care were followed. They de ne a different therapeutic objective in patients with dementia according to the evolutionary stage of their pathology [21]. Regarding chronic antipsychotic treatment, the progressive decrease in doses was proposed in people who had not had behavioral disorders in last 3-6 months [15,22].
Pain: in accordance with Beers/STOPP criteria, the following proposals were made [18, [23][24][25]: i) Tricyclic antidepressants to treat neuropathic pain were avoided, due to their anticholinergic effects. ii) Non-steroidal anti-in ammatory drugs (NSAID) were recommended at the lowest dose and for the shortest time possible. iii) Weak opioids such as tramadol and codeine were recommended only at low doses. iv) Major opiates, such as morphine or oxycodone, should always be combined with a laxative. v) Meperidine is not recommended because of its anticholinergic potential Osteoporosis: it is recommended to withdraw treatment with calcium supplements (except in cases where symptomatic hypocalcemia is being treated), vitamin D or antiresorptive drugs [15] in patients identi ed as at the end-of-life.

Discussion
The study describes a sample of elderly patients from a speci c health region. Globally, the feminization of old age shown in this study, and its rising emphasis as age increases, is a trend described worldwide [27].
The differences detected in the baseline status in institutionalized patients compared to those living at home are similar to those described in other studies [14,28]. It is remarkable that more than half of the people living in nursing homes are identi ed as end-of-life, a higher proportion than that observed in other national and international studies [29,30]. The nding of a higher number of comorbidities in patients living at home is not shared with the rest of the literature [29]; it can be related to less clinical data collection among nursing-home patients than people living at home. However, this data supports the accepted concept that the biggest difference between patients living in nursing homes and those living at home is not the number of diagnoses but the fact that they all present dependence and frailty, which are the characteristics that most determine a high degree of di culty to continue living at home [29].
In accordance with higher degree of frailty detected in the nursing-home setting, a higher proportion of people needed to prioritize a conservative therapeutic aim.
Regarding baseline pharmacological data, contrary to known evidence [26], greater polypharmacy was detected in patients living at home. This can be explained by the fact that these nursing homes had had the possibility of requesting a support work from the territorial geriatrics service in previous years, prior to consultant team (geriatrician and a clinical pharmacist) for this current research. Therefore, although there might had been a turnover of residents during this period, these nursing homes present better gures in terms of polypharmacy than those usually documented in the bibliography.
Regarding DBI, the highest DBI detected in nursing homes does coincide with the rest of the studies [29], and can be explained by the higher prevalence of patients with some degree of cognitive impairment.
Post-MR DBI shows a relevant decrease in both settings, with no statistical differences. This is likely to be related to the higher prevalence of patients with cognitive impairment in nursing homes [14,29].
Post-MR outcomes are especially remarkable, because despite nursing-home residents having a lower average of chronic medications, they presented the same proportion of IP as patients living at home.
Other studies conducted in the nursing home setting have also detected a prevalence of around 90% of IP [14]. Overall, this could suggest that MR in the frailest patients is a bene cial practice, regardless of their average of chronic medications.
It is important to note that a greater number of proposals for pharmacological optimization had been implemented to nursing-home patients than to patients living at home. As a result, there was a greater decline in data related to polypharmacy and therapeutic complexity among nursing-home patients.
Overall, it is important to highlight that the PCP model leads to an increase in the prescription quality with a lower cost -as a result. Thus, the PCP model could be a value-based care, especially in nursing homes. Two main reasons could justify nursing homes as a suitable setting for promoting proper medication optimization: the higher prevalence of patients in end-of-life situation in nursing homes, which is the period of life with most evidence of medication optimization, and the close relationship between physicians, nurses, caregivers and family members that exists in nursing homes, which facilitates the progressive implementation of pharmacotherapeutic proposals and also enables a closer clinical followup.

Conclusions
We can conclude that up to 90% of older people with multimorbidity presented at least one IP, regardless of their place of residence. However, after an individualized medication review, nursing-home patients Consent to participate and consent for publication: Informed consent was obtained from all individual participants included in the study.
Con icts of interest / Competing interest: all authors declare that they have no con icts of interest relevant to the content of this manuscript.
Funding: This study was granted a 'PERIS'-research program, funded by the Health Department of the Catalan Government ( le numbers SLT008/18/00139 and SLT008/18/00152). The funding organization was not involved in the study design, data collection, analysis, and interpretation, writing of the manuscript and submission for publication. No other sources of funding were used to assist in the conduct of this study or preparation of this manuscript.
Authors' contribution: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Molist-Brunet N, Sevilla-Sánchez D, Puigoriol-Juvanteny E, Bajo-Pena L, Cantizano-Baldo I, Cabanas-Collell L and Espaulella-Panicot J. The rst draft of the manuscript was written by Molist-Brunet N and all authors commented on previous versions of the manuscript. All authors read and approved nal manuscript.