Intern Emerg Med
DOI 10.1007/s11739-014-1124-1
Multimorbidity and polypharmacy in the elderly: lessons
Pier Mannuccio Mannucci • Alessandro Nobili
REPOSI Investigators
Received: 1 July 2014 / Accepted: 20 August 2014
Ó SIMI 2014
Abstract The dramatic demographic changes that are
occurring in the third millennium are modifying the mission of generalist professionals such as primary care physicians and internists. Multiple chronic diseases and the
related prescription of multiple medications are becoming
typical problems and present many challenges. Unfortunately, the available evidence regarding the efficacy of
medications has been generated by clinical trials involving
patients completely different from those currently admitted
to internal medicine: much younger, affected by a single
disease and managed in a highly controlled research
environment. Because only registries can provide information on drug effectiveness in real-life conditions,
REPOSI started in 2008 with the goal of acquiring data on
elderly people acutely admitted to medical or geriatric
hospital wards in Italy. The main goals of the registry were
to evaluate drug prescription appropriateness, the relationship between multimorbidity/polypharmacy and such
cogent outcomes as hospital mortality and re-hospitalization, and the identification of disease clusters that most
often concomitantly occur in the elderly. The findings of
3-yearly REPOSI runs (2008, 2010, 2012) suggest the
following pertinent tasks for the internist in order to
REPOSI denotes the REgistro POliterapie SIMI, Società Italiana di
Medicina Interna. The participating units and co-authors are listed in
the Appendix.
P. M. Mannucci (&)
Scientific Direction, IRCCS Foundation Maggiore Hospital
Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
e-mail: piermannuccio.mannuc[email protected]
A. Nobili
Department of Neuroscience, IRCCS Istituto di Ricerche
Farmacologiche Mario Negri, Milan, Italy
optimally handle their elderly patients: the management of
multiple medications, the need to become acquainted with
geriatric multidimensional tools, the promotion and
implementation of a multidisciplinary team approach to
patient health and care and the corresponding involvement
of patients and their relatives and caregivers. There is also
a need for more research, tailored to the peculiar features of
the multimorbid elderly patient.
Keywords Multimorbidity Polypharmacy Aging Drug prescription Multidimensional evaluation Adverse
drug effects
Elderly people with multimorbidity will number around
75 million people in 2050 in Europe, representing more
than 10 % of the entire population [1, 2]. The president of
the Italian Society of Internal Medicine (SIMI) [3] has
recently emphasized a new mission for the internist of the
third millennium, triggered by the shift from the care of
diseases occurring in relatively young people, and mainly
affecting a single organ or system to that of multiple
chronic diseases in the elderly, with the related need for
polypharmacy. Because of this evolving epidemiological
picture, SIMI chose to initiate in 2007 a collaboration
with the IRCCS Mario Negri Institute for Pharmacological Research of Milan and IRCCS Ca’ Granda Foundation
of Milan, with the broad goal of collecting information on
the clinical characteristics and patterns of drug prescription in people older than 65 years of age admitted to
internal medicine and geriatric hospital wards run by
SIMI constituents. The strategy chosen to achieve this
goal was a prospective, non-interventional, multicenter
Intern Emerg Med
Background and issues
Fig. 1 Organization of REPOSI. Asterisk means available form
2010; double asterisk available from 2012
registry (REPOSI, i.e., REgistro POliterapie SIMI),
designed to collect a set of clinical and laboratory data on
elderly patients consecutively hospitalized during 4 index
weeks (one for each season) in 3 years (2008, 2010 and
2012). The data set contained sociodemographic features,
diagnosis on hospital admission and at discharge,
comorbidities and intercurrent clinical and pharmacological adverse events. Moreover, the number and types of
drugs prescribed on admission and discharge were
recorded. After discharge, additional follow-up data were
collected via telephone calls at 3 and 12 months (Fig. 1
shows the main steps of REPOSI).
Figure 2 shows the flowchart of the 4,035 cases included
so far (2008–2010–2012) by 95 medical or geriatric wards
from all over Italy, while Table 1 shows the main characteristics of enrolled patients, who are an accurate and
actual picture of the ill people admitted to hospital wards of
internal medicine and geriatrics. Their average age was
close to 80 years; nearly half of them had some degree of
dependence and a prolonged hospital stay after resolution
of the cause for acute admission. Not unexpectedly, they
took multiple medications. In the next sections of this
article we shall outline again the main issues related to the
management of the oldest adult which led SIMI, Mario
Negri and Maggiore Hospital to conceive and implement
REPOSI, the main data so far obtained in the frame of this
registry, what we have learned, and why the findings
prompt some challenges and changes pertaining to research
and clinical practice for the internist.
In Europe, people aged 80 years or more are the fastest
growing group, so that by 2060 they will be nearly 20 % of
the population [2]. This dramatic increase in life expectancy is a monument to the progress of medical sciences,
improvement in life styles, availability of innovative drugs
and implementation of the welfare state. However, successful aging is a formidable challenge for those responsible for healthcare strategies and the implementation of
the welfare state, with implications on labor markets, social
programs and family dynamics. For instance, a source of
great concern is the growing unbalance between the oldest
old and the still active citizens who must sustain the
societal burden of the latter. This unbalance is epitomized
by the progressive decrease of an index such as the ratio of
the number of active people between 40 and 60 years of
age to those aged 85 years or older. This ratio, as high as
31 in 1974, decreased to 14 in 2010, and is expected to be
as low as 5 in 2030 [4], also owing to the lowering birth
rate, particularly in high-income countries.
Aging is inevitably characterized by a multiplicity of
apparently independent chronic diseases in the same person. Multimorbidity must be distinguished from comorbidity, which defines clinical manifestations stemming as
complications of the clinical course of a clearly identified
index disease. In Italy, the prevalence of chronic diseases
has reached in 2012 the impressive rate of 38 % in those
aged more than 65 years, with values of 50 % at ages
75–85 and 64 % beyond 85 years [5]. Multimorbidity is
almost always accompanied by polypharmacy, the most
widely accepted definition of this situation pertaining to the
daily intake of five or more drugs [6]. According to the
Geriatrics Working Group of AIFA (Agenzia Italiana del
Farmaco), 1.3 million elderly Italians take more than 10
daily drugs, with the age group between 75 and 84 years
recording the highest intake: 55 % take between five and
nine drugs per day, 14 % take ten or more [7]. In terms of
expenditures, the older citizens absorb 60 % (15.7 billion
Euros) of the total cost of drugs (26.3 billions) [8].
Why is polypharmacy so widespread? Because physicians tend to follow the guidelines available for each of the
multiple diseases that affect the elderly, and hence prescribe all the drugs recommended for each disease.
Unfortunately, guidelines hardly take into account multimorbidity and polypharmacy, and clinical trials, i.e., the
basis for drug prescription according to evidence-based
medicine, usually enroll patients completely different from
the elderly: relative young, and highly selected for having
only the disease that is expected to benefit from the drug
under investigation [9]. Clinical trials do investigate a
disease, not the individual patient. Hence, they provide
evidence on efficacy, i.e., the extent to which a drug
Intern Emerg Med
Fig. 2 Flow-chart of the cohort
of 4,035 patients enrolled in
REPOSI. 1 Low quality of data,
2 follow-up not requested, 3
only for REPOSI 2012, 4 ten
wards were unavailable for
12-month follow-up
produces a beneficial effect under ideal conditions, but fail
to provide evidence on effectiveness under real-life circumstances [9, 10].
Polypharmacy is a formidable problem, with a number
of negative implications that are listed in Table 2. Because
20–65 % of the oldest adults take potentially inappropriate
medications, they are at an increased risk of adverse
reactions and hence of repeated visits to the hospital
emergency department (ED), admissions and readmissions
and deaths [11–13]. Some of these drugs may adversely
affect the course of a coexisting disease: a situation called
therapeutic competition, which occurs in at least one-fifth
of the older patients receiving multiple medications [14].
Commonly, complications and symptoms due to inappropriate drug intake are interpreted as the onset of new
conditions or diseases, that are often tackled adding more
drugs to the already existing burden (the so-called prescribing cascade) [15]. Moreover, prescribing errors, an
important cause of harm to patients, are much more likely
to occur when a greater total number of drugs are prescribed [16, 17].
A crucial aspect of appropriate drug prescription is the
need to bolster a patient-centered instead of the current
disease-focused approach, because the latter inevitably
leads to fragmentation in the management of the multimorbidity of the elderly by various specialists, and to the
inappropriate use of healthcare facilities. Centeredness
implies the engagement of older people, their relatives and
caregivers about options and values of treatments. Patients’
feelings and beliefs about their health, medical conditions
and treatment options are key determinants of whether or
not they will comply with the recommended medications.
The issue of adherence clearly highlights the importance of
consideration and in-depth discussion of preferences, in
general and particularly pertaining to the multimorbid
elderly people who use multiple drugs [18]. Many studies
Intern Emerg Med
Table 1 Main characteristics of 4,035 patients enrolled in the REPOSI Registry
Cohort characteristics
Number (N) of patients enrolled
Females, N (%)
721 (54.1)
696 (50.4)
672 (50.8)
Age (years), mean (SD)
79.3 (7.5)
79.0 (7.3)
79.3 (7.4)
409 (30.7)
430 (31.2)
403 (30.5)
607 (45.6)
650 (47.1)
583 (44.1)
316 (23.7)
300 (21.7)
337 (25.5)
Need of caregivers, N (%)
772 (56.5)
689 (52.1)
Number of diagnoses at admission, mean (SD)
4.3 (2.3)
5.8 (2.8)
5.7 (2.8)
Patients at admission with five or more diagnoses, N (%)
571 (42.9)
884 (64.1)
839 (63.4)
Number of drugs at admission, mean (SD)
Patients at admission taking five or more drugs, N (%)
4.9 (2.8)
689 (51.7)
5.3 (2.8)
805 (58.3)
5.4 (3.1)
778 (58.8)
Severity index at admissiona, mean (SD)
1.6 (0.3)
1.7 (0.3)
Age class, N (%)
Comorbidity index at admission , mean (SD)
2.9 (1.7)
3.1 (1.9)
Patients with Barthel index at admissionab
1,289 (94.4)
Barthel index at admission, mean (SD)
78.5 (29.2)
Complete dependence (0–24)
124 (9.6)
Severe dependence (25–49)
86 (6.7)
Moderate dependence (50–74)
167 (13.0
Mild dependence (75–90)
200 (15.5)
Groups according to Barthel index at admission, N (%)
712 (55.2)
Patients with Barthel index at hospital staya, N (%)
No or negligible dependence (90–100)
1,362 (98.7)
1,264 (95.5)
Barthel index at hospital stay, mean (SD)
76.8 (30.7)
72.6 (32.4)
Complete dependence (0–24)
155 (11.4)
169 (13.4)
Severe dependence (25–49)
Moderate dependence (50–74)
111 (8.2)
150 (11.0)
126 (10.0)
175 (13.8)
Mild dependence (75–90)
211 (15.5)
200 (15.8)
Groups according to Barthel index at hospital stay, N (%)
No or negligible dependence (90–100)
735 (54.0)
594 (47.0)
Patients with Short Blessed Testa, N (%)
1,339 (97.0)
1,217 (92.0)
Short Blessed Test, mean (SD)
9.9 (8.2)
9.2 (7.8)
Short Blessed Test, severe (10–28), N (%)
637 (47.6)
541 (44.5)
Patients with Geriatric Depression Scalea, N (%)
1,295 (93.8)
1,121 (84.7)
Geriatric Depression Scale, mean (SD)
1.4 (1.2)
1.4 (1.2)
Dead, N (%)
66 (5.0)
50 (3.6)
42 (3.0)
1,159 (87.6)
Patients discharged, N (%)
1,155 (86.7)
1,159 (84.0)
Number of diagnosis at discharge, mean (SD)
5.9 (2.5)
6.5 (3.0)
6.3 (2.8)
Patients at discharge with five or more diagnosis, N (%)
796 (68.9)
857 (73.94)
834 (72.0)
Number of drugs at discharge mean (SD)
6.0 (2.9)
6.3 (2.8)
6.4 (3.1)
Patients at discharge taking five or more drugs, N (%)
770 (66.7)
838 (72.3)
838 (72.3)
Severity index at discharge, mean (SD)
Comorbidity index at discharge, mean (SD)
1.7 (0.3)
3.0 (1.8)
1.7 (0.3)
3.2 (2.0)
Hospital stay days, mean (SD)
11.1 (8.5)
10.9 (8.2)
11.4 (8.5)
Pts patients
Data not collected in 2008
Data not collected in 2010
Intern Emerg Med
Table 2 Main risks related to polypharmacy
Adverse drug reactions and interactions
Exposure to potentially inappropriate medications
Under-prescribing of recommended drugs (‘‘treatment risk
Medication errors
Poor adherence
Cognitive and functional decline
Occurrence of geriatric syndromes (delirium, falls, incontinence,
behavioral disturbances, malnutrition, etc.)
More institutionalization
various stakeholders (family doctors, pharmacists, relatives, caregivers, and, most importantly, the patients
themselves). A simple approach to drug review is that of
asking some questions, listed as examples in Table 3.
Furthermore, one can choose among several available tools
that help to improve drug prescription, after having chosen
the most suitable for the actual patient [23, 24].
All in all, prescription criteria based upon guidelines and
evidence-based medicine are likely to often be inadequate
in the complex patient admitted to internal medicine wards
in the third millennium, as we shall see in the next sections.
Higher mortality
Greater costs
Main REPOSI findings and their clinical relevance
Table 3 Basic questions for medication review
Has a full medication history been collected?
How long ago has the latter been reviewed?
Are all drugs taken by the patient indicated and likely to be
Is the patient taking any inappropriate or incompatible
Are there actual drug(s) that could be discontinued? Are there
essential drugs that are not actually prescribed?
Are the dosage, dose frequency and formulation appropriate?
Is the patient at high risk of therapeutic competition?
Are drug interactions present?
Is the patient compliant with medications?
have demonstrated that patients’ values related to their
healthcare vary enormously, and differ significantly from
those of their physicians, relatives and caregivers [19].
Elderly people are often over-treated, because many
drugs provide at best a marginal effect in clinical outcomes
that truly matter. For example, anti-hypertension drugs are
perhaps used too widely, because after the age of 80 years
high blood pressure is not a prominent risk factor for stroke
[20]. On the other hand, anti-hypertension drugs may cause
hypotension, with the associated risk of falls in the frail
elderly. By the same token, statins have a modest role in
cardiovascular prevention, but may cause musculoskeletal
pain that facilitates falls [20] and reduces physical activity
in elderly people [21].
Hence, an important task for the internist and other
generalist medical professionals who take care of the
elderly (geriatricians, primary care physicians) is to critically review at regular intervals which drugs are really
needed for optimal patient benefit, and to consider the
option of deprescribing some drugs. On the other hand, in
some instances polypharmacy may lead to lack of prescription of essential medications (the so-called treatment
risk paradox) [22]. Medication revision should involve the
The pattern of results obtained in the frame of the first
3-yearly runs of the registry (2008, 2010, 2012) can be
broadly divided into those pertaining to the appropriateness
of drug prescription; and those on the relationship between
multimorbidity/polypharmacy and such outcomes as mortality in hospital, and soon after discharge, as well as rates
of hospital readmission. Other results pertain to the identification of the disease clusters that more often concomitantly occur in the elderly, their consistency over different
REPOSI runs, as well as the relationship between disease
clusters and clinical outcomes.
Appropriateness of drug prescription
Polypharmacy is inherently associated with a high risk of
inappropriate prescription. For instance, in 6 different
European countries inappropriate drug prescriptions ranged
from 22 to 77 % of hospitalized cases [25]. Pertaining to
the consequences of inadequate prescription, drug-related
adverse events are among the first five causes of in-hospital
death, admission to emergency departments and hospitalization [26, 27]. With this background, prescription
appropriateness was first tackled in REPOSI with reference
to the following frequently used medications: antithrombotic prophylaxis in atrial fibrillation and bedridden medical patients [28–30], proton pump inhibitors [31],
antidepressants [32] and drugs with anticholinergic effects
[33]. Collectively, these studies did show a high degree of
inappropriate prescription, not only at the time of hospital
admission (reflecting the prescriptions of general practitioners as well as patient adherence), but also at discharge
(reflecting the actual prescription of such specialists as
hospital internists and geriatricians). For instance, among
elderly patients with chronic atrial fibrillation, as many as
26 % at admission and 32 % at discharge were taking no
antithrombotic drug despite their high risk of cardioembolism, and 44 and 41 % were on inappropriate thromboprophylaxis according to the risk of embolism dictated by
Intern Emerg Med
the CHADS2 and related scores [28]. Even though in these
patients the cardioembolic risk was higher than the bleeding risk, results of the bleeding scores led to the preferential use of aspirin rather than warfarin [30]. In the oldest
old with atrial fibrillation, aspirin is not only ineffective in
the prevention of thromboembolic stroke, it carries a risk of
bleeding no smaller than that of warfarin [34]. By the same
token, only 15 % of patients received pharmacological
thromboprophylaxis with low molecular weight heparins or
fondaparinux, because the risk of bleeding was deemed to
be more alarming than that of venous thromboembolism,
notwithstanding that these patients were multimorbid and
often bedridden [30]. Furthermore, inappropriate prescription of proton pump inhibitors, very high at admission
(62 %), remained equally high at discharge (63 %). The
main reason for inappropriate prescription was that many
other drugs were concomitantly prescribed [31], in spite of
the fact that the prophylactic efficacy of proton pump
inhibitors is not proven in the absence of gastrointestinal
ailments. Proton pump inhibitors are not free of side effects
particularly relevant for the elderly, such as osteoporosis,
Clostridium difficile infections, hypomagnesaemia and
pneumonia [35].
Overprescription was also observed for drugs used to
manage depression, because at hospital discharge, 24 % of
patients were recommended to use them in spite of the fact
that there was little evidence of depression [32]. It is
known that drugs with anticholinergic effects are associated in the elderly with a high risk of such adverse events
as cognitive and psychomotor impairment, delirium, falls,
unintentional injuries and loss of independence. In the
frame of REPOSI, the use of these drugs was indeed
associated with worse cognitive and functional performance [33]. Antidepressant and antipsychotic drugs, often
inappropriately prescribed in the elderly, are endowed with
strong anticholinergic effects.
decreased the rate of inappropriateness, perhaps because
both versions deal with several drugs not widely used in
Europe [39]. Another important clinical outcome tackled in
REPOSI was early re-hospitalization (the so-called phenomenon of the revolving door), which occurred in 19 %
of patients within 3 months after discharge, and was most
frequently associated with previous hospital admissions,
adverse events causing hospitalization, and diagnoses of
vascular and liver disease [40]. Finally, the search for
simple prognostic markers of clinical significance did show
that a severely reduced glomerular filtration rate was
associated with a threefold increased risk of in-hospital
mortality and a 2.6-fold increased risk of dying within
3 months after discharge [41].
Cluster analysis
There is still poor knowledge on how and why multiple
diseases concomitantly occur in the elderly. Cluster analysis is a statistical technique that allows the identification
of groups of diseases (clusters) that concomitantly occur
apparently by chance [42]. In REPOSI, the hypothesis
underlying the use of this analysis was that knowledge
about the more frequent clusters of diseases may help in
the development of strategies to design cluster-randomized drug trials. The main clusters were those including
heart failure and either chronic renal failure or chronic
obstructive pulmonary disease, which are associated with
a 3- to 4-fold increased risk of in-hospital death and
adverse clinical events during hospitalization [42]. Heart
failure in various combinations with other ailments is also
associated with the highest utilization of multiple drugs
[43]. A comparison of the main disease clusters in the
2008 REPOSI run with those in 2010 did show that the
pattern of co-occurring diseases was broadly similar [44],
strengthening the views of disease associations other than
by chance.
Polypharmacy and clinical outcomes
The expected high rate of polypharmacy at the time of
admission (52 %), rather than decreasing due to the critical
drug review made by expert hospital internists, dramatically increased at discharge (67 %) [36]. In terms of
compatibility between the multiple drugs prescribed, 60 %
of patients were exposed to at least one potential drug–drug
interaction, of which at least one-fourth were potentially
severe [37]. Elderly patients with more severe cognitive
impairment were more likely to die during hospitalization
and in the early post-discharge period [38]. REPOSI also
evaluated whether or not the rate of appropriateness
improved by applying the 2003 and 2012 updated versions
of the Beers criteria for safer drug prescription in the
elderly. There was no evidence that their applications
The role of REPOSI for research in internal medicine
Research is vital to establish the best strategies of care, and
is an important task for each clinician, because it helps to
critically evaluate and improve clinical practice. In this
context, REPOSI must be understood as a research tool that
can be used by the internist to explore many aspects,
questions and problems of their daily practice through a
structured and standardized approach. The current publications stemming from REPOSI describe how this opportunity has been exploited so far. However, in the next few
years, REPOSI should be able to propose new lines of
research in patients with multimorbidity and polypharmacy. Some ideas might be summarized as follows:
Intern Emerg Med
The implementation of REPOSI in a larger number of
internal and geriatric wards, at national as well as
international level, should help to better understand the
characteristics, complexity and effects on relevant
clinical outcomes of the current pattern of care
provided to the hospitalized elderly. In the conclusive
statements of the AIFA Geriatric Working Group,
Bernabei et al. [7] emphasize the need to establish
networks involving elderly patients studied with common assessment instruments and codified information
on medication use. Wider adoption of REPOSI would
help to meet this need, and to design pragmatic clinical
trials in which, for instance, patients are randomized in
relation to disease clusters to receive or not receive a
specific treatment.
There is an urgent need to start a new era of patientoriented trials, in which the clinical complexity of the
elderly with multiple chronic diseases and polypharmacy is the paradigm, and clinical outcomes of
intervention are shared with the patients taking into
account their health priorities. In this context, risk
stratification approaches may be useful methodological
tools to individualize and prioritize treatments [45].
Comparing data of the REPOSI Registry to other data
sets pertaining to the oldest adult could be used to set
up studies of comparative effectiveness research [45],
involving for instance patients selected according to
clusters of the most representative combinations of
chronic diseases, in order to evaluate benefits and
harms of specific interventions, or innovative models of
care on clinical outcomes truly patient relevant (such
as, symptom burden, cognitive impairment, disability
and active life expectancy).
Availability of large patient samples is a prerequisite in
order to be able to implement new approaches of data
analysis meant to assess the complex connections of
multiple chronic diseases. Network analysis represents
a methodology applicable to different fields of research,
ranging from molecular medicine to human, social and
clinical setting [46]. Network analysis could also be
applied to investigate the rationale of multiple drug
prescription, thereby allowing the collection of information on the relationship between drugs and their coprescriptions, and how these patterns differ in different
age and gender groups.
N-of-1 trials [47, 48] are within-patient randomized
multi-period crossover trials that compare, in a doubleblind fashion, therapeutic strategies (e.g., an active
drug versus no treatments, or two different active
therapies) using the actual patient as a control [49]. The
ultimate aim of N-of-1 trials is to objectively and
empirically determine the best therapeutic choice for a
single patient.
Narrative medicine [50, 51] might be an additional tool
in order to study a patient’s experience with cumulative
illnesses, diagnostic and therapeutic burden and their
real-life clinical encounters with different medical
specialists. Narrative medicine bridges the gap between
patients and providers, and teaches that the mode of
care delivery (the process) is just as important as which
type of care is delivered (the content). After having
acquired narrative competence, physicians can join
their patients, recognize their own personal journeys
through medicine and illness, acknowledge kinship
with and duties towards other health care providers, and
inaugurate an interaction with the community at large
on health care. A narrative medicine approach might
also help to elucidate the rationale of therapeutic
choices that have driven the current management of
different illnesses in the absence of evidence-based
What the internist has learnt from REPOSI
In the third millennium, internists and geriatricians must
acquire a leading role, together with primary care physicians, in order to make health care systems fit for the
management of an aging population. Are we ready for this
formidable task?
Until now, medical schools and postgraduate education
have trained physicians to manage single diseases in relatively young people. The success of modern medicine and
the resulting increase of an aging population have utterly
transformed this picture, but medical education and the
resulting healthcare services have hardly succeeded in
coping culturally and practically with this huge shift.
Medical subspecialties (cardiology, pneumology, endocrinology, gastroenterology et alia), which were much fostered in the last part of the second millennium owing to the
dramatic development of specialized technologies and
procedures, are not suited to handle multiple concomitant
diseases. The hospital internist, with an holistic approach to
disease management, should in principle find it easier to
tackle this challenge.
A first most important goal is to critically review all
prescribed drugs, both at the time of hospital admission
and discharge. Setting therapeutic priorities and stopping inappropriate or useless medications favor compliance and quality of life in the elderly.
Another important task is to become acquainted with
the use of multidimensional evaluation tools that
mainly belong to the clinical expertise of geriatricians.
In the elderly, an impaired cognitive status and the
decreased ability to perform the basic activities of
Intern Emerg Med
daily living are accompanied by a reduction of
functional and physical reserves, that ultimately lead
to frailty and a high risk of death. A prompt and timely
recognition of this impairment is potentially able to
improve prognosis, because the sequence of adverse
outcomes is sometimes reversible. The traditional
approach based upon clinical history and physical
examination may be inadequate to pick up subtle
impairments of cognitive and functional status, unless
some instruments of the multidimensional evaluation
are routinely used (such as the Mini-Mental State
Examination [52], the Short Blessed Test [53] and the
Barthel index on the basal activities of daily living
A multidisciplinary team approach is essential to avoid
care fragmentation, to provide a comprehensive evaluation of problems and needs, and to practice a
combination of problem-based and patient-oriented
medicine, i.e., a realistic personalized medicine. To
this end, the internist needs to orchestrate a team
involving nurses, pharmacists, social workers and
clinical pharmacologists, the latter unfortunately often
being lacking in the healthcare settings that handle the
multimorbid and polytreated elderly.
Communication and transparency between hospital
and community care providers is essential in order to
promote continuity and integration of care and reduce
patient’s stress, redundancy, fragmentation and costs.
Coordination, integration and continuity of care means
a realistic assessment of available resources and social/
health services, with inevitable compromises and
negotiations between all involved parties.
Closer involvement of the elderly in the choice of
priorities and aims of clinical and therapeutic decisions
is another important task. While awaiting the greater
availability of electronic health records, which may
help to share the patient’s information between different nodes of the hospital and community services, the
internist must promote and facilitate a close relationship with the patient’s family, primary care physicians
and social workers, both on hospital admission and at
Conclusive remarks
All in all, there are still many gaps in the knowledge
necessary for the internist to optimally and effectively
tackle the many issues related to the health care of the
elderly with multimorbidity and associated polypharmacy.
There is a dramatic need for more focused research in this
field. A registry such as REPOSI, which from 2014 is going
to be a joint effort of Italian and Spanish internists, should
become a permanent observatory on the complexity of
health and care in the elderly. In the near future, we hope to
develop research protocols able to lead to more evidencebased prescription of multiple drugs.
Conflict of interest
Investigators and co-authors of the REPOSI (REgistro
POliterapie SIMI, Società Italiana di Medicina Interna)
Study Group are as follows:
Steering Committee Pier Mannuccio Mannucci (Chair,
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano), Alessandro Nobili (co-chair, IRCCS-Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’,
Milano), Mauro Tettamanti, Luca Pasina, Carlotta Franchi
(IRCCS-Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Milano), Francesco Salerno (IRCCS Policlinico San
Donato Milanese, Milano), Salvatore Corrao (ARNAS
Civico, Di Cristina, Benfratelli, DiBiMIS, Università di
Palermo, Palermo), Alessandra Marengoni (Spedali Civili
di Brescia, Brescia), Maura Marcucci (Geriatric Unit,
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano).
Clincal data monitoring and revision: Eleonora Sparacio, Stefania Alborghetti, Rosa Di Costanzo, Tarek Kamal
Eldin (IRCCS-Istituto di Ricerche Farmacologiche ‘‘Mario
Negri’’, Milano).
Database Management and Statistics: Mauro Tettamanti, Codjo Djignefa Djade (IRCCS-Istituto di Ricerche
Farmacologiche ‘‘Mario Negri’’, Milano).
Domenico Prisco, Elena Silvestri, Caterina Cenci,
Tommaso Barnini (Azienda Ospedaliero Universitaria
Careggi Firenze, SOD Patologia Medica); Giuseppe Delitala, Stefano Carta, Sebastiana Atzori (Azienda Mista
Ospedaliera Universitaria, Sassari, Clinica Medica);
Gianfranco Guarnieri, Michela Zanetti, Annalisa Spalluti
(Azienda Ospedaliera Universitaria Ospedali Riuniti di
Trieste, Trieste, Clinica Medica Generale e Terapia Medica); Maria Grazia Serra, Maria Antonietta Bleve (Azienda
Ospedaliera ‘‘Cardinale Panico’’ di Tricase, Lecce, Unità
Operativa Complessa Medicina); Massimo Vanoli, Giulia
Grignani, Gianluca Casella (Azienda Ospedaliera della
Provincia di Lecco, Ospedale di Merate, Lecco, Medicina
Interna); Laura Gasbarrone (Azienda Ospedaliera Ospedale San Camillo Forlanini, Roma, Medicina Interna 1);
Giorgio Maniscalco, Massimo Gunelli, Daniela Tirotta
(Azienda Ospedaliera Ospedale San Salvatore, Pesaro, Soc
Medicina Interna); Antonio Brucato, Silvia Ghidoni, Paola
Intern Emerg Med
Di Corato (Azienda Ospedaliera Papa Giovanni XXIII,
Bergamo, Medicina 1); Mauro Bernardi, Silvia Li Bassi,
Luca Santi (Azienda Ospedaliera Policlinico Sant’OrsolaMalpighi, Bologna, Semeiotica Medica Bernardi); Giancarlo Agnelli, Alfonso Iorio, Maura Marcucci, Emanuela
Marchesini (Azienda Ospedaliera Santa Maria della Misericordia, Perugia, Medicina Interna e Cardiovascolare);
Elmo Mannarino, Graziana Lupattelli, Pamela Rondelli,
Francesco Paciullo (Azienda Ospedaliera Santa Maria
della Misericordia, Perugia, Medicina Interna, Angiologia,
Malattie da Arteriosclerosi); Fabrizio Fabris, Michela
Carlon, Francesca Turatto (Azienda Ospedaliera Università
di Padova, Padova, Clinica Medica I); Maria Cristina
Baroni, Marianna Zardo (Azienda Ospedaliera Università
di Parma, Parma, Clinica e Terapia Medica); Roberto
Manfredini, Christian Molino, Marco Pala, Fabio Fabbian
(Azienda Ospedaliera - Universitaria Sant’Anna, Ferrara,
Unità Operativa Clinica Medica); Ranuccio Nuti, Roberto
Valenti, Martina Ruvio, Silvia Cappelli (Azienda Ospedaliera Università Senese, Siena, Medicina Interna I);
Giuseppe Paolisso, Maria Rosaria Rizzo, Maria Teresa
Laieta (Azienda Ospedaliera Universitaria della Seconda
Università degli Studi di Napoli, Napoli, VI Divisione di
Medicina Interna e Malattie Nutrizionali dell’Invecchiamento); Teresa Salvatore, Ferdinando Carlo Sasso (Azienda Ospedaliera Universitaria della Seconda Università
degli Studi di Napoli, Napoli, Medicina Interna e Malattie
Epato-Bilio Metaboliche Avanzate); Riccardo Utili,
Emanuele Durante Mangoni, Daniela Pinto (Azienda
Ospedaliera Universitaria della Seconda Università degli
Studi di Napoli, Napoli, Medicina Infettivologica e dei
trapianti); Oliviero Olivieri, Anna Maria Stanzial (Azienda
Ospedaliera Universitaria Integrata di Verona, Verona,
Unità Operativa di Medicina Interna B); Renato Fellin,
Stefano Volpato, Sioulis Fotini (Azienda Ospedaliera
Universitaria Ospedale Sant’Anna, Ferrara, Unità Operativa di Medicina Interna Gerontologia e Geriatria);
Mario Barbagallo, Ligia Dominguez, Lidia Plances, Daniela D’Angelo (Azienda Ospedaliera Universitaria Policlinico Giaccone Policlinico di Palermo, Palermo, Unità
Operativa di Geriatria e Lungodegenza); Giovanbattista
Rini, Pasquale Mansueto, Ilenia Pepe (Azienda Ospedaliera Universitaria Policlinico P. Giaccone di Palermo,
Palermo, Medicina Interna e Malattie Metaboliche);
Giuseppe Licata, Luigi Calvo, Maria Valenti (Azienda
Ospedaliera Universitaria Policlinico P. Giaccone di
Palermo, Palermo, Medicina Interna e Cardioangiologia);
Claudio Borghi, Enrico Strocchi, Elisa Rebecca Rinaldi
(Azienda Ospedaliera Universitaria Policlinico S. OrsolaMalpighi, Bologna, Unità Operativa di Medicina Interna
Borghi); Marco Zoli, Elisa Fabbri, Donatella Magalotti
(Azienda Ospedaliera Universitaria Policlinico S. OrsolaMalpighi, Bologna, Unità Operativa di Medicina Interna
Zoli); Alberto Auteri, Anna Laura Pasqui, Luca Puccetti
(Azienda Ospedaliera Universitaria Senese, Siena, Medicina 3); Franco Laghi Pasini, Pier Leopoldo Capecchi,
Maurizio Bicchi (Azienda Ospedaliera Universitaria Senese, Siena, Unità Operativa Complessa Medicina 2);
Carlo Sabbà, Francesco Saverio Vella, Alessandro Marseglia, Chiara Valentina Luglio (Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Medicina
Interna Universitaria C. Frugoni); Giuseppe Palasciano,
Maria Ester Modeo, Annamaria Aquilino, Pallante Raffaele (Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Medicina Interna Ospedale ‘‘PendeFerrannini’’); Stefania Pugliese, Caterina Capobianco
(Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Clinica Medica I Augusto Murri);
Alfredo Postiglione, Maria Rosaria Barbella, Francesco De
Stefano (Azienda Ospedaliera Universitaria Policlinico
Federico II di Napoli, Medicina Geriatrica Dipartimento
di Clinica Medica); Luigi Fenoglio, Chiara Brignone,
Christian Bracco, Alessia Giraudo (Azienda Sanitaria
Ospedaliera Santa Croce e Carle di Cuneo, Cuneo, S.
C. Medicina Interna); Giuseppe Musca, Olga Cuccurullo
(Azienda Sanitaria Provinciale di Cosenza Presidio
Ospedaliero di Cetraro, Cosenza, Unità Operativa Complessa Medicina Interna); Luigi Cricco, Alessandra Fiorentini (COB Stabilimento Montefiascone, Viterbo, Unità
Operativa Complessa di Geriatria e Medicina); Maria
Domenica Cappellini, Giovanna Fabio, Sonia Seghezzi,
Margherita Migone De Amicis (Fondazione IRCCS Cà
Granda Ospedale Maggiore Policlinico, Milano, Unità
Operativa Medicina Interna IA); Silvia Fargion, Paola
Bonara, Mara Bulgheroni, Rosa Lombardi (Fondazione
IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Medicina Interna 1B); Fabio Magrini, Ferdinando
Massari, Tatiana Tonella (Fondazione IRCCS Cà Granda
Ospedale Maggiore Policlinico, Milano, Unità Operativa
Medicina Cardiovascolare); Flora Peyvandi, Alberto
Tedeschi, Raffaella Rossio (Fondazione IRCCS Cà Granda
Ospedale Maggiore Policlinico, Milano, Medicina Interna
2); Guido Moreo, Barbara Ferrari, Luisa Roncari (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico,
Milano, Medicina Interna 3); Valter Monzani, Valeria
Savojardo, Christian Folli, Maria Magnini (Fondazione
IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Medicina d’Urgenza); Daniela Mari, Paolo Dionigi
Rossi, Sarah Damanti, Silvia Prolo (Fondazione IRCCS Cà
Granda Ospedale Maggiore Policlinico, Milano, Geriatria); Maria Sole Lilleri (Fondazione IRCCS Cà Granda
Ospedale Maggiore Policlinico, Milano, Medicina Generale ad Indirizzo Geriatrico); Luigi Cricco, Alessandra
Fiorentini (COB Viterbo, Stabilimento Montefiascone,
Viterbo, UOC Geriatria e Medicina); Giuliana Micale
(IRCCS Istituto Auxologico Italiano, Milano, Medicina
Intern Emerg Med
Generale ad indirizzo Geriatrico); Mauro Podda, Carlo
Selmi, Francesca Meda (IRCCS Istituto Clinico Humanitas,
Milano, Clinica Medica); Francesco Salerno, Silvia Accordino, Alessio Conca, Valentina Monti (IRCCS Policlinico San Donato e Università di Milano, San Donato
Milanese, Medicina Interna); Gino Roberto Corazza,
Emanuela Miceli, Marco Vincenzo Lenti, Donatella Padula
(IRCCS Policlinico San Matteo di Pavia, Pavia, Clinica
Medica I, Reparto 11); Carlo L. Balduini, Giampiera
Bertolino, Stella Provini, Federica Quaglia (IRCCS Policlinico San Matteo di Pavia, Pavia, Clinica Medica III);
Giovanni Murialdo, Marta Bovio (IRCS Azienda Ospedaliera Universitaria San Martino-IST di Genova, Genova,
Clinica di Medicina Interna 2); Franco Dallegri, Luciano
Ottonello, Alessandra Quercioli, Alessandra Barreca
(Università di Genova, Genova, Medicina Interna 1);
Maria Beatrice Secchi, Davide Ghelfi (Ospedale Bassini di
Cinisello Balsamo, Milano, Divisione Medicina); Wu
Sheng Chin, Laura Carassale, Silvia Caporotundo (Ospedale Bassini, Cinisello Balsamo, Milano, Unità Operativa
di Geriatria); Luigi Anastasio, Lucia Sofia, Maria Carbone
(Ospedale Civile Jazzolino di Vibo Valentia, Vibo Valentia,
Medicina interna); Giancarlo Traisci, Lucrezia De Feudis,
Silvia Di Carlo (Ospedale Civile Santo Spirito di Pescara,
Pescara, Medicina Interna 2); Giovanni Davı̀, Maria Teresa Guagnano, Simona Sestili (Ospedale Clinicizzato SS.
Annunziata, Chieti, Clinica Medica); Elisabetta Bergami,
Emanuela Rizzioli (Ospedale del Delta, Lagosanto, Ferrara, Medicina Interna); Carlo Cagnoni, Luca Bertone,
Antonio Manucra (Ospedale di Bobbio, Piacenza, Unità
Operativa Medicina e Primo Soccorso); Alberto Buratti,
Tiziana Tognin, Nicola Lucio Liberato (Azienda Ospedaliera della Provincia di Pavia, Ospedale di Casorate Primo,
Pavia, Medicina Interna); Giordano Bernasconi, Barbara
Nardo (Ospedale di Circolo di Busto Arsizio, Varese,
Medicina I); Giovanni Battista Bianchi, Sabrina Giaquinto
Ospedale ‘‘SS Gerosa e Capitanio’’ di Lovere, Bergamo,
Unità Operativa Complessa di Medicina Generale, Azienda Ospedaliera ‘‘Bolognini’’ di Seriate, Bergamo; Giampiero Benetti, Michela Quagliolo, Giuseppe Riccardo
Centenaro (Ospedale di Melegnano, Vizzolo Predabissi,
Melegnano, Medicina 1); Francesco Purrello, Antonino Di
Pino, Salvatore Piro (Ospedale Garibaldi Nesima, Catania,
Unità Operativa Complessa di Medicina Interna); Gerardo
Mancuso, Daniela Calipari, Mosè Bartone, Francesco
Gullo (Ospedale Giovanni Paolo II Lamezia Terme, Catanzaro, Unità Operativa Complessa Medicina Interna);
Michele Cortellaro, Marina Magenta, Francesca Perego;
Maria Rachele Meroni (Ospedale Luigi Sacco, Milano,
Medicina 3°); Marco Cicardi, Antonio Gidaro Marina
Magenta (Ospedale Luigi Sacco, Milano, Medicina II);
Andrea Sacco, Antonio Bonelli, Gaetano Dentamaro
(Ospedale Madonna delle Grazie, Matera, Medicina);
Renzo Rozzini, Lina Falanga, Alessandro Giordano
(Ospedale Poliambulanza, Brescia, Medicina Interna e
Geriatria); Paolo Cavallo Perin, Bartolomeo Lorenzati,
Gabriella Gruden, Graziella Bruno (Dipartimento di Scienze Mediche, Università di Torino, Città della Scienza e
della Salute, Torino, Medicina 3); Giuseppe Montrucchio,
Elisabetta Greco, Pietro Tizzani (Dipartimento di Scienze
Mediche, Università di Torino, Città della Scienza e della
Salute, Torino, Medicina Interna 5); Giacomo Fera, Maria
Loreta Di Luca, Donatella Renna (Ospedale San Giacomo
di Monopoli, Bari, Unità Operativa Medicina Interna);
Antonio Perciccante, Alessia Coralli (Ospedale San Giovanni-Decollato-Andisilla, Civita Castellana Medicina);
Rodolfo Tassara, Deborah Melis, Lara Rebella (Ospedale
San Paolo, Savona, Medicina I); Giorgio Menardo, Stefania Bottone, Elsa Sferrazzo (Ospedale San Paolo, Savona,
Medicina Interna e Gastroenterologia); Claudio Ferri,
Rinaldo Striuli, Rosa Scipioni (Ospedale San Salvatore,
L’Aquila, Medicina Interna Universitaria); Raffaella
Salmi, Piergiorgio Gaudenzi, Susanna Gamberini, Franco
Ricci (Azienda Ospedaliera-Universitaria S. Anna, Ferrara, Unità Operativa di Medicina Ospedaliera II); Cosimo
Morabito, Roberto Fava (Ospedale Scillesi d’America,
Scilla Medicina); Andrea Semplicini, Lucia Gottardo
(Ospedale SS. Giovanni e Paolo, Venezia, Medicina
Interna 1); Giuseppe Delitala, Stefano Carta, Sebastiana
Atzori (Ospedale Universitario Policlinico di Sassari,
Sassari, Clinica Medica); Gianluigi Vendemiale, Gaetano
Serviddio, Roberta Forlano (Ospedali Riuniti di Foggia,
Foggia, Medicina Interna Universitaria); Luigi Bolondi,
Leonardo Rasciti, Ilaria Serio (Policlinico Sant’OrsolaMalpighi, Bologna, Unità Operativa Complessa Medicina
Interna); Cesare Masala, Antonio Mammarella, Valeria
Raparelli (Policlinico Umberto I, Roma, Medicina Interna
D); Filippo Rossi Fanelli, Massimo Delfino, Antonio
Amoroso (Policlinico Umberto I, Roma, Medicina Interna
H); Francesco Violi, Stefania Basili, Ludovica Perri (Policlinico Umberto I, Roma, Prima Clinica Medica); Pietro
Serra, Vincenzo Fontana, Marco Falcone (Policlinico
Umberto I, Roma, Terza Clinica Medica); Raffaele Landolfi, Antonio Grieco, Antonella Gallo (Policlinico Universitario A. Gemelli, Roma, Clinica Medica); Giuseppe
Zuccalà, Francesco Franceschi, Guido De Marco, Cordischi Chiara, Sabbatini Marta (Policlinico Universitario A.
Gemelli, Roma, Roma, Unità Operativa Complessa Medicina d’Urgenza e Pronto Soccorso); Martino Bellusci,
Donatella Setti, Filippo Pedrazzoli (Presidio Ospedaliero
Alto Garda e Ledro, Ospedale di Arco, Trento, Unità
Operativa di Medicina Interna Urgenza/Emergenza);
Giuseppe Romanelli, Caterina Pirali, Claudia Amolini
(Spedali Civili di Brescia, Brescia, Geriatria); Enrico
Agabiti Rosei, Damiano Rizzoni, Luana Castoldi (Spedali
Civili di Brescia, Brescia, Seconda Medicina); Antonio
Intern Emerg Med
Picardi, Umberto Vespasiani Gentilucci, Chiara Mazzarelli, Paolo Gallo (Università Campus Bio-Medico, Roma,
Medicina Clinica-Epatologia); Luigina Guasti, Luana
Castiglioni, Andrea Maresca, Alessandro Squizzato, Sara
Contini, Marta Molaro (Università degli Studi dell’Insubria, Ospedale di Circolo e Fondazione Macchi, Varese,
Medicina Interna I); Giorgio Annoni, Maurizio Corsi, Sara
Zazzetta (Università degli studi di Milano-Bicocca Ospedale S. Gerardo, Monza, Unità Operativa di Geriatria);
Marco Bertolotti, Chiara Mussi, Roberto Scotto, Maria
Alice Ferri, Francesca Veltri (Università di Modena e
Reggio Emilia, AUSL di Modena, Modena, Nuovo Ospedale Civile, Unità Operativa di Geriatria); Franco Arturi,
Elena Succurro, Giorgio Sesti, Umberto Gualtieri (Università degli Studi Magna Grecia, Policlinico Mater
Domini, Catanzaro, Unità Operativa Complessa di Medicina Interna); Francesco Perticone, Angela Sciacqua,
Michele Quero, Chiara Bagnato (Università Magna Grecia
Policlinico Mater Domini, Catanzaro, Unità Operativa
Malattie Cardiovascolari Geriatriche); Paola Loria, Maria
Angela Becchi, Gianfranco Martucci, Alessandra Fantuzzi,
Mauro Maurantonio (Università di Modena e Reggio
Emilia, Medicina Metabolica-NOCSAE, Baggiovara, Modena); Roberto Corinaldesi, Roberto De Giorgio, Mauro
Serra, Valentina Grasso, Eugenio Ruggeri, Lorenzo Mauro
Carozza, Fabio Pignatti (Dipartimento di Scienze Mediche
e Chirurgiche, Unità Operativa di Medicina Interna,
Università degli Studi di Bologna/Azienda OspedalieroUniversitaria S.Orsola-Malpighi, Bologna).
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Multimorbidity and polypharmacy in the elderly: lessons from REPOSI