MANAGEMENT OF FRAILTY AT INDIVIDUAL LEVEL - 
CLINICAL MANAGEMENT: SYSTEMATIC LITERATURE REVIEW
Gregor VENINŠEK1, Branko GABROVEC2*
1University Medical Center Ljubljana, Center for Geriatric Medicine, Zaloška 2, 1000 Ljubljana, Slovenia
2National Institute of Public Health, Health Care Center, Trubarjeva 2, 1000 Ljubljana, Slovenia
Received: Aug 14, 2017
Accepted: Jan 23, 2018
Review article
Introduction: To deliver quality management of a frail individual, a clinician should understand the concept 
of frailty, be aware of its epidemiology and be able to screen for frailty and assess it when it is present, and, 
finally, to recommend successful interventions.
Methodology: A systematic literature search was conducted in the following databases: PubMed, Cochrane, 
Embase, Cinahl and UpToDate. The criterion in selecting the literature was that articles were published in the 
period from 2002 to 2017. From 67432 initial hits, 27 publications were selected.
Results: Useful interventions to address frailty are supplementation of vitamin D, proper nutrition, 
multicomponent training, home-based physiotherapy and comprehensive geriatric assessment, particularly 
when performed in geriatric wards.
Conclusion: Comprehensive geriatric assessment is an effective way to decrease frailty status especially when 
performed in geriatric wards. Multicomponent physical training and multidimensional interventions (physical 
training, nutrition, vitamin D supplementation and cognitive training) are effective measures to reduce frailty.
Uvod: Za kakovostno upravljanje krhkega posameznika mora klinik razumeti koncept krhkosti ter prepoznavanje 
in priporočanje uspešnih intervencij.
Metode: Za to raziskavo je bil izveden sistematičen pregled literature v naslednjih bazah: PubMed, Cochrane, 
Embase, Cinahl in UpToDate. Vključitveni kriterij je bil izbor literature, objavljene v zadnjih 15 letih, od leta 
2002 do leta 2017. Od 67.432 zadetkov je bilo izbranih 27 publikacij.
Rezultati: Koristne intervencije za obravnavo krhkosti so dodajanje vitamina D, pravilna prehrana, 
večkomponentna telesna vadba, fizioterapija na domu in obsežna geriatrična ocena, ki se uporablja na 
geriatričnih oddelkih.
Zaključki: Če se celovita geriatrična ocena na geriatričnih oddelkih izvaja, ta povečuje možnost pacientovega 
preživetja in kognicije. Večkomponentna fizična vadba in večdimenzionalne intervencije, ki temeljijo na 
celoviti geriatrični oceni, so učinkovite pri zmanjševanju krhkosti.
ABSTRACT
Keywords: 
frailty, geriatric, 
comprehensive 
geriatric assessment, 
Joint Action 
ADVANTAGE
IZVLEČEK
Ključne besede: 
krhkost, geriatrija, 
geriatrične ocene, 
Joint Action 
ADVANTAGE
*Corresponding author: Tel. + 386 40 381 470; E-mail: branko.gabrovec@nijz.si
Zdr Varst. 2018;57(2):106-115
MENEDŽMENT KRHKOSTI NA RAVNI POSAMEZNIKA – 
KLINIČNI MENEDŽMENT: SISTEMATIČNI PREGLED LITERATURE
Veninšek G, Gabrovec B. Management of frailty at individual level - clinical management: systematic literature review. 
Zdr Varst. 2018;57(2):106-115. doi: 10.2478/sjph-2018-0014.
10.2478/sjph-2018-0014
106
© Nacionalni inštitut za javno zdravje, Slovenija. 
1 INTRODUCTION
Functional capacities in healthy individuals are developed 
and strengthened until adulthood and slowly decline 
thereafter. A decline in multiple physiological systems 
results in frailty (1). The prevalence of frailty progresses 
with age and we can find 2–5% of the population with frailty 
in the age group between 18 and 34 (2). Determinants of 
frailty are gender, age, income, lifestyle, marital status 
and multimorbidity as the key determinant (3). Frailty 
is associated with incapacity and/or multimorbidity, but 
should not be equated with it (4). With older people 
frailty is a common cause condition leading to death. In 
the last year of life, frailty is connected to a persistent 
or advanced disability in basic daily activities, which is 
similar to an individual with organ failure (5).
Comprehensive geriatric assessment (CGA) is the most 
comprehensively researched model for healthcare 
delivery to frail older patients (6).
Frailty among older persons is a dynamic process 
characterised by frequent transitions between frailty 
states over time. Clinical management of frailty at the 
individual level includes prevention at the individual 
level, detection and management of a frail individual 
(7). Priorities of healthcare services and their differences 
between providers and recipients should be taken into 
account particularly in the health care of older patients 
and the design of healthcare policies and research (8).
Determinants of frailty have to be systematically checked 
to be able to recognise an individual who is at a high risk 
to develop frailty (3). 
1.1 Aims and Objectives
Aim: To define interventions in a successful clinical 
management of frail people. 
Objective: To conduct a systematic review of relevant 
literature for the time period from 1 January 2002 to 31 
May 2017. 
2 METHODS
2.1 Review Methods
Descriptive research methodology was used to review 
peer-reviewed medical literature. A systematic review of 
literature was conducted, as it enabled us to obtain data 
from various sources and ensured a holistic understanding 
of the research subject. The search for literature was 
conducted in the PubMed, Cochrane, Embase, Cinahl and 
UpToDate databases by means of several combinations of 
selected search words in the English language and their 
synonyms, with Boolean operators AND or: Comprehensive 
Geriatric Assessment *() OR Frail Disability *() OR Frailty 
treatment *() OR Frail Older adult *() OR Frailty Screening 
*() OR Frailty management *() OR Frailty Intervention 
Therapy *() OR Functional Decline *() OR Frail Older person 
*() OR Geriatric Vulnerable *() OR Elderly Vulnerable *() 
OR Frailty Scale *(); searching in the title, key words and 
the abstract.
The selection criterion for articles to be included in the 
review was that they were published during the last 15 
years. Key words were selected from a proposal of key 
words that was prepared by the task leader and the 
working group focusing on Clinical Management as part 
of the European Commission project ‘Joint Action on 
Frailty Prevention – JA ADVANTAGE,’ Work Package 6 – 
Management of Frailty at Individual Level.
In addition to language and publication time restrictions, 
the main inclusion factors were also peer-review 
scientific journals, international documents, professional 
guidelines, standards and research studies performed in 
the EU which comprehensively investigate and describe 
management of frailty through clinical management. The 
exclusion criteria were: editorials, letters, interviews, 
posters and no access to full text.
We have also included grey documents which were 
identified and proposed by the task leader and the 
working group focusing on Clinical Management as part 
of the European Commission project ‘Joint Action on 
Frailty Prevention – JA ADVANTAGE,’ Work Package 
6 – Management of Frailty at Individual Level. Grey 
documents were identified by means of an opportunistic 
search, that is, a targeted or focused one, based on the 
information that each partner in the project Consortium 
could give regarding their own country. The term grey 
literature was used to describe information which is not 
published commercially or is otherwise hard to find. This 
includes items, such as government reports, NGO reports, 
theses, technical reports, white papers, etc.
2.2 Results of the Review
The total number of all search results was 67432. After 
excluding duplicates and considering inclusion criteria, 
the final 27 articles remained for analysis.
The process of literature review is displayed in a search 
table (Table 1) and in the PRISMA (Preferred Reporting 
Items for Systematic Reviews and Meta-Analysis) diagram 
(9), as shown in Figure 1.
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Table 1.
Figure 1.
Search table.
Flowchart of search strategy and literature selection 
process
Key word No. of hits Chosen hits Repeated 
chosen hits
Repeated 
chosen hits
PubMed
Cochrane
Embase
CINAHL
UpToDate
Other sources
Comprehensive Geriatric Assessment
Frail Disability 
Frailty treatment
Frail Older adult
Frailty Screening
Frailty management
Frailty Intervention Therapy
Functional Decline
Comprehensive Geriatric Assessment
Frail Older person
Geriatric Vulnerable
Elderly Vulnerable
Comprehensive Geriatric Assessment
Frailty Scale
Functional decline
Comprehensive Geriatric Assessment
Frailty Scale
Frail Older adult
Frailty Intervention Therapy
Frail Older person
30541
1332
3689
11223
3
1491
409
14123
287
44
70
175
880
148
11000
410
53
795
305
390
1
67432
12
4
8
6
9
7
9
11
2
2
1
1
2
2
16
5
0
2
13
6
118
12
4
8
4
3
7
9
2
2
1
1
1
0
0
16
5
0
0
0
0
4
1
3
2
2
2
2
2
2
1
1
1
0
0
2
1
0
0
0
0
1
27
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2.3 Quality Assessment of the Review
Results of the quality assessment of systematic literature 
review, as shown in Table 2.
Table 2.
Table 3.
Results of the quality assessment of systematic literature review.
Results of the review and literature analysis.
Criteria
Author and year Research design Sample Research purpose Key findings
Yes No Other
1. Is the review based on a focused question that is adequately formulated and described?
2. Were eligibility criteria for included and excluded studies predefined and specified?
3. Did the literature search strategy use a comprehensive, systematic approach?
4. Were titles, abstracts, and full-text articles dually and independently reviewed  
for inclusion and exclusion to minimize bias?
5. Was the quality of each included study rated independently by two or more reviewers,  
using a standard method to appraise its internal validity?
6. Were the included studies listed along with important characteristics  
and results of each study?
7. Was publication bias assessed?
8. Was heterogeneity assessed? (This question applies only to meta-analyses.)
Kehler et al., 2017
Gobbens et al., 2010
Gill et al., 2006
Fried et al., 2001
Clegg et al., 2013
Kan et al., 2008
Cross-sectional. 
Survey
Cross-sectional
Prospective study
Prospective and 
observational study
Literature review and 
observational study
Literature review, 
Expert panel
n=7353
75 years old 
and older
n=484
70 years and 
older
n=754
65 years 
and older
n=5317
80 years old 
and older
Geriatric 
Advisory Panel
To examine and compare 
the prevalence of frailty in 
Canadians 18–79 years old 
using the Accumulation of 
Deficits and Fried models of 
frailty.
To determine which 
determinants predict frailty 
and domains of frailty.
To determine the transition 
rates between frailty states.
To develop and operationalize 
a phenotype of frailty in older 
adults.
A research on how frailty 
develops, how it might be 
prevented and how it can be 
detected reliably.
To perform a comprehensive 
review of the definitions and 
assessment tools on frailty.
Data show that frailty is prevalent 
already in younger adults, has 
increasing prevalence with age, 
which varies depending on which 
frailty tool is used.
The effect of the determinants 
of frailty differs across frailty 
domains. 
Frailty is a dynamic process, 
characterised by frequent 
transitions between frailty states 
over time. 
The study provides a potentially 
standardised definition for frailty.
Landmark studies have developed 
valid models for frailty.
No consensus on the definition 
of frailty, but there was an 
agreement to consider frailty as 
a pre-disability stage. 
X
X
X
X
X
X
X
X
3 RESULTS 
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Author and year Research design Sample Research purpose Key findings
Dent et al., 2016
Stoicea et al., 2016
Subra et al., 2012
Vellas et al., 2013
Morley et al., 2013
Sutton et al., 2016
Ellis et al., 2011
Theou et al., 2011
Beaudart et al., 2014
Bruyère et al., 2017
Cesari et al., 2015
Literature review
Literature review
Literature and platform 
review, observational 
study
Screening tool review 
and observational 
study
Consensus group
Literature review
Review of randomised 
controlled trials 
Literature review
Literature review, 
Meta-analyse
Literature review
Exploratory analyses
65 years old 
and older
n=29 
Reviews of six 
scales.
65 years old 
and older
n=160
65 years old and 
older
n=442
Delegates 
from 6 major 
international, 
European, and 
US societies.
73 articles 
selected
60 years old and 
older
Two reviews
47 studies 
selected
30 studies 
selected
No data
Mean age=76.8 
years
n=424
An overview of the definitions 
and measurements of frailty 
in research and clinical 
practice.
Review scales for 
measuring frailty.
The presentation of the main 
characteristics of the new 
Platform.
A screening tool for frailty
To create 4 major consensus 
points on the specific form of 
frailty.
To identify existing multi-
component frailty assessment 
tools that were developed to 
assess frailty.
To evaluate the effectiveness 
of CGA in the hospital.
To examine the effectiveness 
of current exercise 
interventions for the 
management of frailty.
To summarise with a meta-
analysis the effects of vitamin 
D supplementation.
A review of the evidence 
regarding the role of 
vitamin D.
To explore whether a physical 
activity intervention can 
reduce prevalence and 
severity of frailty.
A summary of the main strengths 
and limitations of existing frailty 
measurements.
By identifying the most 
time-efficient criteria, a 
comprehensive and clinically 
effective scale, a universal scale 
can be implemented.
The Platform clinically evaluates 
and intervenes on frailty for 
the first time at the general 
population level. 
The use of the GFST may help 
at raising awareness about the 
importance of identifying frailty.
Physical frailty can potentially be 
prevented or treated.
The TFI has the most robust 
evidence of reliability and 
validity.
CGA increases a patient’s 
likelihood of being alive and in 
their own home.
Evidence suggests that exercise 
has a positive impact on some 
physical determinants of frailty.
Vitamin D supplementation has a 
small positive impact on muscle 
strength.
Several studies suggest a 
potential effect of vitamin D on 
physical frailty.
Regular PA may reduce frailty, 
especially in individuals at higher 
risk of disability.
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Author and year Research design Sample Research purpose Key findings
Ng et al., 2015
Song et al., 2010
Puts et al., 2017
Turner et al., 2014
Collard et al., 2012
Gill et al., 2004
Chan et al., 2012
Li et al., 2010
Cameron et al., 2013
Behm et al., 2016
Randomised 
controlled trial
Prospective cohort 
study
Literature review
Literature review, 
Report
Literature review
Randomised 
controlled trial
Randomised 
controlled trial
Randomised 
controlled trial
Randomized 
controlled trial
Randomised 
controlled trial
Mean age=70 
years
n=151
Aged from 65 
to 102 years
n=2740
65 years old 
and older
14 studies 
selected
No data
65 years old 
and older
21 studies 
selected
75 years old 
and older
n=188
65–79 years old
n=117
65 years old 
and older
n=310
Mean age=83,3 
years 
n=216
80 years old 
and older
n=459
To compare the effects 
of 6-month-duration 
interventions vs. control in 
reducing frailty.
To evaluate the prevalence 
and 10-year outcomes of 
frailty in older adults.
To review policies that are 
designed to prevent or reduce 
the level of frailty.
To create proactive, 
integrated, person-centred 
and community-based 
response to frailty.
To systematically compare 
and pool the prevalence of 
frailty, including pre-frailty.
To determine whether a 
home-based physical therapy 
program prevents a decline in 
several higher-level measures 
of physical function.
To report interventions 
targeting the improvement of 
frailty status as an outcome.
To assess the effectiveness 
of CGA.
To determine whether an 
intervention could reduce 
frailty and improve mobility.
To determine whether 
preventive home visits could 
postpone deterioration in 
frailty.
Physical, nutritional, and 
cognitive interventional 
approaches were effective in 
reversing frailty.
The prevalence of frailty 
increases with age and, at any 
age, lessens survival. 
The best interventions and 
policies to prevent or reduce 
the level of frailty.
The British Geriatrics Society 
Fit for Frailty guideline is by 
consensus the best practice 
guidance for managing frailty.
Different operationalization of 
frailty status results in widely 
differing prevalence between 
studies.
Home-based pre-habilitation 
program offered modest, but 
consistent benefits.
The three-month intervention 
resulted in short-term frailty 
status improvement.
CGA showed a favourable 
outcome in frail and pre-frail 
older people.
Frailty and mobility disability can 
be successfully treated.
The results of this study show the 
potential of health promotion to 
older persons. 
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3.1 Summary of Studies Included in Review
3.1.1 Definition of Frailty
Although frailty is a commonly used term to indicate 
older persons at an increased risk for adverse outcomes, 
the consensus about how to define it is lacking (17). 
One consensus definition quotes ‘frailty as a medical 
syndrome with multiple causes and contributors that is 
characterized by diminished strength, endurance, and 
reduced physiologic function that increases an individual’s 
vulnerability for developing increased dependency and/
or death’ (17). Physical frailty is considered to be a 
consequence of a cycle of decreasing energy expenditure, 
negative energy balance and sarcopenia (10). It is a 
state of poor homeostatic reserve due to critically 
decreased physiological reserves and is considered as a 
state of pre-disability (11, 12, 26). Other components, 
such as cognition, mood, social circumstances, living 
environment, income, lifestyle, multimorbidity, disability 
and sensory impairment, should also be included as 
domains of frailty (3, 12). 
3.1.2 Epidemiology of Frailty
Up to 50 years of age, frailty is more prevalent when 
defined by Fried criteria, but after this age, it becomes 
more prevalent when defined as an accumulation of 
deficits or Frailty index (2). In general, the prevalence of 
frailty defined as an accumulation of deficits is 1.3–1.37 
times more prevalent than when it is defined by Fried 
criteria (2, 27). General prevalence of frailty is 9.9% and 
13.6% and of pre-frailty 44.2% and 34.5%, respectively, 
when defined by Fried criteria and by the broad definition 
(27). The prevalence of frailty increases with age, is more 
prevalent in women than in men, and can be as high as 
39.1% in men aged 85 years or older and 45.1% in women 
in the same age group (24).
3.1.3 Tools for Screening and Diagnosing Frailty
There are literally dozens of tools designated to assess 
frailty, ranging from simple to multicomponent (10–15, 
18, 26). There are two principal frailty models, namely: 
the phenotype model (Fried model or CHS Index) and the 
cumulative deficit model (Frailty index) (10, 11). Among 
the definitions of frailty that are valid and reliable for 
predicting the outcome, Fried Frailty Phenotype, Frailty 
Index of Accumulated Deficits and Study of Osteoporotic 
Fractures Index were useful in clinical and population 
settings, while Frailty Index based on CGA, Edmonton 
Frailty Scale and Clinical Frailty Scale were useful only 
in clinical settings (13). In general, of the 38 assessment 
tools, only the Frailty Index-CGA and Tilburg Frailty 
Indicator showed significant evidence of reliability and 
validity (18). There is still no consensus regarding which 
tool should be used for screening and diagnosing frailty 
(12). Fried criteria and Frailty Index of Accumulated 
Deficits appear to be the most robust assessment tools to 
be used by clinicians and researchers today, and should 
consequently prove to be the most useful ones either for 
screening and diagnosing frailty (Fried criteria) or as an 
assessment and follow-up tool (Frailty index derived from 
CGA) (13).
3.1.4 Interventions in Frailty
Supplementation of vitamin D might have positive 
effects on muscle strength and physical frailty in adults 
over 65 years old and vitamin D deficient individuals 
(20, 21). Regular physical activity effectively decreases 
the number of frailty criteria and the prevalence of 
frailty in community-dwelling sedentary older people 
(22). Exercise has a positive impact on some physical 
outcomes and on functional ability in frail older people 
(19). Multicomponent training interventions performed 
three times per week for 30–45 minutes per session over 
a period of more than 5 months seem to be superior to 
other exercise programs (19). A home modification and 
progressive competency-based exercise programme can 
reduce the level of frailty in older people (25).
In a community-dwelling pre-frail or frail older people, 
nutrition, cognitive training, physical activity and 
combination treatment in duration of 6 months improve 
frailty score and frailty status (23). Combined training of 
a shorter duration is effective, but the results are less 
sustainable (28).
CGA consisting of evaluation and management of frail 
older people can be an effective way to decrease frailty 
status (29, 30). When performed in geriatric wards, 
comprehensive geriatric assessment increases a patient’s 
likelihood of being alive, at home and experiencing 
improved cognition (32).
Home-based physiotherapy seems to decrease frailty, but 
preventive home visits are not very effective (31, 33). 
4 DISCUSSION
We identified four main areas essential for clinical 
management of frailty: definition of frailty, epidemiology 
of frailty, tools for screening and diagnosing frailty and 
successful interventions for decreasing frailty.
Frailty is not a disease with a disturbing set of symptoms 
and signs that would prompt an individual to seek the 
attention of medical personnel. A potentially frail 
individual should therefore primarily be approached in a 
proactive manner. 
Studies show a unanimous consent that frailty carries 
the risk of poor outcomes. Defining frailty remains 
elusive, but the concept emerging from the efforts 
to do so encompasses the influence of irreversible or 
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non-preventable (age, ethnicity, etc.) and reversible 
or preventable (morbidity, income, lifestyle, etc.) 
determinants that cause a decline in physiologic reserve, 
resulting in poor homeostatic reserve that can be critically 
challenged with minor intrinsic or extrinsic stressors 
resulting in morbidity, decreased functional ability or 
disability, or death.
As a proactive approach is sensible, individuals should 
be screened and assessed for frailty when present. It 
is neither practical nor feasible to evaluate the entire 
population but targeting those with determinants 
associated with frailty and older population makes sense 
with support in epidemiological data. 
There are many tools to screen for and diagnose or assess 
frailty in an individual person. As screening for frailty 
is performed more feasibly when focusing on physical 
frailty, it could be the first step in clinical management. 
Subsequent assessment should include CGA to identify 
all potential contributors and plan the interventions and 
follow-up. The CGA derived Frailty index is better suited 
for evaluating the effect of interventions than were the 
tools for assessing physical frailty (i.e., Fried criteria).
From a clinical point of view, the evidence that physical 
interventions, provided that they are sufficiently intensive 
and performed over a sufficient time span, are successful 
in the treatment of frailty is highly regarded. To the best 
of our knowledge, only the data from one RCT show both 
the effect of cognitive training as well as the explicit 
effect of nutrition intervention (protein, energy, vitamin 
and mineral supplementation) on frailty (24). Although it 
is recommended to supplement vitamin D in older people 
in order to alleviate the consequences of frailty, there are 
only conditional data to support treatment of frailty with 
vitamin D. In this regard, we consider vitamin D as more 
of a marker than a risk factor or contributor for frailty. 
CGA appears to have a central role in the management 
of frailty. There are robust data of its effectiveness when 
performed in specialized wards for hospitalized frail older 
people, who are the most vulnerable frail population. 
Interventions are much more effective when implemented 
in those populations that at the greatest risk, and in this 
regard, geriatric wards should be highly encouraged to 
perform CGA.
The value of our review lies in a comprehensive 
evaluation of all the elements necessary to provide care 
to a frail person. We believe the presented work is very 
informative, not only for busy clinicians unfamiliar with 
concept of frailty, but also for service planners, providers 
and payers, since frailty prevention, postponement or 
treatment involves many stakeholders and/or requires a 
multidisciplinary approach.
There are some limitations to our review. Because there is 
no generally accepted definition of frailty, we very likely 
missed many studies that could otherwise be included 
in this review. We did not find a substantial body of 
new research on this topic, therefore, the majority of 
interventions have already been more or less firmly and 
explicitly recommended in the report from the consensus 
conference with the participation of experts from six 
major international, European and US societies published 
in 2013 (17).
We are aware of the development of drugs to treat 
sarcopenia and we look forward to studies that will 
evaluate those drugs in the context of frailty prevention 
and treatment (34).
To the best of our knowledge, several questions remain 
unanswered, such as whether different age groups require 
different approaches to the issue of frailty, whether 
management and treatment of multimorbidity can have 
an effect on frailty, and whether public health measures 
can be effective in preventing and treating frailty.
5 CONCLUSION
The aim of this research was to define interventions in a 
successful clinical management of frail people. For the 
purposes of this research, a systematic literature review 
method was used. The method proved to be appropriate 
and the aim was achieved. Our research can serve as a 
base for a comprehensive model of clinical management 
of frailty.
Results of this review show that prevalence of frailty 
ranges from 5% to more than 45%, depending on the 
definition and age group. Although not ideal, Fried 
criteria and Frailty Index of Accumulated Deficits can be 
recommended for clinical work and research purposes. 
They can be used consequently, as Fried criteria are more 
feasible for screening, whereas Frailty Index, derived 
from comprehensive geriatric assessment, is better suited 
for management and follow-up. Comprehensive geriatric 
assessment is a multidimensional, multidisciplinary 
diagnostic instrument addressing medical, psychosocial, 
functional and social capabilities and limitations of older 
persons, which aims to generate a plan of treatment and 
follow-up and is, therefore, a core activity in geriatric 
medicine (6). Multicomponent physical training of 
appropriate duration and frequency, and multidimensional 
interventions combining vitamin D, nutrition, cognitive 
training and physical activity, particularly when based 
on comprehensive geriatric assessment, are effective to 
reduce frailty.
The main drawback of the current literature review is the 
fact that it does not include a meta-analysis of included 
results. 
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CONFLICTS OF INTEREST 
The authors declare that no conflicts of interest exist.
FUNDING 
This publication arises from the Joint Action ‘724099 
/ ADVANTAGE’, which has received funding from the 
European Union’s Health Programme (2014–2020). 
The content of this report represents the views of the 
author only and is his/her sole responsibility; it cannot 
be considered to reflect the views of the European 
Commission and/or the Consumers, Health, Agriculture 
and Food Executive Agency or any other body of the 
European Union. The European Commission and the 
Agency do not accept any responsibility for the use that 
may be made of the information it contains.
ETHICAL APPROVAL
Not applicable.
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