Prevalence and incidence of chronic wounds and related complications: a protocol for a systematic review
Järbrink et al. Systematic Reviews
Prevalence and incidence of chronic wounds and related complications: a protocol for a systematic review
Krister Järbrink 0 1
Gao Ni 0 1
Henrik Sönnergren 1 4
Artur Schmidtchen 1 3
Caroline Pang 1 6
Ram Bajpai 0 1
Josip Car 0 1 2 5
0 Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of Medicine, Nanyang Technological University , 59 Nanyang Drive, Experimental Medicine Building, Singapore 636921 , Singapore
1 Recommendations Assessment, Development and Evaluation; PRISMA-P, Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols; PROSPERO, International Prospective Register of Systematic Reviews
2 Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London , 3rd Floor Reynolds Building, St Dunstan's Road, London W6 8RP , UK
3 Dermatology and Innate Immunity Laboratory, Lee Kong Chian School of Medicine, Nanyang Technological University , 59 Nanyang Drive, Experimental Medicine Building, Singapore 636921 , Singapore
4 Department of Dermatology, Skåne University Hospital , Lasarettsgatan 15, 221 85 Lund , Sweden
5 Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London , 3rd Floor Reynolds Building, St Dunstan's Road, London W6 8RP , UK
6 Medical Library, Lee Kong Chian School of Medicine , 11 Mandalay Road , Singapore 636921 , Singapore
Background: Chronic wounds impose a significant and often underappreciated burden to the individual, the healthcare system and the society as a whole. Preliminary literature search suggests that there are at present no reliable estimates on the total prevalence of chronic wounds for different settings and categories of chronic wounds. Such information is essential for policy and planning purposes as the increasing number of elderly and the prevalence of lifestyle diseases point in the direction of an increased burden. Knowledge about the prevalence and incidence of chronic wounds in relation to population characteristics is important for informing healthcare planning and resource allocation. The objective is to present a transparent process for how to review the existing literature on the prevalence and incidence rates of chronic wounds and resulting implications. Methods/design: We will search electronic bibliographic databases (MEDLINE, EMBASE, the EBM Reviews and Cochrane, Cumulative Index to Nursing and allied Health Literature (CINAHL), PsycINFO, Global Health) and reference lists of included articles. Two investigators will independently screen titles and abstracts and select studies involving adults with chronic wounds. These investigators will also independently extract data using a pre-designed data extraction form that will cover information on demographics, diagnostics including disease prevalence, medical history, hospital and community-based management and outcomes. Subgroup analysis and sensitivity analysis will be performed to address the heterogeneity across studies. Meta-analysis will also be performed if homogeneous group of studies will be found. The collective evidence will be further stratified according to the important background variables if allowed. Discussion: This study will describe the available epidemiological evidence and summarise prevalence and incidence rates of chronic wounds and related complications. A better understanding of the relationship between population profile and the prevalence of chronic wounds and related complications will be helpful in the development of guidelines for patient management. Systematic review registration: PROSPERO CRD42016037355
Chronic wounds; Hard-to-heal ulcers; Wound infection; Ulcer; Wound healing; Diabetic foot; Amputation; Epidemiology; Prevalence; Incidence
A chronic wound can be defined as one that has failed
to proceed through an orderly and timely reparative
process to produce anatomic and functional integrity
within a period of 3 months or that has proceeded
through the repair process without establishing a
sustained, anatomic and functional result [
nomenclature is far from agreed upon, and these wounds are
sometimes referred to as hard-to-heal or difficult-to-heal
wounds/ulcers, and the time span required for chronicity
has been defined in the range 4 weeks up to more than
3 months [
]. Based on the causative aetiologies, the
Wound Healing Society classifies chronic wounds into
four categories: pressure ulcers, diabetic ulcers, venous
ulcers and arterial insufficiency ulcers . Chronic
wounds are often termed ulcers and can be defined as
wounds with a full thickness in depth and a slow healing
tendency. Often disguised as a comorbid condition,
chronic wounds represent a silent epidemic that affects
a large fraction of the world population [
]. It is
estimated that 1 to 2 % of the population will experience a
chronic wound during their lifetime in developed
]. The dramatic increase in the ageing
population will increase these numbers as wound closure
is negatively associated with age [
]. Complications of
chronic wounds include infection such as cellulitis and
infective venous eczema, gangrene, haemorrhage and
lower-extremity amputations. Chronic wounds lead to
disability and disability worsens wound outcomes
resulting in a vicious cycle [
Due to the low base rate of complete healing in the
natural history [
], chronic wounds have a significant
impact on the health and quality of life of patients and
their families, causing pain, loss of function and
mobility, depression, distress and anxiety, embarrassment and
social isolation, financial burden, prolonged hospital
stays and chronic morbidity or even death [
suggests that chronic wounds impose significant and
often underappreciated burden to the individual, the
healthcare system and the society as a whole [
the USA, for example, chronic wounds are reported to
affect 6.5 million patients with more than US$25 billion
each year spent by the healthcare system on treating
wound-related complications . The costly nature of
chronic wound management is further confirmed with
estimates from the UK, where the cost to the National
Health Service of caring for patients with chronic
wounds were conservatively estimated at US$3.4–4.6
billion per year (in 2005) representing around 3 % of the
total estimated out-turn expenditure on health for the
same period [
Preliminary literature search suggests that there are at
present no reliable estimates on the total prevalence and
incidence of chronic wounds for different settings and
categories of chronic wounds [
]. The wide disparity of
the epidemiological estimates arises mainly from
significant heterogeneity in terms of study design and data
collection method [
]. The varieties also come from the
way of reporting prevalence: some report point
prevalence while others report period prevalence [
same disparity is also found in incidence reports. We
aim to embrace a larger number of databases and a
considerable broader search strategy compared to a
previous review [
]. We also intend to thoroughly assess
and consider the quality of included studies and carefully
pay regard to the applied definitions of chronic wounds.
These approaches are believed to provide more reliable
estimates on the prevalence for different settings and
categories of chronic wounds than previously presented.
Such information is essential for policy and planning
purposes particularly as the increasing number of elderly
and the increase in the prevalence of lifestyle diseases
further raise the risk for chronic wounds. The literature
review is intended to gather the existing knowledge and
identify factors of importance to the prevalence of
chronic wounds and to the incidence of complications.
The focus is on chronic wounds in the categories of
pressure ulcers, diabetic ulcers, venous ulcers and
arterial insufficiency ulcers.
Specific review questions are:
What is the prevalence and incidence of chronic
wounds in the categories of pressure ulcers, diabetic
ulcers, venous ulcers and arterial insufficiency
ulcers, for different settings and subgroups
according to internationally published studies?
What is the prevalence and incidence of infections,
gangrene, haemorrhage and limb amputation among
patients with chronic wounds in the categories of
pressure ulcers, diabetic ulcers, venous ulcers and
arterial insufficiency ulcers, for different settings
and subgroups according to internationally
Further knowledge about the distribution of chronic
wounds and related complications in different settings
and among subgroups is essential for informing healthcare
planning and resource allocation. Pooling of such data is
also necessary to monitor trends in disease burden and to
contribute to the design of further etiological studies.
The overall aim of this systematic review protocol is to
present a transparent process for how the information
will be collected on the prevalence and incidence of
chronic wounds and related complications. This will
include the key research questions that this systematic
review will address, a description of systematic literature
search strategies, criteria for inclusion or exclusion of
studies, a description of coding procedures, study quality
measures and statistical procedures for the quantitative
analysis of data from eligible studies.
The methods for this systematic review have been
developed according to the recommendations from the
Preferred Reporting Items for Systematic Review and
Meta-Analysis Protocols (PRISMA-P) 2015 statement
]. This systematic review protocol has been
registered in the International Prospective Register of
Systematic reviews (PROSPERO): CRD42016037355). A
PRISMA-P file is attached (see Additional file 1).
The population of interest will include adult patients
18 years of age and older with pressure ulcers, diabetic
ulcers, venous ulcers and arterial ulcers. Patients with
chronic wounds resulting from surgical wounds and skin
tumours will be excluded.
The primary outcome will be the point prevalence,
period prevalence, cumulative incidence and incidence
rate of chronic wounds in the categories of pressure
ulcers, diabetic ulcers, venous ulcers and arterial ulcers,
and complications thereof in four categories (infections,
gangrene, haemorrhage and limb amputation).
Secondary outcomes will be dropping out, the reasons for that,
and the number of deaths by cause.
Studies will be restricted by design and observational
studies, cross-sectional studies, cohort studies,
casecontrol studies, single arm studies and systemic review/
meta-analyses will be included. Non-research letters and
editorials, seminar reviews, case studies, case series and
animal studies will be excluded. Randomised controlled
trials will be excluded based on methodological
inappropriateness of research design for the type of questions to
Searches will be limited to peer-reviewed full text
articles in English language, and letters, abstracts and
editorials are to be excluded. There will be no
geographical limitation on the included studies.
A systematic search of MEDLINE (Ovid), EMBASE (Ovid),
EBM Reviews and Cochrane (Ovid), Cumulative Index to
Nursing and Allied Health Literature (CINAHL) (EBSCO),
PsycINFO (EBSCO) and Global Health (EBSCO) will be
undertaken. As we are primarily interested in the
contemporary literature on this topic, we will examine publications
from January 2000 through December 2015. Contact with
authors for further information will be made when
necessary. Detailed inclusion and exclusion criteria are presented
in Table 1.
We will develop a comprehensive database containing
all published studies addressing the prevalence and
incidence of chronic wounds (including hard-to-heal
wound/ulcers) and complications thereof in general
populations. To construct a comprehensive set of
possible search terms, we list indexing terms (for example,
subject headings and subheadings, publication types)
and text words used to describe concept clusters (single
words or phrases that may appear in titles or abstracts,
both in full and in various truncations). For instance, we
search pressure ulcer with its keyword “pressure ulcer”
with all heading and subheadings, and then we search
alternative keywords “pressure sore” or “bed ulcer” or
“bed sore” appearing in the title or abstract in the form
of full or truncations. We sought further terms from
clinicians and librarians, and from published strategies
from other groups. The search strategy was developed
by the research team in collaboration with an
experienced medical research librarian at the Lee Kong Chian
School of Medicine. Additional comments and
suggestions were also received from an experienced librarian at
the Karolinska Institutet and incorporated. The search
was revised, as necessary, and the final MEDLINE search
is presented in Additional file 2. After MEDLINE
strategy is finalised, it will be adapted to the syntax and
subject headings of other databases.
The reference lists of all included articles published
from January 2000 and beyond will also be searched for
any additional sources of information. An additional
search will be made using the newly introduced term
“pressure injury” [
] and relevant articles added.
We will implement the search strategies and import all
references identified to EndNote. The search results
from the different electronic databases will be combined
in a single EndNote library and we will remove duplicate
records of the same reports.
Two reviewers will independently screen titles and
abstracts against eligibility criteria to identify potentially
included studies. Specifically, titles and abstracts are
included if they indicate that it was a population-based
or institutional-based study reporting any relevant
information on prevalence or incidence of chronic wounds
and/or complications thereof. In the next phase, we will
retrieve full-text copies of those articles deemed
potentially relevant. Two reviewers will independently assess
the full text of the retrieved articles for compliance with
our eligibility criteria.
Discrepancies between the two reviewers’ judgement
will be resolved by discussion or by the involvement of a
third reviewer. Studies, which appeared to be relevant,
but excluded at this stage will be listed in the table
“Characteristics of excluded studies”, where a reason for
exclusion will be noted. Two reviewers will verify the
final list of included studies. A PRISMA flow diagram of
the study selection procedure will be prepared to
provide an overview of the decisions that are made in
the data collection process.
Data collection process
Two reviewers will independently extract and manage
the data for each of the included studies using an
electronic data extraction form. We will pilot the data
extraction form and amend it according to feedback
received from a panel of experienced colleagues. We
plan to contact study authors in case of any unclear or
missing information. Disagreements between review
authors will be resolved by discussion. A third review
author will act as an arbiter in case disagreements
cannot be resolved. Variations that may depend on
agedistribution, the categorisation of ulcer, study design etc.
will be described clearly.
Data will be extracted on the following.
1. Publication details: title, journal, author, year, city
and country, in which the study was conducted, type
of publication, and source of funding.
2. Design: type of study (observational studies,
crosssectional, cohort, case-control, single arm studies,
Patients with chronic wounds as a result
of surgical wounds and skin tumour.
Randomised controlled trials, case studies,
Abstract, non-research letters and editorials,
systemic review/meta-analyses); aims of study,
method of data collection, response rate, recruitment
and sampling methods, eligibility (inclusion and
3. Study participant details: number of persons
interviewed or surveyed, population characteristics
including setting, age, gender, ethnicity,
demographic information, diagnostics, ulcer
specifications (including stage), complications.
4. Data for outcome measures: all reported
estimates, or sufficient information to calculate
an estimate of the point prevalence, period
prevalence, cumulative incidence and incidence
rate of chronic wounds in the categories of
pressure ulcers, diabetic ulcers, venous ulcers and
arterial ulcers, and complications thereof in four
categories (infections, gangrene, haemorrhage and
5. Limitations: selection bias, response bias,
information bias, limitations of assessment tool(s)
used and limitations reported by study authors.
Risk of bias in individual studies
The risk of bias in included studies will be assessed
using a tool developed specifically for conducting
quality appraisal of studies in systematic reviews of
prevalence data [
]. The instrument addresses critical
issues of internal and external validity that must be
considered when assessing validity of prevalence data
and can be used across different study designs. The
instrumental framework evaluates representativeness,
recruitment, sample size, reporting, data coverage,
condition reliability, statistical analysis and
confounding factors using a simple “yes”, “no”, “unclear” or
“not/applicable”. The outcome of the assessment will
be presented in a table.
Publication bias and selective reporting will be dealt
with by critically assessing study findings, plots will
be made of outcome variables against sample size
] and advice will be taken from GRADE guidelines
No 5 [
Relevant data extracted from eligible studies will be
presented in evidence tables. Meta-analysis of outcome
variables will be conducted if studies are adequately
meeting the inclusion criterion and uniform (or clarity)
in reporting the outcome estimates. A narrative
synthesis will provide summary of the prevalence of chronic
wounds and complications thereof according to age,
setting and category of wound. These grouping variables
will also be used to identify similar patient populations
so that quantitative meta-analyses could be made for
studies with similar design. The extracted incidence and
prevalence figures will be presented with corresponding
standard error and 95 % confidence intervals using the
exact binomial method as described by Clopper and
]. This method produces an exact
confidence interval that is directly based on the binomial
distribution rather than any approximation to the
Further, the individual prevalence and incidence rate
estimates from observational studies will be pooled
using the fixed effect and random effect models [
The choice of random-effects model will be based on
clinical and methodological diversity across the included
studies. We will also perform cumulative meta-analysis, in
which estimates for each year will be determined in order
to calculate the impact of each added study on the pooled
estimates over time. For country-specific pooling of
incidence/prevalence data, the Poisson regression
technique will be used to adjust the covariates [
available, the prevalence-adjusted or incidence-adjusted
odds ratios relating to the stratification of risk of
chronic wound among the patients as discussed in the
respective observational studies will also be pooled
using random effect models. We will investigate the
potential source of heterogeneity related to both
methodological and clinical characteristics of the studies
which will be assessed by the Cochran’s Q test (P value
<0.05 considered significant) and I2 (>50 % representing
moderate heterogeneity) statistics [
]. In the presence
of heterogeneity (I2 > 25 %) [
], subgroup (e.g. age,
sex, setting and clinical categories of chronic wounds)
analyses and univariate meta-regression (P value <0.10
considered significant given the low power of these
tests) will be carried out in order to estimate the effect
of study-level covariates on the estimates of incidence
and prevalence [
]. Sensitivity analyses will be
conducted to identify the study-level factors that best
describe the occurrence of chronic wounds. We will also
perform influence and outlier analyses to determine the
effects of certain studies on the pooled estimates of
chronic wound occurrence [
]. These analyses will
measure how the estimated parameter of a
pooledanalysis would change if noisy studies are eliminated.
The effect of these identified outlier studies will be
neutralised by excluding them from the random effect
model. The publication bias due to study size will also
be addressed and adjusted by inverse-variance
weighting techniques to provide valid information on the
study estimates [
This systematic review and eventually meta-analysis will
be performed to critically examine the world’s relevant
literature on the epidemiology of chronic wounds.
Specifically, we aim to identify and report the estimated
prevalence and incidence of chronic wounds in the categories
of pressure ulcers, diabetic ulcers, venous ulcers and
arterial insufficiency ulcers and related complications
for different settings and subgroups. We will also
identify population characteristics associated with
chronic wounds in the four categories and with the
following complications: infections, gangrene,
haemorrhage and limb amputation. Understanding the rates
of different categories of complications among
patients with chronic wounds could help target patient
subgroups that may benefit from early screening,
prevention, and treatment efforts. In addition, quantifying
the magnitude of chronic wounds will help guide
decision-making for the allocation of scarce healthcare
resources and funding. A further finding of this
systematic review will be the result of the
methodological assessment of the published literature. The
findings of this review will also be compared with
other similar published reviews. Finally, conclusions
will be drawn from this systematic review highlighting
the prevalence and incidence of chronic wounds,
methods of estimation and settings and their
correlates. Limitations of the studies will be discussed in
detail. Implications of the review as well as
suggestions for future research will also be provided.
Additional file 1: PRISMA-P checklist. (DOC 84 kb)
Additional file 2: MEDLINE (Ovid) search strategy. (DOCX 32 kb)
We are grateful to Carl Gornitzki at the university library at the
Karolinska Institutet, Sweden, for invaluable support in the refinement
of the search strategies.
This research is supported by the A*STAR BMRC Strategic Positioning Fund
(SPF) for Skin Biology awarded to the Institute of Medical Biology, and
through internal grant funding from the Lee Kong Chian School of Medicine,
Nanyang Technological University. The views expressed are those of the
authors and not necessarily those of the NTU or A*STAR. Lee Kong Chian
School of Medicine, NTU and A*STAR have no role as organisations in the
planning, conduct or dissemination of the systematic review.
KJ and GN initiated the protocol, conceptualised the research plan for the
proposed systematic review, wrote the manuscript and reviewed it for
important intellectual content. HS, AS, CP, RB and JC critically reviewed the
methodology, wrote the manuscript and reviewed it for important
intellectual content. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
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