Prevention of Foot Ulcer 2020

Received: 1 June 2019 Revised: 1 September 2019 Accepted: 19 September 2019
DOI: 10.1002/dmrr.3270
SUPPLEMENT ARTICLE
Prevention of foot ulcers in the at-risk patient with diabetes:

a systematic review
Jaap J. van Netten1,2,3 | Anita Raspovic4 | Lawrence A. Lavery5 |

Matilde Monteiro-Soares6 | Anne Rasmussen7 | Isabel C. N. Sacco8 | Sicco A. Bus1
on behalf of the International Working Group on the Diabetic Foot (IWGDF)
1
Amsterdam UMC, University of Amsterdam, Department of Rehabilitation Medicine, Amsterdam Movement Sciences, Meibergdreef 9, Amsterdam, The Netherlands
2
School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
3
Diabetic Foot Clinic, Department of Surgery, Ziekenhuisgroep Twente, Almelo, The Netherlands
4
Discipline of Podiatry, School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, Victoria, Australia
5
Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas
6
MEDCIDES: Departamento de Medicina da Comunidade Informaç~ao e Decis~
ao em Saúde & CINTESIS – Center for Health Technology and Services Research,
Faculdade de Medicina, Universidade do Porto, Porto, Portugal
7
Steno Diabetes Center Copenhagen, Gentofte, Denmark
8
Physical Therapy, Speech and Occupational Therapy Department, School of Medicine, University of S~
ao Paulo, S~ao Paulo, Brazil
Correspondence
Jaap J. van Netten, Amsterdam UMC, Abstract
Department of Rehabilitation Medicine, Prevention of foot ulcers in patients with diabetes is important to help reduce the
Academic Medical Center, University of
Amsterdam, Meibergdreef 9, 1105 AZ substantial burden on both patient and health resources. A comprehensive analysis of
Amsterdam, The Netherlands. reported interventions is needed to better inform healthcare professionals about
Email: [email protected]
effective prevention. The aim of this systematic review is to investigate the effective-
Funding information ness of interventions to help prevent both first and recurrent foot ulcers in persons
European Regional Development Fund; North
Portugal Regional Operational Programme, with diabetes who are at risk for this complication. We searched the available medical
Grant/Award Number: NORTE- scientific literature in PubMed, EMBASE, CINAHL, and the Cochrane databases for
01-0145-FEDER-000016
original research studies on preventative interventions. We screened trial registries
for additional studies not found in our search and unpublished trials. Two indepen-
dent reviewers assessed data from controlled studies for methodological quality, and
extracted and presented this in evidence and risk of bias tables. From the 13,490
records screened, 35 controlled studies and 46 non-controlled studies were included.
Few controlled studies, which were of generally low to moderate quality, were identi-
fied on the prevention of a first foot ulcer. For the prevention of recurrent plantar
foot ulcers, there is benefit for the use of daily foot skin temperature measurements,
and for therapeutic footwear with demonstrated plantar pressure relief, provided it is
consistently worn by the patient. For prevention of ulcer recurrence, there is some
evidence for providing integrated foot care, and no evidence for a single session of
education.Surgical interventions have been shown effective in selected patients, but
the evidence base is small. Foot-related exercises do not appear to prevent a first
Abbreviations: IWGDF, International Working Group on the Diabetic Foot; LOPS, loss of protective sensation; PAD, peripheral artery disease; PICOs, population, intervention, control, outcomes;
PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, randomized controlled trial; SIGN, Scottish Intercollegiate Guidelines Network.
Diabetes Metab Res Rev. 2020;e3270. wileyonlinelibrary.com/journal/dmrr © 2020 John Wiley & Sons Ltd 1 of 22
https://doi.org/10.1002/dmrr.3270
2 of 22 VAN NETTEN ET AL.
foot ulcer. A small increase in the level of weight-bearing daily activities does not
seem to increase the risk for foot ulceration. The evidence base to support the use of
specific self-management and footwear interventions for the prevention of recurrent
plantar foot ulcers is quite strong. The evidence is weak for the use of other, some-
times widely applied, interventions, and is practically non-existent for the prevention
of a first foot ulcer and non-plantar foot ulcer.
KEYWORDS
diabetes mellitus, diabetic foot, foot ulcer, home monitoring, podiatry, prevention, self-
management, shoes, surgery, systematic review
1 | I N T RO DU CT I O N needed to properly inform caregivers about effective preventative

treatment.
Foot ulcers are a major complication of diabetes mellitus, with high The aim of this systematic review is to investigate the effective-
morbidity, mortality, and resource utilization.1-3 Yearly incidence is ness of interventions to prevent first and recurrent foot ulcers in per-
estimated to be around 2%, and lifetime incidence lies between 19% sons with diabetes who are at risk for ulceration and do not have a
and 34%.4 Treatment of these foot ulcers is challenging because of current foot ulcer. This systematic review is an update of our review
their multifactorial aetiology, and it places a high burden on patients, published in 2016.22 This systematic review forms the basis for devel-
health-care systems, and society.5 Even when an ulcer is successfully oping the IWGDF guideline on prevention of foot ulcers in at-risk
healed, risk for recurrence is high, with reported recurrence rates of patients with diabetes.23
4
40% in the first year and 65% in the first 3 years, after healing.
Therefore, prevention of foot ulcers is of paramount importance and
has long been recognized as a priority by the International Working 2 | METHODS
Group on the Diabetic Foot (IWGDF).
Not all patients with diabetes are at risk for foot ulceration. Key risk The systematic review was performed according to the Preferred
factors include a loss of protective sensation (LOPS), foot deformity, Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
peripheral artery disease (PAD), or a history of foot ulceration or any guidelines24 and was in line with the consensus and checklist on
4,6
level of lower-extremity amputation. In general, patients without any updating systematic reviews.25 The systematic review was prospec-
of these risk factors are considered not to be at risk for ulceration. Vari- tively registered in the PROSPERO database for systematic reviews in
ous classification and stratification systems based on these risk factors 2014, and this update was prospectively registered under the same
show similar diagnostic/prognostic results (such as sensitivity, specificity, number (CRD42014012964).
7
predictive values, and likelihood ratios) in predicting ulceration. Despite As a start, the population of interest (P), interventions (I), and out-
the popularity and common use of these systems, the evidence base for comes (O) were defined, and clinical questions (PICOs) were formu-
their use is limited, with little validation of their predictive ability.7 lated accordingly. These definitions and PICOs were reviewed for
There are numerous interventions to prevent foot ulcers that are their clinical relevance by the IWGDF Editorial Board and 14 external
used in routine clinical practice and that have been scientifically evalu- experts worldwide, from various geographical regions. The final defini-
ated. The effectiveness of some of these interventions has been system- tions and PICOs are integrated within this article.
atically reviewed, that is, on complex interventions,8 patient education,9
interventions studied in randomized controlled trials (RCTs),10
11 12
population-based screening, podiatry, therapeutic footwear,13 foot- 2.1 | Population
14
wear and offloading interventions, insoles,15 flexor tenotomy,16 and
cost-effectiveness.17 However, each of these reviews has used different The population of interest for this systematic review was people at
inclusion criteria for their study selection, different patient populations, risk of foot ulceration, defined according to the IWGDF risk stratifica-
and a variety of outcomes, which limit comparisons. Further, foot- and tion as “people with diabetes mellitus and peripheral neuropathy.”5
mobility-related exercises to improve foot, ankle, and lower-extremity Peripheral neuropathy was defined as “the presence of symptoms or
function characteristics have not been included in any review, despite signs of peripheral nerve dysfunction, after exclusion of other cau-
their increased clinical use (eg, Sartor et al,18 Melai et al,19 and Mueller ses.”5 This includes a LOPS in the feet, ie, the inability to perceive light
20
et al ) and despite the importance of weight-bearing activity for general pressure or vibration, eg, as applied with a 10-g Semmes-Weinstein
health.21 Finally, none of these reviews conducted a comprehensive monofilament, tuning fork, or a biothesiometer. This population
analysis of all reported preventative interventions. Such an analysis is includes people with or without foot deformities, PAD, or lower-
VAN NETTEN ET AL. 3 of 22
extremity amputation; and both people in remission from foot ulcera- diabetes mellitus.”5 We defined “first-ever ulcer” as the first-ever
tion and those with no foot ulcer history. recorded diabetic foot ulcer in a patient and “Recurrent ulcer” as a
new ulcer in a patient with a previous diabetic foot ulcer, irrespective
of its location and time. We have reported these separately, because
2.2 | Interventions patients with a previous ulcer are at higher risk than are those
without,6 thus requiring more preventative foot care. If a study
We included eight interventions with the goal of preventing a first- included both patients with and without a previous ulcer but did not
ever or recurrent foot ulcer: present data separately for these patients, the primary outcome was
classified based on the majority of included patients. If a study did not
1. Foot self-care: consisting of, but not limited to footwear inspec- specify ulcer history, it was included as “first-ever/recurrent ulcer.”
tion, washing of feet, careful drying between the toes, proper The following outcomes were considered important but not criti-
nail cutting, using emollients to lubricate skin, foot inspection, cal: lower-extremity amputation, ulcer severity (based on depth, ische-
avoiding chemical agents or plasters to remove callus, not walk- mia or infection), ulcer-free survival days, health-related quality of life,
ing barefoot or with only socks or in shoes with holes, not wear- and financial costs. While lower-extremity amputations are important,
ing tight socks, and avoiding foot exposure to excessive cold they are not the primary aim of a preventative intervention, as that
or heat. will be focused on ulcer prevention. No ulcer will generally mean no
2. Structured education about foot self-care: any educational modal- amputation. Moreover, when an ulcer develops, the need for and
ity that is provided to patients in a structured way. This may decision to amputate is greatly affected by the care provided for the
include, but is not limited to, one-to-one verbal education, motiva- ulcer.5 We therefore include this outcome as “important, but not
tional interviewing, educational group sessions, video education, critical.”
booklets, computer software, quizzes, or pictorial education via
animated drawing or descriptive images.
3. Foot self-management: interventions consisting of, but not limited 2.4 | Inclusion and exclusion criteria
to home monitoring systems, lifestyle interventions, telemedicine,
technological applications, and peer support programmes. We included original studies that reported on the population of inter-
4. Treatment of risk factors or pre-ulcerative signs on the foot: for est, at least one of the predefined interventions, and a critically impor-
example, removing callus and treating haemorrhagic callus, tant outcome. We excluded studies on healthy subjects, on persons
protecting blisters and draining when necessary, or treating dry with other diseases but no diabetes, or on persons with diabetes who
skin fissures and cracks not extending into the dermis. were not at risk for foot ulceration. We only included studies enrolling
5. Orthotic interventions: including therapeutic footwear (eg, shoes, persons with an active ulcer if they reported outcomes on ulcer recur-
insoles and orthoses) and walking aids (eg, crutches or stick). We rence after healing of the active ulcer. We excluded studies reporting
defined this as any footwear or insole designed with the intention on interventions with outcomes indirectly related to ulcer prevention,
of offloading pressure from a foot site, for example, with custom- but not reporting any of the critically important outcomes relevant to
made shoes, prefabricated extra-depth shoes, custom-made this review, eg, studies with results on foot care behaviour, knowledge
orthotics/insoles, prefabricated orthotics/insoles, or shoe modifi- and awareness, quality of life, pre-ulcerative lesions, or plantar pres-
cations such as rocker-bottom sole, metatarsal bar, or felted foam. sure, as these were included in a separate systematic review
6. Surgical interventions: eg, Achilles tendon lengthening, tendon (Prospero registry: CRD42018105073). We included systematic
flexor tenotomy, single or pan-metatarsal head resection, meta- reviews and meta-analyses, RCTs, nonrandomized controlled trials,
tarsophalangeal joint arthroplasty, or nerve decompression. case-control studies, cohort studies, (controlled) before-and-after
7. Foot-related exercises: any physical exercise specifically targeting studies, interrupted time series, prospective and retrospective non-
any part of the lower extremity with the aim of changing foot func- controlled studies, cross-sectional studies, and case series but
tion parameters (eg, strength or mobility). excluded case reports. Systematic reviews were only included when
8. Integrated foot care: care given by one or multiple collaborating all publications identified in the systematic review met our inclusion
professionals treating patients on multiple occasions, possibly at criteria, or when a meta-analysis was presented based on publications
multiple locations, with multiple interventions, also including refer- meeting our inclusion criteria. If not, reference checking of the papers
rals between different levels of health care. identified in the systematic review was performed, but the systematic
review itself was excluded.
2.3 | Outcomes
2.5 | Search strategy
Critically important outcomes were first-ever diabetic foot ulcer and
recurrent diabetic foot ulcer. We defined a diabetic foot ulcer as a The literature search was performed on 24 July 2018 and covered
“full thickness lesion of the skin distal to the malleoli in a person with publications in all languages. See Appendix S1 for a detailed
description of the search strings. The following databases were scoring sheet, risk of bias was determined for each study as very low
searched: PubMed, Excerpta Medica Database (EMBASE) via Ovid SP, when scoring ≥8/10, low when scoring 6-7/10, or high when scoring
Cochrane Database of Systematic Reviews, Cochrane Database of ≤5/10. The SIGN level of evidence was determined for each publica-
Abstracts of Reviews of Effect, and Cochrane Health Technology tion (https://www.sign.ac.uk/assets/study_design.pdf). Level 1 refers
Assessment. to systematic reviews or RCTs, and level 2 refers to case-control,
To further assess for possible publication bias or selective cohort, controlled before-and-after designs, or interrupted time series.
reporting of results, the WHO-ICTRP trial registry (http://apps.who. Data were extracted from each included publication with a controlled
int/trialsearch/default.aspx) search was updated, limited from the pre- study design and summarized in the evidence tables. This included
vious search date (30 July 2014) to 25 July 2018. The Clinicaltrials. patient and study characteristics, characteristics of the intervention
gov registry was also searched separately (https://clinicaltrials.gov), and control conditions, and primary and secondary outcomes. One of
limited from 2014 to 25 July 2018 (Appendix S1). Two reviewers the reviewers extracted the data, and the other reviewer checked this
independently assessed identified trials for eligibility on the basis of for content and presentation. All members of the working group thor-
three criteria: patient group, outcomes, and intervention. Reviewers oughly discussed the evidence tables. To prevent any conflict of inter-
obtained status of eligible trials (“completed,” “ongoing,” or “not yet est, reviewers did not participate in the assessment and data extraction
started”) from the databases. Cohen kappa was calculated for agree- of publications of which they were a co-author.
ment. Reviewers solved disagreement concerning eligibility by discus-
sion until consensus was reached. Any relevant publication related to
a completed trial was searched for in the same databases as for the lit- 2.8 | Evidence statements
erature search. If no publications were identified, the principal investi-
gator of the trial was contacted once for more information. Finally, the two reviewers per intervention drew conclusions based on
the strength of the available evidence, formulated as evidence state-
ments and accompanying assessment of the quality of the evidence
2.6 | Eligibility assessment (QoE), according to GRADE.28 The authors rated the QoE for each for-
mulated evidence statement as “high,” “moderate” or “low.” GRADE
Per intervention, teams of two members of the working group inde- defines “high” as “further research is unlikely to change our confidence
pendently reviewed publications by title and abstract for eligibility to in our evidence statement”; “moderate” as “further research is likely to
be included in the analysis, based on four criteria: population, study have an impact on our confidence in our evidence statement”; and
design, intervention, and outcomes. We used the online application “low” as “further research is very likely to have an impact on our confi-
Rayyan for eligibility assessment.26 Cohen kappa was calculated for dence in our evidence statement.”28 The rating was determined based
agreement between reviewers. Reviewers discussed and reached con- on the level of evidence, risk of bias, consistency of results, publication
sensus on any disagreement on inclusion of publications. Subse- bias, effect size, and evidence of dose-response relation.28 All mem-
quently, the same two reviewers independently assessed full-paper bers of the working group discussed these evidence statements until
copies of included publications on the same four criteria for final eligi- consensus was reached.
bility. Conference proceedings, if included after assessment of title
and abstract, were used to search for full-paper publications. If no
full-paper copy of the study was found, we contacted the authors 3 | RE SU LT S
once for more information, to assess for any possible publication bias
or selective reporting of results. In total, 91 publications were included (see for details the PRISMA
flowchart in Figure 1). We will describe the results for each interven-
tion with the concluding evidence statements (Table 1). Risk of bias
2.7 | Assessment of included publications assessment scores of controlled studies can be found in Table 2. All
results per included controlled study are described in the evidence
We used the Scottish Intercollegiate Guidelines Network (SIGN) algo- table (Appendix S2).
rithm for classifying study design for questions of effectiveness
(http://www.sign.ac.uk/pdf/studydesign.pdf). The same two reviewers
per intervention independently assessed included publications with a 3.1 | Foot self-care
controlled study design for methodological quality (ie, risk of bias),
using scoring sheets developed by the Dutch Cochrane Centre (www. PICO: In people with diabetes at risk for foot ulceration, can foot self-
cochrane.nl) and the 21-item score for reporting standards of studies care, compared with no self-care, help prevent a first-ever or recur-
and papers on the prevention and management of foot ulcers in diabe- rent diabetic foot ulcer?
27
tes. Reviewers resolved disagreement regarding risk of bias by dis- Summary of the literature: We found two noncontrolled studies.29,30
cussion until consensus was reached. Depending on the number of In a noncontrolled study of 318 neuropathic patients, who underwent
questions answered with “yes” on the 10 items of the Cochrane four 90- to 120-minute foot educational sessions held during 1 week and
were followed up for at least 3 years, those adherent to the foot care Summary of the literature: We found two systematic reviews
habits taught in the educational session presented with a significantly with meta-analyses,9,31 including six RCTs of which three met our
lower percentage of ulceration: 3.1% vs 31.6%; P < .001.29 Another non- inclusion criteria32-34 and three did not,35-37 as well as one additional
controlled study included 3245 participants with diabetic neuropathy RCT.38 While some RCTs in these meta-analyses included participants
who were educated regarding diabetic foot disease and its complications. without neuropathy, thereby not meeting our inclusion criteria of
At 18-month follow-up, they found a combined ulcer or foot infection “only at-risk patients,” we decided to include a description of both
(with or without ulceration) incidence of 5.8%; those adherent to the meta-analyses, as three of the six included RCTs did meet our inclu-
advice for at least 5 days a week presented with a lower incidence than sion criteria. As neither meta-analysis differentiated between first-
did those who did not (5% vs 26%; P < .0001; Viswanathan et al30). ever and recurrent foot ulcer, we combined these outcomes.
Evidence statement: In people with diabetes at risk of foot ulcer- Adiewere and colleagues31 performed a systematic review with
ation, adherence to foot self-care might reduce the risk of developing meta-analyses with low risk of bias, including six RCTs of which five
a foot ulcer. were with high risk of bias32,34-37 and one with low risk of bias.33 In a
Quality of the evidence: Low. Based only on noncontrolled combined random effect model comparing education about foot self-
studies. care with usual care, meta-analyses over a total of 1349 participants
(680 intervention and 669 control) resulted in a risk ratio (RR) of 0.52
(95% CI, 0.23-1.15; P = .11; I2: 90%) for ulcer prevention. A sub-
3.2 | Structured education about foot self-care analysis on four RCTs33-35,37 for intensive vs brief education (of which
two met our inclusion criteria33,34) resulted in an RR of 0.37 (95% CI,
PICO: In people with diabetes at risk for foot ulceration, can providing 0.14-1.01; P = .05; I2: 91%) for ulcer prevention. Based on two
structured education about foot specific self-care, compared with RCTs,33,35 an RR of 0.57 (95% CI, 0.20-1.63; P = .29; I2: 69%) for
not providing it, help prevent a first-ever or recurrent diabetic foot amputation prevention was found. Dorresteijn and colleagues per-
ulcer? formed a systematic review with meta-analyses,9 but since the four
F I G U R E 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Note: Numbers are given for the 2014 and 2018
literature searches separately, for search strings 1, 2, and 3, and the trial registries. Search string 4 was only done in 2018. Search string 1 included
interventions foot self-care, education, and self-management; search string 2 included treatment of risk factors or pre-ulcerative signs on the foot and
integrated foot care; search string included orthotic and surgical interventions; search string 4 included foot-related exercises. Cochrane CRCT and
Cinahl were not searched in 2018. CRCT, Central Register of Controlled Trials; DARE, Database of Abstracts of Reviews of Effects; DSR, Database of
Systematic Reviews; HTA, Health Technology Assessment; WHO-ICTRP, World Health Organization International Clinical Trials Registry Platform
TABLE 1 Evidence statements per intervention category for the prevention of a first-ever or recurrent diabetic foot ulcer
Intervention Evidence Statement QoE References

Foot self-care In people with diabetes at risk of foot ulceration, Low Viswanathan et al 200530; Calle-Pascual et al
adherence to foot self-care might reduce the 200129
risk of developing a foot ulcer.
Structured education about In people with diabetes at risk for foot Low Adiewere et al 201831; Dorresteijn et al 2014
foot self-care ulceration, there is insufficient robust evidence [9]; Gershater et al 201132; Lincoln et al
that limited structured education alone is 200833; Monami et al 201534; Liang et al
effective in achieving clinically relevant 201235
reductions in foot ulcer risk.
Foot self-management In people with diabetes at risk for foot Low Armstrong et al 200540
ulceration, applying daily antifungal nail
lacquer as a way to increase frequency of foot
self-inspection does not seem to help prevent
a recurrent diabetic foot ulcer.
In people with diabetes at risk for foot Moderate Armstrong et al 200743; Lavery et al 200441;
ulceration, monitoring foot skin temperature at Lavery et al 200742; Skafjeld et al 201544
home, combined with patients contacting a
research nurse and dosing their activity when
abnormal left to right temperature differences
were measured, can help prevent a recurrent
plantar diabetic foot ulcer.
Treatment of risk factors or We did not find any published evidence.
pre-ulcerative signs on the
foot
Orthotic interventions In people with diabetes with moderately Low Rizzo et al 201247; Lavery et al 201246; Scire
increased risk for foot ulceration (IWGDF risk et al 200945
2), therapeutic footwear, including shoes,
insoles or orthoses, may reduce the risk of a
first-ever foot ulcer.
In people with diabetes at high risk for foot Moderate Bus et al 201349; Ulbrecht et al 201448; Uccioli
ulceration (IWGDF risk 3), therapeutic et al 199551; Reiber et al 200250; Viswanathan
footwear, including custom-made shoes or et al 200452; Busch et al 200353; and Reike
insoles with a demonstrated plantar et al 199754
pressure–reducing effect on the plantar
surface of the foot during walking, and that
the patient actually wears, reduces the risk of
a recurrent plantar diabetic foot ulcer.
Surgical interventions In selected patients with diabetes and a Low Mueller et al 200367; Piaggesi et al 199868;
nonhealing plantar forefoot ulcer, Achilles Armstrong et al 200372, 200571, 201270;
tendon lengthening, single or pan-metatarsal Giurini et al 199386; Hamilton et al 200588;
head resection, and metatarsophalangeal joint Petrov et al 199687; Molines-Barroso et al
arthroplasty may reduce the risk of a recurrent 201389; Griffiths et al 199085
plantar foot ulcer after healing of their current
ulcer, when compared with nonsurgical
treatment.
In selected patients with diabetes and a Low Lin et al., 200084; Downs et al 198283
nonhealing plantar foot ulcer, osteotomy may
reduce the risk of a recurrent plantar foot
ulcer after healing of their current ulcer, but it
is not clear in comparison with what form of
standard care.
In selected patients with diabetes and a Low Tamir et al 201491; Rasmussen et al 201393; van
nonhealing toe ulcer, digital flexor tendon Netten et al, 201394; Kearney et al 201095;
tenotomy may reduce the risk of a recurrent Schepers et al 201096; Tamir et al 200892;
toe ulcer after healing of their current ulcer, Laborde et al 200797;
when compared with nonsurgical treatment.
In patients with diabetes at high risk for Low Rasmussen et al 201393; Van Netten et al,
ulceration (IWGDF risk 3), and with abundant 201394; Tamir et al 200892
(Continues)
TABLE 1 (Continued)
Intervention Evidence Statement QoE References

callus on the tip of their toe, a hammertoe or
with thickened nails, flexor tenotomy may
reduce the risk of developing an ulcer.
In people with diabetes at risk of foot ulceration, Low Aszmann et al, 200474; Nickerson and Rader,
there is no convincing evidence to support an 201475; Nickerson, 2010100; Dellon et al,
ulcer prevention effect of nerve 2012101; Nickerson and Rader, 2013102
decompression surgery over good standard of
care.
Foot-related exercises In people with low or high risk for foot ulceration Low LeMaster et al, 2010103; Mueller et al, 201320
(IWGDF risk 1 or 3), foot-related exercises do
not appear to help prevent a diabetic foot
ulcer.
In people with low or high risk for foot ulceration Low LeMaster et al, 2010103; Mueller et al, 201320
(IWGDF risk 1 or 3), a small increase in the
level of weight-bearing daily activities (1000
steps/d, 20% increase) does not seem to
increase the risk for first-ever or recurrent
diabetic foot ulcer.
Integrated foot care In people with diabetes at low or moderate risk Low Van Putten et al, unpublished104; Cisneros et al
for foot ulceration (IWGDF risk 1 or 2), 2010105; Hamonet et al 2010107; Calle-Pascual
integrated foot care does not seem to reduce et al 2002108
the risk of a first foot ulcer, although it may
prove beneficial in specific populations or in
reduction of more complicated ulcers.
In people with diabetes at high risk for foot Low Plank et al 2003106; Dargis et al 199939; Jimenez
ulceration (IWGDF risk 3), integrated foot care et al 2018109; Fujiwara et al 2011110;
may reduce the risk of a recurrent foot ulcer. Hamonet et al 2010107; Armstrong and
Harkless 1998111; Marcinia et al 1998112;
Abbas et al 2011113
Abbreviations: IWGDF, International Working Group on the Diabetic Foot; QoE, Quality of the Evidence determined following GRADE methodology (see
Section 2 for more details).
included RCTs were also part of the six RCTs included in the review programme for five to seven patients, including face-to-face lessons
by Adiewere and colleagues, we excluded this article from further and interactive sessions with preventative self-care exercises.
assessment. They did include one additional study, but it investigated We identified one additional RCT with high risk of bias conducted
education as part of integrated foot care and is included in our review in a Chinese minority group by Liang and colleagues, in 59 participants
under that specific intervention.39 without a previous ulcer.38 They found a significantly lower percent-
Three RCTs included in both meta-analyses did meet our inclu- age of recurrent ulcers after 2 years in those provided with a foot care
sion criteria. In an RCT with high risk of bias, Gershater and colleagues kit and education to patients and caregivers on how to use it, in addi-
found in 131 patients no reduction in ulcer recurrence after 6 months tion to standard care provided by an endocrinologist and diabetes
of one participant-driven 60-minute patient education group session nurse, compared with standard care alone (ie, 2 h of diabetes educa-
in addition to standard care, compared with standard care alone: 48% tion): 0% vs 24.1%; P = .014. While the study investigated an educa-
32
vs 38%; P > 0.05. Lincoln and colleagues, in an RCT with low risk of tional programme, giving the foot care kit to patients might have
bias, found in 172 patients that in addition to standard care, a single improved their adherence to foot self-care habits and reduced ulcer
1-hour education session, followed by a single phone call 4 weeks outcomes.
later, did not significantly reduce ulcer recurrence at 12 months than Evidence statement: In people with diabetes at risk for foot ulcer-
33
did standard care alone: 41.4% vs 41.2%. Monami and colleagues ation, there is insufficient robust evidence that limited structured edu-
prematurely terminated an RCT with high risk of bias after inclusion cation alone is effective in achieving clinically relevant reductions in
of 121 patients at high risk of ulceration because an unplanned foot ulcer risk.
interim analysis found six ulcers during the 6-month follow-up in the Quality of the evidence: Low. Based on one systematic review
control group and none in the intervention group (10% vs 0%; with meta-analyses and four RCTs. There was no publication bias, but
P = .012).34 The educational intervention consisted of a 2-hour we downgraded the strength of the recommendation because of the
TABLE 2 Risk of bias of included publications
8 of 22
Systematic Reviews Cleary >1 Person Comprehensive States If and Review Lists Characteristic Scientific Quality Scientific Quality Appropriate Publication Conflicts of Score
Intervention, reference Defined Select Literature How Limit Included + Included Assessed + Assessed Methods to Bias Interest
Research Studies + Search by Excluded Articles Studies Documented Appropriately Combine Assessed
Question Extract Data Publication Provided Study
Type Results
Structured education
Adiewere et al, 2018 + ? + + − + + + + − + 8/11
RCTs Randomization Independent Patient/Care Outcome Similarity Groups Withdrawal/ Intention to Treat Patients Treated Selective Free from Commercial Score
Intervention, reference Assignment Provider Assessor Dropout Equally Except Reporting Interest
Blinded Blinded Acceptable for Ruled out
(<20%) Intervention
Structured education
Gershater et al, 2011 + + − − + − − + + + 6/10
Lincoln et al, 2008 + + − ? + + + + + + 8/10
Monami et al, 2015 + + − ? + + − ? + + 6/10

Liang et al, 2012 ? ? − ? + + − + + + 5/10
Self-management
Armstrong et al, 2005 + + − ? + ? + + + ? 6/10
Armstrong et al, 2007 + + − − + − − + + + 7/10
Lavery et al, 2004 ? ? − ? + + + + + + 6/10
Lavery et al, 2007 + + − ? + + − + + + 8/10
Skafjeld et al, 2015 + ? − ? + + − + + + 5/10
Orthotic interventions
Scire et al, 2009 + ? − ? + ? + + + + 8/10
Lavery et al, 2012 ? ? − − + − + + + + 5/10
Rizzo et al, 2012 + ? − − + − − + + + 5/10
Ulbrecht et al, 2014 + + − + + − + + + + 8/10
Bus et al, 2013 + + − + + + + + + + 9/10
Reiber et al, 2002 + ? − + + + ? + + + 7/10
Uccioli et al, 1995 + ? − − + ? ? + ? − 3/10
Surgical interventions
Mueller et al, 2003 + + − ? + + − + + + 7/10
Piaggesi et al, 1998 + ? − − + + + + + − 6/10
Foot-related exercises
LeMaster et al, 2010 + + − + + + + + + + 9/10
VAN NETTEN ET AL.
(Continues)
TABLE 2 (Continued)
Mueller et al, 2013 + + − + + + + + + + 9/10

Integrated foot care
Van Putten et al, + + − − + + − + + + 7/10

VAN NETTEN ET AL.
unpublished
Cisneros et al, 2010 ? ? − ? + − − + + + 4/10
Plank et al, 2003 + + − ? + + + ? + + 7/10
Cohort studies Study Groups Selection Bias Intervention Outcome Outcome Assessed Withdrawal/ Selective Loss to Major Selective Free from Commercial Score
Intervention, reference Defined Avoided/ Clearly Clearly Blind for Dropout Follow-up Confounders/ Reporting Interest?
Excluded Defined Defined Exposure Acceptable Excluded Prognostic Ruled Out?
(<20%) Factors
Identified and
Controlled
Orthotic interventions
Viswanathan et al, 2004 ? − + − − ? ? − + ? 3/10
Busch and Chantelau, + − + − ? + + ? + ? 5/10

2003
Reike et al, 1997 + − + + − − ? − + + 5/10
Surgical interventions
Aszmann et al, 2004 − − − − − − − − − − 0/10
Nickerson and Rader, − − + ? − − ? − − ? 0/10

2014
Faglia et al, 2012 + − + + − − ? − + + 5/10
Armstrong et al, 2012 + ? + + + + + − + − 7/10
Armstrong et al, 2005 + − + + ? ? ? − + ? 4/10
Armstrong et al, 2003 + − − + ? − ? − + ? 3/10
Vanlerberghe et al., 2014 − ? + − − + + ? + ? 4/10
Integrated foot care
Dargis et al, 1999 + + ? + − + ? − + + 6/10

9 of 22
risk of bias in the included studies that make up the meta-analyses Quality of the evidence: Moderate. Based on four RCTs, with
and inconsistency in findings. consistent results between the three RCTs at low risk of bias but
downgraded because one additional RCT with high risk of bias gives
inconsistent results. No publication bias.
3.3 | Foot self-management
PICO: In people with diabetes at risk for foot ulceration, can foot self- 3.4 | Treatment of risk factors or pre-ulcerative
management, compared with no self-management, help prevent a signs on the foot
first-ever or recurrent diabetic foot ulcer?
Summary of the literature: We identified five RCTs on this topic, PICO: In people with diabetes at risk for foot ulceration, can treating
40-44
all concerning recurrent foot ulcers. risk factors or pre-ulcerative signs on the foot, compared with not
One RCT with low risk of bias by Armstrong and colleagues treating them, help prevent a first-ever or recurrent diabetic foot
included 70 participants (34 intervention and 36 control). ulcer?
They instructed patients in the intervention group to apply on a Summary of the literature: We did not find any published evi-
daily basis topical antifungal nail lacquer as a way to increase fre- dence to answer this PICO.
quency of foot self-inspection, but they found no benefit after
12 months compared with standard care (5.9% vs 5.6% ulcer inci-
dence; P = .9).40 3.5 | Orthotic interventions
Evidence statement: In people with diabetes at risk for foot ulcer-
ation, applying daily antifungal nail lacquer as a way to increase fre- PICO: In people with diabetes at risk for foot ulceration, can one
quency of foot self-inspection does not seem to help prevent a orthotic intervention, including therapeutic footwear (eg, shoes or
recurrent diabetic foot ulcer. insoles) and walking aids, compared with another or no form of orthotic
Quality of the evidence: Low, based on one RCT only. intervention, help prevent a first-ever or recurrent diabetic foot ulcer?
Three RCTs with low risk of bias and one RCT with high risk of Summary of the literature: We found seven RCTs,45-51 three
bias assessed the preventative effect of daily foot skin temperature cohort studies,52-54 and nine noncontrolled studies.55-63 Given the rel-
measurements, combined with patients contacting a research nurse atively large number of controlled studies, we decided not to discuss
and dosing their activity when abnormal left to right temperature dif- the noncontrolled studies.
ferences were measured.41-44 Two low-risk-of-bias RCTs compared First-ever foot ulcer: In an RCT with low risk of bias in
the intervention with standard care alone, in 225 and 85 patients. 167 patients, Scire and colleagues showed significantly fewer ulcers
Both found significantly fewer ulcers in the intervention group: Lavery (1.1% vs 15.4%, P < .001) and hyperkeratotic lesions (41% vs 84%,
41
and colleagues after 6 months (2.4% vs 16.0%; P < .05) and Arm- P = .002) at 3 months, after the use of one of three types of custom-
strong and colleagues after 18 months (4.7% vs 12.2%; P = .038).43 In made digital silicon orthoses in addition to standard care, compared
the third low-risk-of-bias RCT, the same intervention was compared with standard care alone (ie, sharp debridement, a “soft” accommodat-
with either standard care plus instructions to perform daily foot ing insole, and extra-depth footwear).45
42
inspection or with standard care alone. In 173 patients, Lavery and An RCT with high risk of bias by Lavery and colleagues found that
colleagues showed significantly fewer recurrent ulcers after in 299 patients, of whom 26% had a prior ulcer, insoles designed to
15 months in the intervention group (8.5%) compared with each of reduce shear stress and were worn in extra-depth therapeutic shoes
the other conditions (30.4%, P = .0061, and 29.3%, P = .008, respec- did not significantly reduce ulcer incidence in 18 months, compared
tively). Additionally, patients who were less adherent to daily foot skin with standard insoles (2.0% vs 6.7%, P = .08).46
temperature measurements had substantially higher ulcer recurrence Another RCT with high risk of bias from Rizzo and colleagues47
risk (OR 50.0; P < .001). Finally, in a high-risk-of-bias RCT with involved the initial randomization of 298 patients, 20% with previous
41 patients, Skafjeld and colleagues found no effect on either ulcer foot ulceration, to intensive footwear therapy based on a prescription
recurrence or time to recurrence when comparing this intervention algorithm64 or standard care consisting of footwear advice but no
44
with standard care (39% vs 50% recurrence after 12 mo; P = .532). footwear prescription. Ulcer incidence at 1, 3, and 5 years after the
However, post hoc power analysis showed the study was underpow- intervention was significantly lower in the intensive footwear group
ered and that the mean value of some key characteristics was differ- (11.5%, 17.6%, and 23.5%, respectively) compared with standard care
ent between groups at baseline (such as the number of patients with (38.6%, 61%, and 72%, respectively, P < .0001 at each time point), but
multiple ulcer history). there was a large attrition after 1 year. Some aspects of the methodol-
Evidence statement: In people with diabetes at risk for foot ulcer- ogy of this study are not clear (see evidence table).
ation, monitoring foot skin temperature at home, combined with Evidence statement: In people with diabetes with moderately
patients contacting a research nurse and dosing their activity when increased risk for foot ulceration (IWGDF risk 2), therapeutic foot-
abnormal left to right temperature differences were measured, can wear, including shoes, insoles, or orthoses, may reduce the risk of a
help prevent a recurrent plantar diabetic foot ulcer. first-ever foot ulcer.
Quality of evidence: Low. We reduced the quality of evidence were beneficiaries of prescribed diabetic footwear compared with
from high to low because we found a high risk of bias (5/10, 5/10, 60% in 30 patients who were not reimbursed and therefore wore
and 6/10) in the published papers, no publication bias, but large effect their own footwear (P < .001).53 Reike and colleagues, in a small
sizes (see evidence table), and large confidence intervals around the cohort study with high risk of bias, found no benefit in ulcer recur-
effect. rence at 2 years between patients who accepted a prescription of
Recurrent plantar foot ulcer: An RCT with very low risk of bias orthopaedic footwear and those who did not and wore their own
by Ulbrecht and colleagues randomized 130 patients with metatarsal shoes.54 In all three cohort studies, we could not rule out selection
48
head ulcer history (intervention 66 and control 64). Both the inter- bias, which may have been an important determinant of outcome.
vention and control groups received custom-made insoles based on a Evidence statement: In people with diabetes at high risk for foot
patient's foot shape and were worn in extra-depth diabetic shoes; the ulceration (IWGDF risk 3), therapeutic footwear, including custom-
difference was that the insoles in the intervention group were further made shoes or insoles with a demonstrated plantar pressure–reducing
optimized based on barefoot plantar pressure measurements. While effect on the plantar surface of the foot during walking, and that the
no difference was found between these groups after 15-month patient actually wears, reduces the risk of a recurrent plantar diabetic
follow-up for a composite outcome of plantar pre-ulcerative lesions foot ulcer.
and recurrent foot ulcer (37.9% vs 45.3%; P = .13), the shape and Quality of evidence: Moderate. We reduced the quality of evi-
pressure-based insoles were associated with a significantly lower rate dence for this evidence statement from high to moderate because we
of recurrent plantar foot ulcer than the shape-based insoles only found an overall low risk of bias (9/10, 8/10, 3/10, and 7/10), no pub-
(9.1% vs 25.0%, P = .007). lication bias, and a large effect size, but the findings between the
An RCT with very low risk of bias by Bus and colleagues random- RCTs were inconsistent (CIs cross the 0-line), and there were large
ized 171 patients with plantar foot ulcer history (intervention 85 and confidence intervals around the effect found (imprecision).
control 86). The intervention group received custom-made footwear
with improved pressure-relieving properties guided by in-shoe pres-
sure measurement, and the control group received custom-made foot- 3.6 | Surgical interventions
wear that did not undergo such improvement.49 Overall, there was no
significant difference in plantar foot ulcer recurrence after 18-month PICO: In people with diabetes at risk for foot ulceration, can surgical
follow-up between the groups (38.8% vs 44.2%, P = .48), but a post interventions, in comparison with no surgery, help prevent a first-ever
hoc analysis of the 79 patients (intervention 35 and control 44) who or recurrent diabetic foot ulcer?
wore their footwear for at least 80% of their measured activity Summary of the literature: We found two RCTs,67,68 seven
showed that they had a significantly lower ulcer recurrence incidence cohort studies,69-75 and 27 noncontrolled studies.76-102 We will
with wearing pressure-improved footwear (25.7% vs 47.8%, P = .045). describe the results per the specific surgical intervention.
An RCT with low risk of bias by Reiber and colleagues randomized Achilles tendon lengthening: An RCT with low risk of bias from
400 patients to therapeutic shoes with customized inserts, therapeu- Mueller and colleagues included 63 patients (intervention 30 and con-
tic shoes with prefabricated inserts, or the patient's own footwear.50 trol 33). They found that patients who were treated with Achilles ten-
They found no significant difference in proportion of persons with don lengthening, in addition to total contact casting to heal an active
recurrent ulcer over a 2-year period among the three groups (15%, forefoot ulcer, had a significantly lower recurrence rate at 7-month
14%, and 17%; no P value given). Despite having a low risk of bias, follow-up than had those treated with total contact casting alone
methodological aspects of this study that were not included in the (15% vs 59%, P = .001).67 This difference persisted at 2-year follow-
Cochrane assessment forms have been debated, including the popula- up (38% vs 81%, P = .002).
tion (half did not have LOPS, and “ulcer history” in these patients One noncontrolled retrospective study found that 138 patients
could also include minor abrasions or nonplantar lesions), and the out- treated with Achilles tendon lengthening, compared with a historic
come (for an ulcer to be scored, it needed to be present for at least cohort of 149 patients treated with wound closure surgery for ulcer
30 days).65,66 healing, had, at a mean 3-year follow-up, significantly fewer recur-
An RCT with high risk of bias by Uccioli and colleagues in rences (2% vs 25%, P < .001) but significantly more transfer lesions
69 patients found a significantly lower proportion of patients with a (12% vs 4%, P = .001).76 Several other noncontrolled studies reported
foot ulcer over a 1-year period in those who had worn therapeutic that there were fewer recurrent ulcers (0-20%) during 17-48-month
shoes compared with those who continued to use their own shoes follow-up after successful healing of a neuropathic ulcer with Achilles
51
(27.7% vs 58.3%, P = .009). tendon lengthening.77-82
A cohort study with high risk of bias by Viswanathan and col- Single or pan-metatarsal head resection: An RCT with low risk of
leagues found among 241 patients there were significantly fewer bias by Piaggesi and colleagues68 included 41 patients with a diabetic
recurrent ulcers after 9 months in patients using therapeutic sandals foot ulcer (21 intervention and 20 control). They compared patients
52
compared with those using sandals with a hard leather board insole. who were treated for ulcer healing with removal of bone segments
Another cohort study with high risk of bias by Busch and Chantelau underlying the lesion compared with conservative (nonsurgical) treat-
found a 15% ulcer recurrence rate over 12 months in 62 patients who ment. They found at 6-month follow-up significantly fewer recurrent
ulcers in the surgical group: 14% vs 41%, P < .01. In a retrospective 21 patients who underwent osteotomy for healing of forefoot
cohort study with high risk of bias, Faglia and colleagues found in ulcers.90
207 patients no significant differences in ulcer recurrence rates after a Evidence statement: In selected patients with diabetes and a
mean 40.6-month follow-up between those patients treated with surgi- nonhealing plantar foot ulcer, osteotomy may reduce the risk of a
cal bone removal of the toe (n = 110) vs metatarsal head resection or recurrent plantar foot ulcer after healing of their current ulcer, but it is
minor amputation of the toe or ray (n = 97): 15.5% vs 17.3%; not clear in comparison with what form of standard care.
69
P = .851. A retrospective cohort study from Armstrong and colleagues, Quality of evidence: Low. Based on one controlled study with
with low risk of bias, found among 92 patients (46 cases and 46 controls) high risk of bias and one noncontrolled study only.
that there were fewer recurrent ulcers at 1 year in those treated with Digital flexor tendon tenotomy: Seven retrospective case series
pan-metatarsal head resection compared to those treated nonsurgically of percutaneous digital flexor tendon tenotomies performed in
for their plantar forefoot ulcers (15.2% vs 39.1%, P = .02).70 In addition, patients to heal apex toe ulcers included a total 231 treated
there were fewer foot infections in the surgical group (35.5% vs 64.5%, patients.91-97 They found recurrence rates between 0% and 20% over
P = .047). Another retrospective cohort study from Armstrong and col- a mean follow-up between 11 and 36 months. Three of the seven
leagues, with high risk of bias, found significantly lower recurrence rates studies assessed effects of digital flexor tendon tenotomy of a toe
at 6-month follow-up after healing in the 22 patients treated with single that had no ulcer at the time of the procedure but an impending ulcer
metatarsal head resection compared with the 18 who received conser- (ie, abundant callus on tip of the toe or thickened nails). They found in
vative offloading (5% vs 28%, P = .04).71 One prospective and four ret- a total 58 treated patients (all IWGDF risk 3) no ulcer in a mean of
rospective noncontrolled studies, including between 10 and 11 to 31 months of follow-up.92-94
119 patients, on the effects of pan-metatarsal head resection reported Tendon transfer and fascia release: Two noncontrolled studies
recurrent ulcer rates between 0% and 41% after a mean 13.1 to from the same research group, one on the effects of plantar fascia
74 months of follow-up.85-89 release in 60 patients with a forefoot ulcer and one on the effect of
Metatarsophalangeal joint arthroplasty: One retrospective flexor hallucis longus tendon transfer in nine patients with a plantar
cohort study by Armstrong and colleagues with high risk of bias in heel ulcer, found no ulcer recurrence after 24-month follow-up.98,99
41 patients (intervention 21 and control 20) found that for primary Evidence statement: In selected patients with diabetes and a
treatment of a plantar foot ulcer, those undergoing meta- nonhealing toe ulcer, digital flexor tendon tenotomy may reduce the
tarsophalangeal joint arthroplasty of the great toe had significantly risk of a recurrent toe ulcer after healing of their current ulcer, when
fewer recurrent ulcers at 6-month follow-up than those receiving total compared with nonsurgical treatment.
contact casting (5% vs 35%, P = .02).72 Evidence statement: In patients with diabetes at high risk for
Two small noncontrolled studies of patients who underwent ulceration (IWGDF risk 3), and with abundant callus on the tip of their
either inter-phalangeal joint arthroplasty or resection of the proximal toe, a hammertoe or with thickened nails, flexor tenotomy may reduce
phalanx of the great toe found no recurrent ulcers at either 26 months the risk of developing an ulcer.
or 2 to 5 years of follow-up after primary healing.83,84 Quality of evidence: Low. Based on noncontrolled studies only.
Evidence statement: In selected patients with diabetes and a Nerve decompression: One retrospective cohort study by
nonhealing plantar forefoot ulcer, Achilles tendon lengthening, single Aszmann and colleagues, with high risk of bias, found that among
or pan-metatarsal head resection, and metatarsophalangeal joint 50 patients with neuropathic pain without a previous ulcer, there was
arthroplasty may reduce the risk of a recurrent plantar foot ulcer after a significantly lower ulcer and amputation incidence over a mean of
healing of their current ulcer, when compared with nonsurgical 4.6-year follow-up in the affected leg treated with decompression of
treatment. the peroneal nerve than the contralateral (control) leg (0 vs 15 events
Quality of evidence: Low. Nearly all controlled studies on the [12 ulcers and 3 amputations]; P < .001).74 A retrospective cohort
topic are observational studies, and there are more noncontrolled study, with high risk of bias, by Nickerson and Rader, assessed
than controlled studies. The effect size in reducing risk of recurrence 42 patients with painful neuropathy and failed pharmacologic treat-
is large for some surgical interventions, but the inconsistency between ment for effect of nerve decompression in the previously ulcerated
studies and confidence interval around the effect size are large foot; they found that over a mean of 35.8-month follow-up ulcer
(imprecision). recurrence was significantly lower in the operated limb compared with
Osteotomy: A retrospective cohort study with high risk of bias by the nonoperated limb (1.6% vs 7% per patient per year; P = .048).75
Vanlerberghe and colleagues included 76 patients (intervention One retrospective and two prospective noncontrolled studies pres-
22 and control 54). They found that osteotomy plus arthrodesis, pri- ented low percentages of recurrent ulcers (2.6%-4.3% per patient
marily undertaken to heal metatarsal head ulcers, resulted in a signifi- year) after 1 to 5.5 years of follow-up with decompression of the
cantly lower rate of combined recurrence and amputation when peroneal and tibial nerves in diabetic patients with (symptomatic)
compared with conservative treatment (7.5% vs 35.5%, P = .0013), peripheral neuropathy and a previous ulcer.100-102
although data on recurrent ulcers alone were not significantly differ- Evidence statement: In people with diabetes at risk of foot ulcer-
ent between groups (7.5% vs 18%, P = .14).73 One noncontrolled ation, there is no convincing evidence to support an ulcer prevention
study presented no recurrent ulcers during 13-month follow-up in effect of nerve decompression surgery over good standard of care.
Quality of evidence: Low. Observational studies only, with high 47% vs 36%) during the 12 weeks of the study. In comparing the
risk of bias and lacking comparison with standard of care conservative weight-bearing group with the non–weight-bearing group, there was
treatment. a statistically significant increase of 29 m for the 6-minute-walking
test (95% CI, 6-51; P = .014) and 1178 steps for the daily number of
steps (95% CI, 150-2205; P = .026) in the weight-bearing group.
3.7 | Foot-related exercises Evidence statement: In people with low or high risk for foot
ulceration (IWGDF risk 1 or 3), foot-related exercises do not appear
PICO: In people with diabetes at risk for foot ulceration, can foot- to help prevent a diabetic foot ulcer.
related exercises, compared with no foot-related exercises, help pre- Evidence statement: In people with low or high risk for foot
vent a first-ever or recurrent diabetic foot ulcer? ulceration (IWGDF risk 1 or 3), a small increase in the level of weight-
PICO: In people with diabetes at risk for foot ulceration, can the bearing daily activities (1000 steps/day, 20% increase) does not seem
level of weight-bearing daily activities be safely increased without to increase the risk for first-ever or recurrent diabetic foot ulcer.
increasing risk for a first-ever or recurrent diabetic foot ulcer? Quality of evidence: Low. Based on two RCTs with very low risk
Summary of the literature: We found two RCTs,20,103 both with a of bias (9/10, 9/10); there was no publication bias or inconsistency of
mixed group of participants who were either at risk (IWGDF risk 1) or results across studies, but neither study was powered for the outcome
at high-risk (IWGDF risk 3) for ulceration. Neither study was powered of ulcer prevention.
to detect differences in ulcers between groups.
An RCT by LeMaster and colleagues,103 with low risk of bias,
included 79 participants with diabetes and neuropathy (IWGDF risk 3.8 | Integrated foot care
1 [58%] or IWGDF risk 3 [42%]). The intervention group (n = 41) under-
took foot-related exercises administered by a physical therapist for an PICO: In people with diabetes at risk for foot ulceration, can providing
initial 3 months (ie, leg strengthening and balance exercises), and a self- integrated foot care, compared with not providing integrated foot
monitored walking programme, motivational calls (ie, 10-min call from a care, help prevent a first-ever or recurrent diabetic foot ulcer?
nurse) for the subsequent 9 months, diabetic foot care education, and Summary of the evidence: We found three RCTs,104-106 one
regular foot care, while the control group (n = 38) received foot care cohort study,39 and seven noncontrolled studies.107-113
education and foot care alone. There were no differences between First-ever ulcer: An unpublished RCT with low risk of bias by Van
groups in total ulcer incidence (n = 9 in both groups; 22% and 24% in Putten and colleagues enrolled 569 neuropathic patients without a
intervention and control group, respectively) or ulcer duration (74 vs foot ulcer in the previous 12 months.104 They found that integrated
51.5 d, respectively), or in the incidence rate of weight-bearing ulcers foot care, consisting of podiatric treatment given at least twice a year
(0.02 vs 0.12 ulcers/person-year-at-risk, respectively) at 12-month in addition to standard care, did not significantly reduce ulcer inci-
follow-up. Total daily step count decreased in both groups between dence in 3 years over standard care alone (10% vs 11%; P = .89).
baseline and 12 months nonsignificantly in the intervention group (from However, the participants in the integrated foot care group had signif-
3335 to 3183 steps), while the reduction in the control group was sig- icantly fewer infected or deep ulcers (11% vs 37%; P ≤ 0.03).
nificant (from 3.350 to 2.921; P < .05). Between baseline and 6 months, Cisneros and colleagues, in an RCT with high risk of bias in
steps taken during 30-minute exercise bouts significantly increased in 53 patients, found after 24 months of integrated foot care a lower but
the intervention group (from 482 to 548 steps; P < .05) and decreased not significantly reduced ulcer incidence compared with standard care
nonsignificantly in the control group (from 495 to 465 steps). The differ- (38.1% [8/30] vs 57.1% [8/23]; P = .317).105
ence at 6 months between both groups was statistically significant In a noncontrolled study of 24 patients who visited a multi-
(P < .01). At 12 months, however, the difference was no longer signifi- disciplinary foot clinic for preventative care, patients did not present
cant (510 vs 477 steps). In the 23 (29%) participants with an increase in with any ulcers in a 20-month retrospective analysis (3.46 consultations
steps (either total steps, or during 30-min exercise bouts), the median per patient), but an ulcer was found in 16.7% of patients in a 20-month
increase was 898 total daily steps. prospective analysis (0.23 consultations per patient).107 Another non-
20
An RCT by Mueller and colleagues, with low risk of bias, controlled study of 308 patients who were followed up for a mean
included 29 participants (IWGDF risk 1 [86%] and IWGDF risk 4.6 years found a significantly lower ulcer incidence for those patients
3 [14%]). The weight-bearing intervention group (n = 15) participated who were adherent to integrated foot care compared with those who
in 12 weeks of foot-related exercises provided by a physical therapist were not adherent (0.2% vs 4.4% [P < .01] in a lower-risk category and
(ie, stretching and strengthening foot and ankle exercises, and weight- 0.5% vs 4.3% [P < .01] in a higher-risk category of patients).108
bearing aerobic exercise—walking) and was compared with a non– Evidence statement: In people with diabetes at low or moderate risk
weight-bearing group (n = 14) undergoing the same stretching and for foot ulceration (IWGDF risk 1 or 2), integrated foot care does not
strengthening exercises but non–weight-bearing aerobic exercise (sta- seem to reduce the risk of a first foot ulcer, although it may prove benefi-
tionary bike). They also found no difference between groups in the cial in specific populations or in reduction of more complicated ulcers.
incidence of ulceration (1 vs 3 ulcers in 1 vs 2 participants; 7% vs Quality of evidence: Low. Because the evidence statement is
14%, respectively) or formation of lesions (7 vs 6 in 7 vs 5 participants; based on two RCTs, one with high risk and one with low risk of bias,
with inconsistent results, we downgraded the quality of evidence included 35 controlled studies, including 23 RCTs, and described a
from high to low. further 46 noncontrolled studies. Of these publications, only three
For a recurrent ulcer: In an RCT with low risk of bias, Plank and controlled and two noncontrolled studies were identified in the
colleagues included 93 patients (intervention 47 and control 44).106 updated search. The evidence base to support some interventions is
They compared integrated foot care (4-weekly chiropody treatment quite strong and based on several high-quality RCTs, whereas more
visits free of charge in addition to standard care) with standard care high-quality controlled studies are required for other interventions.
alone. After 2 years, they found no significant difference in ulcer inci-
dence between groups in the “per patient” analysis (38% vs 57%;
P = .09), but the incidence of ulcers was significantly lower in the chi- 4.1 | Foot self-care
ropody group in the “per foot” analysis (22% vs 38%; P = .03).
In a prospective cohort study with high risk of bias in 145 neuro- Unlike the first version of this systematic review,22 we now define
pathic patients (intervention 56 and control 89), Dargis and colleagues “foot self-care” as a separate intervention category, different from
found that multidisciplinary foot care given at least once every foot self-management. Specifically, foot self-care constitutes a variety
3 months resulted in significantly fewer ulcers than standard foot care of activities designed to reduce the risk of foot complications associ-
39
after 2 years: 30.4% vs 58.4%; OR: 0.31, P < .01. ated with diabetes that a patient can perform at home, either alone or
In a noncontrolled study, a comparison was made of ulcer recur- with the support of other non-professional carers. These aspects of
rence rates in a period before and after introduction of integrated foot foot self-care are mostly considered basic information provided to
care at one centre in Spain.109 In the period 2008-2010, 77 out of people with diabetes. However, evidence supporting the preventative
130 patients (59%) had ulcer recurrence, while in 2010-2014, this was effect of these interventions in preventing foot ulceration is limited.
49 out of 150 (33%); the multivariate hazard ratio between these two We found only two noncontrolled studies on this topic; these studies
periods of 0.60 was statistically significant (P = .007). In another suggest that adherence to foot self-care might help prevent foot
noncontrolled study, 88 patients with varying risk grades received ulceration.29,30 This lack of evidence might be the result of this care
integrated nursing care consisting of foot care, treatment of pre- being considered basic or standard, and clinicians and researchers
ulcerative signs, and education.110 Of the 26 patients with a previous may therefore not see the need to investigate this. However, future
ulcer (IWGDF risk 3), none of them had ulcer recurrence during studies are needed to further investigate the outcomes associated
2-year follow-up. In a 20-month prospective noncontrolled study, with adherence to foot self-care and to develop a better evidence
higher adherence to multidisciplinary care was associated with a base for supporting these foot self-care activities or not.
2.5-fold reduced ulcer recurrence rate.107 In another noncontrolled
study, patients who were adherent to once every 1 to 2 months of
preventative care in a multidisciplinary diabetes clinic for 3 years had 4.2 | Structured education about foot self-care
a lower ulcer recurrence rate than had nonadherent patients (5.4% vs
81.8%, P < .0001).111 A case series of patients who received inte- There is insufficient robust evidence that limited patient education alone
grated foot care by a trained diabetes nurse reported an 8% ulcer is effective in achieving clinically relevant reductions in risk of a foot
recurrence per year.112 Finally, the implementation of the IWGDF ulcer.31-34,38 Structured education can have many forms, with different
“Step by Step” programme, aimed at ulcer prevention in lower income methods, at various intervals, of different lengths, and with different
countries, demonstrated in one noncontrolled study a lower ulcer inci- educators. Finding what type of structured education is most beneficial
dence in one centre when compared with preimplementation data.113 in foot ulcer prevention will require further investigations. Furthermore,
Evidence statement: In people with diabetes at high risk for foot many educational interventions focus primarily on improving foot self-
ulceration (IWGDF risk 3), integrated foot care may reduce the risk of care knowledge or adherence to the foot self-care.9 This may be benefi-
a recurrent foot ulcer. cial in itself for people with diabetic foot disease, but we did not fully
Quality of evidence: Low. The evidence statement is based on consider this to be within the scope of ulcer prevention for the current
one RCT and one cohort study, both with low risk of bias, and six non- review. More evidence from well-designed studies is needed on this
controlled studies. Although the results are relatively consistent, they topic. Rather than focusing solely on education, these studies should
are based on studies of small numbers of patients, and they showed take a broader behavioural perspective and include different forms of
only small effect sizes, so we downgraded the quality of evidence structured education, account for adherence to changes in behaviour,
from high to low. and take patient preferences into account. An example of such an inter-
vention has recently been published.114
4 | DISCUSSION
4.3 | Foot self-management
In this systematic review, we updated our search of the literature for
publications on interventions to prevent first and recurrent foot ulcers Self-management is important in prevention as foot ulcers nearly always
in persons with diabetes who are at risk for ulceration.22 Overall, we develop outside the clinical setting. We consider foot self-management
to differ from foot self-care by targeting prevention of diabetic foot For first-ulcer prevention, one RCT found that prescribing foot-
ulceration through the additional use of materials such as via home wear according to a structured consensus-based algorithm resulted in
monitoring systems or other technological applications. We found no fewer ulcers than not prescribing footwear.47 While this may seem
support for the daily use of antifungal nail lacquer as a surrogate to obvious, it is useful to have evidence to support this basic tenet of
help improve frequency of foot inspection and early recognition of foot care. Further, one trial on custom-made orthoses showed a
foot problems to prevent foot ulcers.40 In contrast, we found strong reduction of ulcer risk,45 while a trial on shear reducing insoles did not
support for the use of home monitoring of foot skin temperature, to find significant differences between the groups.46 We therefore con-
inform subsequent preventative actions taken when abnormal tem- clude that therapeutic footwear, including shoes, insoles, or orthoses,
peratures are recorded, so as to prevent a recurrent foot ulcer. This is may reduce the risk of a first-ever foot ulcer in someone with a mod-
based on the results of three high-quality RCTs from a single erately increased risk for foot ulceration; however, further research in
research group that were conducted in three different clinical set- this population is urgently needed.
tings.41-43 Foot temperature monitoring provides instantaneous and For recurrent ulceration, two high-quality RCTs found that
clinically meaningful feedback on the risk of ulceration. Patient directly measuring the plantar pressure on the plantar surface of the
adherence to the daily measurement of foot temperature proved to foot can help improve the design and pressure-reducing capacity of
42
be an important component in clinical outcome, and therefore, this the provided footwear, and this resulted in reduced ulcer risks when
should be monitored in any future studies. An additional RCT on the patients wear their footwear.48,49 This suggests some underlying
outcomes of this intervention was recently published reporting no principles that can guide footwear prescription, to move towards a
effect of the intervention, but it was underpowered.44 The positive more data-driven and scientific approach.119,120 We therefore con-
findings from the above-mentioned studies, all with low risk of bias, clude that therapeutic footwear for ulcer prevention needs to have a
led us to an overall assessment that monitoring foot skin temperature demonstrated plantar pressure–reducing effect. Further, adherence
at home can help prevent a recurrent plantar diabetic foot ulcer. The to wearing the footwear is crucial.49 However, achieving better
published positive findings do require confirmation in well-designed adherence is a challenge. Observational studies suggest that a per-
studies by other research groups in other regions of the world, in ceived benefit is associated with better adherence,121,122 but a first
which cost-effectiveness and feasibility of implementation should be attempt to improve adherence via this pathway, a pilot RCT using
addressed, as this procedure is currently not implemented in routine motivational interviewing, found only somewhat improved adher-
clinical practice. Technological advancements in the monitoring of ence, and only at the short-term.123 More research on this topic is
foot temperature that reduce the user burden, such as with auto- needed, to better understand how adherence to wearing therapeutic
matic detection of impending problems115 or thermal cameras for footwear can be improved. In these studies, adherence should be
the smartphone,116 may improve the usability of this approach. quantitatively monitored.124,125
4.4 | Treatment of risk factors or pre-ulcerative 4.6 | Surgical interventions

signs on the foot
With only few exceptions, surgical interventions are primarily studied
It is widely considered standard clinical practice to treat risk factors or in the context of ulcer treatment. However, because surgery most
pre-ulcerative signs on the foot, such as removing callus or treating often changes foot structure, it may have an enduring preventative
fissures. However, we found no evidence that such treatments pre- effect after healing. From the limited number of controlled studies,
vent foot ulcers. Some evidence supports treatment of surrogate out- Achilles tendon lengthening, single or pan-metatarsal head resection,
117,118
comes, such as callus removal to reduce plantar pressure. and metatarsophalangeal joint arthroplasty appear to reduce ulcer
However, all pre-ulcerative treatments are subject to clinical varia- recurrence risk in selected patients with nonhealing ulcers when com-
tions, such as in skills of practitioners, frequency of treatment, and pared with nonsurgical treatment.67,68,70-72,83-89 Several other surgical
duration of treatment. Thus, we need controlled trials on these inter- offloading procedures, such as osteotomy and digital flexor tendon
ventions in relation to foot ulcer prevention to better understand the tenotomy, are promising for helping prevent ulcer recurrence.73,90-99
potential effects of such variations and to define optimal treatment of Based on the results of a few case series, flexor tenotomy may even
pre-ulcerative signs. have value in preventing a first-ever foot ulcer in patients with abun-
dant callus on the tip of their toes or thickened nails.92-94 These out-
comes require confirmation in well-designed studies.
4.5 | Orthotic interventions As a separate group of surgical interventions, studies on nerve
decompression have found low ulcer incidence rates over extended
For this intervention, controlled studies on the prevention of a first follow-up periods in patients both with or without a prior foot ulcer
ulcer have considered both orthoses and footwear, while all controlled who are experiencing neuropathic pain.74,75,100-102 However, risk of
studies on the prevention of a recurrent ulcer have considered thera- bias in these studies was high, and study design was not always
peutic footwear. appropriate, often lacking comparison with standard care. Efficacy has
not yet been assessed within an RCT design, and most of the studies found evidence suggesting that integrated foot care may reduce the
performed have been done by the same research group. Therefore, risk of a recurrent foot ulcer.39,106,107,109-113 All reported integrated
there is no convincing evidence to support an ulcer prevention effect foot care programmes lacked sufficient detail on the treatment given,
of nerve decompression over good standard of care. which limits reproducibility of the study findings, translation to set-
We realize that studies on surgical interventions with the appro- tings other than those studied, and analysis of the part(s) of the care
priate design are not always easy or ethical to perform, as surgery is that drive the outcomes. Additionally, limited description of the edu-
sometimes a last-resort approach after failed conservative treatment, cation given and footwear prescribed hinders comparison with studies
usually does not allow randomization of patients, and benefits should on these specific topics. Future studies should describe integrated
be considered with respect to the possible harms. For example, Achil- foot care in more detail.
les tendon lengthening can negatively influence locomotion and may,
as other procedures do, increase risk of transfer ulcers.67,126 Never-
theless, more controlled, high-quality studies, such as one ongoing 4.9 | Other considerations and limitations
trial,127 are needed before we can make evidence-based statements
about the safety and efficacy of surgical interventions to prevent ulcer Readers should consider several issues related to this systematic
recurrence. review.
First, the population of interest of our review was limited to per-
sons with diabetes at risk for foot ulceration, since these patients are
4.7 | Foot-related exercises expected to benefit more from preventative interventions than
patients who are not at risk.6 Studies were excluded if information on
Foot- and mobility-related exercises have not been studied as an clinical presentation to define “at risk” was insufficient or if the “at risk”
intervention aiming for ulcer prevention. However, we found two population was not specifically analysed. For example, the paper on
RCTs investigating the effects of a combination of foot-related exer- education by Malone and colleagues35 provided no information on
20,103
cises and a walking programme that did report ulcer outcomes. ulcer healing in their study population of patients with an active foot
Both trials were not powered to detect a difference in this outcome ulcer, yet this information is essential to adequately assess ulcer recur-
nor to prove equivalence. Despite this shortcoming, the differences rence. Another example is the study on foot screening and treatment
between both groups were very small (9 ulcers in both groups in one by McCabe and colleagues,132 which provides no information on the
trial; 1 vs 3 ulcers in the other trial), while patients in the intervention number of high-risk patients in the control group, and outcomes are
arm increased their weight-bearing activity. We therefore conclude not presented specifically for persons at risk. Other studies focused on
that while foot- and mobility-related exercises do not appear to help a population with specific comorbidities, such as chronic kidney dis-
prevent foot ulcers, they can be considered safe to increase a patient's ease requiring dialysis treatment.133,134 Even though foot ulcer risk is
level of weight-bearing activity without increasing the risk for ulcera- high in this population,135-137 the lack of specific reporting of findings
tion. Other studies on this topic primarily aimed to reduce risk factors for the patients at risk limits assessment of effectiveness of an inter-
for ulceration, such as plantar pressure reduction or redistribution, but vention for at-risk patients. For similar reasons, we did not assess the
did not report ulcer outcomes.128-131 Considering the health advan- efficacy of lifestyle interventions or intensified glucose treatment,138
128-131
tages resulting from specific foot-related exercises, or from as they target a general population of patients with diabetes mellitus.
general weight-bearing activity,21 these interventions can be consid- We made one exception, by including the systematic review and meta-
ered for this population. However, no definitive conclusions can yet analysis by Adiewere and colleagues, even though this was partly
be drawn because of the limited evidence available, and further based on studies that included patients who were not at risk.31 How-
research is strongly advised. ever, because the majority of patients in the meta-analysis was at risk,
we decided to include these outcomes. Overall, we strongly advocate
for the reporting of results in intervention studies that are specific for
4.8 | Integrated foot care the population at risk, with risk reported according to a validated strati-
23
fication system (eg, ), and with each item of such a system reported
In most studied integrated foot care programmes, the key responsible separately for the population included as well (eg, neuropathy, foot
professional was a podiatrist or chiropodist, who worked alone or in a deformities, ulcer, and amputation history).
multidisciplinary setting.39,104-113 Integrated foot care differed Second, in this systematic review on interventions, we did not
between studies but always included foot treatment by an adequately analyse or describe risk factors for ulcer development and ulcer risk
trained professional, structured education, and prescription of appro- classification systems. Despite the importance of this topic, ulcer risk
priate footwear, with a regular examination of the patient and their classification is only considered an intervention when a classification
feet. Frequency of foot treatment varied from once per month to is linked directly to a strategy based on referral of patients for treat-
once per 6 months. ment.139 No such studies were identified. It remains crucial to better
No evidence was found to support integrated foot care to pre- understand if the way in which we stratify risk is effective for ulcer
vent a first-ever foot ulcer.104,105 To prevent a recurrent ulcer, we prevention.
Third, we lacked clear definitions and assessment methods for advantage of this approach was a better division of the work over the
our primary outcome “first or recurrent ulcer” in many studies. The assessors and avoiding authors having to assess publications they (co-)
use and reporting of a standardized definition for diabetic foot ulcers, authored, thereby minimizing bias.
together with a clear description of methods for assessing outcomes,
are a key recommendation in the reporting standards for studies on
diabetic foot disease by Jeffcoate and colleagues.27 Furthermore, we 5 | CONC LU SIONS
did not consider amputation as a primary outcome in this systematic
review, because it depends largely on ulcer treatment and is therefore The evidence base to support the use of specific self-management
not a specific outcome for prevention in the nonulcerated foot. Also, and footwear interventions for the prevention of recurrent plantar
amputation is an elective procedure and not a natural outcome from foot ulcers is quite strong. The evidence is weak for the use of other,
an intervention. As a consequence, we did not consider the existing sometimes widely applied, interventions and is practically non-
population-based studies only reporting on amputation prevention existent for the prevention of a first foot ulcer and nonplantar foot
(eg, Krishnan et al140 and Larsson et al141). ulcer. More controlled studies of high quality are needed in these
Fourth, a key aspect of prevention that plays a critical role in out- areas, so as to better inform health-care professionals about effective
4,142
come is treatment adherence. Studies on different interventions preventative treatment in diabetic foot disease.
assessed for in this systematic review consistently report that those
patients who do not adhere to an intervention present with signifi- CONFLIC T OF INT ER E ST
cantly worse outcomes.29,30,42,49,107,108,111 Future studies on ulcer Production of the 2019 IWGDF Guidelines, including this systematic
prevention should incorporate a measure of treatment adherence, review, was supported by unrestricted grants from Molnlycke
preferably one that is objective, and investigate and implement strate- Healthcare, Acelity, ConvaTec, Urgo Medical, Edixomed, Klaveness,
gies to improve adherence. Reapplix, Podartis, Aurealis, SoftOx, Woundcare Circle, and Essity.
Fifth, the overall quality of studies on interventions to prevent a These sponsors did not have any communication related to the sys-
foot ulcer in at-risk patients with diabetes should further improve, so tematic reviews of the literature or related to the guidelines with
that stronger recommendations for clinical practice can be made. working group members during the writing of the guidelines and have
Studies should conduct a power analysis, ensure adequate blinding not seen any guideline or guideline-related document before
whenever possible, use intention-to-treat analysis, and follow the publication.
27
reporting standards for studies on diabetic foot disease. More clarity Full conflict of interest statements of all authors can be found
is required in the description of study populations, interventions, out- online at www.iwgdfguidelines.org.
comes, and outcome assessment. In addition, more focus should be
put on cost-effectiveness studies, to inform those responsible for allo- AC KNOWLEDG EME NT S
cating health-care resources. The authors gratefully acknowledge the help from Joost Daams, MA,
Sixth, this update of our systematic review resulted in only five clinical librarian from Amsterdam UMC, Amsterdam, the Netherlands,
newly included studies. Four years ago, we concluded that there is an for his help with designing the search strings and performing the liter-
urgent need for properly executed controlled studies on ulcer preven- ature search. Matilde Monteiro-Soares's work was financed by Project
22
tion. Apparently, the paucity of studies in this field remains. How- “NORTE-01-0145-FEDER-000016” (NanoSTIMA) that is financed by
ever, with some protocols for RCTs or descriptions of interventions the North Portugal Regional Operational Programme (NORTE 2020),
published recently,114,127,143,144 and some other ongoing RCTs identi- under the PORTUGAL 2020 Partnership Agreement, and through the
fied in our registry search, we hope that our next update will result in European Regional Development Fund (ERDF). We would like to
more included studies of high-quality. thank the following external experts for their review of our PICOs for
Seventh, we operated in five different twosomes in our search of clinical relevance: Lee Brentnall (Australia), Snjezana Bursac (Bosnia),
the literature, which can be considered a strength but also a limitation. Dr Nalini Campillo (Dominican Republic), Heidi Corcoran (Hongkong),
This means that no single author has assessed all records identified in Jill Cundell (United Kingdom), Mieke Fransen (Belgium), Alfred Gatt
our search. We did not formally test inter-assessor variability, and it is (Malta), Hanan Gawish (Egypt), Yamile Jubiz (Colombia), Hermelinda
therefore not possible to quantify potential differences. However, Pedrosa (Brazil), Sharad Pendsey (India), Ingrid Ruys (the Netherlands),
each record was screened by two authors independently, and if one and Zhangrong Xu (China). We would like to thank Benjamin A. Lipsky
of those considered it for inclusion, it was included in the next stage. (on behalf of the IWGDF editorial board) and James Woodburn (inde-
All disagreements in subsequent stages were discussed in person by pendent external expert) for their peer review of the manuscript.
the two assessors, and they reached consensus. Further, a team meet-
ing was held to discuss potential differences in assessment before AUTHOR CONTRIBU TIONS
choices were finalized. Finally, one assessor (J.v.N.) had access to all J.v.N. designed the search strings, performed the literature search,
assessments and did some informal consistency checks that did not assessed the literature, extracted data, and drew conclusions within
result in different outcomes of excluded papers. We therefore think “interventions 4 & 8” and “trial registries”; checked and completed the
that this division of tasks did not affect inclusion of publications. The evidence and risk of bias tables; and wrote the manuscript. AnitaR.
assessed the literature, extracted data, and drew conclusions within 12. Buckley CM, Perry IJ, Bradley CP, Kearney PM. Does contact with a
“interventions 1-3 & 7” and critically reviewed and edited the manu- podiatrist prevent the occurrence of a lower extremity amputation
in people with diabetes? A systematic review and meta-analysis.
script. L.L. assessed the literature, extracted data, and drew conclu-
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Prevention of Foot Ulcer 2020

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Received: 1 June 2019 Revised: 1 September 2019 Accepted: 19 September 2019

Prevention of foot ulcers in the at-risk patient with diabetes:

Jaap J. van Netten1,2,3 | Anita Raspovic4 | Lawrence A. Lavery5 |

1 | I N T RO DU CT I O N needed to properly inform caregivers about effective preventative

Intervention Evidence Statement QoE References

Intervention Evidence Statement QoE References

Adiewere et al, 2018 + ? + + − + + + + − + 8/11

Gershater et al, 2011 + + − − + − − + + + 6/10

Lincoln et al, 2008 + + − ? + + + + + + 8/10

Monami et al, 2015 + + − ? + + − ? + + 6/10

Armstrong et al, 2005 + + − ? + ? + + + ? 6/10

Armstrong et al, 2007 + + − − + − − + + + 7/10

Lavery et al, 2004 ? ? − ? + + + + + + 6/10

Lavery et al, 2007 + + − ? + + − + + + 8/10

Skafjeld et al, 2015 + ? − ? + + − + + + 5/10

Scire et al, 2009 + ? − ? + ? + + + + 8/10

Lavery et al, 2012 ? ? − − + − + + + + 5/10

Rizzo et al, 2012 + ? − − + − − + + + 5/10

Ulbrecht et al, 2014 + + − + + − + + + + 8/10

Bus et al, 2013 + + − + + + + + + + 9/10

Reiber et al, 2002 + ? − + + + ? + + + 7/10

Uccioli et al, 1995 + ? − − + ? ? + ? − 3/10

Mueller et al, 2003 + + − ? + + − + + + 7/10

Piaggesi et al, 1998 + ? − − + + + + + − 6/10

Mueller et al, 2013 + + − + + + + + + + 9/10

Van Putten et al, + + − − + + − + + + 7/10

Cisneros et al, 2010 ? ? − ? + − − + + + 4/10

Plank et al, 2003 + + − ? + + + ? + + 7/10

Viswanathan et al, 2004 ? − + − − ? ? − + ? 3/10

Busch and Chantelau, + − + − ? + + ? + ? 5/10

Reike et al, 1997 + − + + − − ? − + + 5/10

Aszmann et al, 2004 − − − − − − − − − − 0/10

Nickerson and Rader, − − + ? − − ? − − ? 0/10

Faglia et al, 2012 + − + + − − ? − + + 5/10

Armstrong et al, 2012 + ? + + + + + − + − 7/10

Armstrong et al, 2005 + − + + ? ? ? − + ? 4/10

Armstrong et al, 2003 + − − + ? − ? − + ? 3/10

Vanlerberghe et al., 2014 − ? + − − + + ? + ? 4/10

Integrated foot care

Dargis et al, 1999 + + ? + − + ? − + + 6/10

4.4 | Treatment of risk factors or pre-ulcerative 4.6 | Surgical interventions

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