DFA Guides You Through

This year’s research in diabetic foot

disease

Scientific and clinical developments

between Diabetes Week 2016 and 2017

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Introduction

Diabetic Foot Australia (DFA) aims to end avoidable amputations in a generation. DFA has engaged

with multiple partner organisations across Australia to create a national body for people suffering

diabetic foot disease. A multidisciplinary approach to the patient with diabetic foot disease is critical

to the delivery of a gold standard of treatment. DFA also advocates a coordinated approach by

health professionals, researchers, government and industry as critical to achieving our vision of

ending avoidable amputations in a generation.

A key objective of DFA is supporting health professionals to improve clinical and quality of life

outcomes for people with diabetic foot disease, and providing diabetic foot researchers with the

infrastructure to accelerate high quality research. One method to achieve these aims is the “DFA

Guides You Through” series. In this series, DFA summarizes and translates important diabetic foot

disease research topics to help support clinicians and researchers.

The current “DFA Guides You Through” document, which is part of our Diabetes Week 2017 actions,

discusses the latest scientific and clinical developments in diabetic foot disease. Since Diabetes Week

2016, we have seen a great variety of developments. Keeping track of what is out there and finding

the time to read it seems a near impossible job at times. We therefore “guide you through” the most

important developments between July 2016 and July 2017.

In this document, we follow the chapters of the International Working Group on the Diabetic Foot

(IWGDF) Guidance. We start with research on epidemiology, and continue with the five chapters

that make up the IWGDF Guidance: prevention, footwear and offloading, peripheral artery disease,

diabetic foot infection and wound healing interventions.

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Contents

1. Epidemiology ................................................................................................................................... 4

2. Prevention of diabetic foot ulcers................................................................................................... 6

3. Footwear and offloading ................................................................................................................. 8

4. Peripheral artery disease .............................................................................................................. 10

5. Diabetic foot infection .................................................................................................................. 12

6. Wound healing interventions ....................................................................................................... 14

Conclusion ............................................................................................................................................. 16

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1. Epidemiology

Epidemiology is the backbone of many studies, as it accurately describes the problem of diabetic

foot disease and the enormous burden it poses on people suffering from the disease, clinicians, and

society. The last twelve months have seen various unique papers on this topic.

Armstrong, Boulton and Bus published one of the most important papers in the field of the last

decade (1). They show, in the New England Journal of Medicine, that the lifetime incidence of foot

ulceration in people with diabetes lies between 19% and 34%. For people with a healed foot ulcer,

the one-year ulcer recurrence is a staggering 40%; this increases to 60% after three years. As

advocated by the authors, by others and by DFA, this is further evidence that it is better to use the

word “diabetic foot remission” when you talk with your patients, rather than telling them their ulcer

has healed.

Another major document comes from the UK, where the second report from the National Diabetes

Foot Care Audit England and Wales was published (2). Based on data from an impressive 11,073

patients, they conclude that “The longer it takes for someone with a new diabetic foot ulcer to reach

expert assessment the more likely it is that the ulcer will be severe. It seems likely that pathways

designed to shorten time to expert assessment would reduce the frequency of severe ulcers.” A

conclusion any Australian clinician can use in their daily practice. At the same time, this report

should stimulate us to implement the Australian Diabetic Foot Ulcer Minimum Dataset (3), so that

we can discuss our own findings here in the future.

For the Australian situation, a large prospective population-based study identified the real burden of

(diabetic) foot disease in our hospitals. Lazzarini and colleagues closely examined 733 inpatients

from five hospitals, resulting in a sample representative for Australia (4). Overall, almost 10% had

active foot disease. Of the people with diabetes (a quarter of all inpatients), almost 20% had active

foot disease present. These results show that the burden of foot disease, both in people with but

also in people without diabetes, is higher than expected.

Two papers report detailed findings on the costs of diabetic foot disease, always an important

argument in discussions with health authorities or government. Based on a systematic review of all

papers ever published on this topic (5), it can be estimated that an ulcer episode in Australia costs

around 20,000 dollars, which increases to 35,000-70,000 when hospitalisation or amputation is

needed. However, the majority of these costs are unnecessary, as shown by research from

Queensland (6): 2.7 billion dollar can be saved in Australia when evidence-based care is

implemented, because such care reduces ulceration rates as well as hospitalisation and

amputations. What are we waiting for?

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References:

(1) Armstrong DG, Boulton AJ, Bus SA. Diabetic foot ulcers and their recurrence. N.Engl.J.Med. 2017;376:2367-

2375.

(2) Healthcare Quality Improvement Partnership, National Diabetes Audit. National Diabetes Foot Care Audit

Report 2014-2016. 2017;V1.0.

(3) Diabetic Foot Australia. The Australian Diabetic Foot Ulcer Minimum Dataset. 2016; Available at:

https://www.diabeticfootaustralia.org/for-researchers/australian-diabetic-foot-ulcer-minimum-dataset-

dictionary/. Accessed March 22, 2017.

(4) Lazzarini PA, Hurn SE, Kuys SS, Kamp MC, Ng V, Thomas C, et al. The silent overall burden of foot disease in

a representative hospitalised population. Int Wound J 2016 Oct 3.

(5) Petrakis I, Kyriopoulos IJ, Ginis A, Athanasakis K. Losing a foot versus losing a dollar; a systematic review of

cost studies in diabetic foot complications. Expert Rev Pharmacoecon Outcomes Res 2017 Mar 17:1-16.

(6) Cheng Q, Lazzarini PA, Gibb M, Derhy PH, Kinnear EM, Burn E, et al. A cost-effectiveness analysis of optimal

care for diabetic foot ulcers in Australia. Int Wound J 2016 Aug 4.

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2. Prevention of diabetic foot ulcers

The field of foot ulcer prevention is slowly growing, after having been the Cinderella in diabetic foot

disease research for many years. Looking at last year’s research, it is probably the most exciting field

for those with an interest in technology and other cutting-edge developments.

It has been shown many years ago that temperature home monitoring can prevent foot ulcers, yet

this has not led to temperature measurements being implemented in clinical practice. This is

probably the result of both poor, user-unfriendly, technology and questionable diagnostic accuracy.

Smarter technology might solve both these problems. The most important new study on this topic

comes from the US, where researchers and company representatives present a ‘temperature

sensing bath-mat’, with new data on diagnostic accuracy (7). The bath-mat is an important

improvement in usability, and able to accurately diagnose almost all foot ulcers before they

occurred. However, this came at the cost of 57% false-positives, a number that needs to improve

before temperature home monitoring can be widely used in clinical practice. The most likely cause

of these false-positives is thermal asymmetry, as shown by UK researchers to exist in the general

population (8). With the current technology (and with developments to be expected), these false-

positives may be reduced by developing smarter algorithms. For that, however, more research and

developments are needed.

The other target area in ulcer prevention are smart insoles and smart socks. ‘Smart’ is obviously a

buzz-word, so some caution is needed when reading the studies on these technologies. Originally,

the focus of smart insoles was put on continuous plantar pressure measurements and feedback,

such as in the insoles in the study of Najafi and colleagues (9). These insoles seem to be one step

closer to daily practice now, although questions on how to implement them still need to be

answered. New developments include integrating plantar pressure measurements with

temperature, range of motion, or vibration stimulation (e.g. (10)), but it is hard to see these making

the step to clinical practice in the next year.

The most important aspect to keep in mind when reading of such technological developments is that

they serve to support a purpose – foot ulcer prevention. While some technology is undoubtly

awesome, keep asking yourself whether it is also practical in clinical practice: can you integrate it in

your clinic, or will it cost extra time that is not available? Will it lead to overtreatment, because of

over-diagnosis (such as in the case of 57% false-positives following temperature monitoring), or will

it lead to a false sense of security and therefore treatment delays? Which of your patients can

actually use the technology, just the tech-savvy, or almost anyone? We cannot yet answer most of

these questions. While this should not prohibit technological development, more and critical

research is needed, and clinicians and patients would do well in providing their user perspective.

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References:

(7) Frykberg RG, Gordon IL, Reyzelman AM, Cazzell SM, Fitzgerald RH, Rothenberg GM, et al. Feasibility and

Efficacy of a Smart Mat Technology to Predict Development of Diabetic Plantar Ulcers. Diabetes Care 2017

Jul;40(7):973-980.

(8) Macdonald A, Petrova N, Ainarkar S, Allen J, Plassmann P, Whittam A, et al. Thermal symmetry of healthy

feet: a precursor to a thermal study of diabetic feet prior to skin breakdown. Physiol Meas 2017 Jan;38(1):33-

44.

(9) Najafi B, Ron E, Enriquez A, Marin I, Razjouyan J, Armstrong DG. Smarter sole survival: will neuropathic

patients at high risk for ulceration use a smart insole-based foot protection system? Journal of diabetes

science and technology 2017(symposium/special issue):1-12.

(10) Najafi B, Mohseni H, Grewal GS, Talal TK, Menzies RA, Armstrong DG. An Optical-Fiber-Based Smart Textile

(Smart Socks) to Manage Biomechanical Risk Factors Associated With Diabetic Foot Amputation. J Diabetes Sci

Technol 2017 May 01:1932296817709022.

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3. Footwear and offloading

Even though this is one of the oldest fields in diabetic foot disease research, new evidence and new

initiatives keep coming to the fore. Following seminal trials in the last few years, and new

recommendations in the IWGDF Guidance, plantar pressure measurements are becoming a ‘must-

have’ in clinical practice, rather than a nice-to-have. It is therefore now time to implement the

footwear developments from the last years and implement them in clinical practice. First and

foremost, plantar pressure measurements should become a routine measurement in daily clinical

practice, but Australia has a long way to go. With this new publication on their implementation

experiences, New Zealand is showing us the way forward (11).

In offloading for ulcer healing, some important gaps were filled last year. First, Anita Raspovic and

colleagues from Melbourne studied felt padding (12). While knee-high devices are recommended in

all guidelines, felt padding remains the most frequently used offloading intervention in clinical

practice. However, felt padding had hardly been studied properly before this research. Two

messages can be taken home from their findings: first, felt-padding does provide some plantar

pressure reduction, but (inter)nationally recommended gold-standard offloading devices are much

better in offloading a diabetic foot ulcer. Second, if felt-padding is the only available offloading

method possible in a patient, it needs to be changed on a weekly basis to keep its offloading

capacity.

Another important study is an extensive health technology assessment of lightweight fibreglass heel

casts in the management of heel ulcers (13). Jeffcoate and colleagues from the UK investigated

whether a simple, removable and lightweight fibreglass cast would speed up healing of heel ulcers,

after having observed positive outcomes in a case series. Against their expectations, they conclude

that “although the provision of a lightweight heel cast may benefit some individuals, this study

found no evidence to recommend that this be adopted in routine clinical practice.” Unfortunately,

and despite their great efforts, other offloading methods to improve outcomes of heel ulcer healing

are needed.

Offloading with an adequate device is often not enough. When a device is removable, a patient

needs to adhere to the treatment. While the importance of adherence is known from both clinical

practice and secondary analyses, it has never received full attention in research. Technological

advancement now create possibilities to objectively measure adherence, and the first results of such

a study come from the US (14). Their study confirms our thoughts on the importance of adherence,

as they show that greater adherence relates to better ulcer-related clinical outcomes. However,

many questions on the intricacy of this relation remain unanswered, as well as the most important

question of all: how do we improve adherence? Let’s hope some answers to that will come in the

next year(s).

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A final development in this field is the measuring of shear stress. Shear stress is the resultant of

movement of a foot over the antero-posterior (forward-backward) and mediolateral (left-right) axes,

which is different from the peak pressure measured along the vertical axis. Shear may be

understood by the chainsaw comparison: a running chainsaw may easily cut the branch of a tree,

while continuously applying pressure alone (i.e.: pressing the chainsaw against the tree) will not

break this branch. While peak pressure has been measured for years, shear stress can now be

measured with new sensors. Yavuz and colleagues had already shown that ulcers not always develop

on the location with the highest peak plantar pressure, but also on locations where there’s no major

plantar pressure but only high shear (15). They follow this up with a new study, showing that peak

shear is significantly higher in people with a history of foot ulceration (16). A Japanese study looked

at the ratio between plantar pressure and shear (17). Their findings indicate that high pressure might

only lead to callus formation when it is accompanied by low shear; however, seeing the

shortcomings in the study, this hypothesis needs more research before it can be safely and validly

concluded. While measuring shear is an important development in offloading, there is much that we

still do not know with regard to its role in ulcer development, and its direct application to clinical

practice is uncertain. Whereas peak pressure has been investigated in large cohorts and

preventative intervention trials, shear stress has (still) only been studied in small groups of patients,

with varying results. This will hopefully change in the future, when shear pressure measuring

equipment may become widely available.

References:

(11) Gurney JK, Kersting UG, Rosenbaum D, Dissanayake A, York S, Grech R, et al. Pedobarography as a clinical

tool in the management of diabetic feet in New Zealand: a feasibility study. J Foot Ankle Res 2017 Jun 9;10:24-

017-0205-6. eCollection 2017.

(12) Raspovic A, Waller K, Wong WM. The effectiveness of felt padding for offloading diabetes-related foot

ulcers, at baseline and after one week of wear. Diabetes Res Clin Pract 2016 Nov;121:166-172.

(13) Jeffcoate W, Game F, Turtle-Savage V, Musgrove A, Price P, Tan W, et al. Evaluation of the effectiveness

and cost-effectiveness of lightweight fibreglass heel casts in the management of ulcers of the heel in diabetes:

a randomised controlled trial. Health Technol Assess 2017 May;21(34):1-92.

(14) Crews RT, Shen BJ, Campbell L, Lamont PJ, Boulton AJ, Peyrot M, et al. Role and Determinants of

Adherence to Off-loading in Diabetic Foot Ulcer Healing: A Prospective Investigation. Diabetes Care 2016

Aug;39(8):1371-1377.

(15) Yavuz M, Master H, Garrett A, Lavery LA, Adams LS. Peak Plantar Shear and Pressure and Foot Ulcer

Locations: A Call to Revisit Ulceration Pathomechanics. Diabetes Care 2015 Nov;38(11):e184-5.

(16) Yavuz M, Ersen A, Hartos J, Schwarz B, Garrett AG, Lavery LA, et al. Plantar Shear Stress in Individuals With

a History of Diabetic Foot Ulcer: An Emerging Predictive Marker for Foot Ulceration. Diabetes Care 2017

Feb;40(2):e14-e15.

(17) Amemiya A, Noguchi H, Oe M, Takehara K, Ohashi Y, Suzuki R, et al. Shear Stress-Normal Stress (Pressure)

Ratio Decides Forming Callus in Patients with Diabetic Neuropathy. J Diabetes Res 2016;2016:3157123.

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4. Peripheral artery disease

The big debates identified in the 2015 IWGDF Guidance on Peripheral Artery Disease (PAD) were

endovascular treatment vs. bypass surgery; angiosome based treatment; and when not to

revascularize. These have seen limited progress in the last year. However, some other interesting

papers have been published last year.

An important development for surgeons is the Korean approach to “supermicrosurgery”. After a

presentation at the International Symposium on the Diabetic Foot introducing the concept, a paper

was now published describing the methods and results of this tiny surgical approach (18). The study

concerns a retrospective review of 95 cases, so caution is needed when interpreting the findings.

However, the authors describe a flap survival rate of 90.5% and limb salvage rate of 93.7% in a

population with complex foot problems. This suggests that “supermicrosurgery” extends the

possibilities for reconstruction in those with severe ischemic diabetic foot and limited

revascularization options using current methods, some of your most difficult patients.

Other developments related to peripheral artery disease concern its diagnosis and classification. In

2014, Joseph Mills and colleagues presented the Wound, Ischemia, and foot Infection (WIfI)

classification system (19). This classification system is more extensive than the University of Texas

system. Even though it can be considered complex, it is still applicable in daily clinical practice (20).

Two papers have been published last year externally validating this system (21,22). Both study show

good findings. These studies not only increase the applicability of WIfI, it also shows the merit of

validating existing classification systems, rather than inventing new ones. I would hereby challenge

Australian clinics to collect data according to the Australian Diabetic Foot Ulcer Minimum Dataset

(3), and use that to validate classification systems such as WIfI. Such an undertaking is immediately

useful from both a clinical and a scientific point of view.

Three final papers that are worth mentioning point to an increasing importance of Toe-Brachial

Index (TBI) measurements. In the IWGDF Guidance, TBI is only mentioned as a test to exclude PAD

when values exceed 0.75. Australian research now shows that values <0.6 are associated with an

increased risk of foot disease, which points at TBI as a potentially useful screening tool (23).

Additional Australian research shows that it is feasible for podiatrists in busy clinical practice to

perform these measurements (24). Finally, research from the US shows that TBI, as well as skin

perfusion pressures, is among the most sensitive and cost-effective strategies to improve PAD

identification (25). Combined, these suggests a move away from ABI towards more frequent TBI

measurements in daily clinical practice.

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References:

(18) Suh HS, Oh TS, Lee HS, Lee SH, Cho YP, Park JR, et al. A New Approach for Reconstruction of Diabetic Foot

Wounds Using the Angiosome and Supermicrosurgery Concept. Plast Reconstr Surg 2016 Oct;138(4):702e-9e.

(19) Mills JL S, Conte MS, Armstrong DG, Pomposelli FB, Schanzer A, Sidawy AN, et al. The Society for Vascular

Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia,

and foot infection (WIfI). J Vasc Surg 2014 Jan;59(1):220-34.e1-2.

(20) Game F. Classification of diabetic foot ulcers. Diabetes Metab Res Rev 2016 Jan;32 Suppl 1:186-194.

(21) Mathioudakis N, Hicks CW, Canner JK, Sherman RL, Hines KF, Lum YW, et al. The Society for Vascular

Surgery Wound, Ischemia, and foot Infection (WIfI) classification system predicts wound healing but not major

amputation in patients with diabetic foot ulcers treated in a multidisciplinary setting. J Vasc Surg 2017

Jun;65(6):1698-1705.e1.

(22) Ward R, Dunn J, Clavijo L, Shavelle D, Rowe V, Woo K. Outcomes of Critical Limb Ischemia in an Urban,

Safety Net Hospital Population with High WIfI Amputation Scores. Ann Vasc Surg 2017 Jan;38:84-89.

(23) Lanting SM, Twigg SM, Johnson NA, Baker MK, Caterson ID, Chuter VH. Non-invasive lower limb small

arterial measures co-segregate strongly with foot complications in people with diabetes. J Diabetes

Complications 2017 Mar;31(3):589-593.

(24) Tehan PE, Chuter VH. A targeted screening method for non-invasive vascular assessment of the lower

limb. J Foot Ankle Res 2016 Dec 7;9:48.

(25) Barshes NR, Flores E, Belkin M, Kougias P, Armstrong DG, Mills JL S. The accuracy and cost-effectiveness of

strategies used to identify peripheral artery disease among patients with diabetic foot ulcers. J Vasc Surg 2016

Dec;64(6):1682-1690.e3.

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5. Diabetic foot infection

The most important development in the field of diabetic foot infection is the coming of age of new

techniques. These techniques allow assessment of the microbiome in the wound that advances the

culture-based sampling methods (either tissue or swab), and start to pave the way for new thoughts

on how to treat these infections.

Various DNA-based techniques are available, and these are beautifully summarized in this review

(26). Using such techniques, it is for example possible to investigate biofilms or fungi residing in the

wound, or to examine the entire microbiome rather than the bacterial communities that respond

better to culturing. The latter was investigated by Malone and colleagues, who showed that chronic

diabetic foot ulcers have a highly polymicrobial microbiome, whereas ulcers with a duration less

than six weeks only had one dominant species (27). However, antimicrobial treatment failure was

not related to the microbiome. In another recent study by the same group, they used DNA-

techniques to show all diabetic foot ulcers contained biofilms (28). It is not yet clear, however, if

there is a causal link between the biofilms and a patient’s response to antimicrobial treatment.

Further work continues on this interesting area, and can be expected in the coming year.

A study by Kalan and colleagues reported fungi to be prevalent, dynamic and associated with

delayed healing (29). Unfortunately, they used swabs to obtain their samples for analyses, which

means they may have included fungi that simply reside on wound surfaces as well. With further

difficulties in fungi assessment, it is unlikely that this will soon become part of daily clinical practice.

The same holds for the DNA techniques used by Malone and colleagues, which require enormous

computer calculating power. However, with technological advancements, this might be in your clinic

sooner than you expect. Keeping updated with the exciting new research in this area will hopefully

help the transition to bring these advancements to daily practice.

Two papers with direct application to today’s clinical practice also deserve the attention. The first

paper is an arduous study from the UK, trying to provide answers to the debate on wound swab vs.

tissue sample (30). While a tissue finds more pathogens, it also brings a risk of pain or bleeding, and

is harder to use. The authors refrain from an unequivocal answer, and provide four scenarios

including a mixture of both methods (see here (https://www.diabeticfootaustralia.org/research-

article/1433/) for a more extensive discussion of both methods). But if you would be forced to

choose one option, this study underlines the IWGDF recommendation of doing a tissue sample,

rather than a wound swab, when possible.

The other paper is a position paper on antimicrobial stewardship (31). The paper is written directly

for clinicians dealing with wounds, where the use of antibiotics is common, and in cases

unnecessary. The document provides guidance for clinicians on diagnosing infections, optimal

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culture and specimen collection, and how to engage with antimicrobial stewardship. It is hoped by

the authors that this will improve antimicrobial stewardship in the context of reducing the

unnecessary use of antibiotics and the antibiotic resistance debate and potential worldwide threat.

A must-read (and a well-written document) for anyone who sees potentially infected wounds on a

weekly basis.

Finally, Queensland research reminds us of the scale of diabetic foot infections (32). Infections are

not only present in new patients who enter your clinic, but the researchers found (in a very large and

representative sample) that 4 patients out of 10 with uninfected ulcers will develop an infection

before their ulcer is healed. This mostly occurred in patients with ulcers that took more than 3

months to heal. These Queensland findings confirm the importance of trying to speed up healing,

and of continuous infection vigilance while the ulcer of your patient is still open.

References:

(26) Malone M, Gosbell IB, Dickson HG, Vickery K, Espedido BA, Jensen SO. Can molecular DNA-based

techniques unravel the truth about diabetic foot infections? Diabetes Metab Res Rev 2017

Jan;33(1):10.1002/dmrr.2834. Epub 2016 Jul 5.

(27) Malone M, Johani K, Jensen SO, Gosbell IB, Dickson HG, Hu H, et al. Next Generation DNA Sequencing of

Tissues from Infected Diabetic Foot Ulcers. EBioMedicine 2017 Jun 27.

(28) Johani K, Malone M, Jensen S, Gosbell I, Dickson H, Hu H, et al. Microscopy visualisation confirms multi-

species biofilms are ubiquitous in diabetic foot ulcers. Int Wound J 2017 Jun 23.

(29) Kalan L, Loesche M, Hodkinson BP, Heilmann K, Ruthel G, Gardner SE, et al. Redefining the Chronic-Wound

Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing. MBio 2016

Sep 6;7(5):10.1128/mBio.01058-16.

(30) Nelson EA, Wright-Hughes A, Brown S, Lipsky BA, Backhouse M, Bhogal M, et al. Concordance in diabetic

foot ulceration: a cross-sectional study of agreement between wound swabbing and tissue sampling in

infected ulcers. Health Technol Assess 2016 Nov;20(82):1-176.

(31) Lipsky BA, Dryden M, Gottrup F, Nathwani D, Seaton RA, Stryja J. Antimicrobial stewardship in wound

care: a Position Paper from the British Society for Antimicrobial Chemotherapy and European Wound

Management Association. J Antimicrob Chemother 2016 Nov;71(11):3026-3035.

(32) Jia L, Parker CN, Parker TJ, Kinnear EM, Derhy PH, Alvarado AM, et al. Incidence and risk factors for

developing infection in patients presenting with uninfected diabetic foot ulcers. PLoS One 2017 May

17;12(5):e0177916.

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6. Wound healing interventions

Probably one of the most controversial topics in the field of diabetic foot disease, and for sure one of

the most complex for scientific developments. Wound healing interventions concern dressings or

technological interventions (such as negative pressure or hyperbaric oxygen), all with the aim of

enhancing wound healing. But that’s exactly where the problems start in this field: how do you

define ‘enhancing wound healing’? Should one dressing or one technological intervention improve

wound healing by such an extent that it results in significantly more healed ulcers compared to

standard care? Or is wound healing related to a myriad of factors, and should a dressing or

technology only target (and improve) one of those?

The ‘healing’ approach is the traditional approach, where interventions aim to significantly improve

wound healing. However, as the IWGDF notes in their Guidance, this has resulted in many trials with

low evidence and poor design (33). The ‘one factor approach’ has seen products that target one

specific factor (e.g. pain or ease of use), with better trials backing their statements. However, these

studies often miss cost-effectiveness analyses. For more expensive products that only target a small

part of the healing process, however, such information is needed before health authorities and

clinicians can be expected to choose the more expensive solutions.

The debate in the field is growing, and some exciting developments are underway. For example, the

Wound Innovations clinic in Brisbane is combining innovative healthcare with health economic cost-

modelling studies. The first results of these developments can be expected in the coming year(s). For

this current DFA Guides You Through, however, we can only present some more traditional new

studies published in the last twelve months.

A new intervention kid on the block is continuous oxygen delivery. Two randomized controlled trials

have been published on this intervention, both from experienced US researchers. Both trials had

adequate sample size (122 and 100 participants), but the findings were markedly different. Driver

and colleagues found 54% wound healing in oxygen treatment, versus 49% in the control group (34).

They conclude that oxygen treatment does not offer any benefit. Niederauer and colleagues, on the

contrary, report a clear benefit from oxygen therapy, with 46% vs. 22% wound healing (35). How can

these differences be explained? A critical question to answer is: what care did the control group

receive? The 22% wound healing in the second study seems very low, while the 49% by Driver and

colleagues seems more realistic of current standard of care. This question can never be satisfactorily

answered in the limited space of a scientific paper, but it is what clinicians should keep in mind.

Looking at current standard practice in Australia, continuous oxygen therapy needs to be studied

better and in comparison with appropriate (and preferably local) standard of care before it can make

the step to daily practice.

15

The most scientifically rigorous paper from the last twelve months is a Cochrane review on topical

antimicrobial agents, by Dumville, Lipsky and colleagues (36). Cochrane reviews are well-known for

being very thorough, very extensive, almost impossible to read, and with a conclusion that is likely to

state that more research is needed. Even though this is indeed the case with this review, the authors

make some important statements for clinical practice. They suggest, based on low quality of

evidence, that “use of an antimicrobial dressing instead of a non-antimicrobial dressing may increase

the number of diabetic foot ulcers healed over a medium-term follow-up period.” However, before

this conclusion is applied in clinical practice as a rationale to start using any antimicrobial dressing

for all patients, some considerations are important. Various antimicrobial dressings are available at

the market. The results of five studies were pooled to reach this overarching conclusion, but this

does not mean that any specific product will work. This finding reflects the combination of those five

products. Further, the reported effect was small (a Risk Ratio of 1.28). With the increasing costs of

some dressings, cost-effectiveness is still an issue that needs to be solved. Duration of treatment and

patient selection in relation to antimicrobial dressings or interventions could also not be answered

based on this review. Regardless, this study is still an important step for antimicrobial treatments,

showing some high-quality evidence pointing at potential increases in diabetic foot ulcer healing.

References:

(33) Game FL, Attinger C, Hartemann A, Hinchliffe RJ, Londahl M, Price PE, et al. IWGDF guidance on use of

interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev 2016

Jan;32 Suppl 1:75-83.

(34) Driver VR, Reyzelman A, Kawalec J, French M. A Prospective, Randomized, Blinded, Controlled Trial

Comparing Transdermal Continuous Oxygen Delivery to Moist Wound Therapy for the Treatment of Diabetic

Foot Ulcers. Ostomy Wound Manage 2017 Apr;63(4):12-28.

(35) Niederauer MQ, Michalek JE, Armstrong DG. A Prospective, Randomized, Double-Blind Multicenter Study

Comparing Continuous Diffusion of Oxygen Therapy to Sham Therapy in the Treatment of Diabetic Foot Ulcers.

J Diabetes Sci Technol 2017 Feb 01:1932296817695574.

(36) Dumville JC, Lipsky BA, Hoey C, Cruciani M, Fiscon M, Xia J. Topical antimicrobial agents for treating foot

ulcers in people with diabetes. Cochrane Database Syst Rev 2017 Jun 14;6:CD011038.

16

Conclusion

The last twelve months have seen various interesting developments, both scientifically and clinically,

in the field of diabetic foot disease. In this “DFA Guides You Through” we have described the most

important developments in epidemiology, prevention, footwear and offloading, peripheral artery

disease, infection and wound healing interventions.

For clinicians, we hope this document helps to keep track of the latest research in the field, and

stimulate you to implement research findings in daily clinical practice.

For researchers, we hope this documents helps to show the gaps and point at relevant

developments, to accelerate your diabetic foot disease research and innovation in Australia.

For everyone, we hope you enjoyed reading this, while we guided you through the scientific and

clinical developments of 2016 and 2017. For those who cannot wait until our next yearly overview,

remember that we publish various “latest research” posts every month on our website

(https://www.diabeticfootaustralia.org/for-researchers/latest-research/). Keep a sharp eye out on

our social media to read when a new one is online.

We look forward to further advancements in diabetic foot disease research and treatment in 2017

and 2018 that may contribute to ending avoidable amputations in a generation.