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Title: Burden of diabetic foot disorders, guidelines for management, and disparities in implementation in Europe: a systematic literature review

Kristien van Acker1; Philippe Léger2; Agnes Hartemann3; Abhineet Chawla4; Mohd Kashif Siddiqui4

1

Diabetologie: Heilige Familie, Rumst and Centre Santé des Fagnes, Chimay, Belgium

Tisseltsesteenweg 64 B 2830, Willebroek, Belgium

Consultant for Diabetology ,Tropical Institute, Antwerp

President Elect for Diabetic Foot Program IWGDF/IDF

2Clinique Pasteur, Vascular Medecine, Toulouse France

3Hôpital Pitié-Salpêtrière, 83 bld de l’Hôpital, Endocrinology, Nutrition and Diabetes Department, 75651 PARIS Cedex 13, France

4HERON Health Pvt. Ltd., 3rd Floor, DLF Tower E, Rajiv Gandhi IT Park, Chandigarh, 160101, UT, India

Name: van Acker K

Corresponding Author

Address: Tisseltsesteenweg 64 B 2830, Willebroek, Belgium

Email: dr.k.van.acker@mac.com

Fax: 0032 3 886 66 02

Telephone: 0032 475 58 40 58

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/dmrr.2523

Abstract

Objective

The study aimed to assess the economic and quality of life (QoL) burden of diabetic foot

(DF) disorders and to identify disparities in the recommendations from guidelines and the

current clinical practice across the EU5 (Spain, Italy, France, UK, and Germany) countries.

Methods

Literature search of electronic databases (MEDLINE®, Embase®

Results

, and Cochrane Database of

Systematic Reviews) was undertaken. English language studies investigating economic and

resource burden, QoL, and management of DF disease in the EU5 countries were included.

Additionally, websites were screened for guidelines and current management practices in DF

complication in EU5.

DF complications accounted for a total annual cost of €509 million in the UK and €430 per

diabetic patient in Germany, during 2001. The cost of DF complications increased with

disease severity, with hospitalisations (41%) and amputation (9%) incurring 50% of the cost.

Medical devices (orthopaedic shoes, shoe lifts, and walking aids) were the most frequently

utilised resources. Patients with DF complications experienced worsened QoL, especially in

those undergoing amputations and with non-healed ulcers or recurrent ulcers. Although

guidelines advocate the use of multidisciplinary foot care team (MFC), the utilisation of MFC

was suboptimal.

Conclusions

DF disorders demonstrated substantial economic burden and have detrimental effect on QoL,

with more impairment in physical domain. Implementation of the guidelines and set-up of

multidisciplinary clinics for holistic management of the DFD varies across Europe and

remains suboptimal. Hence, guidelines need to be reinforced to prevent DF complications and

to achieve limb salvage if complications are unpreventable.

KEYWORDS: Diabetic foot, multidisciplinary foot care, quality of life, cost, economic

burden

Introduction

Diabetes mellitus, a condition characterised by high blood glucose levels, is associated with

the risk of developing severe co-morbidities and complications including heart disease,

stroke, blindness, kidney disease, nerve damage, and foot complications. According to the

International Diabetes Federation, 366 million people in 2011 had diabetes with the numbers

projected to rise to 552 million by 2030 [1]. Diabetic foot (DF) complications are a common

cause of non-traumatic limb amputations leading to disability [2]. According to the National

Health and Nutrition Examination Survey (as cited in Deshpande 2008), during 1999 to 2004

the prevalence of diabetes-related microvascular complications including chronic kidney

disease (27.8%) (defined as microalbuminuria), foot problems (22.9%) (foot lesions or

numbness, foot/toe amputations), and eye damage (18.9%) was higher than the prevalence of

macrovascular complications including heart attack (9.8%), chest pain (9.5%), coronary heart

disease (9.1%), congestive heart failure (7.9), and stroke (6.6%) [3]. With the increasing

prevalence of obesity, population growth, aging, urbanisation, and physical inactivity the

number of people with diabetes is increasing and so are the cases of DF complications, thus

increasing the spending on the management and treatment of diabetes and foot complications

[4;5]. According to the International Working Group on the Diabetic Foot (IWGDF), every

year approximately 4 million people develop a new DF ulcer, with developed countries

utilising 12% to 15% and developing countries utilising 40% of healthcare resources for

diabetes [6]. Further, every 30 seconds somewhere in the world a patient has an amputation

due to diabetes, leading to significant economic burden [7].

In the UK, the total direct cost to NHS for DF complication (foot ulcers and amputations)

was estimated to be €1.61 billion (converted per historical exchange rate of 2001), which is

approximately 10% of the total annual direct cost associated with Type 1 and Type 2 diabetes

[8]. DF problems have demonstrated a significant fiscal financial burden on National Health

Service (NHS) primarily due to outpatient costs, increased bed occupancy, and prolonged

stays in hospital [9]. The economic burden of DF complications in other European countries

is likely to be underestimated or unmeasured due to the availability of limited published

evidence. Therefore, this systematic review was conducted to assess the economic and quality

of life burden of DF disorders in the EU5 countries. Additionally, we sought to evaluate

whether the DF care practice in EU5 is synchronised with the rapidly evolving DF care

practice guidelines.

Methods

A systematic review was conducted in adult patients with or at a particular high risk of DF

problems in any care setting. The review was conducted and reported according to the

Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.

Study objectives

In order to meet the overall objective of this review, independent but seemingly research

related questions have been framed, which included: ''What is the disease burden due to DF

complications?''; ''What is the cost of lower extremity amputations in the EU5?"; "What are

the direct and indirect cost and resource utilisation associated with the treatment of DF ulcers

in primary care and secondary care?"; "What is the impact of DF amputations on patients

QoL?"; "Do there remained a harmony among the DF management guidelines in EU5 are in

harmony with respect to the multidisciplinary approach of foot care?"; and "Whether the

current clinical practice for DF care in EU5 is in line with the DF management guidelines?"

Data sources

Literature databases including MEDLINE®, Embase®, and the Cochrane Database of

Systematic Reviews were searched from 2000 to October 2011 for studies investigating the

economic/resource burden, QoL, and management of patients with DF disorders in the EU5

countries (Spain, Italy, France, UK, and Germany). The review was limited to studies

published in English from 2000 to the date of commencing this review (October 2011). The

key search terms used were ‘foot ulcer’, ‘diabetic foot’, ‘multidisciplinary management’,

‘economics’, ‘health care utilisation’, ‘quality of life’, ‘socioeconomics’, ‘limb salvage’,

‘amputation’, and ‘mortality’. In addition, websites were screened for guidelines and current

management practices for patients with diabetes and foot disorders in the EU5 countries.

Additionally, bibliographic searches of included studies were performed in the case of data

gap in the included evidence.

Study eligibility

Studies assessing cost, resource utilisation, and quality of life associated with DF

complication in EU5 were eligible for inclusion. Studies reporting data for adult patients with

or at a particular high risk of DF problems in any care setting were only eligible. With respect

to multidisciplinary DF care in EU5, studies reporting recommendations of multidisciplinary

DF care in EU5 were eligible. Studies reporting current clinical pattern for DF care in EU5

were eligible if they report objectivised data on component variable of multidisciplinary DF

care such as referral rate, vascular imaging frequency etc. Studies published in English

language were only eligible for inclusion. There was no restriction to study design, with

method of data collection being either prospective or retrospective.

Study selection

Bibliographic details and abstracts of all citations detected by the search were downloaded

into the HERON Systematic Review Database, a bespoke SQL-based internet database. A

team of reviewers, information scientists specializing in evidence-based medicine,

independently determined the eligibility of each publication. Citations were first screened

based on the title/abstract supplied with each citation by applying the defined set of eligibility

criteria described above. Duplicates of citations (due to overlap in the coverage of the

databases) were excluded at this first pass of the citations. Full-text copies were ordered for

studies that potentially met the eligibility criteria. The eligibility criteria were then applied to

the full-text publications in a second pass of the citations, with each publication reviewed by

single reviewer.

Data extraction

Each citation was first screened based on the abstract. Full texts of potential abstracts were

obtained electronically for evaluation of eligibility. All full text articles were assessed for

eligibility as per a predefined protocol. All studies included after the second pass of the

citations underwent data extraction using a specifically designed data extraction grid. Data

were extracted by a single reviewer and double checked by an independent reviewer. Only

one dataset per study was compiled from all publications relating to that study so as to avoid

double-counting patients.

Results

Literatures searching yielded 1137 studies, of these 391 were identified potentially relevant

for detailed evaluation. In total 11 studies were included in the systematic review. Happich

and colleagues reported data on economic burden and resource utilisation as well as quality

of life in patients with DF complications [11]. Therefore, six studies contributed to the data

on economic burden and resource utilisation and six studies reported data on quality of life in

patients with DF complications (Figure 1).

Economic burden and resource utilisation in diabetic foot disorder

Six studies contributed to the included evidence for economic burden and resource utilisation.

Two studies presented data from Germany [10;11], while one study each presented data from

the UK [12] and France [13]. Two were multinational studies, with one being conducted

across 10 European countries [14] and the other being in Australia, Canada, France,

Germany, Italy, and Spain [15].

The total annual cost of DF complications was estimated as €509 million in the UK in 2001

[12]. The data for Germany for the cost year 2001 indicated that the total annual cost per

patient for managing DF complication was €551 [10]. The EURODIALE study, a prospective

study on patients with new DF ulcer conducted at 14 centres across Europe, reported that the

total treatment cost per patient for DF ulcer in 2005 was € 10 091, with amputation (€889)

and hospitalisation (€3892) approximating 50% of the total direct cost [14]. It was observed

that across the studies conducted in Germany, France, Italy, and Spain wherein, of the various

DF complications, the costs due to amputations were the highest [15] (Table 1). The high

costs associated with DF complications requiring amputations may primarily be attributed to

the higher utilisation of resources by patients undergoing amputations than patients with other

DF complications; hospitalisation costs and cost of medical devices were observed as the key

cost drivers [11;14]. Besides hospital stay and use of medical devices, the other frequently

utilised resources were antibiotic therapy, dressing changes, neurological examinations,

medication, diagnostic examinations (nerve conduction velocity, doppler-sonography,

electromyogram, and other examinations), and transportation [11;13;14] (Table 2).

Published evidence suggests that the cost of treating DF ulcers increases as the severity of

ulcers increases. A study conducted by Girod and colleagues, in France, demonstrated a

higher total costs to treat Wagner grade 4 or 5 gangrene than the costs to treat Wagner grade

1 superficial lesions (€3591 vs. €1728; cost year 1999) [13]. A similar trend was observed in

the EURODIALE study conducted across 10 European countries (Belgium, Czech Republic,

Denmark, Germany, Italy, Slovenia, Spain, Sweden, Netherlands, and United Kingdom),

wherein patients with both infection and peripheral arterial disease (PAD) demonstrated

higher total costs (€16 835) than patients with no infection or PAD (€4504) [14] (Table 3).

The observed increase in DF ulcer costs with the severity of foot ulcers may be attributed to

the higher utilisation of resources in the more severe groups than the less severe groups.

Patients with both infection and PAD or ischaemia reported a longer hospital stay, a higher

use of antibiotic therapy, more inpatient and outpatient care, and a higher number of

transports than patients without infection, PAD, or ischaemia [14] (Table 4).

Quality of life in patients with diabetic foot complications

Six of the included studies reported data on quality of life in patients with DF complications.

Two studies were conducted in France [16;17], while one study each was conducted in the

UK [18], Spain [19], and Germany [11]. One trial was undertaken in multicentre setting,

being conducted in USA, UK, and Europe [20].

The treatment of DF ulcers is costly and is associated with increased mortality, development

of morbidity, and reduced QoL. Patients with DF ulcers are generally imposed with a

regimen of reduced mobility owing to the requirement to reduce pressure on the affected foot,

thus affecting their QoL [21]. Further, patients with DF ulceration are observed to be

suffering from reduced QoL in terms of pain, time lost from work, and reduction in social

activities leading to social isolation and loneliness.

The study by Garcia-Morales and colleagues reported a significantly lower mean (standard

deviation) score on all the eight SF-36 domains for patients with diabetes and foot ulcer than

patients with diabetes and no foot lesions (50.9 [18.9] vs. 68.6 [18.2]; p<0.001) [19]. Physical

functioning and the role physical domain of the SF-36 scale were the most severely

compromised domains of physical health as reported across two studies [16;20]. As reported

in a study by Happich and colleagues, the physical health of patients with DF ulcers,

amputations, and neuropathy was affected to a greater extent than the mental health, as

indicated by a much lower physical component summary score than mental component

summary score (MCS) [11].

Additionally, based on the SF-36 subscales of physical and social functioning, worse QoL

was observed for patients with non-healed and recurrent ulcers than patients with healed

ulcers (p<0.05) [20]. These results were supported in the study by Winkley and colleagues,

wherein significant deterioration in MCS score of the SF-36 scale was noted in both patients

with non-healed ulcers (mean difference [95% CI]: -6.54 [-12.64 to -0.44]) and in patients

with recurrent ulcers (mean difference [95% CI]: -5.30 [-9.87 to -0.73]) than patients with

healed ulcers [18]. Caregivers of patients with unhealed ulcers also demonstrated a

significantly worse QoL than the caregivers of patients with healed ulcers based on MCS and

role emotional domain of the SF-36 scale (p≤0.05, for both) [20]. Other factors that were

correlated to the poor QoL of patients with DF complications were site of principal lesion,

severity of DF ulcers, and time to ulcer progression [16;19].

Amputation of the lower leg was observed to render poor QoL, with patients who had

undergone amputation reporting a greater deterioration in their Daily Activities and Leisure

Scale of the SF-36 domains than those who had not undergone amputation (p<0.05) [16]. The

MCS score based on the SF-36 scale in patients with amputations was also significantly

lower than patients not undergoing amputations (mean difference [95% CI]: -8.10 [14.46 to -

1.75]) [18]. However, minor amputations reported improved QoL on the bodily pain domain

of the SF-36 scale than patients with current ulcers [17].

Guidelines on multidisciplinary management of diabetic foot complications

Literature search in the biomedical databases did not retrieve any published article in the

searched time frame, on recommendations on multidisciplinary DF care in any of the EU5

countries. Additional searches of websites resulted in identification of eight relevant

guidelines for the management of DF disorders.

'International consensus and practical guidelines on the management and the prevention of

the diabetic foot' by the International Working Group on Diabetic Foot (IWGDF) is the most

widely used clinical guideline for the management of DF [22]. Other guidelines that are used

in the EU5 region include NICE and Scottish Intercollegiate Guidelines Network (SIGN)

guidelines in the UK [9;23;24], Chiropodist-podiatrist consultations for preventing foot

lesions in diabetics in France [25;26], National disease management guideline for DF

prevention and therapy in Germany [27], and Clinical practice guideline for type 2 diabetes in

Spain [28].

The first international guidelines by the IWGDF were launched in 1999 and were

subsequently updated in 2007 and 2011 [29]. These guidelines are implemented throughout

the world with local adaptation based on the socio-economic conditions and healthcare access

system. IWGDF guidelines have become the standard of management across various

European countries [14], including regions of Pistoia, Italy [30]. According to IWGDF,

management of DF requires a multidisciplinary approach with three levels of foot-care

management: level 1 (general practitioner, diabetic nurse, and podiatrist); level 2

(diabetologist, surgeon [general and/or vascular and/or orthopaedic], diabetic nurse and

podiatrist); and level 3 (Specialized foot centre with multiple disciplines specialized in DF

care). The multidisciplinary team must work in both primary and secondary care settings. The

IWGDF, however agreed that setting up fully functional multidisciplinary team from the

outset is not an easy task, hence should be built up in a step-by-step process introducing the

various disciplines at different stages. The IWGDF has stated that initiation of

multidisciplinary teams to deal DF problems has resulted in drop in amputation rates [29].

The recommendations from NICE are also in line with those of IWGDF. According to the

NICE guidelines, each hospital should have a multidisciplinary foot care team comprising a

diabetologist, a surgeon with the relevant expertise in managing DF problems, a diabetes

nurse specialist, a podiatrist, a tissue viability nurse, and a wound care nurse. Any patient,

inpatient or outpatient, identified with DF problem should be referred to the multidisciplinary

foot care team within 24 hours of initial examination [9]. The multidisciplinary team should

monitor patient’s response to initial medical, surgical, and diabetes management, and should

assess specialist wound care, debridement, pressure off-loading and/or other surgical

interventions. Additionally, vascular assessment should be performed to determine the need

for further interventions [9]. Other EU5 guidelines were also in line with NICE and IWGDF

for multidisciplinary management of DF care [24-28]. According to SIGN, patients with

active foot disease should be immediately referred to a multidisciplinary foot team, followed

by agreed and tailored management according to patients’ need. SIGN considers that foot

lesions are more likely to lead to amputation in the absence of multidisciplinary team [24].

Guideline in France also have emphasised the role of multidisciplinary team in preventing

and controlling DF complications [26]. The guideline also highlighted the role of

Chiropodist-podiatrists, who is a part of the multidisciplinary team, in the prevention and

consultation of DF complications [25]. Spanish guidelines recommend structured

programmes for screening, risk stratification, and prevention of DF and for the treatment of

risk foot [28].

Thus an optimal management of DF problem requires a multidisciplinary approach not only

in terms of providing healthcare solutions but also in evaluating the quality of healthcare

delivered by the primary and secondary care settings.

Current gaps in the management of diabetic foot complications

The EURODIALE consortium was founded in 1999 to identify the differences in disease-

specific factors, management strategies, and organisational aspects of DF care across 10

European countries at the 14 participating centres [31]. Data from the study indicated that the

percentage of patients with late referrals (ulcers with duration >3 months) (mean [range]:

27% [6%-55%]) varied considerably not only across the countries but also between centres in

the same country (Figure 2) [32]. Factors leading to late referrals included lack of awareness

of the importance of prompt institution of care, lack of clear referral guidelines, and financial

barriers [32]. Use of vascular assessment also varied considerably from 19.6% to 85.9%

(Figure 3). The proportion of patients undergoing vascular assessment was significantly

lower in the primary care setting (39%) compared to those receiving treatment from a

specialist (67%, p<0.001). Factors leading to the underuse of vascular procedures included

presence of a non-functional leg, spontaneous healing of the ulcer, very poor health status of

the patient, and professional beliefs [32].

According to a study by Morbach and colleagues, podiatric care in France was poorly

reimbursed and only 20% of patients with diabetes were screened for neuropathy [33]. In the

French ENTRED study conducted in 2002, 18% of patients reported they could not afford

diabetes care because of its cost, with podiatric care costs being the reason for

discontinuation in 28% of the cases [34]. In 2008, the French healthcare system eventually

initiated the reimbursement of podiatric care for people with diabetes but only for those at

high risk of ulceration or amputation (Wagner grade 2 or 3) [35]. In the study by Richard and

colleagues, patients with DF infections had poor prognosis with a LEA rate of 48%, in spite

of the guideline recommended care being delivered at specialised centres [36]. Similar

observations were evident in Germany, where despite of clearly defined interfaces, less than

20% of patients with diabetes and foot problems were referred to the specialised DF clinics

from primary care [33].

In a study conducted in France in 2003 using National hospital discharge database, a lower

limb arterial investigation and a lower limb arterial revascularisation were reported in 55%

and 33% of people with diabetes and lower limb amputations, respectively [35]. Arterial

investigations were more often reported when a second amputation was undertaken (one

amputation in 2003: 53%; two amputations: 66%; three or more amputations: 73%); and

somewhat more often when the amputation was above the toe level: toe 52%; foot 57%;

below-the-knee 56%; above-the-knee 58%. The low rate of lower limb arterial investigation

reflects a lack of adequate management of DF lesions in France [35].

Discussion

The study aimed to assess the economic and QoL burden of diabetic foot (DF) disorders and

to identify disparities in the recommendations from guidelines and the current clinical

practice across the EU5 countries. Based on the studies included in the review it was

observed that DF complications including ulceration, infection, gangrene, and LEAs, often

encountered in patients with diabetes, are associated with considerable costs and utilisation of

resources including hospitalisations, antibiotic therapies, and transport. Complications

requiring amputation primarily drive the high cost and resource use associated with DF

ulcers. DF complications are associated with a worsening QoL, both physical and mental

health aspects, in patients with diabetes, with amputations affecting the QoL substantially. By

2030 the number of diabetes cases was estimated to reach 552 million, 9.9% of the world’s

adult population. Thus the incidence of diabetes related complications including foot

disorders would also increase substantially. For healthcare providers and reimbursement

agencies these figures could be alarming, as this will cause a major cost burden on health

resources [1]. When compared with other diseases, DF complications have demonstrated an

economic and resource utilisation burden comparable to that associated with cancer,

depression, lung disease, and musculoskeletal diseases [37]. In a study by Clarke and

colleagues, patients experiencing DF complications reported the highest first complication

costs £8459 (95% CI: £5295, £13 200) than patients experiencing non-fatal myocardial

infarction (£4070), fatal myocardial infarction (£1152), fatal stroke (£3383), non-fatal stroke

(£2367), ischaemic heart disease (£1959), heart failure (£2221), cataract extraction (£1553),

and blindness in one eye (£872) [38]. Similar to the trend observed above, the CoDiM study

reported high per patient average complication costs with amputations (€10 801),

gangrene/ulcer (€4748) than heart failure (€2599), myocardial infarction (€3214), angina

pectoris (€1995), other ischemic heart disease (€1284), and eye diseases (€722) [10]. Thus,

indicating that there is an unmet need in terms of lack of appropriate prevention and

management programmes for dealing with foot complication aspect of diabetes.

Although all DF complications are difficult to prevent, appropriate prevention and

management programmes may reduce the number of DF complications. The importance of

specialised foot clinic for diabetic patients was first published in 1986 [39]. Use of

multidisciplinary foot care teams both in primary and secondary care is expected to reduce

incidence of foot ulcerations, amputation rates, and improvement in limb salvage rates [9;29].

In addition, a general lack of awareness regarding the seriousness of foot ulceration in

patients with diabetes, despite guidelines on patient-centred education, was observed [40].

The International Diabetes Federation (IDF) named 2005 as the ‘year of the foot’ as the

theme for the World Diabetes Day to raise awareness on the increasing endemic of diabetes

and persuade the global community for better prevention and management of diabetic foot

complications [41].

Guidelines recommend early detection and prevention strategies in patients with diabetes and

‘at risk’ of foot complications. In patients with DF complications, overwhelming evidence

suggest that optimal use of multidisciplinary approach would result in improved care of DF

problems and will improve limb salvage rates. During 1998 to 2000, in the UK, the rate of

total amputation decreased by 25%, while during 2004 to 2008 the rate decreased by 9.1%

[42;43]. A study conducted in Belgium by Alexandrescu and colleagues concluded that

improvement in limb salvage rates after the initiation of multidisciplinary effective team

activity (after 2005) was significant than that was observed before its initiation (hazard ratio:

2.35; [95% CI: 1.04 - 5.31]; p=0.04) [44]. A study in France showed that the establishment of

a local multidisciplinary management team, based on international recommendations, led to a

low rate of major amputations (2.5%), trans-metatarsal amputations (2.5%), and no Chopart

or Lisfranc amputation in 118 high-risk patients with foot ulcer followed-up for 7 months

[45]. A decline in the amputation rates was also evident across other European countries

including Germany (decline of 48.8% from 1990 to 2004) and Netherlands (decline of 34.6%

from 1991 to 2000) [46;47]. A multidisciplinary approach with a close follow-up and early

intervention in dedicated centres improved limb salvage rate in patients with diabetes and

critical limb ischaemia by up to 96% during 2003 to 2006, in the UK [48]. Care and follow-

up of patients with foot at risk using multidisciplinary consultation was effective not only in

curative treatment, but also in primary and secondary prevention in France [49]. In Italy,

implementation of the International Consensus on the DF guidelines in 1999 resulted in

increased rates of peripheral revascularisation followed by reduction in major amputations

associated with DF in the area of Pistoia (Tuscany) [33;50].

Benefits of effective management of DF ulcers using multidisciplinary approach also

translated into cost saving, as evident from the studies undertaken in European countries. The

implementation of guidelines by the multidisciplinary group in France demonstrated a

decrease in costs related to use of antimicrobial agents and microbiology laboratory workload

for DF ulcers (€75 731 in 2003 to €17 859 in 2007) [51]. The study by Ortegon and

colleagues reported improved life expectancy, gained quality adjusted life-years, and reduced

incidence of foot complications with guideline-based care (comprising of intensive glycaemic

control and optimal foot care) than standard care treatment [52]. In the study by Tennvall and

colleagues, intensified prevention strategy was reported to be cost-effective in patients with

different risks for foot ulcers and lower extremity amputations [53].

The management of DF complications, however, remains suboptimal despite availability of

comprehensive treatment guidelines. There still remains a considerable variation in the

amputation rates across hospitals. A recent review of the hospital statistics of amputation

rates across PCTs in England indicated a ten-fold variation in the incidence of major

amputations in diabetes. The study showed no univariate associate between total amputations

and risk factors such as social deprivation or smoking prevalence. These data indicate

towards a marked variation in the quality of care among PCTs. A major factor contributing to

could be lack of or suboptimal use of specialised teams at certain centres ([54]). Inadequate

use of vascular imaging and revascularisation and low referral rates could be the other factors

that may have contributed to this variation in amputation rates. Non-invasive vascular testing

is recommended by the IWGDF guidelines for diagnosis and quantification of PAD, for

predicting wound healing of a DF ulcer, and for follow-up and control of treatment [29];

however, a review of EURODIALE study indicated underuse of vascular imaging in 14 [55].

One of the key findings of the EURODIALE study was the marked variation in late referral

rates between and within counties [32].

Given these inconsistencies between treatment guidelines and the clinical practice,

reformation of healthcare services at primary and secondary care level could be deemed as

the critical step in the optimal management of DF complications. Use of quality-assurance

system based on benchmarking technique, such as Initiative for the Promotion of Quality and

Epidemiology of Diabetes Mellitus in Germany, would improve the quality of care [56;57].

Further research to identify any correlation between incidence of amputation rates and

markers of quality of DF care, e.g. multidisciplinary team and speed of referral to specialist

services, would enable healthcare providers to design appropriate strategy to improve DF

care.

Limitations of this review

The present review is limited by its descriptive appraisal of included studies. The key

objective of this study was to identify how interplay of seemingly related components of DF

care impacts the overall DF management and the related cost. The review had limited focus

on the prevention strategies in ‘at risk’ patients with diabetes, although it forms an important

part of DF management in the multidisciplinary diabetic foot clinic’s. Assuming that

published data on economic and clinical outcomes of DF complications will be inadequate to

establish a correlation through quantitative analysis, a statistical model was not used in this

review.

Conclusion

Current guidelines on DFD indicate effective management of the disease leading to

prevention of amputations as the major cost and QoL driver. However, implementation of the

guidelines and set-up of multidisciplinary clinics for holistic management of the DFD varies

across EU5. Results from the review indicate that there is underuse of imagining,

revascularisation, and referrals to specialist. There is an unmet need to reinforce the guideline

to obtain favourable outcomes in terms of preventing DF complications to the extent possible

and achieving limb salvage where DF complications are unpreventable. Further, education of

the practitioners and patients along with early referral and effective management can lead to

favourable outcomes for patients with DFD. Better management of the diabetic complications

in the long run can have an enormous cost savings and offset to some extent the burden of

rising incidence of diabetes. The review is limited by the descriptive appraisal of included

evidence, warranting further research to establish a correlation between the seemingly related

components of DF care. Further, prospective research in this area is needed to provide better

understanding of the interrelated management and prevent the rising burden of DFD.

Acknowledgements

The authors thank Shweta Takyar and Dibyajyoti Mazumder at HERON Health Pvt. Ltd. for

contributing to the preparation of the draft manuscript and Karine Levesque from Abbott, for

providing support in conducting the review.

Author contributions

Siddiqui MK. and Chawla A. were responsible for study design, data extraction, and

reporting; van Acker K, Léger J, and Hartemann A contributed to the study concept, design,

and data interpretation. All authors contributed to the development and review of the draft

manuscript, and approved the final submitted version.

Conflict of interest

The study was funded by Abbott. Siddiqui MK. and Chawla A. are employees of HERON

Health Pvt. Ltd., India, which was commissioned to undertake the research for this study by

Abbott.

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Table 1: Costs per diabetic patient for various diabetic foot complications across EU5 countries

Study name Country Year

Cost of amputation (Euro)

Cost of gangrene (Euro)

Cost of ulcer (Euro) Cost of ulcer with infection (Euro)

Prompers 2008b

10 European countries

2005 €25 222 - €7722 (healed ulcer); €20

064 (unhealed ulcer within 12 months)

-

Ray 2005

Germany ¶

2003 €22 096 €3186 €877 €1783

Ray 2005

France ¶

2003 €31 998 €2266 €1142 €1999

Ray 2005

Italy ¶

2003 €10 177 - - -

Ray 2005

Spain ¶

2003 €14 787 €5611 - -

Happich 2008* Germany

2002 €21 476 - €4911 - Prior

2002 €12 588

von Ferber 2007

Germany 2001 €10 801 €4748 -

€: Euro; *Represents costs of complications per diabetic patient and year; ¶

SOURCE: [10; 11; 14; 15]

Data represents direct costs; -Represents no data reported

Table 2: Percentage of patients with diabetic foot complications using various resources

Resources used Happich 2008 (DIMCO study) (Germany) Girod 2003 (France)

Foot ulcers Amputation (2002)

Amputation (before 2002) Foot ulcers

Visits to investigator due to neuropathy 96.90% 95.80% 91.50% -

Number of visits (Mean visits/patient) 19.30 21.30 21.00 -

Neurological examinations 80.70% 87% 83.70% -

Nerve conduction velocity 9.70% 30.40% 9.30% -

Doppler-sonography 51.60% 52.20% 46.50% 60% Electromyogram 3.20% 17.40% 4.70% -

Other examinations 45.20% 52.20% 53.50% 62.70%

GP visits (Mean visits/patient) 0.30 2.00 0.20 - Internist visits (Mean visits/patient) 0.00 0.20 0.00 -

Diabetologist visits (Mean visits/patient) 0.70 0.20 0.50 53.50%

Neurologist visits (Mean visits/patient) 0.60 0.80 0.40 -

Other visits (Mean visits/patient) 0.60 0.40 0.50 -

Total number of visits to other physicians (Mean visits/patient) 1.90 3.20 1.50 -

Medication 81.30% 54.20% 57.50%

Antibiotics: 72%; vasodilators: 45%; LMWH: 27%; platelet anti-aggregants: 26%

Medical devices 59.40% 95.80% 78.70% - Transport 31.30% 75.00% 44.70% - Non-drug therapy 21.90% 25.00% 17% - Home help 31.30% 54.20% 29.80% - Nursing 28.10% 66.70% 44.70% - Early retirement 15.60% 8.30% 21.30% -

Hospitalisations 31.20% 100% 25.50% 80% (average 3.28 hospitalisation/patient)

Other services 6.30% 4.20% 10.60% - Temporary working disability 15.60% 8.30% 6.40% - Rehabilitation 0.00% 20.80% 8.50% -

Prosthesis - - -

Orthopedic shoes: 31%; shoes with partial support: 22%; soles: 21%

Sick leaves - - - 11% (for 2 to 82 days) GP: General Practitioners; LMWH: Low Molecular Weight Heparin; Represents medical devices mainly included orthopaedic shoes, shoe lifts, and walking aids; -Represents data not reported

SOURCE: [11; 12]

Table 3: Total costs for different grades of severity of foot complications Study name Country Cost

year Type of cost Total cost per disease severity grade (Euro)

Wagner classification Grade 1 Grade 2 Grade 3 Grade 4/5

Girod 2003 France 1999 Total cost €1727.78 €2182.63# €2410.65# €3590.56# #

Wound classification

Group A Group B Group C Group D Prompers 2008a

10 European 2005 Total cost €4504 €9273 €9851 €16 835

€; Euro; #

SOURCE: [13; 14]

Data presented for monthly healthcare costs per patient consumer; Grade 1: patients with superficial lesion; Grade 2: patients with deep extension; Grade 3: patients with teninitis; Grade 4/5: patients with gangrene; Group A: patients with no infection or Peripheral Artery Disease (PAD); Group B: patients with infection with no PAD; Group C: patients with no infection with PAD; Group D: patients with both infection and PAD

Table 4: Mean (range) of procedures per patient according to disease severity group

Resource used Group A Group B Group C Group D

Hospital stay (weeks) 0.66 (0-12) 1.91 (0-31) 2.53 (0-36) 3.90 (0-52)

Ipsilateral amputation below the ankle 0.10 (0-2) 0.18 (0-2) 0.22 (0-4) 0.40 (0-4)

Revascularisation 0.03 (0-2) 0.02 (0-1) 0.22 (0-3) 0.41 (0-8)

Diagnostic procedures and investigations 2.24 (0-18) 3.20 (0-23) 3.35 (0-25) 4.54 (0-22)

Antibiotic therapy: total number of daily doses 29.80 (0-619) 43.10 (0-350) 35.40 (0-327) 46.7 (0-361)

Offloading*1.90 (0-11) and foot

care equipment 2.40 (0-15) 2.29 (0-14) 2.38 (0-12)

Medical specialist consultations 5.60 (0-36) 7.01 (0-60) 6.50 (0-101) 9.52 (0-106)

Paramedic consultations 5.51 (0-69) 7.72 (0-80) 6.72 (0-91) 7.50 (0-106) *

SOURCE: [14]

Offloading includes: temporary footwear, orthopaedic shoes, TCC, insoles, orthoses, and other casts; Group A: patients with no infection or Peripheral Artery Disease (PAD); Group B: patients with infection with no PAD; Group C: patients with no infection with PAD; Group D: patients with both infection and PAD

Figure 1. Trial flow

Figure 2. Percentage of late referrals

Figure 3. Percentage of patients undergoing vascular investigation