A Randomized Controlled TrialComparing Telemedical andStandard Outpatient Monitoring ofDiabetic Foot UlcersDiabetes Care 2015;38:1723–1729 | DOI: 10.2337/dc15-0332

OBJECTIVE

The role of telemedical monitoring in diabetic foot ulcer care is still uncertain. Ouraim was to compare telemedical and standard outpatient monitoring in the careof patients with diabetic foot ulcers in a randomized controlled trial.

RESEARCH DESIGN AND METHODS

Of the736 screened individualswith diabetic foot ulcers, 401met theeligibility criteriaand were randomized between October 2010 and November 2014. The per-protocoltelemedical monitoring consisted of two consultations in the patient’s own home andone consultation at the outpatient clinic. Standard practice consisted of three out-patient clinic visits. The three-visit cyclewas repeated until study end point. The studyend points were defined as complete ulcer healing, amputation, or death.

RESULTS

One hundred ninety-three individuals were randomized to telemedical monitor-ing and 181 to standard care. Demographics were similar in both groups. A cause-specific Cox proportional hazards model showed no difference in individualsmonitored through telemedicine regarding wound healing (hazard ratio 1.11[95% CI 0.87, 1.42], P = 0.42) or amputation (0.87 [0.54, 1.42], P = 0.59). Wefound a higher mortality incidence in the telemedical monitoring group comparedwith the standard outpatient monitoring group (8.68 [6.93, 10.88], P = 0.0001).

CONCLUSIONS

The findings of no significant difference regarding amputation and healing betweentelemedical and standard outpatient monitoring seem promising; however, for tele-medicalmonitoring, a highermortality throws into question the role of telemedicineinmonitoring diabetic foot ulcers. Further studies are needed to investigate effects oftelemedicine on mortality and other clinical outcomes and to identify patient sub-groups that may have a poorer outcome through telemedical monitoring.

Diabetes currently affects .387 million people worldwide, and this number is ex-pected to rise to .592 million individuals worldwide by 2035 (1). In Denmark,320,545 people suffer from diabetes, and it is estimated that a further 200,000individuals are undiagnosed; a further 750,000 have impaired glucose tolerance(2). Approximately 7–15% of the population with diabetes will have one or severalfoot ulcers during a lifetime, and up to 70% of these ulcers will recur during a 5-yearperiod (3). Diabetic foot ulcers lead to ;500 major amputations every year in

1Department of Medical Endocrinology, OdenseUniversity Hospital, Odense, Denmark2Department of Orthopaedic Surgery, OdenseUniversity Hospital, Odense, Denmark3Epidemiology, Biostatistics and Biodemogra-phy, University of Southern Denmark, Odense,Denmark4Department of Internal Medicine, Odense Uni-versity Hospital, Odense, Denmark5Department of Orthopaedic Surgery, KoldingHospital, Kolding, Denmark

Corresponding author: Knud B. Yderstraede,knud.yderstraede@rsyd.dk.

Received 15 February 2015 and accepted 6 June2015.

Clinical trial reg. no. NCT01608425, clinicaltrials.gov.

This article contains Supplementary Data onlineat http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc15-0332/-/DC1.

© 2015 by the American Diabetes Association.Readers may use this article as long as the workis properly cited, the use is educational and notfor profit, and the work is not altered.

Benjamin S.B. Rasmussen,1

Johnny Froekjaer,2 Mads R. Bjerregaard,1

Jens Lauritsen,2 Joergen Hangaard,4

Claus W. Henriksen,5 Ulrich Halekoh,3 and

Knud B. Yderstraede1

Diabetes Care Volume 38, September 2015 1723

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GINGTEC

HNOLO

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Denmark, incurring a high financial bur-den (4). The cost of a major amputationwas estimated to be $59,000–$87,000 in1995 (5). Individuals with diabetes arealso at an increased risk of developingcardiovascular disease, which is the mostcommon cause of premature death amongthis population (6). The presence of a footulcer is associated with higher all-causemortality (7), and one study showed a30-daymortality of 30% after amajor am-putation and.50%mortality 1 year afteramputation (8).An aging population with comorbid-

ities challenges the health care system(9), and this has led to a growing interestin technical solutions to reduce thenumber of hospital and outpatient clinicvisits. Telemedicine is a growingmedicalfield that has the potential to deliverhealth care services from a distance (10).It covers a range of technologies for treat-ment and monitoring, and the creation ofinnovative health solutions has the poten-tial to improve patient quality of life at alow cost (11). In the present clinical trial,telemedicine was defined and usedas a tool for monitoring patients at hometo reduce the number of outpatient visits(i.e., telemedical monitoring).The evidence of telemedical monitoring

of ulcers is characterized by heterogeneityin studymethods and the interventions ap-plied,making it difficult to assess the safetyand efficacy of telemedicine (12,13). Anumber of randomized controlled trialshave investigated the potential and feasi-bility of telemedicine in ulcer care (14–19),but only two of these present clinical out-comes (15,18). Only one nonrandomizedstudy focused specifically on diabetic footulcers and telemedicine (20). The aim ofthe present study was to compare tele-medical and standard outpatient monitor-ing in the care of patientswith diabetic footulcers with a focus on ulcer healing andamputation.

RESEARCH DESIGN AND METHODS

ReportingThis studywas reportedusing theCONSORT(Consolidated Standards of ReportingTrials) guidelinesonpragmatic randomizedcontrolled trials (21). The study was a partof the Renewing Health project, a Euro-pean study aimed at investigating the useof telemedicine in various settings. How-ever, this study was conducted and re-ported independently (22). The MAST(Model for Assessment of Telemedicine)

was used in this setup, providing a struc-ture for multidisciplinary assessment ofthe outcomes of telemedical applications,and includes seven major domains. Themodel guides researchers in evaluatingmature technology in health care. Thethird domain (clinical effectiveness) wasused as a framework for the presentstudy (23). The trial protocol in Danish isavailable on request.

Trial DesignWe report on a multicenter pragmaticrandomized controlled clinical trial. In a4-month preliminary phase, patientswere assigned by 2:1 randomization in fa-vor of telemedicine to allow us to gainexperience with the telemedicine service.Thereafter, a 1:1 randomization betweentelemedical and standard outpatientmon-itoringwasused. The studywasperformedaccording to the Declaration of Helsinki IIand was registered with the Danish DataProtection Agency (2008-58-0035) and theU.S. National Institutes of Health. The re-gional ethics committee noted thatethics approval was not required forthis kind of study because it addressedpotential differences in monitoring andnot treatment.

Study PopulationThe study took place in the Region ofSouthern Denmark (RSD), which in-cludes five general hospital units withoutpatient clinics specializing in ulcercare. The area included 22municipalities.These outpatient clinics and municipali-ties are funded and driven by the gov-ernment. The population of the RSD is1.2 million, and the estimated foot ulcerprevalence is 7% among citizens with di-abetes. In 2013, 77,040 individuals wereliving with a diagnosis of diabetes in theRSD (2). Potential study participants wereidentified at the outpatient clinics of thefive general hospital units between Octo-ber 2010 and November 2014. Inclusioncriteria were adults with diabetes aged.18 years residing in the RSD andhaving a diabetic foot ulcer and referralto an outpatient clinic by a general prac-titioner or a hospital department. We ex-cluded individuals with conditions thatwould affect compliance (i.e., psychiatricdisease, dementia, alcohol abuse), com-peting conditions suspected to be thecause of the ulcer (i.e., gout, rheumatoidarthritis, uremia requiring dialysis), pastinclusion in the project, and expected ul-cer healing within 4 weeks.

Study InterventionEligible participants were treated accord-ing to standard clinical guidelines (24). Theparticipants were medically and surgicallystratified before randomization to tele-medical or outpatient monitoring. Theper-protocol telemedical monitoring con-sisted of two consultations in the patient’sown home using telemedicine and oneconsultation at the outpatient clinic. Stan-dard treatment comprised three outpa-tient clinic visits. The three-visit cycle wasrepeated as necessary for each patient un-til study end point. If a patient presentedwith two or more foot ulcers, one ulcerwas selected as the treatment or interven-tion focus (index ulcer) before randomiza-tion. In a few cases, an index ulcer was notdefined before randomization; thus, wedefined the ulcer meeting one of the endpoints first as the index ulcer. The ulcersnot included as an index ulcer were trea-tedaccording to recommendedguidelines,but these were disregarded in this study.

Patients monitored with telemedicinewere treated according to the algorithmshown in Fig. 1. No frequency of telemed-icine consultations or clinic visits waspredefined by the protocol butwas drivenby clinical judgment at every consultationbe it telemedical or control. Municipalnurses provided standard daily care undersupervision of a nurse specialized in ulcercare. The telemedical consultations wereconducted by telephone or online writtenconsultations between the specializedmunicipal nurse and physicians at the out-patient clinic. These consultations weresupplemented by an uploaded image ofthe ulcer and a detailed written assess-ment through the online database (25).If needed, the treatment strategy was re-vised, and the next consultation (telemed-ical or standard) and the indication forfurther images were agreed on by thenurse and physician. If the treatment orthe patient’s health condition neededcloser supervision by a hospital specialist(i.e., physician, podiatrist, nurse special-ist), deviation from the workflow algo-rithm was allowed.

Patients randomized to standard carefollowed the usual practice and treat-ment provided by the outpatient clinic.All visits and consultations took place inthe outpatient clinics. Patients stayed inthe study until ulcer healing, amputation,or death. If a patient did not meet any ofthe end points within 1 year (365 days),their condition was considered chronic,

1724 Telemedicine and Diabetic Ulcers Diabetes Care Volume 38, September 2015

and they were terminated from thestudy.

OutcomesThe primary outcome of the overall studywas the number of hospital admissions,including the number of inpatient days re-lated to ulcer treatment and surgical pro-cedures. These data will be publishedelsewhere. We report here the study endpoints of ulcer healing, amputation, anddeath. All end points reported in this studywere the first to occur for each patient.Amputations below the ankle were classi-fied asminor and those from the ankle andabove as major.

Sample Size CalculationAprevious study showed a reduction in theproportion of patients using the emer-gency department from 73% in the controlgroup to42% in the telemedicalmonitoringgroup (26). Similarly, the average numberof emergency department visits was re-duced from 2.05 to 0.84 during a 2-yearperiod. The sample size estimate for thepresent study was 180 patients in eachgroup based on the proportion of patientsusing the emergency department. Wechose to include 400 patients (200 in

each group) to adjust for an estimated10% dropout rate.

Randomization ProcedureThe participants were included and evalu-ated by the clinical staff at the participatingoutpatient clinics. Eligible patients werescreened for inclusion and exclusion crite-ria, and the cause of noneligibility wasnoted. The clinical staffs were suppliedwith checklists of the procedures requiredfor each patient. When a patient hadprovided written consent for participationin the trial, manual randomization was car-ried out using sealed, sequentially num-bered envelopes containing a letterassigning thepatient toeither the telemed-ical monitoring or the control group. Ran-domization was performed in blocks of12 patients (6 to telemedical monitoringand 6 to control). The 12 letters of assign-ment were placed in separate envelopes,which were sealed and scattered twice in arandom order and then assigned a serialnumber. The 12 envelopes were thengrouped inoneblock (inone largeenvelope).Grouped letters of assignment were pre-pared and distributed to the participatingclinics from the Department of Quality andResearch/Health Technology Assessment

at Odense University Hospital. Staff at theoutpatient clinic opened one envelopein sequential order at the time of patientinclusion.

Statistical MethodContinuous variables are expressed asmean6 SD and median and interquartilerange, and categorical variables are pre-sented as percentages. Data from partici-pants who discontinued (chose not toparticipate or left the study area) duringthe study period or still had an unhealedulcer after 1-year follow-up were cen-sored. Patients lost to follow-up were cen-sored on the date of last known follow-up.Data were analyzed through a competing-risks multistate model among death,amputation, and healing (27). Cumulativeincidence functions for amputation andhealing were calculated for the telemedi-cal and control groups separately using theAalen-Johansen estimator. Cause-specificCox proportional hazards models were ad-justed for age at entry, sex, andmunicipal-ity as a cluster effect. Hazard ratios (HRs)and 95% CIs are based on these models.The HRs reported in this article comparethe intervention to the control group.

The proportional hazards assumptionwas assessed and retained in the analy-sis. P, 0.05 was considered statisticallysignificant. All analyses were carried outusing the development environment R(28) and R packages survival (29) andetm (empirical transition matrix) (30).

RESULTS

Study PopulationOf 736 individualswith diabetic foot ulcersidentified in the 4-year screening period,401 were randomized as eligible partici-pants, and 374 were included in the finalanalysis (193 [52%] in the telemedicalmonitoring group and 181 [48%] in thecontrol group) (Fig. 2). Median time inthe study was 74 and 91 days in the tele-medical monitoring and control groups,respectively. The mean number of tele-consultations was 3.0 (95% CI 2.55, 3.47)in the telemedical monitoring group. Thebaseline demographics showed equal dis-tribution of selected variables in the twogroups (Table 1).

Complete HealingOf 374 participants, 271 (73%) experi-enced complete healing within thestudy period. Of these, 138 (72%) werefrom the telemedical monitoring group(n = 193) and 133 (73%) from the control

Figure 1—Generic workflow with telemedical monitoring and standard outpatient monitoring.

care.diabetesjournals.org Rasmussen and Associates 1725

group (n = 181). We found no differencebetween the two groups with respectto incidence of healing (Fig. 3, leftpanel). After adjustment for age, sex,and municipality, a cause-specific Coxproportional hazards model showed nodifference in completed healings (HR1.11 [95% CI 0.87, 1.42], P = 0.42).

AmputationOf 374 participants, 47 (13%) underwentamputation. Of these, 21 (11%) werefrom the telemedical monitoring group(n = 193) and 26 (14%) from the controlgroup (n = 181). We found no differencebetween the two groups with respect toincidence of amputation (Fig. 3, right

panel). After adjustment for age, sex, andmunicipality, a cause-specific Cox propor-tional hazardsmodel showedno difference(HR 0.87 [95% CI 0.54, 1.42], P = 0.59). Inthe telemedical monitoring group, 12 am-putations were major and 9 minor. In thecontrol group, 15 amputations were majorand 11 minor. No difference was found innumbers between the groups.

MortalityOf 374 participants, 9 (2.4%) died. Ofthese, eight (4%) deaths occurred in thetelemedical group (n = 193) and one(0.5%) in the control group (n =181). Afteradjustment for age, sex, andmunicipality,a cause-specific Cox proportional hazards

model showed a significant difference be-tween the two groups (HR 8.68 [95% CI6.93, 10.88], P = 0.0001). This differencecould not be explained by considering ad-ditional covariates, including smoking orcomorbidity. Of the nine patients whodied, two died at home, four in a regularhospital department, and three in the in-tensive care unit. All had chronic heartdisease, four had chronic kidney disease,and one had prostatic cancer. The aver-age age was 72 6 8 years, and male:female ratio was 8:1. Six patientshad sepsis, five pneumonia, and onegangrene.

CONCLUSIONS

In this randomized controlled clinical trialof telemedical monitoring versus stan-dard outpatient monitoring of diabeticfoot ulcers, we found no between-groupdifferences in healing or amputation.However, significantly higher mortalitywas found among those monitored bytelemedicine.

Few other studies have looked intothe clinical effects of telemedical moni-toring of diabetic foot ulcers. A non-randomized study by Wilbright et al. (20)showed no significant difference betweenthe telemedical group and the controlgroup in time to complete healing of dia-betic ulcers. The present results also dem-onstrate no difference with respect tohealing and amputation and thus suggestthat telemedicine is at least as good asstandard clinic visits. In addition, we foundno difference regarding the level of ampu-tations. These results indicate that the clin-ical information (i.e., general health,woundcondition) gained through telemed-ical monitoring was sufficient. Of note, allpatients were medically and surgicallystratified before randomization to ensurethe proper care for each patient during thetrial despite monitoring method. Otherstudies have documented reduced timeto healing with telemedicine (31,32) buttypically included ulcers of mixed etiologyand different approaches to telemedicine,thus making validating comparisons be-tween studies difficult (13). These resultsseem promising for the further use of tele-medicine in wound care.

Current knowledge on the effects oftelemedicine has been established throughlow-powered studies (33), and clinical tele-medical trials of ulcers havemainly focusedonhealing as theprimary outcomewithoutconsideration of other clinical outcomes,

Figure 2—Patient flow in the randomized controlled study of telemedical monitoring (interven-tion) vs. standard outpatient monitoring (control).

1726 Telemedicine and Diabetic Ulcers Diabetes Care Volume 38, September 2015

such as amputation andmortality. Becausediabetic foot ulcers are associated with ahigh risk of amputationand85%ofpatientswith amputation initially present with a di-abetic foot ulcer (34,35), data on this andother risks associated with diabetic ulcersshould be collected when evaluating newinterventions.The significant difference in mortality

between the telemedical and standardoutpatient monitoring groups could notbe explained by the selected variables.Further investigation of comorbiditiesand other possible reasons has been un-dertaken. A possible explanation couldrelate to the physicians’ clinical assess-ment through telemedicine dependingon secondhand information from anurse and an uploaded image of the ul-cer; thus, some vital information couldbe missed. This would seem unlikely,however, given the insignificant differ-ences in healing and amputation be-tween the two groups. Furthermore,the municipal nurses were experiencedin ulcer care. The findings contrast withthose of theWhole SystemDemonstratortelemedical study that showed a lowermortality in the intervention group(odds ratio 0.54 [95% CI 0.39, 0.75])(36). The authors of this study did notinclude individuals with diabetic foot

ulcers per se in the highly fragile group(comprising both high comorbiditiesand high mortality) (7), which might ex-plain the differences. The rather lowmortality reported in our study should

be seen in relation to the statisticalmethod used.Strengths and LimitationsOne of the study limitations is that clini-cians could deviate from the telemedical

Table 1—Baseline characteristics of patients with diabetic ulcers randomized to either telemedical or standard outpatientmonitoring

Telemedical monitoring(n = 193)

Standard outpatient monitoring(n = 181)

Age at inclusion (years) 66.8 6 13.0 66.7 6 12.8

Men 151 (78) 129 (71)

BMI (kg/m2) 28.9 6 6.2 28.9 6 6.0

Smokers 42 (26) 30 (20)

Nonsmokers 119 (74) 119 (80)

Type 1 diabetes 24 (15) 25 (16)

Type 2 diabetes 131 (85) 127 (84)

Years of diabetes at inclusion 14 (7–20) 14 (7–21)

Ulcer duration before inclusion* 1 (1–2) 1 (1–3)

ComorbiditiesHeart disease 64 (34) 59 (33)Hypertension 135 (70) 133 (74)Cerebrovascular disease 21 (11) 17 (9)Chronic pulmonary disease 11 (6) 20 (11)Connective tissue or rheumatic disease 10 (6) 9 (5)Liver disease 1 (1) 3 (2)Diabetes 193 (100) 181 (100)Hemiplegia 1 (1) 3 (2)Renal disease 17 (9) 11 (6)Cancer 6 (3) 1 (1)Other 36 (19) 42 (23)

Data are mean 6 SD, n (%), or median (interquartile range). *For ulcer duration of less than 14 days, 0 months was chosen as duration.

Figure 3—Cumulative probability of healing and amputation as a function of time. Dashed linesrepresent 95% CIs.

care.diabetesjournals.org Rasmussen and Associates 1727

workflow if required by the clinical con-dition. This ethical and clinical choice wasdriven by the local clinicians to ensure thebest care for the individual patient. Fur-thermore, the telemedical monitoringwas provided by several outpatient clinicswith small variations in clinical approach.These differences were anticipated be-cause of the overall study design andpragmatic trial approach investigatingtelemedical monitoring of diabetic ulcersin a real-life setting. We did try, however,to minimize the differences by ensuringoverall guidelines and the per-protocol al-gorithm. This approachmay have affectedthe internal validity of the trial butensured a high external validity (37).We used manual randomization at an

individual level to minimize selectionbias (38) and found that the overallblock randomization worked well. Anintention-to-treat approach was appliedin thedata analysis, but several participantshad to be excluded mainly due to formerparticipation or insufficient data as shownin Fig. 2. Additionally, some patients allo-cated to the telemedical monitoring groupdid not receive monitoring according tothe suggested algorithm. This was donewith respect to ethical considerations.Steventon et al. (36) noted some of thesame limitations in the Whole SystemDemonstrator study, one of the largeststudies todate investigating a telemedicalapproach to health care.The clinical data were retrieved from

the electronic patient records and theonline database used for the telemedi-cal monitoring. This minimized doubleregistration but may have affected thedata quality as reflected in the numberof missing answers in the baseline data.A full set of baseline data can be found inthe Supplementary Data.Evaluation of a complex intervention

such as telemedical monitoring requiresassessment of clinical, organizational, eco-nomical, and patient-related aspects(23,39). The MAST was used as a multidis-ciplinary approach to the evaluation oftelemedical monitoring, and the clinicaldata reported here represent only onepart of the assessment. Results on organi-zational, economical, and patient-relatedaspects will be published separately.

Clinical and Research ImplicationsNotwithstanding the limitations of thisstudy, the findings suggest that patientswith diabetic foot ulcers monitored with

telemedicine are at higher risk of deaththan patients attending standard outpa-tient visits. No obvious reason was foundthat could explain these results. On the ba-sis of the promising results regarding heal-ing and amputation, we recommend acautious approach to the use of telemedi-cine in the monitoring of diabetic foot ul-cers. Furthermore, ano-toleranceapproachto noncompliant ulcers is recommendeduntil more evidence is presented. The iden-tification of particularly vulnerable patientsis essential, and future studies should inves-tigate the possible influence of ulcer sizeand severity.

To the best of our knowledge, this studyis the largest clinical trial involving telemed-ical monitoring of diabetic foot ulcers.Furthermore, it is the first to evaluate tele-medical monitoring of patients with dia-betic foot ulcers in a randomized clinicalcontrolled setting. The findings of no signif-icant difference regarding amputation andhealing seem promising; however, for tele-medical monitoring, a higher mortalitythrows into question the role of telemedi-cine inmonitoring diabetic foot ulcers. Fur-ther studies are needed to investigate theeffects of telemedicine on mortality andother clinical outcomes and to identify pa-tient subgroups that may have poorer out-come from telemedical monitoring.

Acknowledgments. The authors thank theirmedical colleagues at the other participatingsites as well as the municipal and outpatientclinic nurses and the patients for their partici-pation in this study. They also thank consultantPer Riegels Nielsen, Esbjerg Hospital, and con-sultant Rolf Jelnes, Sønderborg Hospital. Theauthors thank medical writer Claire Gudex, Uni-versity of Southern Denmark, for comments andlanguage editing of the manuscript.Funding. The study was funded by the ABTFund (Applied Citizen Technology) from theDanish Ministry of Finance, ABT funds fromthe Region of Southern Denmark, and the EUproject Renewing Health.Duality of Interest. No potential conflicts ofinterest relevant to this article were reported.Author Contributions. B.S.B.R. contributed tothe study performance, data handling andanalysis, and writing and review of the manu-script. J.F. contributed to the study concept anddesign, study performance, data analysis, andreview of the manuscript. M.R.B., J.L., and U.H.contributed to the data handling and analysisand review of the manuscript. J.H. and C.W.H.contributed to the study concept and design,study performance, and review of the manu-script. K.B.Y. contributed to the study conceptand design, study performance, data handlingand analysis, and writing and review of themanuscript. J.F. and K.B.Y. are the guarantors of

this work and, as such, had full access to allthe data in the study and take responsibility forthe integrity of the data and the accuracy of thedata analysis.

References1. International Diabetes Federation. Diabetesfacts and figures [Internet], 2014. Available fromhttps://www.idf.org/worlddiabetesday/toolkit/gp/facts-figures. Accessed 21 June 20152. Diabetesforeningen. Diabetes i Danmark [Inter-net], 2014. Available from http://www.diabetes.dk/presse/diabetes-i-tal/diabetes-i-danmark.aspx.Accessed 21 June 2015 [in Danish]3. Boulton AJ, Vileikyte L, Ragnarson-TennvallG, Apelqvist J. The global burden of diabeticfoot disease. Lancet 2005;366:1719–17244. Danish Health and Medicines Authority. Di-abetic foot ulcer – a health technology assess-ment. Medicinsk Teknologivurdering 2011;13:1399–2481 [in Danish]5. Apelqvist J, Ragnarson-Tennvall G, Larsson J,Persson U. Long-term costs for foot ulcers indiabetic patients in a multidisciplinary setting.Foot Ankle Int 1995;16:388–3946. FowlerMJ. Microvascular andmacrovascularcomplications of diabetes. Clin Diabetes 2008;26:77–827. Brownrigg JR, Davey J, Holt PJ, et al. The asso-ciationof ulcerationof the footwith cardiovascularand all-cause mortality in patients with diabetes:a meta-analysis. Diabetologia 2012;55:2906–29128. Kristensen MT, Holm G, Kirketerp-Møller K,Krasheninnikoff M, Gebuhr P. Very low survivalrates after non-traumatic lower limb amputa-tion in a consecutive series: what to do? InteractCardiovasc Thorac Surg 2012;14:543–5479. Christensen K, Doblhammer G, Rau R, VaupelJW. Ageing populations: the challenges ahead.Lancet 2009;374:1196–120810. World Health Organization. TelemedicineOpportunities and Developments in MemberStates: Report on the Second Global Survey oneHealth. Global Observatory for eHealth Series.Vol. 2. Geneva, Switzerland, World Health Orga-nization, 200911. Saner H. eHealth and telemedicine: currentsituation and future challenges. Eur J Prev Car-diol 2013;20(Suppl.):1–212. Chanussot-Deprez C, Contreras-Ruiz J. Tele-medicine in wound care: a review. Adv SkinWound Care 2013;26:78–8213. Nordheim LV, Haavind MT, Iversen MM. Ef-fect of telemedicine follow-up care of leg andfoot ulcers: a systematic review. BMC HealthServ Res 2014;14:56514. Vowden K, Vowden P. A pilot study on thepotential of remote support to enhance woundcare for nursing-home patients. J Wound Care2013;22:481–48815. TerryM,Halstead LS,O’Hare P, et al. Feasibilitystudyofhomecarewoundmanagementusing tele-medicine. Adv Skin Wound Care 2009;22:358–36416. Dobke MK, Bhavsar D, Gosman A, De NeveJ, De Neve B. Pilot trial of telemedicine as adecision aid for patients with chronic wounds.Telemed J E Health 2008;14:245–24917. Ameen J, Coll AM, Peters M. Impact of tele-advice on community nurses’ knowledge of ve-nous leg ulcer care. J Adv Nurs 2005;50:583–59418. Santamaria N, Carville K, Ellis I, Prentice J.The effectiveness of digital imaging and remote

1728 Telemedicine and Diabetic Ulcers Diabetes Care Volume 38, September 2015

expert wound consultation on healing rates inchronic lower leg ulcers in the Kimberley regionof Western Australia. Prim Intention 2004;12:62–64, 66–68, 7019. Finkelstein SM, Speedie SM, Demiris G,Veen M, Lundgren JM, Potthoff S. Telehome-care: quality, perception, satisfaction. TelemedJ E Health 2004;10:122–12820. Wilbright WA, Birke JA, Patout CA, VarnadoM, Horswell R. The use of telemedicine in themanagement of diabetes-related foot ulcera-tion: a pilot study. Adv Skin Wound Care 2004;17:232–23821. Zwarenstein M, Treweek S, Gagnier JJ,et al.; CONSORT Group; Pragmatic Trials inHealthcare (Practihc) Group. Improving the re-porting of pragmatic trials: an extension of theCONSORT statement. BMJ 2008;337:a239022. REgioNs of Europe WorkINg toGether forHEALTH [Internet], 2009. Available fromhttp://www.renewinghealth.eu/en. Accessed21 June 201523. Kidholm K, Ekeland AG, Jensen LK, et al. Amodel for assessment of telemedicine applica-tions: mast. Int J Technol Assess Health Care2012;28:44–5124. Danish Health andMedicines Authority (Ed.).National Clinical Guideline for Diagnosis andTreatment of Diabetic Foot Ulcers. Copenhagen,

Denmark,DanishHealth andMedicinesAuthority,2013 [in Danish]25. Danish Telemedicine A/S. Available fromhttps://www.pleje.net. Accessed 21 June201526. Rees RS, BashshurN. The effects of TeleWoundmanagement on use of service and financial out-comes. Telemed J E Health 2007;13:663–67427. Beyersmann J, Allignol A, Schumacher M.Competing Risks and Multistate Models withR. New York, Springer, 201228. R Development Core Team. R: A Languageand Environment for Statistical Computing.Vienna, Austria, R Foundation for StatisticalComputing, 201429. Therneau T. A package for survival analysis in S,R package version 2.37-7 [Internet], 2014. Availablefrom http://cran.r-project.org/web/packages/survival/index.html. Accessed 6 May 201530. Allignol A, Schumacher M, Beyersmann J.Empirical transition matrix of multi-state mod-els: the etm package. J Stat Softw 2011;38:1–1531. Kobza L, Scheurich A. The impact of tele-medicine on outcomes of chronic wounds inthe home care setting. Ostomy Wound Manage2000;46:48–5332. Summerhayes C, McGee JA, Cooper RJ,Ghauri ASK, Ranaboldo CJ. Introducing leg ulcer

telemedicine into rural general practice.Wounds UK 2012;8:28–3633. Ekeland AG, Bowes A, Flottorp S. Methodolo-gies for assessing telemedicine: a systematic re-view of reviews. Int J Med Inform 2012;81:1–1134. Apelqvist J, Larsson J. What is the most ef-fective way to reduce incidence of amputationin the diabetic foot? Diabetes Metab Res Rev2000;16(Suppl. 1):S75–S8335. Frykberg RG, Zgonis T, Armstrong DG, et al.;American College of Foot and Ankle Surgeons.Diabetic foot disorders. A clinical practice guide-line (2006 revision). J Foot Ankle Surg 2006;45(Suppl.):S1–S6636. Steventon A, Bardsley M, Billings J, et al.;Whole System Demonstrator Evaluation Team.Effect of telehealth on use of secondary careand mortality: findings from the Whole SystemDemonstrator cluster randomised trial. BMJ2012;344:e387437. Treweek S, Zwarenstein M. Making trialsmatter: pragmatic and explanatory trials andthe problem of applicability. Trials 2009;10:3738. Hahn S, Puffer S, Torgerson DJ, Watson J.Methodological bias in cluster randomised tri-als. BMC Med Res Methodol 2005;5:1039. Aas IH. A qualitative study of the organiza-tional consequences of telemedicine. J TelemedTelecare 2001;7:18–26

care.diabetesjournals.org Rasmussen and Associates 1729