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Abstract

The US diabetic foot ulcer (DFU) incidence is 3-4% of 22.3 million diagnosed diabetes cases plus 6.3 million undiagnosed, 858 000 cases total. Risk of recurrence after healing is 30% annually. Lower extremity multiple nerve decompression (ND) surgery reduces neuropathic DFU (nDFU) recurrence risk by >80%. Cost effectiveness of hypothetical ND implementation to minimize nDFU recurrence is compared to the current $6.171 billion annual nDFU expense. A literature review identified best estimates of annual incidence, recurrence risk, medical management expense, and noneconomic costs for DFU. Illustrative cost/benefit calculations were performed assuming widespread application of bilateral ND after wound healing to the nDFU problem, using Center for Medicare Services mean expense data of $1143/case for unilateral lower extremity ND. Calculations use conservative, evidence-based cost figures, which are contemporary (2012) or adjusted for inflation. Widespread adoption of ND after nDFU healing could reduce annual DFU occurrences by at least 21% in the third year and 24% by year 5, representing calculated cost savings of $1.296 billion (year 3) to $1.481 billion (year 5). This scenario proffers significant expense reduction and societal benefit, and represents a minimum 1.9× return on the investment cost for surgical treatment. Further large cost savings would require reductions in initial DFU incidence, which ND might achieve by selective application to advanced diabetic sensorimotor polyneuropathy (DSPN). By minimizing the contribution of recurrences to yearly nDFU incidence, ND has potential to reduce by nearly $1 billion the annual cost of DFU treatment in the United States.

Keywords

diabetes diabetic foot diabetic neuropathy nerve decompression diabetic foot ulcer diabetic foot ulcer recurrence

The economic costs of diabetes mellitus (DM) represent a mammoth $245 billion expense to America and its medical system. An estimated 22.3 million Americans are living with diabetes and at least 6.3 million more are believed to be undiagnosed.^1,2 $176 billion is spent annually on direct costs for diabetic care, $80 billion of which are foot related expenses comprising a significant direct and indirect cost to society.^1,3 For the diabetic population as a whole, risk of developing a foot ulcer is 3 to 6% annually, a condition frequently requiring hospital admission.^4,5 Inpatient care is the largest contributor to cost, predominantly for infections, sepsis or gangrene requiring amputation. Of diabetic amputations, 84% are preceded by an ulcer.⁶ Of diabetic foot ulcer (DFU) cases, 50% become infected, 20% of which require major or minor amputation for resolution.⁷ Disastrously, 15% of all DFU will require an amputation,⁸ an event related to mortality as high as 15% in the first year.⁹ Avoidance of primary and recurrent DFU seems an attractive target for minimizing health care expenditures, amputations and costs to society, as shown in Figures 1 and 2.

Figure 1.

Avoiding recurrent nDFUs with ND will achieve savings by requiring care for fewer ulcers.

Figure 2.

Markov states for diabetes and DFU. Diabetes cases have 3% annual risk of developing a DFU, with healed DFU having 25-30%/year risk of recurrence. ND appears to lower recurrence risk to 4.6% or less. Approximately 13.6% of DFUs remain unhealed despite “best care.”⁶³ Since no evidence is available on failure to heal a DFU occurring after ND, we assume equivalence.

The Lower Extremity Amputation Prevention program of the U.S. Health Resources and Services Administration promotes the education of physicians and patients on the presence and importance of neuropathy, encouraging patient vigilance, attention to skin care, early recognition of skin breakdown, callus trimming and routine podiatric care for ulcer prevention. Lavery and colleagues have reviewed current treatment recommendations, their relative effectiveness, and the continuing challenges to ulcer prevention.⁴ They noted DFU recurrence rates as high as 80% annually; particularly in the presence of vascular compromise. Their review concluded by suggesting that overall DFU incidence could be reduced by over 50% if current treatment guidelines were routinely applied, still leaving at-risk patients a distressing 30% annual risk of ulcer recurrence.

One therapeutic approach to both primary prevention of neuropathic DFU (nDFU) and protection against recurrence was not explored by Lavery and collaborators. This is the outpatient surgical procedure known as external neurolysis, or nerve decompression (ND). ND is a therapy directed at nerve entrapment, a common secondary physical complication of diabetic sensorimotor polyneuropathy (DSPN),¹⁰ targeting the neuropathic origin of the cascade of diabetic foot complications. Nerves enlarge in DSPN due to a sequence of metabolic events.^11-15 Entrapment of nerve trunks commonly follows in longstanding diabetes as enlarged nerve trunks must glide and function in unyielding fibro-osseous anatomic tunnels, which are themselves stiffened and contracted by advanced glycation end products in the Maillard reaction. Clinically, these secondary, DSPN-associated entrapments are present in up to 33% of this patient population.¹⁰ Multiple nerve entrapments can generate the classic stocking/glove anesthesia patterns described clinically.¹⁴ Given this nerve/tunnel size mismatch, decompression of entrapped nerve trunks is reasonable to consider for minimizing contributions of secondary entrapment neuropathy to DSPN signs, symptoms and sequelae.^16,17 A similar accommodative approach to nerve trunk enlargement, compressions and entrapment has been applied with success for more than 50 years in the case of leprosy neuritis.¹⁶

Since Dellon’s 1988 optimistic enumeration of reasons for treating DSPN symptoms with ND surgery,¹⁷ significant supportive clinical evidence has accumulated. The frequent nerve compression present secondarily in DSPN is identified by Tinel’s percussion test at anatomic entrapment sites. When first described,¹⁸ the indication for ND was relief of pain, although recovery of sensibility was frequently noted as well. Infrequent foot ulceration, foot related hospitalizations, and amputation complications were noted following neurolysis.^{18,19,25,26-29} Yet scant academic or clinical acceptance of this therapeutic approach exists.³⁰ Skeptics assert the subjective improvements in pain and sensibility reported post-ND could be merely placebo, bias or natural disease progression effects.³¹

Objective evidence would rebut or nullify theoretical objections to ND based on bias and placebo confounders in studies of subjective pain and sensibility changes. There is now significant evidence which uses objective outcome measures providing such perspective. Aszmann et al have prospectively studied DFU occurrence or amputation after unilateral ND in painful DSPN, using patients’ contralateral leg as their own control.³² Zhang et al reported zero primary ulcerations in the 18 months following bilateral ND in 352 diabetics with advanced DSPN symptoms.²⁷ The same cohort showed significant recovery of slowed preoperative nerve conduction velocities at 3 months after ND. Evidence of immediate intraoperative recovery of EMG activity during ND has been presented to scientific conferences.³³ Long-term recurrence protection has been reported after ND in nDFU with nerve entrapment, demonstrating >80% recurrence reduction.^15,26-29 Such evidence suggests ND has potential for a monumental impact on future DFU incidence, prevalence and associated health care expense and noneconomic costs.³⁴ This report estimates economic benefits potentially available to society if ND were widely applied to healed nDFU cases to minimize recurrence (Figure 2).

Methods

The ND literature suggests that nDFU recurrences can be reduced from 30% per patient per year(pppy) to 4.6% or less, an 85% reduction.^4,15,26,29 This implies that an individual future year’s nDFU tally of recurrences can be greatly reduced, though not abolished, by ND. Our illustration is based on review of DFU and ND literature (see Table 1 and Table 2) published since 1988 using the most recent and conservative estimates of prevalence of diabetes {DM},¹ incidence of neuropathic DFU{I^nDFU},³⁵ change in nDFU incidence following ND treatment {delta I^nND}, and treatment cost per nDFU {cost}. Historical rates of primary neuropathic DFU and reported DFU recurrence rates were compared to ND literature. Using SPSS version 22 (IBM, Amonk, NY), a chi-square analysis was performed and reported as odds ratios (OR) with 95% confidence intervals.

Table 1.

Recurrence of DFU After ND in 6 Studies of Cases With DSPN, Tinel’s Sign, and Adequate Circulation.

Report	Annual ulceration risk (follow-up)
Azsmann et al 2005³⁰	0% (4.5 years)
Nickerson 2010¹⁵	4.6% (2.5 years)
Dellon, Muse et al 2012²⁶	3.8% (N/A)
Zhang et al 2013²⁵	0% (1.5 years)
Nickerson and Rader 2013²⁷	2.3% (5 years)
Nickerson and Rader 2014²⁴	1.6% (years 3-5)

Table 2.

Variables and Sources for Figures Used in Calculations.

Variable	Article	Figure
US diabetic population	National Diabetes Fact Sheet, CDC 2011	28.6 million
DFU incidence	Margolis 2011⁵	3-6%
Proportion of DFU in neuropathic, nonischemic class (nDFU)	Armstrong 2011³⁵	35-65%
Annual cases of nDFU	Here calculated	858 000 × 35% = 300 000
12-month recurrence risk post-ND from Table 1	Nickerson 2010¹⁵	0-4.6%
Mean incremental treatment cost to third parties for a new DFU	Rice 2014³⁴	$13 622
Medicare reimbursement for unilateral ND operative procedure	CMS data year 2013	$1143
Private and government insurer professional services payments for nDFU care	Here calculated	$4.091 billion

Non-third-party-payer direct societal costs identified in Table 3 include patient copay expense, private payments for provider care, neuroactive pain medication expense, and such indirect costs as lost productivity, disability payments, absenteeism, and family care.³⁴ Additional benefits such as subsequent amputation avoidance, minimization of recalcitrant healing cases and decreased mortality were not included in our calculations. Data used in calculations are in bold in subsequent tables, and quoted costs are in US dollars (2012) or older values adjusted for medical cost inflation.

Table 3.

Identifiable Costs Calculated for the United States.

Variable	Article	Figure
Supply costs specific to DFU treatment—$1000/DFU patient	Rice et al 2014³⁴	$300 million
Private copay costs (20% assumed for both Medicare and private insurance)	DM cost 2011- Govt. = 63%, Private Ins = 34%, Self pay = 3%	$700 million
Private payments to providers (presumed to be at rates equal to private insurance)	DM costs. Diabetes Care 2013; 3% × 273 000 × $16 880 = 1.38 × 10⁸	$138 million
Productivity/absentee/disability losses	Rice et al 2014³⁴	$3259/case × 273 000 = $890 million
Cost of neuroactive pain medication, $3800-4680/case; 10% of DM population has significant pain; pain meds eliminated after ND for 50%	Udall 2012⁶², Valdivia 2013²³	300 000 × .10 × .50 × $3800 = $57 million

To illustrate the potential for ND to generate cost reductions, Figure 2 and Table 4 display a scenario where ND is applied to a single year’s entire population of nDFUs. Pertinent Markov states are illustrated in Figure 1. Changes in the total of new primary nDFU and recurrences are tracked during the subsequent 3 and 5 year periods. DFU prevalence and incidence are held steady and historical recurrence risk is taken to be 25%, 40%, 60%, and 70% at 1, 2, 3, and 5 years.^36,37 The calculation depends on the proportion of first ulcerations to DFU recurrences, data that are not routinely reported. However, 2 articles have described recurrence cohorts in such a way that this can be calculated.^38,39 Their recurrence proportions are 40% and 59.3%, from which we presume annual nDFU recurrences to be approximately half. For post-ND recurrence risk we use 4.6% per/patient year, the highest rate in Table 1.¹⁵ Total nDFU numbers generated by historical treatment and recurrence rates are then compared to anticipated results after ND. Recurrent nDFUs calculated in column 3 of Table 4 are the sum of the 4.6% recurrence risk of ND-treated cases times each prior year’s declining intact number of healed DFUs.

Table 4.

Comparison of Post-ND and Historical Ulcer Recurrence Rates.

Year	Annual DFU events	Recurrences at historic (% rate)	Recurrences post-ND, at 4.6%/pt/yr	Total DFU cases, ND vs historical
Base year, year 0	100 total (50% recurrent)
End year 1 F/U	50 new	(25%) = 25^yr0	5^yr0	155 vs 175
End year 2	50 new	(40%) = 40^yr0 + 12^yr1 = 52	4.6^yr0 + 2.3^yr1 = 7	212 vs 252
End year 3	50 new	(60%) = 60^yr0 + 20^yr1 + 12^yr2 = 92	4.4^yr0 + 2.2^yr1 + 2.3^yr2 = 9	271 vs 342 (21% reduction)
End year 4	50 new	(65%) ^estimated = 65^yr0 + 30^yr1 + 20^yr2 + 12^yr3 = 127	4.2^yr0 + 2.1^yr1 + 2.2^yr2 + 2.3^yr3 = 11	332 vs 427
End year 5	50 new	(70%) = 70^yr0 + 37^yr1 + 30^yr2 + 20^yr3 + 12^yr4 = 169	4^yr0 + 2.0^yr1 + 2.1^yr2 + 2.2^yr3 + 2.3^yr4 = 13	395 vs 519 (24% reduction)

The purging of future nDFU cases by application of ND to every neuropathic ulcer is estimated. After 5 years there is a 24% reduction in total DFU cases requiring treatment. Additional recurrences occurring from years prior to base year are not included, but would only magnify the results favoring ND. Assumptions are a steady state of DM population and incidence, the historical risk of DFU recurrence, and post-ND ulcer recurrence risk of 4.6%/year.

Results

Seven historical reports of DFU recurrence^32,40-45 were compared to 3 reports of ND cohorts.^15,27,32 The historical reports had varying levels of implementation of “standard” foot care vs insoles or footwear. A weighted average of these historical recurrence rates was calculated (range: 5-58%) resulting in a mean 20.4% (SD = 0.17). This result for nonsurgical standard/experimental care represents a lower recurrence rate than typically reported in the literature. Reports assessed for DFU recurrence included 303 patients who received ND, and 1276 patients who received standard care. Following ND, 4 (1.3%) patients had recurrent ulceration compared to 260 (20%) of the historical care group, a much reduced hazard risk (OR = 0.05, 95% CI = 0.02-0.14).

Only 1 sizeable historical report exists for primary ulcer incidence with standard preventive measures.⁴⁶ Twenty-eight of 921 patients had primary ulceration of their feet, while 0/404 patients receiving ND experienced primary ulceration.^27,32 Conservative estimation of 1/404 was used for statistical analysis, and ND showed a statistically significant decreased OR for primary ulceration (OR = 0.08, 95% CI = 0.01-0.58).

The expense to third-party insurance payers for nDFU care by medical professionals is as follows:

DM \times {Incidence}^{DFU} \times %^{DFU} neuropathic \times average nDFU reimbursed cost = 28.6 \times 10^{6} \times . 03 \times . 35 \times $ 4.091 billion 3^{rd} party provider payments .

Additional expenses to society are listed in Table 3 and include supply costs, private payments to providers, 20% copay for insured cases, expense of neuroactive pain drugs like tricyclic antidepressants, gabapentin, and pregabalin, productivity losses, absenteeism, and disability payments. These total $300 + $700 + $138 + $890 + $57 million, respectively. Adding to $4.091 billion gives a grand total of $6.171 billion minimum annual cost to society for nDFU, equaling $20 570 per case cost for 300 000 neuropathic DFUs.

After 3 and 5 years, a 21% and 24% annual reduction in total DFU events could be realized if ND were routinely employed after healing of nDFUs. For year 3, this represents a potential benefit of .21 × $6.171 billion, or $1.296 billion. By year 5, the annual savings reaches 24%, or $1.481 billion. This requires an investment expense of $686 million (300 000 nDFU × $1143/ leg × 2 legs/case), representing a 2.16 × return on investment. Future years would see similar continued savings.

Discussion

Despite the reported success of ND, many question how surgery could be effective in a metabolic disorder such as diabetes. This is really no more curious than the successful surgical approaches to diabetic retinopathy, cardiovascular or peripheral vascular disease, and nephropathy with renal failure. Surgical practitioners do understand that peripheral nerve trunk entrapment is secondary to, not causal of the changes induced in nerves by diabetic metabolic disease. Yet these secondary changes can nevertheless be amenable to surgical modification.¹³ The entrapment of nerve trunks is like a “napkin ring” effect, triggering demyelination, altering sensory and motor nerve function and causing pain. The target of ND is this secondary physical entrapment and the associated objective changes in nerve conduction velocity (NCV), evoked EMG and further, yet to be identified, functional parameters found when DSPN is allowed to progress unabated.⁴⁷

In this illustration amputation costs are included for the initial DFU treatment course, as they are well recorded in the DFU literature. But amputations forestalled by avoided recurrences in future years are an additional benefit, not estimated here. Nor does our calculation acknowledge the ongoing recurrences recognized in years 1-5 from the ulcers healed in years preceding base year. Additional prospective benefits include a decrease in unhealed or recalcitrant ulcers, decreased expenses for ongoing treatment and infection risk, deferred early mortality from fewer DFU cases at risk of infection and sepsis, an improved patient quality of life and relief of caretaker burden. All of these are suggested in the DFU and ND literature but figures were not well enough quantified to include in our example.

Benefits would accrue to differing parties. Cost reductions and copay amounts would accrue to third-party payers and self-payers. Clinics and institutions might limit DFU care losses. Surgeons would benefit with revenue from ND, offsetting other parties’ savings. Employers, patients, families, and caregivers would share the indirect benefits of reduced disability cost, absenteeism, and retained capability.

Our Table 4 illustration trims the 3-year nDFU recurrence total from 92 to 24 cases, a 76% reduction. But this yields total cost reduction of only 21%, due to continued generation of new primary ulcers from the DSPN reservoir with secondary entrapments. For a greater total cost reduction, primary ulcer incidence must decrease. ND may be useful for this purpose.^27,28,32 Zhang’s 352 DSPN patients, with adequate circulation and the highest possible Toronto Clinical Symptom Scores, developed not a single primary ulcer in the 18 months following bilateral ND. This group should have accumulated 16 DFUs (352 × 3% × 1.5 yr) in that period.²⁷ Azsmann found a DFU rate of 0% at 4.5 years in the operated legs of 50 painful DSPN patients while their contralateral nonoperated limbs suffered a 30% incidence of ulcer or amputation, P < .001.³²

An unknown question is how DSPN cases could be selected for prophylaxis of initial DFU by ND. The reports of Yudovsky et al⁴⁸ indicate that hyperspectral imaging of oxy/deoxy-hemoglobin ratios can identify, with 90% sensitivity, and 2 months prior to ulceration, those plantar skin areas about to break down in DSPN patients. Non-invasive hyperspectral screening could allow rapid, efficient focused application of prophylactic ND to the specific individuals at particular risk for initial DFU.

Neuroischemic cases offer yet another opportunity for savings. An estimated 50% of DFUs are neuroischemic,³⁵ and around 65% of such cases will heal with current offloading care. The definition of neuroischemic ulcer varies, from absence of palpable foot pulse, to ankle-brachial index values < 0.9, or toe pressures < 45 mm Hg. Trignano et al show that neuroischemic values of foot trancutaneous pO2 can be reestablished and maintained for a year at > 45 mm Hg in 90% of cases.⁴⁹ Currently there is little evidence to guide selection of appropriate neuroischemic candidates. ND might be secondary or supplementary to interventions which improve circulation, but its value for neuroischemic ulceration certainly warrants further investigation.

It is certainly intriguing that ND protects against nDFU recurrence despite unchanged risk factors like plantar pressure concentrations, tight gastro-soleus muscles, lost ankle ROM, past DFU/amputation history, foot deformity, high BMI, and smoking history. The nervous system plays a critical role in tissue homeostasis, a factor particularly important in DSPN complications.⁵⁰ Scientific literature links diabetes and vascular phenomena like hyperemic flare, reduced capillary circulation and neuropeptide reductions.^51-55 Altered oxygen delivery, fluid filtration, and inflammatory response undoubtedly make the feet of DSPN patients more susceptible to tissue damage. These factors might explain anecdotal reports that ND may be useful in shortening healing time for the recalcitrant 15% of indolent, torpid DFU cases and the 10% which remain unhealed until patient demise.

Surgical site infection, reported by Wukich⁵⁶ to be nearly 13% for patients with diabetes and neuropathy, cannot be ignored. Zhang’s prospective study included 560 bilateral procedures on advanced DSPN and healed DFU cases, with >3000 separate incisions, but reported zero surgical site infections.²⁷ These are significantly different infection rates (P < .0001), and suggest that resolution of secondary entrapment effects by ND may be immediately altering the infection risk. A reduction in the number of DFU wounds should diminish infectious events with lower infection numbers limiting subsequent sepsis, gangrene, and lower extremity amputations requiring expensive inpatient care.^26-28,32 ND in the DSPN patient seems to have low infection rates, and is certainly less risky than having a DFU recur.

Beyond the favorable economics of ND, indirect benefits can include a better quality of life, caregiver relief, and deferred mortality. The overlying patient-centered goal in DFU care ought to be ulcer-free survival with intact limbs. Traditional treatments provide such survival for only 36 - 45% at 12 months.⁵⁷ In contrast, ND produced intact legs and ulcer-free survival in 59% after 5 years, suggesting its superiority as therapy, at least for the painful, Tinel-positive nDFU subgroup.²⁹

This exercise is limited by a number of assumptions and estimations. Little of the ND literature and few DFU studies^58-60 are level 1 evidence-based science. Due to limited quality historical and ND data on primary foot ulceration, stringent meta-analytical techniques were not applied. Comparative statistical figures should be interpreted accordingly. Neurolysis cohorts are primarily patients with painful neuropathy, adequate circulation, and a Tinel sign at anatomic compression points. There is no evidence that painless, Tinel-negative DSPN cases react differently than our illustrative group in objective measures (NCV, EMG, infection risk, DFU incidence, recurrence, or amputation risk) but this issue has not been specifically studied. Available economic data is not sorted by circulatory status, so generalizing overall DFU data to the nDFU could be challenged.

Contributions to continuing recurrences from ulcers initially presenting prior to base year are excluded, but would only magnify the calculated benefit. This number might be around 80 additional recurrences available for ND and recurrence protection if Apelqvist’s risk of 70% by 5 years³⁵ is applied to the population which provided the 50 recurrences presumed in the base year. Benefits of ND would accumulate as time progresses, to eventually reach a limit, since all possible recurrences would have occurred. Of course, new primary wounds and nonoperated recurrent cases in years’ subsequent to the base year could still benefit.

There is no information available on whether ND might provide enough durable, long lasting recurrence protection to diminish the need for patient education, footwear, shoe inserts, routine podiatric follow-up, or other current “best care” and aftercare recommendations. This could be a fruitful future research area.

The representative illustration of DFU incidence change depends on the proportion of ulcers which are primary versus recurrent, a statistic rarely reported. If the 1:1 ratio on which these calculations are based were incorrect, the projections would need adjustment. Greater benefit would occur if recurrences were a higher percentage, as larger cost reductions would occur. If lower, reductions of initial DFU rates would be necessary to achieve similar results.

Our use of a calculated weighted average yearly recurrence risk (20.4%) one-third lower than Lavery et al’s impression of 30%⁴ means the OR calculation may understate the magnitude of protection that ND provides.

It is certain that ND would never be applied to 100% of nDFU cases, due both to withheld patient consent and medical contraindication. Yet the illustration seems persuasive that ND could be an efficient public policy tool to accomplish meaningful reductions in the expense of care for the common and costly DSPN foot complications. Neuropathic DFU then might be seen once again as potentially “cured” rather than only “in remission.”⁶¹

Conclusions

The large and increasing cost of care for diabetic foot problems is determined by the high incidence of DSPN and DFU, large expenses for complication treatment, and the appalling frequency of recurrences. The outpatient surgical procedure of ND at multiple fibro-osseous tunnels for decompression of lower extremity peripheral nerve trunks appears to give significant protection against ulcer recurrence. If confirmed by clinical experience, external neurolysis applied to the 35% of DFU cases thought to be primarily neuropathic, by the third program year could potentially reduce costs by at least $1.296 billion annually. This would require expenditure of $686 million with the cost/benefit ratio being at minimum 1.9:1. Annual savings would reach $1.790 billion by year 5. We suggest that this currently available, effective, but infrequently used therapy could provide $1 billion economic and social benefit annually within 5 years by limiting the complications and cost of DSPN foot problems. With the illustrative calculations presented here, we wish to challenge those skeptical of the ND approach to participate in the design and performance of studies which will either bolster or conclusively terminate the widespread reluctance to acknowledge value in ND for DSPN foot complications.

Footnotes

Abbreviations

DFU, diabetic foot ulcer; DSPN, diabetic sensorimotor polyneuropathy; NCV, nerve conduction velocity; ND, nerve decompression; nDFU, neuropathic DFU; OR, odds ratio.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

American Diabetes A. Economic costs of diabetes in the U.S. in. 2012. Diabetes Care. 2013;36(4):1033-1046.

Boulton

Vileikyte

Ragnarson-Tennvall

Apelqvist

. The global burden of diabetic foot disease. Lancet. 2005;366(9498):1719-1724.

Driver

Fabbi

Lavery

Gibbons

. The costs of diabetic foot: the economic case for the limb salvage team. J Vasc Surg. 2010;52(3 suppl):17S-22S.

Lavery

La Fontaine

Kim

. Preventing the first or recurrent ulcers. Med Clin North Am. 2013;97(5):807-820.

Margolis

Malay

Hoffstad

. Incidence of Diabetic Foot Ulcer and Lower Extremity Amputation Among Medicare Beneficiaries, 2006 to 2008. Rockville, MD: Agency for Healthcare Research and Quality; 2011.

Boulton

. The diabetic foot: from art to science. The 18th Camillo Golgi lecture. Diabetologia. 2004;47(8):1343-1353.

Driver

Wrobel

Armstrong

. Foot ulcers in the diabetic patient, prevention and treatment. Vasc Health Risk Manage. 2007;3(1):65-76.

Albert

. Cost-effective management of recalcitrant diabetic foot ulcers. Clin Podiatr Med Surg. 2002;19(4):483-491.

Morbach

Furchert

Groblinghoff

. Long-term prognosis of diabetic foot patients and their limbs: amputation and death over the course of a decade. Diabetes Care. 2012;35(10):2021-2027.

10.

Vinik

Mehrabyan

Colen

Boulton

. Focal entrapment neuropathies in diabetes. Diabetes Care. 2004;27(7):1783-1788.

11.

Riazi

Bril

Perkins

. Can ultrasound of the tibial nerve detect diabetic peripheral neuropathy? A cross-sectional study. Diabetes Care. 2012;35(12):2575-2579.

12.

Lee

Dauphinée

. Morphological and functional changes in the diabetic peripheral nerve using diagnostic ultrasound and neurosensory testing to select candidates for nerve decompression. J Am Podiatr Med Assoc. 2005;95:433-437.

13.

Sessions

Nickerson

. Biologic basis of nerve decompression surgery for focal entrapments in diabetic peripheral neuropathy. J Diabetes Sci Technol. 2014;8(2):412-418.

14.

Dellon

. Diabetic neuropathy: medical and surgical approaches. Clin Podiatr Med Surg. 2007;24(3):425-448.

15.

Nickerson

. Low recurrence rate of diabetic foot ulcer after nerve decompression. J Am Podiatr Med Assoc. 2010;100(2):111-115.

16.

Nickerson

. A review of therapeutic nerve decompression for neuropathy in Hansen’s disease with research suggestions. J Reconstr Microsurg. 2010;26(4):277-284.

17.

Dellon

. A cause for optimism in diabetic neuropathy. Ann Plast Surg. 1988;20(2):103-105.

18.

Dellon

. Treatment of symptomatic diabetic neuropathy by surgical decompression of multiple peripheral nerves. Plast Reconstr Surg. 1992;89(4):689-697;discussion 698-699.

19.

Dellon

Mackinnon

Seiler

WAT

. Susceptibility of the diabetic nerve to chronic compression. Ann Plast Surg. 1988;. 20(2):117-119.

20.

Ducic

Taylor

Dellon

. Relationship between peripheral nerve decompression and gain of pedal sensibility and balance in patients with peripheral neuropathy. Ann Plast Surg. 2006;56(2):145-150.

21.

Dellon

. Neurosurgical prevention of ulceration and amputation by decompression of lower extremity peripheral nerves in diabetic neuropathy: update 2006. Acta Neurochirurgica Suppl. 2007;100:149-151.

22.

Blount

Peled

Dexter

Nagle

Maloney

Dellon

. Sympathetic nerves in the tarsal tunnel: implications for blood flow in the diabetic foot. Plast Reconstr Surg. 2008;122(1):188-191.

23.

Valdivia

JMV

Weinand

Maloney

Blount

Dellon

. Surgical treatment of superimposed, lower extremity, peripheral nerve entrapments with diabetic and idiopathic neuropathy. Ann Plast Surg. 2013;70(6):675-679.

24.

Rosson

Larson

Williams

Dellon

. Tibial nerve decompression in patients with tarsal tunnel syndrome: pressures in the tarsal, medial plantar, and lateral plantar tunnels. Plast Reconstr Surg. 2009;124(4):1202-1210.

25.

Baltodano

Basdag

Bailey

. The positive effect of neurolysis on diabetic patients with compressed nerves of the lower extremities: a systematic review and meta-analysis. Plast Reconstr Surg. 2013;1(4):e24.

26.

Nickerson

Rader

. Nerve decompression after diabetic foot ulceration may protect against recurrence: a 3-year controlled, prospective analysis. J Am Podiatr Med Assoc. 2014;104(1):66-70.

27.

Zhang

Zhong

Yang

Shi

Guowei

. Evaluation of the clinical efficacy of multiple lower-extremity nerve decompression in diabetic peripheral neuropathy. Br J Neurosurg. 2013;27(6):795-799.

28.

Dellon

Muse

Nickerson

. Prevention of ulceration, amputation, and reduction of hospitalization: outcomes of a prospective multicenter trial of tibial neurolysis in patients with diabetic neuropathy. J Reconstr Microsurg. 2012;28(4):241-246.

29.

Nickerson

Rader

. Low long-term risk of foot ulcer recurrence after nerve decompression in a diabetes neuropathy cohort. J Am Podiatr Med Assoc. 2013;103(5):380-386.

30.

Melenhorst

Overgoor

Gonera

Tellier

Houpt

. Nerve decompression surgery as treatment for peripheral diabetic neuropathy: literature overview and awareness among medical professionals. Ann Plast Surg. 2009;63(2):217-221.

31.

Cornblath

Vinik

Feldman

Freeman

Boulton

. Surgical decompression for diabetic sensorimotor polyneuropathy. Diabetes Care. 2007;30(2):421-422.

32.

Aszmann

Tassler

Dellon

. Changing the natural history of diabetic neuropathy: incidence of ulcer/amputation in the contralateral limb of patients with a unilateral nerve decompression procedure. Ann Plast Surg. 2004;53(6):517-522.

33.

Dargis

Pantelejeva

Jonushaite

Vileikyte

Boulton

. Benefits of a multidisciplinary approach in the management of recurrent diabetic foot ulceration in Lithuania: a prospective study. Diabetes Care. 1999;22(9):1428-1431.

34.

Rice

Desai

Cummings

AKG

Birnbaum

Skornicki

Parsons

. Burden of diabetic foot ulcers for Medicare and private insurers. Diabetes Care. 2014;37(3):651-658.

35.

Armstrong

Cohen

Courric

Bharara

Marston

. Diabetic foot ulcers and vascular insufficiency: our population has changed, but our methods have not. J Diabetes Sci Technol. 2011;5(6):1591-1595.

36.

Apelqvist

Larsson

Agardh

. Long-term prognosis for diabetic patients with foot ulcers. J Intern Med. 1993;233(6):485-491.

37.

Nabuurs-Franssen

Huijberts

Nieuwenhuijzen Kruseman

Willems

Schaper

. Health-related quality of life of diabetic foot ulcer patients and their caregivers. Diabetologia. 2005;48(9):1906-1910.

38.

Abbott

Vileikyte

Williamson

Carrington

Boulton

. Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration. Diabetes Care. 1998;21(7):1071-1075.

39.

Monami

Longo

Desideri

Masotti

Marchionni

Mannucci

. The diabetic person beyond a foot ulcer: healing, recurrence, and depressive symptoms. J Am Podiatr Med Assoc. 2008;98(2):130-136.

40.

Reiber

Smith

Wallace

. Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial. JAMA. 2002;287(19):2552-2528.

41.

Uccioli

Faglia

Monticone

. Manufactured shoes in the prevention of diabetic foot ulcers. Diabetes Care. 1995;18(10):1376-1378.

42.

Busch

Chantelau

. Effectiveness of a new brand of stock “diabetic” shoes to protect against diabetic foot ulcer relapse. A prospective cohort study. Diabetic Med. 2003;20(8):665-669.

43.

Lavery

Higgins

Lanctot

. Preventing diabetic foot ulcer recurrence in high-risk patients use of temperature monitoring as a self-assessment tool. Diabetes Care. 2007;30(1):14-20.

44.

Armstrong

Holtz-Neiderer

Wendel

Mohler

Kimbriel

Lavery

. Skin temperature monitoring reduces the risk for diabetic foot ulceration in high-risk patients. Am J Med. 2007;120(12):1042-1046.

45.

Lavery

Higgins

Lanctot

. Home monitoring of foot skin temperatures to prevent ulceration. Diabetes Care. 2004;27(11):2642-2647.

46.

Lavery

Peters

Williams

. Reevaluating the way we classify the diabetic foot: restructuring the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care. 2008;31(1):154-156.

47.

Levine

Barrett

Hank

Yamasaki

Nickerson

. A pilot trial of peripheral nerve decompression for painful diabetic neuropathy (P01.125). Paper presented at: American Academy of Neurology; 2013; San Diego, CA.

48.

Yudovsky

Nouvong

Schomacker

Pilon

. Assessing diabetic foot ulcer development risk with hyperspectral tissue oximetry. J Biomed Optics. 2011;16(2):026009.

49.

Trignano

Fallico

Chen

. Evaluation of peripheral microcirculation improvement of foot after tarsal tunnel release in diabetic patients by transcutaneous oximetry [published online ahead of print January 13, 2015]. Microsurgery.

50.

Schaper

Huijberts

Pickwell

. Neurovascular control and neurogenic inflammation in diabetes. Diabetes/Metab Res Rev. 2008;24(suppl 1):S40-S44.

51.

Wahlberg

Jorneskog

. Patients with diabetes and critical limb ischemia have a high peripheral vascular resistance. Ann Vasc Surg. 1997;11(3):224-229.

52.

Pradhan Nabzdyk

Kuchibhotla

Guthrie

. Expression of neuropeptides and cytokines in a rabbit model of diabetic neuroischemic wound healing. J Vasc Surg. 2013;58(3):766-775.

53.

Jörneskog

Brismar

Fagrell

. Skin capillary circulation is more impaired in the toes of diabetic than non-diabetic patients with peripheral vascular disease. Diabet Med. 1995;12(1):36-41.

54.

Jörneskog

Brismar

Fagrell

. Pronounced skin capillary ischemia in the feet of diabetic patients with bad metabolic control. Diabetologia. 1998;41(4):410-415.

55.

Moura

Cruz

Carvalho

. The effect of neurotensin in human keratinocytes—implication on impaired wound healing in diabetes. Exp Biol Med. 2014;239(1):6-12.

56.

Wukich

McMillen

Lowery

Frykberg

. Surgical site infections after foot and ankle surgery: a comparison of patients with and without diabetes. Diabetes Care. 2011;34(10):2211-2213.

57.

Jeffcoate

Chipchase

Ince

Game

. Assessing the outcome of the management of diabetic foot ulcers using ulcer-related and person-related measures. Diabetes Care. 2006;29(8):1784-1787.

58.

Macaré van Maurik

JFM

Schouten

MEL

ten Katen

van Hal

Peters

EJG

Kon

. Ultrasound findings after surgical decompression of the tarsal tunnel in patients with painful diabetic polyneuropathy: a prospective randomized study. Diabetes Care. 2014;37(3):767-772.

59.

Macaré van Maurik

ter Horst

van Hal

Kon

Peters

. Effect of surgical decompression of nerves in the lower extremity in patients with painful diabetic polyneuropathy on stability: a randomized controlled trial [published online ahead of print November 7, 2014]. Clin Rehabil.

60.

Macaré van Maurik

JFM

Oomen

RTW

van Hal

Kon

Peters

EJG

. The effect of lower extremity nerve decompression on health-related quality of life and perception of pain in patients with painful diabetic polyneuropathy: a prospective randomized trial [published online ahead of print February 25, 2015]. Diabetic Medicine.

61.

Miller

Salloum

Button

Giovinco

Armstrong

. How can I maintain my patient with diabetes and history of foot ulcer in remission? [published online ahead of print August 20, 2014]. Int J Lower Extrem Wounds.

62.

Udall

Harnett

Mardekian

. Costs of pregabalin or gabapentin for painful diabetic peripheral neuropathy. J Med Econ. 2012;15(2):361-370.

63.

Ince

Game

Jeffcoate

. Rate of healing of neuropathic ulcers of the foot in diabetes and its relationship to ulcer duration and ulcer area. Diabetes Care. 2007;30(3):660-663.

Illustration of Cost Saving Implications of Lower Extremity Nerve Decompression to Prevent Recurrence of Diabetic Foot Ulceration

Abstract

Keywords

Methods

Results

Discussion

Conclusions

Footnotes

Abbreviations

Declaration of Conflicting Interests

Funding

References