Epidemiology and Health Care Costs for Diabetic Foot Problems

2 Epidemiology and Health Care Costs for Diabetic Foot Problems Gayle E. Reiber, MPH, PhD and Lynne V. McFarland, MS, PhD INTRODUCTION The global prevalence of diabetes is predicted to double by the year 2030 from 2.8% to 4.4% (1). Of individuals with diabetes, a substantial number will develop lower extremity disease including peripheral neuropathy, foot ulcers, and peripheral arterial disease (PAD). In this chapter, the current epidemiology of lower extremity disease in individuals with diabetes is reviewed with a focus on foot ulcers. Population-based and hospital discharge survey data from several sources illustrate the magnitude of the problem in the United States. Analytic and experimental studies conducted in several countries, which used robust multivariable modeling techniques, are discussed to describe foot ulcer risk factors. The chapter concludes with information on the economic impact of lower extremity disease, primarily diabetic foot ulcers. LOWER EXTREMITY DISEASE IN DIABETES The majority of lower extremity disease in people with diabetes is treated in outpatient, clinic, or office settings. Surveillance of lower extremity disease is uncommon in these health care settings. Therefore, to estimate the extent of this problem, the 1999 2000 population-based US Health and Nutrition Survey conducted interviews and lower limb examinations in a sample of the population. These data provide an accurate estimate of the frequency of lower extremity disease, specifically diabetic foot ulcers, peripheral neuropathy, and PAD in individuals ages 40. The prevalence (history) of peripheral neuropathy ( 1 insensate area) in people with diabetes was 28.5% and the prevalence of PAD (defined as an ankle brachial index of <0.9) was 9.5%. The prevalence for both conditions was double that observed in individuals without diabetes. In people with diabetes, 7.7% met the criteria for a history of foot ulcer which was three times higher than that observed in persons without diabetes (2). HOSPITAL DISCHARGE FREQUENCY AND RATES Hospital discharge data from several national surveys are available to describe the magnitude of lower extremity disease in hospitalized individuals. Trends in lower extremity conditions were tracked over a 10-year interval, 1993 2002, using data From: The Diabetic Foot, Second Edition Edited by: A. Veves, J. M. Giurini, and F. W. LoGerfo Humana Press Inc., Totowa, NJ 39

40 Reiber and McFarland Fig. 1. Frequency of lower extremity conditions in the US population with diabetes/1000. Hospital discharge data for ulcer/inflammation/infection (ulcer), peripheral neuropathy, and peripheral arterial disease, 1993 2002. (Source: Centers for Disease Control [4]). Fig. 2. Age-adjusted hospital discharge rates for lower extremity disease in the US population with diabetes/1000. Ulcer/inflammation/infection (ulcer), peripheral neuropathy, and peripheral arterial disease, 1993 2002. (Source: Centers for Disease Control [4]). from the US National Hospital Discharge Survey, in order to determine the number of hospital discharges in people with diabetes and lower extremity disease. The International Classification of Disease CM-9 codes used were: diabetes ICD-9-CM 250; foot ulcer/infection (454, 707.1, 680.6 680.7, 681.1, 682.6 682.7, 711.05 711.07, 730.05 730.07, 730.15 730.17, 730.25 730.27, 730.35 730.37, 730.85 730.87, 730.95 730.97, 785.4); peripheral neuropathy (337.1, 357.2, 355, 358.1, 713.5, 094.0, 250.6); and peripheral arterial disease (250.7, 440.2, 442.3, 443.8, 443.9, 444.22) (3,4). Figure 1 shows that the frequency of lower extremity conditions requiring hospitalization for people with diabetes and foot ulcers increased from 81/1000 to 100/1000 between 1993 and 2002. Hospitalizations for peripheral neuropathy increased from 36/1000 to 58/1000 whereas hospitalizations for peripheral arterial disease were 85/1000 in 1993, increased to a high in 1997 of 121/1000 and declined to 93/1000 by 2002. Figure 2 shows the age-adjusted hospital discharge rates for foot ulcers, peripheral neuropathy,

Epidemiology and Health Care Costs 41 Table 1 Frequency of US Hospitalization for Ulcer-Related Conditions in Individuals With Diabetes by Diagnosis, 2001 2002 ICD-CM Estimated frequency Type of ulcer codes 2001 2002 Cellulitis, abscess, or infected ulcer 681.1 26,685 29,347 Other cellulitis and abscess, foot except toes 682.7 81,367 83,954 Ulcer of lower limbs, except decubitus 707.1 209,088 216,785 Osteomyelitis 730.07 60,989 66,591 730.17 730.27 730.37 730.87 730.97 Chronic nonhealing ulcers 707.0 129,466 134,274 707.9 Atherosclerosis of lower limb with ulcer or 440.23 83,546 78,983 gangrene 440.24 Source: Nationwide Inpatient Sample, 2001, 2002 (6). and PAD from 1993 to 2002 using US hospital discharge survey data as the numerator and the US diabetes prevalence from the National Health Interview Survey applied to census population estimates as the denominator. Important methodological changes were made to the denominator used in the survey in 1997 when the diagnosis of diabetes was lowered from 145 mg/dl to 127 mg/dl and other denominator computations influenced by Census data. Age-adjusted hospital discharge rates for foot ulcers declined from 8.5/1000 in 1993 to 6.2/1000 in 2002. Age- and gender-specific foot ulcer rates for individuals with diabetes hospitalized with foot ulcers show the hospitalization rates increased steadily with age, from 5.5/1000 for ages 0 44; 6.4/1000 for ages 45 64; 8.8/1000 for ages 65 75; and finally 11.2/1000 for those aged 75+. The age-adjusted ulcer rates were 6.5/1000 in males and 6.1/1000 in females. Extensive missing hospital discharge data on racial and ethnic categories preclude an accurate estimate of these variables. The age-adjusted trend in peripheral neuropathy hospitalizations showed a slight increase between 1993 and 2002 from 5/1000 to 5.7/1000. The age-adjusted hospital discharge rate for PAD peaked in 1996 at 7.8/1000, then declined by over half to 3.6/1000 in 2002. These estimates exclude long-term care facility and federal hospital patients from the numerator. FOCUS ON FOOT ULCERS Foot ulcers are defined as a cutaneous erosion extending through the dermis to deeper tissue, resulting from various etiological factors and are characterized by an inability to self-repair in a timely and orderly manner (5). Table 1 shows the frequency of specific foot ulcer-related conditions in people with diabetes based on the Nationwide Inpatient Sample for 2001 and 2002 (6). Estimates for the three most frequent conditions reported in 2002 were 216,785 discharges for lower limb ulcer, except decubitus; 134,274 discharges for

42 Reiber and McFarland Table 2 Population-Based Diabetic Foot Ulcer Incidence and Prevalence from Selected Studies First Foot ulcer annual Foot ulcer author (reference) Population studied incidence/100 prevalence/100 Abbott (17) Cohort of 6613 patients in 2.2 4.7 6 district clinics in NW England followed for 2 years, type 1,2 diabetes Borssen (32) 375 patients Umea County 2 10.0 IDDM Sweden, age 15 50, 9.0 NIDDM type 1 = 298, type 2 = 77 Kumar (12) Cross-sectional study of 1 5.3 811 type 2 patients from three UK cities Lavery (33) Cohort of 1666 patients, 3.4 San Antonio, TX, 51% Mexican Americans, followed for 2 years Malgrane (34) 664 patients from 16 15.8% French diabetes centers MMWR (35) 2000 2002 BRFSS US 11.8% survey of adults >18 years Moss (15) Cohort of 2990 patients with 2.4 younger 9.5 younger late and early onset diabetes 2.6 older 10.5 older Ramsey (28) Nested case control study in 1.9 HMO, 8905 type 1, type 2 Walters (14) Cross-sectional study of 1077 4.1 7.4 type 1, 2 patients in 10 UK general medicine practices chronic nonhealing ulcer; and 83,954 discharges for cellulitis and abscess of the foot, excluding toes. Long-term care facility and federal hospital patients are also excluded from these estimates. Selected geographic population-based incidence and prevalence data are available from nine studies (Table 2) and show the annual ulcer incidence (new onset) ranges from 1% to 4.1% depending on the risk profile of the population. Prevalence (history) of foot ulcer in these diabetic populations ranges from 4.7% to 15.8%. The lifetime risk of a foot ulcer in people with diabetes has been estimated at 15% (7). In a study of causal pathways leading to foot ulcers involving patients in a US and British setting, 77% of the causal pathway included minor trauma as the initiating event. The most common components in development of foot ulcers in these settings were peripheral neuropathy (78%), minor trauma (77%), and deformity (63%) (8). A study of 669 patients with diabetic foot ulcers reported the three most common ulcer-initiating events were trauma owing to ill-fitting footwear (21%), falls (11%), and self-inflicted foot care injuries such as trimming the nails (4%) (9).

Epidemiology and Health Care Costs 43 Table 3 Anatomic Site and Outcome of Diabetic Foot Lesions in Two Prospective Studies All lesions N = 314; Most severe lesion Apelqvist (36) a N = 302; Reiber (11) b Lesion site, % Toes (dorsal and plantar surface) 51 52 Plantar metatarsal heads, midfoot, and heel 28 37 Dorsum of foot 14 11 Multiple ulcers 7 NA Total 100 100 Lesion outcomes Re-epithelialization/primary healing 63 81 Amputation at any level 24 14 Death 13 c 5 Total 100 100 a Study included consecutive patients whose lesions were characterized according to Wagner Criteria from superficial nonnecrotic to major gangrene. b Study patients were enrolled with a lesion through the dermis that could extend to deeper tissue. c Includes eight amputees who had not yet met the 6-month healing criteria. The anatomic location of a foot lesion has both etiological and treatment implications. Table 3 presents data from two large prospective studies showing the most common ulcer sites were the toes (dorsal or plantar surface), followed by the plantar metatarsal heads (10,11). The authors caution that ulcer severity is more important than ulcer site in determining the final outcome (10). RISK FACTORS FOR FOOT ULCERS Independent risk factors for diabetic foot ulcers were identified from 10 selected analytic or experimental studies that used multivariate modeling techniques to control confounders. Results summarized in Table 4 show the most consistent independent risk factors for foot ulcers were measures of peripheral neuropathy, measures of peripheral vascular disease, and prior foot ulcer. Several other independent risk factors also were identified. Long duration of diabetes, even after controlling for age, was a statistically significant finding in three studies (12 14). In the study by Rith-Najarian (13), long duration of diabetes increased the risk of foot ulcers over sixfold comparing persons with a diabetes duration 9 years to those with a duration of 20 + years. Peripheral neuropathy was assessed using several semiquantitative and quantitative measures, and neurological summary scores. Nine studies found an association between peripheral neuropathy and foot ulcers, and one study not showing an association had no lower limb peripheral neuropathy measures (15). In randomized clinical trials using vibration perception threshold (VPT) 25 as an entry criteria, Abbott and colleagues (16) identified both baseline VPT and a combined score of reflexes and muscle strength as significant predictors of incident foot ulcers. In Abbott s cohort study, VPT was not a significant predictor in the final model, whereas abnormal neuropathy disability score, insensitivity to the 10-g monofilament, and abnormal ankle reflexes were significantly

Table 4 Risk Factors for Foot Ulcers in Patients With Diabetes Mellitus From the Final Analysis Models of Select Studies Peripheral Peripheral neuropathy arterial (monofilament, disease reflex, vibration, (low AAI, Author (reference) Study design, Long DM Male or neurological TcPO 2 or High Foot History and type of analysis diabetes type Age duration gender summary score) absent pulses) HbA1c deformity Smoking Ulcer Abbott (16), Cox RCT, patients 0 0 Monofilament, Exclusion Exclusion regression analysis with VPT 25; + VPT + MI criteria criteria (US, UK, DPN score Canada), type 1 = 255, type 2 = 780 Abbott (17), Cox Cohort, 6613 + 0 0 0 VPT; + reflex + AAI + pulses + 0 + regression analysis type 1 or 2, + monofilament patient + neuropathy followed disability score 2 years, NW UK Boyko (19), Cox Cohort, 0 + Monofilament + AAI 0 + Charcot 0 + regression analysis veterans; + TcPO2 type 1 = 48, type 2 = 701; followed mean 3.7 years Carrington (18), Cohort, 169 0 + Motor nerve 0 0 Control Cox proportional patients with conduction factor hazards diabetes, 22 velocity nondiabetic controls 44

Kumar (12), logistic Cross-sectional + + NDS + 0 0 regression 811 type 2 from UK general practices Litzelman RTC 352 type 0 0 0 + Monofilament 0 0 + (22,23,24), GEE 2 patients, + thermal followed sensitivity 1 year Moss (15), Logistic Cohort, 1878 + in older + + older regression patients with onset onset early and late onset diabetes, followed 4 years Pham (20), Logistic Cohort, 248 0 0 0 + NDS + VPT regression patients at + monofilament three sites, followed 30 months Rith-Najarian (13), Cohort, 358 + + Monofilament 0 Chi-square analysis type 2 Chippewa Indians, followed 32 months Walters (14), Cohort, 10 + + Absent light + Absent pulses, 0 Logistic regression UK general touch + impaired 0 doppler practices pain, perception 1077 type 1, 2 0 VPT +, significant positive association; 0, no association; blank, not addressed; GEE, generalized estimating equations; AAI, ankle arm index; DM, diabetes; HbA1c, hemoglobin A1c; MI DPN score, Michigan diabetic peripheral neuropathy score; NDS, neuropathy disability score; RCT, randomized controlled trial; TcPo2, VPT = vibration perception threshold transcutaneous oxygen tension. 45

46 Reiber and McFarland associated with a subsequent foot ulcer (17). Carrington reported motor nerve conduction velocity as the best predictor of new ulcer after removing prior ulcer history from the model. Over the 6-year follow-up interval, 37% of these study participants developed at least one foot ulcer (18). Several studies identified increased ulcer risk in patients unable to detect the 5.07 monofilament, a semiquantitative measure of light touch (13,17,19 23). There was no statistically significant association between monofilament findings and foot ulcer risk in two other studies (14,16). Peripheral arterial disease was measured as absent pulses, decreased transcutaneous oxygen tension (TcPO 2 ), and a low ankle arm index (AAI). These variables were significant in the final ulcer prediction model in four studies. Low TcPO 2 indicating diminished skin oxygenation, and low ankle arm index, suggesting impaired large vessel perfusion, were both independent predictors of foot ulcers in the study by Boyko (19). In this study, laser Doppler flowmetry did not predict foot ulcer. Kumar (12) defined peripheral vascular involvement as the absence of two or more foot pulses or a history of previous peripheral revascularization. He found this variable was a significant predictor of foot ulcers. Walters (14) found that an absent dorsalis pedis pulse was associated with a 6.3-fold increased risk of foot ulcer (95% CI 5.57 7.0). Abbott found that reduced number of pedal pulses (0 2) was associated with a 1.57 increased risk of new foot ulceration (17). Glycated hemoglobin was measured in four studies; only one reported an independent association between elevated HbA1 c or blood glucose levels and foot ulcers in the final model. In a cohort study by Moss, the odds ratio was 1.6 (95% CI 1.3 2.0) showing the significant association between high levels of HbA1 c and subsequent foot ulcers (15). Five of the studies reported in Table 4 address the relationship between foot deformity and subsequent foot ulcer. Abbott found an abnormal foot deformity score of 3 6 increased the relative risk to 1.57 (95% CI 1.22 2.02). The foot deformity score includes muscle wasting, hammer toes, bony prominences, Charcot arthropathy, and limited joint mobility (17). The study by Boyko (19) found an independent association between Charcot deformity and foot ulcer, but other foot deformities were not independent ulcer predictors. Foot deformity did not enter the final analytic model in the studies by Rith-Najarian, Litzelman, or Walters (13,14,24). The relationship between smoking and foot ulcers was assessed in four studies reported in Table 4. Smoking was only of borderline significance in the older population in the Wisconsin study (15). The risk associated with a prior history of ulcers and amputations was assessed in four studies. Boyko, Abbott, and Litzelman (17,19,24) reported a prior history of ulcers significantly increased the likelihood of a subsequent ulcer. Kumar (12) reported a relationship between prior amputation and subsequent ulcer. Boyko s (19) cohort study also identified higher body weight, insulin use, and history of poor vision as three additional independent predictors of foot ulcer. Health care access and availability of diabetes education has been reported to influence development of foot ulcers. In a randomized trial conducted by Litzelman (24) in a county hospital population, patients were randomized to education, behavioral contracts, and reminders as concurrently their providers received special education and chart prompts. The control population in this study received usual care and education. After 1 year, patients in the intervention group reported more appropriate foot self-care behaviors, including inspection of feet and shoes, washing of feet, and drying between toes.

Epidemiology and Health Care Costs 47 Table 5 Direct Cost for Foot Ulcers in Persons With Diabetes From Two Studies No. of Author patients/study Average episode Inpatient Outpatient (reference) type Outcome cost (US $) cost (%) cost (%) Apelqvist Prospective 314 Primary healing $6664 *, $44,790 ** 61 39 (27) general internal = 63%, healed after medicine amputation = 24% patients Ramsey Nested case- Primary healing $27,987 total 18 82 (28) control study = 84%, amputation attributable in HMO of = 16% cost 8905 type 1,2 *No surgery **Including amputation Patients in the intervention group developed fewer serious foot lesions including ulcers than did those in the control group (24). Foot ulcers recur in many patients with diabetes (25). Abbott (17) reported prior podiatry clinic attendance as a risk factor for foot ulcer. This variable is likely intermediary in the pathway and a proxy for other conditions. Risk factors for foot ulcer recurrences were addressed in a UK study by Mantey and colleagues (26). Diabetic patients with an initial foot ulcer and two ulcer recurrences were compared with patients with diabetes who had only one ulcer and no recurrences over a 2-year interval. The authors reported greater peripheral sensory neuropathy and poor diabetes control in the ulcer recurrence group. Members of the ulcer recurrence group waited longer from observing a serious foot problem until seeking care and consumed more alcohol than did the group without ulcer recurrences (26). HEALTH CARE COSTS Optimally, the estimation of diabetic foot ulcer costs spans an entire ulcer episode from lesion onset to final resolution. Two studies provided direct costs associated with the entire diabetic foot ulcer history (Table 5). This methodology captures the many inpatient and outpatient costs/charges associated with foot ulcers and is preferable to reporting only charge for a single hospitalization or limited time interval (27,28). The study by Apelqvist (27) followed 314 patients across an entire ulcer episode, from ulcer presentation until final resolution. Healing was achieved in 2 months in 54% of patients, in 3 4 months in 19% of patients, and in 5 months in 27% of patients. There were 63% of patients who healed without surgery at an average cost of $6664. Lower limb amputation was required for 24% of patients at an average cost of $44,790. The 13% of patients who died before final ulcer resolution were excluded from this analysis. The proportion of all costs that were related to hospitalization was 39% among ulcer patients and 82% among amputees (27). Ramsey s nested case control study was conducted in a large HMO involving 8905 patients with diabetes. In this group, 514 individuals with diabetes developed one or more foot ulcers and 11% of these patients required amputation. Costs were computed for the year before the ulcer and

48 Reiber and McFarland Table 6 Ulcer Reimbursement to Hospitals for Patients With and Without Diabetes, 2002 Medstat (private) a Medicare b Length Average $ Length Average $ DRG Condition of stay Reimbursement of stay reimbursement 18 Peripheral neuropathy 5.6 9036 5.5 4782 with complications 19 Peripheral neuropathy 4.8 6061 3.6 3034 without complications 277 Cellulitis >age 17 4.8 6823 5.7 4000 with complications 278 Cellulitis >age 17 3.4 4426 4.2 2192 without complications 271 Skin ulcers 11 11,638 7.3 5227 238 Osteomyelitis 5.9 9913 8.7 7376 130 Peripheral arterial 5.1 7743 5.6 4554 disease with complications 131 Peripheral arterial 4.3 5768 4.1 2375 disease without complications DRG, diagnostic-related group. Source: a Medstat Group, Thompson Corporation, 2005; and b Centers for Medicare and Medicaid Services, 2005. the 2 years following the ulcer for both cases and controls. The excess costs attributed to foot ulcers and their consequences were $27,987 per patient for the 2-year period following ulcer presentation (28). A Markov model was developed to estimate lifetime health and economic effects of optimal metabolic and foot prevention and treatment strategies for patients with type 2 diabetes in the Netherlands. Modeling allocated patients to management according to guidelines or standard care. The authors reported guideline-based care improved qualityadjusted life years, decreased foot complications, and cost (29). In the United States, hospital care for lower extremity disease includes both a hospital and a physician component. Table 6 provides the hospital length of stay and reimbursement for lower extremity conditions described earlier in the chapter. Physician, outpatient, and other follow-up care costs would be added across the ulcer episode to these figures for a complete estimate of direct costs. Length of stay and reimbursement by diagnostic-related group (DRG) codes is shown for patients receiving private hospital care (Medstat) and Medicare. For example, under DRG 271, skin ulcer hospitalizations were longer for private patients (11 days) than Medicare patients (7.3 days). The average reimbursement to the private hospital was $11,638 whereas the reimbursement for the shorter Medicare hospitalization was $5227. Table 6 also has DRG codes for peripheral neuropathy with and without complications, cellulitis with and without complications, osteomyelitis and peripheral arterial disease with and without complications (30,31). Payment for the health care provider is not included in these figures.

Epidemiology and Health Care Costs 49 SUMMARY Persons with diabetes who develop foot ulcers are at high risk for subsequent foot ulcers and amputations. The hospital discharge rate for foot ulcers has decreased in the United States in recent years; however methodological differences may be partially responsible. The major independent risk factors for foot ulcers identified from populationbased, analytic and experimental studies include measures of peripheral neuropathy, peripheral vascular disease, and a history of a prior ulcer. Specific evidence is available demonstrating the benefit of better blood glucose control, and self-care strategies learned through patient education to prevent lesions in high-risk patients. The average private hospital reimbursement for a foot ulcer was $11,638 for 11 days, whereas Medicare reimbursement for foot ulcer conditions was $5227 for 7.3 days. The direct economic cost attributable to foot ulcers from onset for 2 years approaches $28,000. Guideline-based care is reported to improve outcomes and provide cost savings in comparison with standard care. REFERENCES 1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(5):1047 1053. 2. Gregg EW, Sorlie P, Paulose-Ram R, et al. Prevalence of lower-extremity disease in the U.S. adult population >40 years of age with and without diabetes. Diabetes Care 2004;27(7):1591 1597. 3. ICD-9-CM Professional for Hospitals, (2004,), International Classification of Diseases. (Hart AC, Hopkins CA, eds.), Volumes 1 3, 6th ed., St. Anthony Publishing/Medicode, Ingenix, 2003. 4. CDC. Data & Trends Diabetes Surveillance System Hospitalizations for Lower Extremity Conditions: Methodology. National Center for Chronic Disease Prevention and Health Promotion, Diabetes Public Health Resource, Available at: http://www.cdc.gov/ diabetes/statistics/hosplea/methods.htm [accessed 7/05]; 2005. 5. Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 1994;130:489 493. 6. AHRQ. Healthcare Cost and Utilization Project (HCUP), Nationwide Inpatient Sample, 2001, 2002. Available at: http://www.hcup-us.ahrq.gov (accessed 7/05). 7. Palumbo P, Melton L. Peripheral Vascular Disease and Diabetes. US Government Printing Office, Washington, DC, 1985. 8. Reiber G, Vileikyte L, Boyko E, et al. Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care 1999;22(1):157 162. 9. Macfarlane RM, Jeffcoate WJ. Factors contributing to the presentation of diabetic foot ulcers. Diabet Med 1997;14(10):867 870. 10. Apelqvist J, Castenfors J, Larsson J. Wound classification is more important than site of ulceration in the outcome of diabetic foot ulcers. Diabet Med 1989;6:526 530. 11. Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg 1998;176(2A):5S 10S. 12. Kumar S, Ashe HA, Fernando DJS, et al. The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population-based study. Diabet Med 1994;11:480 484. 13. Rith-Najarian SJ, Stolusky T, Gohdes DM. Identifying diabetic patients at high risk for lowerextremity amputation in a primary health care setting. Diabetes Care 1992;15(10):1386 1389. 14. Walters DP, Gatling W, Mullee MA, Hill RD. The distribution and severity of diabetic foot disease: a community study with comparison to a non-diabetic group. Diabet Med 1992;9:354 358.

50 Reiber and McFarland 15. Moss SE, Klein R, Klein BEK. The prevalence and incidence of lower extremity amputation in a diabetic population. Arch Intern Med 1992;152:610 616. 16. Abbott CA, Vileikyte L, Williamson S, Carrington AL, Boulton AJM. Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration. Diabetes Care 1998;21:1071 1075. 17. Abbott CA, Carrington AL, Ashe H, et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med 2002;19:377 384. 18. Carrington AL, Shaw JE, Van Schie CHM, Abbott CA, Vileikyte L, Boulton AJM. Can motor nerve conduction velocity predict foot problems in diabetic subjects over a 6-year outcome period? Diabetes Care 2002;25(11):2010 2015. 19. Boyko E, Ahroni JH, Stensel V, Forsberg RC, Davignon DR, Smith DG. A prospective study of risk factors for diabetic foot ulcer: the Seattle Diabetic Foot Study. Diabetes Care 1999;22:1036 1042. 20. Pham H, Armstrong DG, Harvey C, Harkless LB, Giurini J, Veves A. Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial. Diabetes Care 2000;23:606 611. 21. Frykberg RG, Lavery LA, Pham HT, Harvey C, Harkless L, Veves A. Role of neuropathy and high foot pressures in diabetic foot ulceration. Diabetes Care 1998;21(10):1714 1719. 22. Litzelman DK, Marriott RJ, Vinicor F. The role of footwear in the prevention of foot lesions in patients with NIDDM. Diabetes Care 1997;20(2):156 162. 23. Litzelman DK, Marriott DJ, Vinicor F. Independent physiological predictors of foot lesions in patients with NIDDM. Diabetes Care 1997;20(8):1273 1278. 24. Litzelman DK, Slemenda CW, Langefeld CD, et al. Reduction of lower extremity clinical abnormalities in patients with non-insulin-dependent diabetes mellitus. A randomized, controlled trial. Ann Intern Med 1993;119(1):36 41. 25. Maciejewski ML, Reiber GE, Smith DG, Wallace C, Hayes S, Boyko EJ. The effectiveness of diabetic therapeutic footwear in preventing reulceration. Diabetes Care 2004;27:1774 1782. 26. Mantey I, Foster AVM, Spencer S, Edmonds ME. Why do foot ulcers recur in diabetic patients. Diabet Med 1999;16:245 249. 27. Apelqvist J, Ragnarson-Tennvall G, Persson U, Larson J. Diabetic foot ulcers in a multidisciplinary setting: an economic analysis of primary healing and healing with amputation. J Intern Med 1994;235:463 471. 28. Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 1999;22(3):382 387. 29. Ortegon MM, Redkop WK, Niessen LW. Cost-effectiveness of prevention and treatment of the diabetic foot. Diabetes Care 2004;27:901 907. 30. HCFA. DRG Inpatient Billing Data, 2002: Health Care Finance Administration, Bureau of Data Strategy and Management, 2005. 31. MEDSTAT. DRG Guide Descriptions and Normative Values. Ann Arbor, MI, 2005. 32. Borssen B, Bergenheim T, Lithner F. The epidemiology of foot lesions in diabetic patients aged 15 50 years. Diabet Med 1990;7:438 444. 33. Lavery LA, Armstrong DG, Wunderlich RP, Tredwell J, Boulton AJM. Predictive value of foot pressure assessment as part of a population-based diabetes disease management program. Diabetes Care 2003;26(4):1069 1073. 34. Malgrange D, Richard JL, Leymarie F. Screening diabetic patients at risk for foot ulceration. A multi-centre hospital-based study in France. Diabetes Metab 2003;29(3):261 268. 35. MMWR. History of foot ulcer among persons with diabetes United States 2000 2002. Morb Mortal Wkly Rep 2003;52(45):1098 1102. 36. Apelqvist J, Larsson J, Agard C. Long term prognosis for diabetic patients with foot ulcers. J Int Med 1993;233:485 491.

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