Epidemiology, Morbidity and Risks

• Abou-Zamzam AM Jr, Gomez NR et al: A prospective analysis of critical limb ischemia: factors leading to major primary amputation versus revascularization. Ann Vasc Surg 21(4):458-63, 2007. In our aging population, primary major amputations (AMP, below-knee or above-knee) continue to be performed despite advances in revascularization. We hypothesized that not only patient comorbidities but also the system of health-care delivery affected the treatment of patients with critical limb ischemia (CLI). A prospective analysis of patients presenting with CLI was undertaken to determine whether patient-specific factors or healthcare delivery factors (system-related) influenced treatment with primary AMP versus lower extremity revascularization (LER). The patient-specific factors age, gender, race/ethnicity, presence of coronary artery disease, cerebrovascular disease, tobacco use, diabetes mellitus (DM), dialysis dependence (end-stage renal disease, ESRD), hypertension, hyperlipidemia, stage of CLI (rest pain, minor or major tissue loss), history of revascularization, and functional status (living situation and ambulatory status) were recorded. The system-related factors time from onset of CLI to vascular surgery evaluation and type of insurance (managed care/other insurance) were also noted. The influence of patient-specific and system-related factors on the primary treatment modality (AMP versus LER) was determined with univariate and multivariate analyses. A total of 224 patients presented with CLI between March 1, 2001, and March 1, 2005. Patients were treated with primary major AMP in 97 cases (43%) and revascularization in 127 cases (57%). On univariate analysis, nonwhite race/ethnicity, DM, ESRD, major tissue loss, dependent living situation, and nonambulatory status were all significant predictors of AMP versus LER (all P < 0.01). On multivariate analysis, major tissue loss, ESRD, DM, and nonambulatory status remained independent predictors of AMP versus LER (all P < 0.05). The system-related factors of time to vascular surgery evaluation (mean 8.6 weeks, 7.1 vs. 9.3 weeks AMP versus LER, P = 0.60) and type of insurance (managed care, 17% vs. 24% AMP vs. LER, P = 0.15) had no influence on treatment. Fifty-four percent of all primary major AMPs were performed due to extensive gangrene or infection present at initial vascular evaluation which precluded limb salvage. Major tissue loss, ESRD, DM, and nonambulatory status are all independent predictors of treatment with primary AMP as opposed to revascularization. Treatment of CLI is determined by patient-specific factors and does not appear to be adversely influenced by system-related factors. Efforts toward improving limb salvage may be best directed at aggressive treatment of medical comorbidities to prevent the late complications of CLI. Earlier recognition of tissue loss and referral to the vascular specialist may lead to improved limb salvage.

• Adler AI, Ahroni JH, Boyko EJ and Smith DG: Lower extremity amputation in diabetics. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers. Diabetes Care 22: 1029-1035, 1999. Authors' summary: Objective: To identify risk factors for lower- extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. Research design and methods: This is a prospective study of 776 U.S. veterans in a general medical clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazard models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. Results: Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < 51 mm Hg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio - 1.1-7.8), lower extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an arm ankle index <0.81 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. Conclusions: This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes. Comments: The physician should have two main responsibilities in caring for the new diabetic patient: spare the patient from the harmful effects of hyperglycemia as much as possible and preserve islet cell function as much as possible. Weight reduction and early use of insulin are the best tools to achieve these goals. These proper goals are ignored by many algorithms in the literature. The patient is first given a period to see the effects of diet. Then, oral agents are added in increasing amounts until finally after up to several years of poor control, the pancreas is exhausted and insulin is started. No wonder the eventual use of insulin is associated with poor outcomes. These investigators enlisted patients with no baseline foot problems immediately putting them at risk for amputation. What risk factors become important when one looks at patients already having non-healing ulcers. See Dillon (Angiology 1997) in our pneumatic boot library. There we find among 1035 patients with 2177 episodes followed up to 15 years that smoking, hemodialysis, inability to walk and an aggressive vascular surgeon become risk factors also.

• Albers M, Fratezi AC, De Luccia N: Assessment of quality of life of patients with severe ischemia as a result of infrainguinal arterial occlusive disease. J Vasc Surg 16: 54-9, 1992. The purpose of this cohort study was to assess the quality of life of patients with severe ischemia as a result of infrainguinal arterial occlusive disease. Spitzer's QL-INDEX was selected to measure quality of life at baseline and at 3, 6, and 12 months. On the basis of initial treatment, 61 patients were grouped as follows: IC (conservative, n = 31), IR (arterial reconstruction, n = 14), and IA (major amputation, n = 16). After 12 months of follow-up, 48 patients were similarly regrouped according to ultimate treatment as follows: UC (n = 19), UR (n = 9), and UA (n = 20). At 12 months the mean score was significantly higher than the baseline in IC (6.43 vs 3.84, p less than 0.0001) as well as IR (5.64 vs 3.57, p less than 0.01), but not in IA (4.43 vs 3.62). The QL-INDEX mean score was lower in UA than in UC (4.15 vs 6.58, p less than 0.01) or UR (4.15 vs 7.11, p less than 0.0001). The correlation between QL-INDEX and an arbitrary scale was also high (r = 0.726, p less than 0.001). In conclusion, quality of life of patients with limb ischemia can be confidently assessed, improves during the first year of follow-up if major amputation is avoided, and improves and is sustained by a functioning graft.Comments: Hey! Some folks may get better with conservative therapy. Rushing into a questionable procedure may not be the best course for all.

• Albers M, Romiti M, et al: An updated meta-analysis of infrainguinal arterial reconstruction in patients with end-stage renal disease. J Vasc Surg 45:536-42, 2007. BACKGROUND: A previous meta-analysis reported on the mid-term outcomes of infrainguinal bypass grafts in patients with critical limb ischemia and end-stage renal disease. Given the competing interest in endovascular procedures, the results of bypass surgery must be assessed as precisely as possible for future comparison. In this study, the original meta-analysis was refined and updated by increasing the number of studies reviewed, estimating primary graft patency, extending follow-up time, and investigating the problem of early amputation despite a patent graft. METHODS: Studies published from 1987 through 2005 were identified from two electronic databases. Two investigators independently extracted the survival data from life tables, survival curves, and texts. Pooled survival curves were then constructed for graft patency, limb salvage, and patient survival according to a random-effects protocol for meta-analysis. RESULTS: Of 28 articles included, 18 reported amputation despite a patent graft in 84 (10%) out of 844 limbs, and 25 described a perioperative mortality of 88 (8.8%) out of 996 patients. The 5-year pooled estimate (SE) was 50.4% (15.4%) for primary patency, 50.8% (19.0%) for secondary patency, 66.6% (11.2%) for limb salvage, and 23.0% (11.7%) for patient survival. No publication bias was detected. CONCLUSIONS: Limb salvage can be achieved in most end-stage renal disease patients who undergo bypass surgery for critical ischemia, but survival is poor. To avoid early amputation despite a patent graft, bypass grafting should not be offered to patients with a great amount of tissue loss or extensive infection.

• Ann Abou-Zamzam AM Jr, Teruya TH, Killeen JD, Ballard JL: Major lower extremity amputation in an academic vascular center. Vasc Surg 17:86-90, 2003. Major lower extremity amputations continue to be performed despite an aggressive policy of revascularization. Factors leading to amputation were analyzed to determine whether a reduction in the limb loss rate is possible. A retrospective analysis of a prospectively maintained vascular registry was performed to identify patients undergoing above-knee amputation (AKA), below-knee amputation (BKA), and lower extremity revascularization (LER) for limb salvage between January 1, 1999 and January 1, 2002. Patient demographics, comorbidities, insurance carriers, and indications for operative intervention were analyzed. Greater than one-half of all major lower extremity amputations are performed in patients who have failed attempts at revascularization or who are not candidates for LER due to anatomic factors. However, one-quarter of eventual amputees present very late to the vascular surgeon with extensive gangrene or infection that precludes limb salvage. Prompt patient referral and treatment may improve outcome in this group of patients. In our study, insurance issues did not appear to affect treatment. Renal failure continues to play a major role in limb loss.

• Apelqvist J, Larsson J and Agardh C-D: Medical risk factors in diabetic patients with foot ulcers and severe peripheral vascular disease and their influence on outcome. J Diabetes & its Complications. 6(3):167-74, 1992. Of 208 consecutive diabetic patients with severe peripheral vascular disease (systolic toe pressure less than or equal to 45mmHg), 38.5% healed primarily (toe pressure 30+/-13), 39.9% healed after minor or major amputation (toe pressure 22+/-15) and 21.6% died (toe pressure 20+/-14). Of 153 patients with no palpable pulses, 36% healed primarily. Of 72 with rest pain, 47% had an amputation and 25% healed primarily. Peripheral edema and proteinuria commonly associated with amputation. Percentage primary healing related to ulcer location: Metatarsal head I-V (60%), Dig I, dorsal and plantar surface (47%), Mid-foot and heel (44%), Dig II-V on dorsal or plantar surface or ulcer on dorsum of foot (38%), for more than 3 ulcers (4%).

• Apelqvist J, Larsson J and Agardh C: Long-term prognosis of diabetic patients with foot ulcers. J Internal Med 233:485-491, 1993. (Lund, Sweden) Of 558 consecutive diabetic admissions for foot ulcers from 7/83-12/90, 468 healed primarily (345) or after minor or major amputations (123) and 90 died before healing occurred. The 468 with healed legs were followed prospectively: years of observation: 1 year, 3 years and 5 years; percentage of patients with new foot ulcer: 34%, 61% and 70% respectively; percentage of new amputations and history of primary healing: 3%, 10% and 12% respectively; percentage of new amputations and history of amputation: 13%, 35% and 48% respectively; survival and history of primary healing: 92%, 73% and 58% respectively; and survival and history of amputation: 80%, 59% and 27% respectively.

• Apelqvist J, Ragnarson-Tennvall G, Persson U, Larsson J: Diabetic foot ulcers in a multidisciplinary setting. An economic analysis of primary healing and healing with amputation. J of Int Med 235:463-471, 1994. Healing with amputation was associated with high costs mainly due to multiple and extended hospitalization. Potential cost savings in preventive and multidisciplinary foot care.

• Apelqvist J, Ragnarson-Tennvall G, Larson J and Persson U: Long-term costs for foot ulcers in diabetic patients in a multidisciplinary setting.Foot & Ankle International 16: 388-394, 1995. Abstract: "The purpose of this study was to analyze long-term costs for foot ulcers in diabetic patients. Patients were treated and followed prospectively by a foot care team. A retrospective economic analysis was performed of costs for 274 patients during three years from healing of an initial foot ulcer, with or without amputation. Costs were estimated for inpatient care, outpatient care, home care and social service. The cost calculations include costs due to complications and disability related to the initial ulcer, and costs for prevention of new ulcers. Expected total present value cost per patient during three years of observation was $26,700 (U.S. dollars) for primary healed patients with critical ischemia and $16,100 for primary healed patients without critical ischemia. For patients who healed with an amputation, the corresponding costs were $43,100 after a minor amputation and $63,100 after a major amputation. When estimating the costs for diabetic foot ulcers, it is not sufficient to calculate short-term costs. Long-term costs are high, mainly due to increased need for home care and social service, but also due to costs for recurrent ulcers and new amputations." In their introduction, the authors point out that the short-term prognosis for diabetic patients treated in a multidisciplinary setting is good and that the average total direct cost for patients who healed primarily has been estimated to be $8500 while that for those who healed with amputation was $43,000 for minor amputation and $65,000 for major amputations. For their study, the authors defined critical ischemia as a systolic toe blood pressure under 45 mm Hg or a systolic ankle blood pressure under 80 mmHg.. A minor amputation was defined as one below the ankle and a major amputation as one above the ankle.

• Armstrong DG, Lavery DA, Harkless LB: Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care 21:855-859, 1998. Patients were assessed 6 months after their initial evaluation to see if an amputation had been performed. The authors concluded that outcomes deteriorated with increasing grade and stage of wounds when measured using the University of Texas Wound Classification System. The authors graphed the prevalence of amputations within each of their categories as follows:

  Stage	Grade "0"	Grade "1"	Grade "2"	Grade "3"
  A	Pre or Postulcerative lesion completely epithelized - 0 amp	Superficial wound, not involving tendon, capsule or bone - 0 amp	Wound penetrating to tendon or capsule - 0 amp	Wound penetrating to bone or joint - o amp
  B	Infection - 12.5% amp	Infection - 8.5% amp	Infection - 28.6% amp	Infection 92% amp
  C	Ischemia - 25.0% amp	Ischemia - 20.0% amp	Ischemia - 25.0% amp	Ischemia - 100% amp
  D	Infection and Ischemia - 50.0% amp	Infection and Ischemia - 50.0% amp	Infection and Ischemia - 100% amp	Infection and Ischemia - 100% amp

  Comments: "Neuropathy" is missing from their classification. But neuropathic patients in trouble present with infected penetrating ulcers which lead to amputations. The authors have a classification that in their experience is associated with a progressive risk of amputations. And they do have impressive percentages for amputations. The reader is invited to review our patient history section to see how many amputations can be averted. It appears that they may need the Circulator Boot in their part of Texas.

• Armstrong DG, Nguyen HC, Lavery LA, van Schie CH, Boulton AJ, Harkless LB: Off-loading the diabetic foot wound: a randomized clinical trial. Diabetes Care 24:1019-22, 2001. OBJECTIVE--To compare the effectiveness of total-contact casts (TCCs), removable cast walkers (RCWs), and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes. RESEARCH DESIGN AND METHODS--In this prospective clinical trial, 63 patients with superficial noninfected, nonischemic diabetic plantar foot ulcers were randomized to one of three off-loading modalities: TCC, half-shoe, or RCW. Outcomes were assessed at wound healing or at 12 weeks, whichever came first. Primary outcome measures included proportion of complete wound healing at 12 weeks and activity (defined as steps per day). RESULTS--The proportions of healing for patients treated with TCC, RCW, and half-shoe were 89.5, 65.0, and 58.3%, respectively. A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities (89.5 vs. 61.4%, P = 0.026, odds ratio 5.4, 95% CI 1.1-26.1). There was also a significant difference in survival distribution (time to healing) between patients treated with a TCC and both an RCW (P = 0.033) and half-shoe (P = 0.012). Patients were significantly less active in the TCC (600.1 +/- 320.0 daily steps) compared with the half-shoe (1,461.8 +/- 1,452.3 daily steps, P = 0.04). There was no significant difference in the average number of steps between the TCC and the RCW (767.6 +/- 563.3 daily steps, P = 0.67) or the RCW and the half-shoe (P = 0.15). CONCLUSIONS--The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities, the RCW and the half-shoe. Comments: Here we see that contact casting promotes inactivity and improves healing rates versus special shoewear. It is, of course, very difficult to walk heel-toe in a contact cast. These same concepts apply to prophylactic foot care. See Litzelman et al below.

• Axelrod DA, Upchurch GR Jr, DeMonner S, Stanley JC, Khuri S, Daley J, Henderson WG, Hayward R: Perioperative cardiovascular risk stratification of patients with diabetes who undergo elective major vascular surgery. J Vasc Surg 35(5):894-901, 2002. BACKGROUND: The importance of diabetes mellitus (DM) as an independent risk factor for perioperative cardiac morbidity after vascular surgery is controversial. This study examined the impact of DM on perioperative outcomes and length of stay in patients who underwent major vascular surgery. METHODS: Patients who underwent elective aortic reconstruction (n = 2792), lower extremity bypass (n = 3838), carotid endarterectomy (n = 5522), and major amputation (n = 3883) from 1997 to 1999 were identified in the National Surgical Quality Improvement Program database of the Department of Veterans Affairs. Outcomes assessed were death, cardiovascular complications (myocardial infarction, stroke, need for cardiopulmonary resuscitation), and length of stay. Multivariable logistic and linear regression models were used to control for patient demographics, procedure type, comorbidities, and diabetic complications. RESULTS: Before adjustment for potential confounders, patients with diabetes had a higher incidence rate of perioperative death (3.9% versus 2.6%; P =.001) and cardiovascular complications (3.3% versus 2.6%; P =.01) when compared with patients without diabetes. After controlling for comorbid conditions, procedure type, and diabetic complications, only patients with DM who underwent treatment with insulin were at statistically increased risk for cardiovascular complications (odds ratio [OR], 1.48; 95% CI, 1.15 to 1.91). Neither DM treated with insulin (OR, 1.10; 95% CI, 0.85 to 1.41) nor DM treated with oral medications (OR, 0.96; 95% CI, 0.73-1.28) was an independent risk factor for death. Important independent risk factors for death included several conditions that are commonly associated with diabetes, including proteinuria, elevated creatinine level, history of congestive heart failure, and history of cerebrovascular accident. DM was also found to increase length of stay by as much as 38% even after adjustment for comorbidities. CONCLUSION: Patients with diabetes have a higher incidence rate of death and cardiovascular complications. However, after controlling for specific comorbid conditions, the only independent association was between patients with insulin treatment and the risk of cardiovascular complications. DM does not appear to be an independent risk factor for postoperative mortality. All patients with diabetes, regardless of insulin use, have a prolonged length of stay after major vascular surgery.

• Back MR, Leo F, Cuthbertson D, Johnson BL, Shamesmd ML, Bandyk DF: Long-term survival after vascular surgery: specific influence of cardiac factors and implications for preoperative evaluation. J Vasc Surg 40:752-60, 2004. OBJECTIVE: We sought to identify specific determinants of long-term cardiac events and survival in patients undergoing major arterial operations after preoperative cardiac risk stratification by American College of Cardiology/American Heart Association guidelines. A secondary goal was to define the potential long-term protective effect of previous coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) in patients with vascular disease. METHODS: Four hundred fifty-nine patients underwent risk stratification (high, intermediate, low) before 534 consecutive elective or urgent (<24 hours after presentation) open cerebrovascular, aortic, or lower limb reconstruction procedures between August 1996 and January 2000. Long-term follow-up (mean, 56 +/- 14 months) was possible in 97% of patients. The Kaplan-Meier method was used for survival data. Long-term prognostic variables were identified with the multivariate Cox proportional hazards model and contingency table analysis censoring early (<30 days) perioperative deaths. RESULTS: While 5-year survival was 72% for the overall cohort, cardiac causes accounted for only 24% of all deaths, and new cardiac events (myocardial infarction, congestive heart failure, arrhythmia, unstable angina, new coronary angiography, new CABG or PCI, cardiac death) affected only 4.6% of patients per year during follow-up. High cardiac risk stratification level (hazards ratio [HR], 2.2, 95% confidence interval [CI], 1.4-3.4), adverse perioperative cardiac events (myocardial infarction, congestive heart failure, ventricular arrhythmia; HR, 2.2; 95% CI, 1.2-4.1), and age (HR, 0.33; 95% CI, 0.2-0.6) were independently prognostic for latemortality. Preoperative cardiac risk levels also correlated with new cardiac event rates ( P < .01) and late cardiac mortality ( P = .02). Modestly improved survival in patients who had undergone CABG or PCI less than 5 years before vascular operations compared with those who had undergone revascularization 5 or more years previously and those at high risk without previous coronary intervention (73% vs 58% vs 62% 5-year survival; P = .02) could be demonstrated with univariate testing, but not with multivariate analysis. Type of operation, urgency, noncardiac complications, and presence of diabetes did not affect long-term survival. CONCLUSION: Despite cardiac events being a less common cause of late mortality after vascular surgery, perioperative cardiac factors (age, preoperative risk level, early cardiac complications) are the primary determinants of patient longevity. Patients undergoing more recent (<5 years) CABG or PCI before vascular surgery do not have an obvious survival advantage compared with patients at high cardiac risk without previous coronary interventions.

• Bakker K, van Houtum WH, Schaper NC: Diabetic foot care in the Netherlands: an evaluation. Practical Diabetes International 15:41-42, 1998. The authors found that 32% of their hospitals had a podiatrist specifically for the care of diabetic patients and that 16% of the hospitals had a specialized diabetes foot care clinic. The presence or absence of the podiatrist or the foot care clinic did not affect the relative risk of diabetes-related lower extremity amputation possibly because of overlapping of hospital services within the regions studied.

• Benotmane A, Mohammedi F, Ayad F, Kadi K, Medjbeur S, Azzouz A: Management of diabetic foot lesions in hospital: costs and benefits. Diabetes Metab 2001 27:688-94, 2001. OBJECTIVE: The aim of this study was to evaluate the direct and indirect costs associated with diabetic-related foot lesions in patients hospitalized in a department of Endocrinology and Diabetology (36 beds). MATERIAL AND METHODS: Direct costs included costs associated with hospital stay, laboratory testing, medical and surgical treatment. Lesions were classified in 3 groups (I, II, III) according to their importance (Wagner classification). RESULTS: Among 1,779 admissions for diabetes, 163 (i.e., 9.16%) were related to a foot lesion. The stay in hospital for these lesions reached 7,247 days over a 5-year period, with an average stay duration of 45 days per lesion. Mean length of hospital stay varied according to the importance of the lesion: 26.87 days, 48.25 days, 57.12 days for group I, II and III, respectively. The total cost amounted to 914,534.39 US dollars and the mean cost 5,610.64 US dollars. Mean cost was 3,326.76, 5,712.24, 7,399.74 US dollars for group I, II and III, respectively. Nearly 80% of the financial costs were due to hospital stay. Primary healing occurred in 59.09% of the patients (n=78); 17.4% (n=23) of the patients required major amputation, 14.4% (n=19) minor amputation. Death rate reached 9.1% (n=12). CONCLUSION: An increase in length of stay and costs with importance of the lesion was identified. The strategy of care of the diabetic lesions should be based upon the prevention of ulcer formation: it seems actually the best mean (the least expensive) in a developing country where financial resources are very limited. This prevention should be made through regular patient education, appropriately fitted shoes, and regular careful examination by a General Practitioner or a Diabetologist.

• Benson K, Hartz AJ: A comparison of observational studies and randomized, controlled trials. N Engl J Med.342:1878-86, 2000. BACKGROUND: For many years it has been claimed that observational studies find stronger treatment effects than randomized, controlled trials. We compared the results of observational studies with those of randomized, controlled trials. METHODS: We searched the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition. We then searched the Medline and Cochrane data bases to identify all the randomized, controlled trials and observational studies comparing the same treatments for these conditions. For each treatment, the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis-of-variance procedure and then compared with the combined magnitude of the effects in the randomized, controlled trials that evaluated the same treatment. RESULTS: There were 136 reports about 19 diverse treatments, such as calcium-channel-blocker therapy for coronary artery disease, appendectomy, and interventions for subfertility. In most cases, the estimates of the treatment effects from observational studies and randomized, controlled trials were similar. In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the randomized, controlled trials. CONCLUSIONS: We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials.

• Black N: Why we need observational studies to evaluate the effectiveness of health care. British Medical Journal 1996, 312:1215-1218. Department of Public Health and Policy, London School of Hygiene and Tropical Medicine.The view is widely held that experimental methods (randomised controlled trials) are the "gold standard" for evaluation and that observational methods (cohort and case control studies) have little or no value. This ignores the limitations of randomised trials, which may prove unnecessary, inappropriate, impossible, or inadequate. Many of the problems of conducting randomised trials could often, in theory, be overcome, but the practical implications for researchers and funding bodies mean that this is often not possible. The false conflict between those who advocate randomised trials in all situations and those who believe observational data provide sufficient evidence needs to be replaced with mutual recognition of the complementary roles of the two approaches. Researchers should be united in their quest for scientific rigour in evaluation, regardless of the method used.

• Bouter KP, Storm AJ, de Groot RRM, Uitslager R, Erkelens DW and Diepersloot RJA: The diabetic foot in Dutch hospitals: epidemiological features and clinical outcome. Eur J Med 2: 215-8, 1993. For the years 1988 and 1989 information from the Dutch Information System on Health Care. 20.4% of all hospitalized diabetics had foot problems. Mean age 71.3 +/-12.1 years of 1988 and 71.2 +/-11.9 for 1989. Partial limb amputations more common in males. Mean hospital stay 40.0 days in 1988 and 38.3 days in 1989 with limb amputees staying longer than non-amputees (P < 0.001). Overall in hospital mortality 10% and highest in patients stages Wagner 4 -5. Mortality higher in Wagner 1 & 2 patients versus those with osteomyelitis (P< 0.001). About 10% discharged to rehabilitation center or nursing home.

• Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Davignon DR and Smith DG: A prospective study of risk factors for diabetic foot ulcer. The Seattle diabetic foot study. Diabetes Care 22:1036-1042, 1999. Abstract: Objective: Little prospective research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents. We prospectively studied the effects of diabetes characteristics, foot deformity, behavioral factors, and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 limbs. Research design and methods: Eligible subjects included all diabetic enrollees of a general medical clinic without foot ulcer, of whom 83% agreed to participate. Baseline assessment included history and lower limb-limb physical examination, tests for sensory and autonomic neuropathy, and measurements of macro- and microvascular perfusion in the foot. Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal, with a mean follow-up of 3.7 years. Results: Using stepwise Cox regression analysis, the following factors were independently related to foot ulcer risk: foot insensitivity to the 5.07 monofilament (relative risk [95% CI] 2,2 (1.5-3.1), past history of amputation 2.8 (1.8-4.3) or foot ulcer 1.6 (1.2-2.3), insulin use 1.6 (1.1-2.2), Charcot deformity 3.5 (1.2-9.9), 15 mmHg higher dorsal foot transcutaneous PO2 0.8 (0.8-0.9), 20 Kg higher body weight 1.2 (1.1-1.4), 0.3 higher ankle-arm index 0.8 (0.7-1.0), poor vision 1.9 (1.4-2.6), and 13 mmHg orthostatic blood pressure fall 1.2 (1.1-1.5). Higher ulcer risk was associated with hammer/claw toe deformity and a history of laser photocoagulation in certain subgroups. Unrelated to foot ulcer risk in multivariate models were diabetes duration and type, race, smoking status, diabetes education, joint mobility, hallux blood pressure, and other foot deformities. Conclusions: Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcer risk, thereby providing support for a multifactorial etiology for diabetic foot ulceration.

• Campbell WB, Johnson JA St, Kernick VFM and Rutter EA: Lower limb amputation: striking the balance. Ann R Coll Surg Engl 76:205-209, 1994. Patients with a median age of 76 (43-96 years) had leg amputations for ischemia, 69 of the 210 having previously undergone bypass grafting. The failed bypass group and the non-bypass group both had predominantly BK's and had about the same reversion rate. Only 16% achieved near normality with the use of their prosthesis.

• Campbell WB, Verfaillie P, Ridler BM, Thompson JF:Non-operative treatment of advanced limb ischaemia: the decision for palliative care. Eur J Vasc Endovasc Surg 19:246-9, 2000.Department of Surgery, Royal Devon and Exeter Hospital, Exeter, EX2 5DW, UK. OBJECTIVES: to identify and describe patients with advanced limb ischaemia who were selected for palliative care, rather than surgical intervention. DESIGN: case-note review of patients identified from a prospective register. MATERIALS AND METHODS: thirty patients (22 female; median age 87 years) were identified during 1993-1998, for whom a clearly documented decision was made for palliative care, rather than major amputation or possible revascularisation. RESULTS: two-thirds of the patients had limiting cardiac problems, two-thirds were immobile, and 47% had suffered a stroke. Half had three or more important co-morbidities. Twelve (40%) had unsalvageable acute ischaemia. There were clear records of the decision about non-intervention being made by a consultant in 87%; being discussed with the patient in 43%; and with known relatives in 90%. Survival after this decision ranged from <24 hours to 42 days (median 3.5 days). CONCLUSION: there is a small subgroup of patients with advanced ischaemia who are best treated palliatively, and who have not been well described before. Recognising these patients, recording discussions about their management, and a high standard of terminal care are all important.

• Carrington AL, Abbott CA, Griffiths J, et al.: A foot care program for diabetic unilateral lower-limb amputees. Diabetes Care 24:216-21, 2001. OBJECTIVE: To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees. RESEARCH DESIGN AND METHODS: Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of approximately 3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient. RESULTS: For the patients referred to the foot care program, there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle-brachial pressure index was significantly lower for the bilateral amputees (0.75 +/- 0.04) compared with the unilateral amputees (0.90 +/- 0.03, mean +/- SEM, P < 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 +/- 2.16 vs. 31.20 +/- 0.85 mmHg, P < 0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient. CONCLUSIONS: PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies.

• Cheshire NJ, Wolfe JH, Noone MA, Davies L, Drummond M: The economics of femorocrural reconstruction for critical leg ischemia with and without autologous vein. J Vasc Surg 15: 167-74, 1992. It is well established that primary arterial reconstruction, even to crural vessels, is cheaper than amputation. Reintervention increases expenditure and may produce mean costs exceeding those of primary amputation. Furthermore, secondary amputation may eventually become necessary. Femorocrural grafts have the highest average "reconstruction policy" cost (i.e., primary procedure and all further operations necessary during follow-up). We must therefore seek support for this potentially expensive form of treatment. In conjunction with health economists we have compared the average policy cost of 130 reconstructions with grafts exceeding 70 cm in length (89 vein grafts, 41 polytetrafluoroethylene grafts with a distal vein collar) with 67 vascular amputations, at mean follow-up of 3 years. One-month mortality rate after reconstruction was less than 1% but was 10% after amputation. At 3 years, however, 20% of both groups were dead. Overall 3-year patency is 65% (72% for vein grafts, 48% for polytetrafluoroethylene grafts). Ninety-seven percent of irreversible graft occlusions resulted in amputation in these patients. After autologous vein grafting reintervention, our follow-up showed increased mean costs from $6898 to $15,024 per patient. After prosthetic grafting, the higher reintervention rate increased from $6898 to $20,416. These mean costs remained less than amputation, reintervention, and additional mobility costs, which amounted to a mean of $21,726 per patient. Important differences in outcome were observed: 70% of patients undergoing amputation were confined to the home compared with only 9% of patients undergoing reconstruction; 30% of patients undergoing amputation were confined to bed or had to use a wheelchair compared with 1% of patients undergoing reconstruction.

• Concato J, Shah N, Horwitz RI: Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med. 342(25):1887-92, 2000. BACKGROUND: In the hierarchy of research designs, the results of randomized, controlled trials are considered to be evidence of the highest grade, whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects. We used published meta-analyses to identify randomized clinical trials and observational studies that examined the same clinical topics. We then compared the results of the original reports according to the type of research design. METHODS: A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of randomized, controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention. For each of five topics, summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual randomized, controlled trials and the individual observational studies. RESULTS: For the five clinical topics and 99 reports evaluated, the average results of the observational studies were remarkably similar to those of the randomized, controlled trials. For example, analysis of 13 randomized, controlled trials of the effectiveness of bacille Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 (95 percent confidence interval, 0.34 to 0.70) among vaccinated patients, as compared with an odds ratio of 0.50 (95 percent confidence interval, 0.39 to 0.65) from 10 case-control studies. In addition, the range of the point estimates for the effect of vaccination was wider for the randomized, controlled trials (0.20 to 1.56) than for the observational studies (0.17 to 0.84). CONCLUSIONS: The results of well-designed observational studies (with either a cohort or a case-control design) do not systematically overestimate the magnitude of the effects of treatment as compared with those in randomized, controlled trials on the same topic.

• Connelly J, Airey M, Chell S.: Variation in clinical decision making is a partial explanation for geographical variation in lower extremity amputation rates. Br J Surg 88(4):529-35, 2001. Division of Public Health, Nuffield Institute for Health, University of Leeds, 71-75 Clarendon Road, Leeds LS2 9PL, UK. BACKGROUND: Rates of lower extremity amputation vary significantly both between and within countries. The variation does not appear to support differences in need as an explanation. This study set out to see if variations in clinical decision making might contribute to the explanation. METHODS: Based on an extensive audit database of lower extremity amputations and revascularization operations, a decision model was produced. Drawing on items in this model allowed the selection of six clinical cases that differed in their probability of having amputation as the outcome. Two cases had 80 per cent or more, two cases had 45--55 per cent and two cases had 20 per cent or less probability of amputation. Each of ten consultant vascular surgeons looked at these cases without knowledge of their probability of outcome and decided on amputation or revascularization. RESULTS: Overall the chance-adjusted level of agreement (kappa coefficient) between the decisions made by ten surgeons on the six clinical cases and the actual outcome was 0.46, indicating a moderate level of agreement. The kappa coefficient for individual surgeons showed complete agreement (kappa = 1) for four, substantial agreement (kappa = 0.66) for four, fair agreement (kappa = 0.32) for one and no agreement other than at a chance level (kappa = 0) for one surgeon. CONCLUSION: Variations in the clinical decisions made by vascular surgeons given the same patient are likely to explain at least a part of the observed geographical variation in rates of lower extremity amputation. Consensus guidelines may enable more consistent decision making for this problem.

• Cooperman M, Pflug B, Martin Jr EW and Evans WE: Cardiovascular risk factors in patients with peripheral vascular disease. Surgery 84:505, 1978. 8.5% operative mortality rate among elderly patients undergoing peripheral arterial vascular surgery. Authors recognized 5 main risk factors: congestive heart failure, prior myocardial infarction, prior stroke, heart arrhythmia and abnormal EKG.

• Corti MC, Guralnik JM, Salive ME et al: Serum albumin level and physical disability as predictors of mortality in older persons. JAMA 272:1036-1042, 1994. The mortality rate is shown to increase with decreasing levels of serum albumin. The serum albumin level may serve as an indicator of all-cause mortality in older persons. Comment: Older patients with severe peripheral vascular disease are commonly debilitated and have low serum albumin levels. Diminished protein stores are a well known factor decreasing wound healing. Here it is seen that low protein stores also predict death. The "foot doctor" must learn to treat the whole patient.

• Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR , McCann T J and Browner D: Mortality over a period of 10 years in patients with peripheral arterial disease.N Engl J Med 326:381-6, 1992.BACKGROUND. Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication, and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease, as diagnosed by noninvasive testing. In this study, we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease. METHODS. We examined 565 men and women (average age, 66 years) for the presence of large-vessel peripheral arterial disease by means of two noninvasive techniques--measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound. We identified 67 subjects with the disease (11.9 percent), whom we followed prospectively for 10 years. RESULTS. Twenty-one of the 34 men (61.8 percent) and 11 of the 33 women (33.3 percent) with large-vessel peripheral arterial disease died during follow-up, as compared with 31 of the 183 men (16.9 percent) and 26 of the 225 women (11.6 percent) without evidence of peripheral arterial disease. After multivariate adjustment for age, sex, and other risk factors for cardiovascular disease, the relative risk of dying among subjects with large-vessel peripheral arterial disease as compared with those with no evidence of such disease was 3.1 (95 percent confidence interval, 1.9 to 4.9) for deaths from all causes, 5.9 (95 percent confidence interval, 3.0 to 11.4) for all deaths from cardiovascular disease, and 6.6 (95 percent confidence interval, 2.9 to 14.9) for deaths from coronary heart disease. The relative risk of death from causes other than cardiovascular disease was not significantly increased among the subjects with large-vessel peripheral arterial disease. After the exclusion of subjects who had a history of cardiovascular disease at base line, the relative risks among those with large-vessel peripheral arterial disease remained significantly elevated. Additional analyses revealed a 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease that was both severe and symptomatic. CONCLUSIONS. Patients with large-vessel peripheral arterial disease have a high risk of death from cardiovascular causes.

• Currie CJ, Morgan CL and Peters JR: The epidemiology and cost of inpatient care for peripheral vascular disease, infection, neuropathy, and ulceration in diabetes. Diabetes Care 21:42-48, 1998. Authors' abstract: Objective - To describe the epidemiology and costs of the acute care of peripheral vascular disease, infection, neuropathy, and ulceration in a U.K. population with special consideration of those patients with diabetes. Research design and methods - Routine data describing inpatient care for a 4-year period were analyzed (financial years 1991/1992 to 1994/1995). These data had undergone record-linkage to draw together records from the same patient, and records of patients with diabetes were flagged. Cost estimates were determined by attributing a diagnosis-related cost-weight to each record. Results - A total of 4,245 admissions (`1.2% of all admissions) had a primary diagnosis of peripheral vascular disease, infection, neuropathy, or ulceration, and 7,379 (2.1%) admissions had these categories recorded in any one of six diagnostic fields. These figures were generated by 3,159 and 4,751 patients, respectively. This represented a range of crude annual incidence of admission of between 1.9 and 2.9 per 1,000 people. Patients with diabetes accounted for 625 (15.4%) of primary admissions, a crude annual incidence of admission of 18.8 per 1,000. The age-standardized relative risk for admission for patients with diabetes to the nondiabetic population was 7.61 for men and 6.85 for women. The length of stay for patients with diabetes was almost twice that of the nondiabetic population (15.5 vs 8.7 days). The relative risk of hospital mortality (diabetes vs non-diabetes) was 2.83. Surgical procedures were carried out on 857 patients, 272 (31.2%) with diabetes. This represented an age-standardized relative risk of 31.19. The estimated cost of admissions for primary diagnoses in these categories over 4 years was L 6,128,211 ($9,743,855). Patients with diabetes accounted for L1,236,623 ($1,966,230), an excess of 87% attributed to the diabetic state. Conclusions - Diabetes is confirmed as a significant risk factor for peripheral vascular disease, infection, neuropathy, and ulceration. The severity of these disorders in terms of increased risk of hospital mortality, length of stay, and risk of surgical procedure is also demonstrated for those patients with diabetes.

• Cusick M, Meleth AD, Agron E, Fisher MR, Reed GF, Knatterud GL, Barton FB, Davis MD, Ferris FL 3rd, Chew EY; Early Treatment Diabetc Retinopathy Study Research Group.: Associations of mortality and diabetes complications in patients with type 1 and type 2 diabetes: early treatment diabetic retinopathy study report no. 27. Diabetes Care 28:617-25, 2005. OBJECTIVE: Diabetes is a leading cause of morbidity and mortality. The purpose of this study is to assess the associations between diabetes complications and mortality in the Early Treatment Diabetic Retinopathy Study (ETDRS). RESEARCH DESIGN AND METHODS: We examined demographic, clinical, and laboratory characteristics of the 3,711 subjects enrolled in the ETDRS, a randomized controlled clinical trial designed to evaluate the role of laser photocoagulation and aspirin therapy for diabetic retinopathy. The outcome assessed was all-cause mortality. Multivariable Cox proportional hazards regression was used to assess associations between diabetes complications and mortality for type 1 and type 2 diabetes separately. RESULTS: The 5-year estimates of all-cause mortality were 5.5 and 18.9% for patients with type 1 and type 2 diabetes, respectively. In patients with type 1 diabetes, amputation (hazard ratio [HR] 5.08 [95% CI 2.06-12.54]) and poor visual acuity (1.74 [1.10-2.75]) remained significantly associated with mortality, after adjusting for other diabetes complications and baseline characteristics. In patients with type 2 diabetes, macrovascular disease and worsening levels of nephropathy, neuropathy, retinopathy, and visual acuity are associated with progressively increasing risks of mortality, after controlling for other baseline risk factors. CONCLUSIONS: Amputation is the strongest predictor for mortality in patients with type 1 diabetes. All complications independently predict mortality in patients with type 2 diabetes. There is an increased risk for mortality as the degree of each complication worsens. Additional studies are needed to investigate the effectiveness of tertiary prevention to decrease mortality in these patients.

• Danne T, Weber B, Dinesen B and Mortensen HB:Threshold of HbA1c for effect of hyperglycemia on the risk of diabetic microangiopathy. Diabetes Care 19:183, 1996. Berlin Retinopathy Study with an increase in retinopathy around a HbA1c of 9.0%. Krolewski et al found more microalbuminuria above 8.1%. Recommendations based on the Diabetes Control and Complications Trial aim for values under 7.0%. A Joslin study noted a threshold of 8.1%. Comments: Certainly patients with HbA1c values regularly over 8% would do well to examine their diabetes program and question their doctor regarding his/her goals for them. All too often patients are not told what normal fasting blood glucose values are (60 to 105 mg/dl) and are assured that values under 200 mg/dl are satisfactory. Such patients would do well to get a new doctor..

• Dillingham TR, Pezzin LE, Shore AD: Reamputation, mortality, and health care costs among persons with dysvascular lower-limb amputations. Arch Phys Med Rehabil 86:480-6, 2005. OBJECTIVES: To examine 12-month reamputation and mortality rates as well as acute and postacute medical care costs among a large cohort of persons with dysvascular amputations. DESIGN: Retrospective cohort study. SETTING: General community. PARTICIPANTS: Medicare beneficiaries identified from the Centers for Medicare and Medicaid Services data as undergoing a lower-limb amputation secondary to vascular disease in 1996. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Twelve-month reamputation and mortality rates, and acute and postacute medical care costs, by initial amputation level and presence or absence of diabetes. RESULTS: A total of 3565 persons, corresponding to 71,300 Medicare beneficiaries nationwide, were identified from the claims data as undergoing lower-limb amputations in 1996. Twenty-six percent of them required subsequent amputation procedures within 12 months, and more than one third died within 1 year of their index amputation. Acute and postacute medical care costs associated with caring for beneficiaries with a dysvascular amputation exceeded $4.3 billion yearly. There were marked differences in patient characteristics, progression of amputation to higher levels, service use, and mortality among dysvascular amputees with and without a comorbidity of diabetes. Diabetic amputees were younger than those without diabetes; they were also more likely to be men, to have more comorbidities, and to have undergone their first amputation at an earlier age than persons with dysvascular amputations who did not have diabetes. Although diabetic amputees were less likely to die within 12 months of the index amputation, they died at a significantly younger age than their nondiabetic counterparts. Progression to a higher level of limb loss occurred most frequently (34.5%) among persons with an initial foot or ankle amputation. Diabetic amputees were more likely than nondiabetic amputees to experience progression to a higher amputation level for all initial amputation levels. CONCLUSIONS: This study provides information that can be used by physicians when counseling patients about expected outcomes of dysvascular amputations at different levels.

• Driver VR, Madsen J, Goodman RA: Reducing Amputation Rates in Patients With Diabetes at a Military Medical Center: The Limb Preservation Service model. Diabetes Care. 2005 Feb;28(2):248-53, 2005. OBJECTIVE: To describe and evaluate the Limb Preservation Service (LPS), a multidisciplinary, state-of-the-art, foot care clinic for patients with diabetes at Madigan Army Medical Center (MAMC). Evaluation criteria include the overall incidence of lower-extremity amputation (LEA) and the distribution of the anatomic level of amputation between 1999 and 2003. RESEARCH DESIGN AND METHODS: This is a retrospective study of the incidence and types of LEAs performed in patients with diabetes at MAMC. Patients with diagnosed diabetes and LEA procedures were identified by ICD-9-Clinical Modification (CM) codes. Hospital and clinic characteristics that are integral to the success of the program are described. RESULTS: The number of patients at MAMC with diagnosed diabetes increased 48% from 1999 to 2003; however, the number of LEAs decreased 82% from 33 in 1999 to 9 in 2003. Amputations of the foot, ankle, and toe comprise 71% of amputations among patients with diabetes. CONCLUSIONS: The results of this study provide evidence of the value of a focused multidisciplinary foot care program for patients with diabetes. Associations between the creation of the LPS and LEA rates are discussed. Comments: This paper provides tremendous encouragement for those trying to improve the lot of the diabetic through multidiscipline clinics. Certainly the best treatment of the diabetic foot ulcer is its prevention. This group significantly increased their detected population of diabetics hopefully providing preventive measures an opportunity to manifest themselves. In the not too distant past, some physicians thought there were two kinds of diabetes: that with complications and that without complications. Further, they thought they might be different diseases. Today, the outlook of diabetic patients is not too different; those without complications may deny they have the disease and not seek help until they do indeed have complications. In the above study, it is interesting to note that about one third of the patients listed as having high risk feet thought themselves to have minimal risk. Again, in the past there were many surgeons who noted that "whittling" on the diabetic leg was common; patients spent many months in the hospital having one lesser amputation after another until the leg was finally removed. Some felt justified, hence, in performing a major amputation immediately although there might be some likelihood of a successful lesser operation. The effect of variation in the decision making process is noted above by Connelly et al. It is obvious that the incidence of major amputations per 1000 diabetic patients will vary considerably with the numbers and composition of the known diabetic population. It would be interesting to know how the MAMC succeeded in saving limbs among patients presenting with each of the Wagner stage 1-5 classifications.

• Ebskov B: Relative mortality and long term survival for the non-diabetic lower limb amputee with vascular insufficiency. Prosthet Orthot Int 23(3):209-16, 1999. The Danish Amputation Register, Department of Orthopaedic Surgery, Herlev Hospital, University of Copenhagen. On a well defined non-diabetic amputation group with vascular insufficiency consisting of 10,191 amputations during the period 1982 to 1992 the Standard Mortality Rate (SMR) and the long term survival (Kaplan-Meyer) were analysed. The SMR for the total group was 8.6 (8.4-8.9) times the expected mortality the first year after amputation, decreasing to 3.2 (3.3-3.4) the second year. SMR in relation to age, gender and level of amputation was analysed. In the long term survival studies the median survival time (50% survival) for the total group was 1.8 years. Significant relation was found between the long term survival and gender, age and level of amputation.Comments: Amputations for vascular insufficiency in diabetics and non-diabetics alike bode poorly for life expectancy.

• Ecker ML and Jacobs BS: Lower extremity amputation in diabetic patients. Diabetes 19:189, 1970. Failure to heal in 15.1% of BK's and 4.7% AK's - 96% of BK's able to use prostheses v/. 55% AK amputees.

• Eggers PW, Gohdes D, Pugh J: Nontraumatic lower extremity amputations in the Medicare end-stage renal disease population. Kidney Int 56(4):1524-33, 1999.Division of Health, Information and Outcomes, HealthCare Financing Administration, Baltimore, Maryland 21244-1850, USA. peggers@ncfa.gov - BACKGROUND: Nontraumatic lower limb amputation is a serious complication of both diabetic neuropathy and peripheral vascular disease. Many people with end-stage renal disease (ESRD) suffer from advanced progression of these diseases. This study presents descriptive information on the rate of lower limb amputation among people with ESRD who are covered by the Medicare program. METHODS: Using hospital bill data for the years 1991 through 1994 from the Health Care Financing Administration's ESRD program management and medical information system (PMMIS), amputations were based on ICD9 coding. These hospitalizations were then linked back to the PMMIS enrollment database for calculation of rates. RESULTS: The rate of lower limb amputation increased during the four-year period from 4.8 per 100 person years in 1991 to 6.2 in 1994. Among persons whose renal failure was attributed to diabetic nephropathy, the rates in 1991 and 1994 were 11.8 and 13.8, respectively. The rate among diabetic persons with ESRD was 10 times as great as among the diabetic population at large. Two thirds died within two years following the first amputation. CONCLUSIONS: The ESRD population is at an extremely high risk of lower limb amputation. Coordinated programs to screen for high-risk feet and to provide regular foot care for those at high risk combined with guidelines for treatment and referral of ulceration are needed.Comments: ESRD patients on hemodialysis are especially at risk. Hypovolemia associated with excessive dialysis promotes hypotension. When the feet are elevated to maintain the cerebral circulation, blood flow to the feet may cease and may be lost if the foot elevation is excessive. Flow can be easily and quickly restored with boot therapy.

• Eikhoff HJ, Hanson B, Lorentzen JE: The effect of arterial reconstruction on lower limb amputation rate. Acta Chir Scand 502:181-187, 1980. National Computer showed no decrease in amputations in Denmark.

• Eneroth M, Persson BM: Amputation for occlusive arterial disease. A prospective multicentre study of 177 amputees. Int Orthop 16:383-7, 1992. All major amputations of the lower limb due to occlusive arterial disease were studied prospectively and consecutively during one year in the 5 hospitals in Malmohus county, Sweden. The patients were followed for 6 months after the primary amputation of which 136 were through the tibia, 6 through the knee and 35 through the femur. One hundred and seventy-seven patients (92 men and 85 women) were included; 49% were 80 years or older and 40% were diabetic. At 6 months, 85 of the surviving 109 patients had healed stumps, 10 were not healed and 14 had been revised or reamputated. Half the survivors used a prosthesis daily. There was no significant difference in healing related to sex, age, diabetes or the level of amputation, but diabetics were more often bilateral amputees. The mortality at 6 months was 38% and at 4 years 72%.

• Eneroth M, Apelqvist J, Troeng T, Persson BM: Operations, total hospital stay and costs of critical leg ischemia. A population-based longitudinal outcome study of 321 patients. Acta Orthop Scand 67:459-65, 1996. In a longitudinal analysis of all 321 patients in a defined population having surgery for critical leg ischemia during 1 year in Malmohus county (0.53 million inhabitants), Sweden, we investigated all vascular procedures and amputations on both legs, total hospital stay and hospital costs from the first procedure in each patient until death or at follow-up at least 6 years postoperatively. The first (key) operation during the inclusion year was a reconstructive vascular procedure in 96 patients, a restorative vascular procedure in 111 and a major amputation in 114 patients. One third of those with a reconstructive and half of those with a restorative key procedure had an ipsilateral major amputation. The mean number of surgical procedures and length of hospital stay among all patients were 3 (1-19) procedures and 117 (1-1097) days, respectively. Of the total number of days in hospital, less than half were in surgical departments, 10% in other acute-care departments and almost half in rehabilitation clinics and nursing homes. The total hospital and surgical costs among all patients were USD 15.1 million (mean USD 47,000/patient), with no significant differences in relation to the key operation. We conclude that patients who have undergone surgery for critical leg ischemia accumulate very high total long-term hospital costs due to the need for repetitive surgery and long hospital stays. Our findings also show that a longitudinal study, including hospital stay in departments other than surgical, is necessary for a correct cost-and-outcome analysis.

• Gianfortune P, Pulla RJ and Sage R: Ray resections in the insensitive or dysvascular foot: A critical review. J Foot Surg 24: 103-107, 1985. Authors' summary: The records of 28 patients who underwent 37 ray resections at the Hines Veterans' Administration Hospital and Loyola University Medical Center were reviewed. Indications included gangrene, osteomyelitis, or both. Underlying medical diagnoses included diabetes, chronic ethanol abuse, arteriosclerosis obliterans, and gout. The overall success rate was only 34%. These results suggest that the usefulness of ray resections as a definitive procedure in such cases may be limited.

• Gillespie DL, LaMorte WW, Josephs LG, Schneider T, Floch NR and Menzoian JO: Characteristics of patients at risk for perioperative myocardial infarction after infrainguinal bypass surgery: an exploratory study. Ann Vasc Surg 9:155-162, 1995. Perioperative myocardial infarction associated not only with a history of angina and prior myocardial infarction but also with use of antiarrhythmic agents, nitrates, calcium channel blockers and aspirin. Also associated were ST-depression, higher WBC and duration of surgery.

• Greant PH and Van den Brande P: Amputation in elderly and high-risk vascular patients. Ann Vasc Surg 1990; 4:288-290. Summary: 58 patients underwent lower limb amputation over a 30 month period. Mean age of the patients was 72 years. Cardiovascular and metabolic risk factors were present in the majority of patients. Postoperative, one-year and three-year mortality rates were 24, 40 and 76% respectively. Contralateral amputation was required in one-third of the patients after a mean period of 8 months. Only younger and healthier patients returned to a meaningful social life after appropriate prosthetic fitting. In view of the high mortality and morbidity rates, above-knee amputation seems a better choice than below-knee amputation in these elderly and high-risk patients.

• 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: 1999-2000 national health and nutrition examination survey. Diabetes Care. 27:1591-7, 2004. OBJECTIVE-Although lower-extremity disease (LED), which includes lower-extremity peripheral arterial disease (PAD) and peripheral neuropathy (PN), is disabling and costly, no nationally representative estimates of its prevalence exist. The aim of this study was to examine the prevalence of lower-extremity PAD, PN, and overall LED in the overall U.S. population and among those with and without diagnosed diabetes. RESEARCH DESIGN AND METHODS-The analysis consisted of data for 2,873 men and women aged >/=40 years, including 419 with diagnosed diabetes, from the 1999-2000 National Health and Nutrition Examination Survey. The main outcome measures consisted of the prevalence of lower-extremity PAD (defined as ankle-brachial index <0.9), PN (defined as >/=1 insensate area based on monofilament testing), and of any LED (defined as either PAD, PN, or history of foot ulcer or lower-extremity amputations). RESULTS-Of the U.S. population aged >/=40 years, 4.5% (95% CI 3.4-5.6) have lower-extremity PAD, 14.8% (12.8-16.8) have PN, and 18.7% (15.9-21.4) have any LED. Prevalence of PAD, PN, and overall LED increases steeply with age and is higher (P < 0.05) in non-Hispanic blacks and Mexican Americans than non-Hispanic whites. The prevalence of LEDs is approximately twice as high for individuals with diagnosed diabetes (PAD 9.5% [5.5-13.4]; PN 28.5% [22.0-35.1]; any LED 30.2% [22.1-38.3]) as the overall population. CONCLUSIONS-LED is common in the U.S. and twice as high among individuals with diagnosed diabetes. These conditions disproportionately affect the elderly, non-Hispanic blacks, and Mexican Americans.

• Griffiths GD and Wieman TJ: The influence of renal function on diabetic foot ulceration. Arch Surg 125: 1567-1569, 1990. Creatinine clearance, peripheral neuropathy and peripheral vascular disease all found to be independently associated with the formation of foot lesions. Renal function had no bearing on the severity of the lesions or the capacity to heal. Authors conclude that attempting to preserve limbs in the kidney patients is justified. Comment: Among their 281 diabetic foot patients, only three were on hemodialysis and none were on peritoneal dialysis or had had renal transplants.In our experience, these patients are at risk. In the hemodialysis patients, the removal of fluid with its frequently associated hypotension is commonly treated by elevating the feet thus blanching the skin for hours.... and promoting tissue necrosis. Again, in the transplant patient, the usage of steroids and other anti-rejection medications may potentially interfere with the recognition by immune cells of necrotic tissues and thus delay the healing process and/or the ability to resist infection.

• Griffiths GD and Wieman TJ: Meticulous attention to foot care improves the prognosis in diabetic ulceration of the foot. Surgery Gynec & Obstet 174:49-51, 1992. 21 patients developed ulcers while in prophylactic foot program and 150 patients referred with ulcers already present. Better prognosis, fewer ulcers/patient, healing time shorter, fewer major and minor amputations and a reduction of mean hospital days from 30 to 12.8 days in patients from prophylactic clinic.

• Hamdan AD, Saltzberg SS, Sheahan M, Froelich J, Akbari CM, Campbell DR, LoGerfo FW, Pomposelli FB Jr: Lack of association of diabetes with increased postoperative mortality and cardiac morbidity: results of 6565 major vascular operations. Arch Surg 137:417-21, 2002. HYPOTHESIS: A number of preoperative factors, including diabetes mellitus (DM), have been cited as increasing risk in patients undergoing major vascular operations. In smaller studies at our institution we have not found this to be apparent. This study reviewed all major vascular operations to confirm our bias that DM is not associated with increased mortality or cardiac morbidity. DESIGN: Case series retrospectively reviewed from a vascular registry established in 1990. SETTING: Tertiary care center. PATIENTS: Consecutive sample of 6565 patients who underwent lower extremity revascularization or carotid or aortic procedures, grouped by presence or absence of DM. MAIN OUTCOME MEASURES: Postoperative mortality, congestive heart failure, or myocardial infarction. RESULTS: Patients with DM made up 62.3% of the population, and those without diabetes, 37.7%. Average age of the DM group was 67.1 years, with 61.3% male and 38.7% female. Average age of the non-DM group was 70.6 years, with 61.8% male and 38.2% female. The rates of overall postoperative mortality, myocardial infarction, and congestive heart failure were 1.14%, 1.59%, and 1.13%, respectively. Comparing the DM with the non-DM group, these rates were 0.96% vs 1.46%, 1.77% vs 1.30%, and 1.13% vs 1.14%, respectively. Using multivariate analysis, the DM group had an inverse relationship to perioperative death, with an odds ratio of 0.53 (P =.01). The factors that were associated with increased mortality were hemodialysis and history of congestive heart failure. Previous myocardial infarction was the only factor that predicted postoperative myocardial infarction. Kaplan-Meier survival curves showed a significantly decreased survival in the DM group during the next 5 years (P<.001). CONCLUSIONS: Diabetes alone does not confer a higher mortality or cardiac morbidity rate with major vascular procedures. However, long-term survival is significantly worse in this group of patients. Comments: Whenever one reports results far above those reported elsewhere one does well to look closely. This is Harvard, of course, and Harvard expects to do well. First, it is to be noted that their mortality rates were better than average for both diabetics and non-diabetics; the Harvard pill works for all. However, the pill does not offer lifelong protection; long-term mortality rate are significant. The authors used logistic regression analysis Æ a statistical method to look for independent risk factors that might predict an increase in morbidity and mortality during hospitalization for surgery evaluating risks posed by hypertension, coronary artery disease, renal failure and smoking, in addition to diabetes. Their results showed that diabetes alone did not pose an added risk for patients, a finding in contrast to previous studies. If the diabetic had had a previous myocardial infarction, a postoperative infarction had an increased likelihood. Are they telling us that a diabetic who has not yet developed any complications may do as well as non-diabetics?… at least at Harvard and Michigan? See Axelrod et al.

• Harrington C, Zagari MJ, Corea J, Klitenic J: A cost analysis of diabetic lower-extremity ulcers. Diabetes Care 23:1333-8, 2000.OBJECTIVE: Our objectives were to 1) estimate the prevalence of diabetes and diabetic lower-extremity ulcers in the Medicare population, 2) characterize Medicare population-specific costs for lower-extremity ulcer episodes, and 3) evaluate potential cost savings associated with better healing of lower-extremity ulcers. RESEARCH DESIGN AND METHODS: Prevalence and costs of diabetic lower-extremity ulcers were obtained by an analysis of Medicare claims data from 1995 and 1996 Standard Analytic Files (5% sample). RESULTS: Medicare expenditures for lower-extremity ulcer patients were on average 3 times higher than those for Medicare patients in general ($15,309 vs. $5,226). Lower-extremity ulcer-related spending accounted for 24% of total spending for lower-extremity ulcer patients. Most of the ulcer-related costs accrued on the inpatient side (73.7%); proportionately smaller amounts went to physicians and nursing home facilities. To determine the potential effect of better diabetic ulcer management, a model was created that estimated the impact on costs with improved healing rates. Improving the 20-week healing rate from 31 to 40% would save Medicare $189 per episode. CONCLUSIONS: Lower-extremity ulcers cost the Medicare system $1.5 billion in 1995. Any wound care intervention that could prevent even a small percentage of wounds from progressing to the stage at which inpatient care is required may have a favorable cost effect on the Medicare system.

• Hirsch AT, Hartman L, Town RJ, Virnig BA: National health care costs of peripheral arterial disease in the Medicare population. Vasc Med 13:209-15, 2008. AbstractLower extremity peripheral arterial disease (PAD) is prevalent in the Medicare population and is associated with high rates of myocardial infarction, stroke, amputation, and death. Nevertheless, national health expenditures for PAD are not known. We hypothesized that PAD-related costs are high, increase with age, and that treatment rates would be less than known PAD prevalence. The objective was to determine national health care expenditures for PAD in the United States. PAD-related treatment costs were calculated in the elderly, non-disabled Medicare population. The cost analysis relied on the 5% control population for the linked SEER-Medicare data and Medicare claims for the calendar year 2001, identifying PAD cases based on diagnosis and procedure codes. Costs were aggregated separately for inpatient and outpatient treatment and estimates adjusted to reflect the Medicare population. A total of $4.37 billion was spent on PAD-related treatment and 88% of expenditures were for inpatient care. Medicare program outlays totaled $3.87 billion, while enrollees (or their supplemental insurance) spent the remaining $500 million. In total, 6.8% of the elderly Medicare population received treatment for PAD. Treatment increased with age at rates of 4.5%, 7.5%, and 11.8% for individuals aged 65-74, 75-84, and >85 years, respectively. PAD-related costs accounted for approximately 13% of all Medicare Part A and B expenditures for the PAD-treated cohort, and 2.3% of total Medicare Part A and B expenditures. In conclusion, US national PAD-related costs are high, associated with inpatient care, and increase with age. PAD is treated at rates lower than the known PAD prevalence as only approximately one-third of the population with known PAD had detectable PAD-related health care costs in our analysis. The potential impact of earlier PAD detection and use of outpatient preventive strategies on total national PAD health care costs is unknown.

• Hodge MJ, Peters TG and Efird WG:Amputation of the distal portion of the foot. Southern Medical J 82:1138-1142, 1989. Abstract: For 101 patients, initial amputation of 124 extremities involved some distal portion of the foot. Amputations done for arteriosclerosis healed in 8 of 21 cases (38%), compared with 40 of 77 extremities (52%) in diabetic patients. Presence of cellulitis (44 cases) and absence of a popliteal pulse (44 cases) had no significant effect on success of amputation. , but a palpable foot pulse was significantly associated with a successful outcome (29/35 cases, or 83%) (P < 0.005). Serial amputations to preserve the foot were successful for 18 of 31 extremities (58%), a success rate equal to that of the entire series, 72 of 124 (58%). Attempts to preserve the distal portion of the foot were not associated with mortality. Cellulitis and absence of a distal pulse are not contraindications to attempting preservation of the extremity, although the best results occur when distal extremity pulses are present. In nearly six of every ten cases amputation of the distal portion of the foot resulted in a successful outcome.

• Humphrey ARG, Dowse GK, Thoma K and Zimmet PZ: Diabetes and nontraumatic lower extremity amputations. Incidence, risk factors, and prevention -a 12-year follow-up study in Nauru. Diabetes Care 19:710-714, 1996. The study describes the incidence and risk factors for lower extremity amputations in Nauru, "which has the highest national prevalence of diabetes in the world." Nauru is an isolated island in the Central Pacific Ocean with a 1992 population of 6,831 ethnic Nauruans. The incidence of first LEAs in Nauruans > or = age 25 with NIDDM was 8.1 per 1,000 person years in the study cohort and an estimated 7.6 per 1,000 person years nationally. Amputations were associated significantly with lower BMI, lower blood pressure, higher fasting plasma glucose level and longer duration of diabetes at baseline, but levels of other risk factors, including cigarette smoking, plasma triglycerides, and plasma cholesterol, were also elevated in amputees. There were no amputations among individuals with baseline fasting plasma glucose levels under 7.8 mmol/l (140 mg/dl) irrespective of the duration of diabetes. Amputations decreased after the start of a national prevention program. Comments: Those doubting the value of the control of diabetes might note the lack of amputations among the patients with fasting glucoses under 140 mg/dl.

• Humphrey LL, Ballard DJ, Butters MA, Palumbo PJ and Hallett JW: The epidemiology of lower extremity amputation in diabetes: a population based study in Rochester, Minnesota. Diabetes 1989, 38 Suppl 2:33A. Between 1945 and 1984 the incidence rate of amputation increased for both male and female diabetics. Each 10 year increase in age at the time of diagnosis is the most significant risk factor for amputation. Despite advances in therapy, amputation will continue to be an important public health problem particularly as the population ages.

• Hunink MGM, Wong JB, Donaldson MC, Meyerovitz MF, de Vries J and Harrington DP: Revascularization for femoropopliteal disease, A decision and cost-effectiveness analysis. JAMA 274:165-171, 1995. Introductory points of the authors include references to 400,000 hospitalizations for peripheral arterial disease annually including an estimated 50,000 angioplasties, 110,000 bypass operations and 69,000 foot or lower limb amputations. They apply multiple assumptions based on published data to a hypothetical cohort of patients with chronic femoropopliteal disease with lesions amenable to either angioplasty or bypass. For 65-year-old men with disabling claudication and a femoropopliteal stenosis or occlusion and for 65-year-old men with chronic critical ischemia and a femoropopliteal stenosis, initial angioplasty increased quality-adjusted life expectancy by 2 to 13 months and resulted in deceased lifetime expenditures compared with bypass surgery For patients with chronic critical ischemia and femoropopliteal occlusion, initial bypass surgery increased quality-adjusted life expectancy by 1 to 4 months and resulted in deceased lifetime expenditures compared with angioplasty. Sensitivity analysis demonstrated that angioplasty would always be the preferred initial treatment if the angioplasty 5-year patency rate exceeds 30%. The quoted mortality and morbidity data was taken from 26 studies published since 1985 involving 4800 angioplasty procedures and 4500 bypass operations. A procedural mortality rate of 0-7.4% for angioplasty and 0.6 to 9.7% for bypass was noted. Major procedural cardiopulmonary, renal or cerebrovascular complications occurred in 0.2 to 11% of angioplasty patients and 2.7 to 13% of bypass patients. Estimated costs in 1990 dollars were 2443-11809 for angioplasty and 9331-33367 for bypass. Amputation costs plus rehabilitation were estimated at $22346. Annual costs post amputation were estimated at $88765 for treatments and $23000 for nursing care (based on the estimate that 29% of all amputees required nursing care at an average cost of $1520 per week)... conservative estimates as later their figure for amputees becoming immobilized and dependent on nursing care is 29 to 38%. Because charges seldom reflect actual costs, the authors comment that they adjusted charge data by the collection-to-charge ratio.Comments: In comparison, boot therapy has no mortality or morbidity. It may suffer, however, from a longer duration of treatment. One can do a lot of booting for these costs.

• Isakov E, Budoragin N, Shenhav S, Mendelevich I, Korzets A and Susak Z: Anatomic sites of foot lesions resulting in amputation among diabetic and non-diabetics. Am J Phy Rehabil 74:130-133, 1995. The site of the lesion leading to amputation was located in the digits 62.2%, under the metatarsal heads 8%, along the midfoot and heel 8.5%, on the dorsum of the foot 3.3% and around the ankle joint or lower leg 5.7% of the time.

• Jaar BG, Astor BC, Berns JS, Powe NR: Predictors of amputation and survival following lower extremity revascularization in hemodialysis patients. Kidney Int 65:613-20, 2004. BACKGROUND: Peripheral vascular disease (PVD) has become increasingly common in end-stage renal disease (ESRD) patients, leading to an increase in the rate of revascularization and amputation. We studied the prognosis of ESRD patients undergoing their first revascularization procedure. METHODS: We conducted a longitudinal cohort study of hemodialysis patients enrolled in special studies of the United States Renal Data System. Cox proportional hazards analysis was used to assess the independent effect of type of initial revascularization procedure on lower extremity amputation and all-cause, cardiac, and infectious mortality over 3 years, after adjustment for sociodemographic, clinical, and biologic baseline characteristics. RESULTS: Eight hundred patients underwent an initial revascularization procedure by surgical bypass or angioplasty. The overall incidence of subsequent amputation was 16.3/100 person-years, 22.6 for bypass, and 5.7 for angioplasty. After adjustment for patient characteristics, the risk of amputation was higher for bypass versus angioplasty [relative hazard (RH) 4.00; 95% CI 2.46 to 6.57], for black versus white patients (RH 1.49; 95% CI 1.04 to 2.15), for uninsured or patients on Medicaid versus patients with private insurance or on Medicare (RH 1.65; 95% CI 1.12 to 2.72), and for patients with diabetes versus no diabetes (RH 2.51; 95% CI 1.67 to 3.76). Compared with patients who underwent angioplasty, the risk of all-cause (RH 1.37; 95% CI 1.10 to 1.70), cardiac (RH 1.50; 95% CI 1.08 to 2.09), and infectious (RH 2.17; 95% CI 1.10 to 4.29) mortality was greater among patients who underwent bypass. CONCLUSION: Risk of amputation following revascularization procedures was positively associated with type of procedure, black race, uninsured/Medicaid, and diabetes status. Risk of death was also higher following bypass. While this might reflect underlying severity of disease, patient education, screening, and optimal care of lower extremities should be emphasized to detect PVD at an early stage of the disease process.

• Jensen LP, Nielsen OM, Schroeder TV: The importance of complete follow-up for results after femoro-infrapopliteal vascular surgery. Eur J Vasc Endovasc Surg 12(3):282-6, 1996. Department of Vascular Surgery, National University Hospital, Rigshospitalet, Copenhagen, Denmark. Summary: OBJECTIVES: The aim of this study was to assess the reliability of patency rates calculated on basis of data from a standard vascular registry. DESIGN AND SETTING: Since 1989, all patients undergoing infrainguinal bypass procedures have been offered a standard follow-up programme at 3 month intervals and all data have been recorded prospectively in a vascular registry. As part of a randomised trial on adjuvant medication in femorocrural bypass surgery, 102 patients, operated on between 1990 and 1992 were independently and simultaneously monitored. This subgroup was examined at 3 and 12 months postoperatively and 100% follow-up was obtained. After completion of the trial we calculated the patency and survival rates using life-table methods and compared the results based on the vascular registry with those achieved in the clinical trial. RESULTS: Comparing the results from the two databases revealed a marked discrepancy between the calculated figures: primary (68% in the registry and 52% in the trial) and secondary patency rates (90% vs. 63%), limb survival (97% vs. 77% as well as patients survival rates (95% vs. 85%). The differences could be explained by a substantial number of patients being lost to follow-up according to the vascular registry database and the fact that these patients turned out to have a significantly increased rate of graft thrombosis, limb amputation and death, respectively. CONCLUSIONS: Life-table statistics may inadvertently become unreliable if a large proportion of patients is lost to follow-up, since failure to examine the patient for any reason may be related to the patients health. In addition to the number of patients at risk, it is suggested, that life-table plots should be supplemented with information on the number of patients lost to follow-up.

• Jonsson B and Persson U: Diabetes- A study in health economics. Lund: Swedish Institute of Health Economics, 1981. Peripheral vascular disease the most costly complication of diabetes in terms of hospital bed days used.

• Kay TW and Martin FI: Heel ulcers in patients with long-standing diabetes who wear anti-embolism stockings. Med J Aust 145:29-1, 1986. Four diabetic patients present who developed heel ulcers after application of antiembolism stockings after major surgery. Conclude that such stocking should likely not be used in such patients with neuropathy and PVD. Comment: There are few studies showing that the stockings work anyhow.

• Koch M, Trapp R, Hepp W: Impact of femoropopliteal bypass surgery on the survival and amputation rate of end-stage renal disease patients with critical limb ischemia. Med Klin (Munich) 102:107-11, 2007. BACKGROUND AND PURPOSE: The appropriate medical approach to treat patients with end-stage renal disease (ESRD) and critical limb ischemia (CLI) is still controversial. The goal of this study was to investigate the survival rate of ESRD patients with foot ulcers who underwent femoropopliteal bypass surgery versus patients who did not receive any major surgical interventions. PATIENTS AND METHODS: A 5-year Kaplan-Meier survival analysis of 99 ESRD subjects with foot ulcers, stage IV, recruited in the authors' single-center study between 1997 and 2005, was performed. 27 patients underwent bypass surgery because of meeting standard eligibility criteria for this procedure, and 72 patients received only conventional treatment due to their poorer vascular condition. Patients were censored upon major amputation during the observation period. Start of the observation was date of ulcer diagnosis. RESULTS: Survival rate was 16.2% (standard error [SE], 0.08) in the bypass group versus 18.6% (SE, 0.06) in the non-bypass group (p = 0.92; log-rank test). Median time to bypass surgery was 0.36 years (range, 0-2.65 years) after ulcer diagnosis. Six patients of 27 (22.2%) were censored due to major amputation in the bypass group versus 25 patients of 72 (34.7%) in the non-bypass group. CONCLUSION: These results may suggest that bypass surgery in ESRD patients with foot ulcers as treatment of CLI is not the appropriate surgical approach, since this procedure does not seem to cause a better survival than in patients who could not undergo revascularization surgery because of their poorer overall vascular condition.

• Korn P, Hoenig SJ, Skillman JJ, Kent KC: Is lower extremity revascularization worthwhile in patients with end-stage renal disease? Surgery 128:472-9, 2000. Division of Vascular Surgery, New York Presbyterian Hospital, New York, NY 10021, USA. BACKGROUND: The purpose of this study was to review the results of lower extremity revascularization in patients with end-stage renal disease and to determine in these patients the functional benefit and cost of an aggressive approach to limb preservation. METHODS: During a 5-year period at our institution, 33 bypass operations were performed on 31 limbs of 23 dialysis-dependent patients. Indications for revascularization were limited (18) or extensive (12) tissue loss or ischemia without tissue loss (3). Procedures included aortobifemoral bypass (1), femoropopliteal bypass (10), and femorotibial/pedal bypass (22). A digital or transmetatarsal amputation was performed in 57% of limbs. RESULTS: The 30-day primary patency was 100%. Cumulative primary and secondary patency rates at 2 years were 65% and 79%, respectively. Limb salvage was 67% and 59% at 1 and 2 years, respectively. Patient survival was poor (47% at 2 years). Peritoneal dialysis was predictive of poor survival (P <.001). Four of 5 patients on peritoneal dialysis died within 3 months of intervention. Extensive tissue loss was predictive of a diminished rate of limb salvage (P =.027). Only 39% of limbs with extensive tissue loss were salvaged at 1 year compared with 78% and 100% of limbs with limited and no tissue loss, respectively. The average hospital cost was $44,308 per year of limb salvage. CONCLUSIONS: Although revascularization of ischemic limbs in dialysis patients can be achieved with an excellent initial graft patency and reasonable limb salvage, patient survival is poor and costs are high. A selective approach to revascularization in these complicated patients may be indicated. For patients treated with peritoneal dialysis and for those with extensive tissue loss, primary amputation may be the preferred approach.Comments: The dialysis procedures themselves put these patients at risk for limb loss. With excessive fluid removal, these patients are frequently hypotensive and tilted backward in their chairs with their legs raised to increase blood flow to their heads. During such episodes, blood flow to the feet may be sacrificed and, if the episode is prolonged, arterial thrombi and tissue necrosis may ensue. Loss of bypasses may also result. In this study, as in many surgical series without controls, we find that 67% legs existing at a year were salvaged or more accurately were intact because or in spite of vascular surgery. Success was inversely related to the extent of tissue damage.

• Lavery LA, Lavery DC and Quebedeaux-Farnham TL: Increased foot pressures after great toe amputation in diabetes. Diabetes Care 18:1460-1462, 1995. Authors' results: Peak foot pressures were significantly higher under the first metatarsal head (P=0.046), lesser metatarsal heads (P<0.001), and toes (P><0.001) in feet with a great toe amputation compared with the contralateral foot without an amputation. Pressure under the heel was higher on the contralateral foot. Authors' conclusions: After a great toe amputation, pressure distribution of the foot is significantly altered. Because preamputation risk factors such as peripheral neuropathy, foot deformity, and limited joint mobility for many of these patients remain unchanged, an increase in foot pressures contributes to an increased risk of reulceration and reamputation in these patients.

• Lavery LA, Higgins KR, Lanctot DR, et al.: Home monitoring of foot skin temperatures to prevent ulceration. Diabetes Care 27:2642-7, 2004. OBJECTIVE: To evaluate the effectiveness of at-home infrared temperature monitoring as a preventative tool in individuals at high risk for diabetes-related lower-extremity ulceration and amputation. RESEARCH DESIGN AND METHODS: Eighty-five patients who fit diabetic foot risk category 2 or 3 (neuropathy and foot deformity or previous history of ulceration or partial foot amputation) were randomized into a standard therapy group (n = 41) or an enhanced therapy group (n = 44). Standard therapy consisted of therapeutic footwear, diabetic foot education, and regular foot evaluation by a podiatrist. Enhanced therapy included the addition of a handheld infrared skin thermometer to measure temperatures on the sole of the foot in the morning and evening. Elevated temperatures (>4 degrees F compared with the opposite foot) were considered to be "at risk" of ulceration due to inflammation at the site of measurement. When foot temperatures were elevated, subjects were instructed to reduce their activity and contact the study nurse. Study subjects were followed for 6 months. RESULTS: The enhanced therapy group had significantly fewer diabetic foot complications (enhanced therapy group 2% vs. standard therapy group 20%, P = 0.01, odds ratio 10.3, 95% CI 1.2-85.3). There were seven ulcers and two Charcot fractures among standard therapy patients and one ulcer in the enhanced therapy group. CONCLUSIONS: These results suggest that at-home patient self-monitoring with daily foot temperatures may be an effective adjunctive tool to prevent foot complications in individuals at high risk for lower-extremity ulceration and amputation.

• Lehto S, Rönnemaa, Pyörälä K and Laakso M: Risk factors predicting lower extremity amputations in patients with NIDDM. Diabetes Care 19:607-612, 1996. The authors accepted only amputations performed because of atherosclerotic vascular disease based on clinical diagnosis at the time of hospital admission as their endpoint. They report significant relative risks (95% CI) for the following: retinopathy 3.6 (P<0.001); urinary protein 1.3 (P=0.003); total cholesterol > 6.2 mmol/l, 1.8 (P=0.047); fasting blood glucose > 13.4mmol/l, 2.5 (P<0.001); HbA1 (>10.7%), 2.4 (P=0.001); duration of diabetes (>9.0 years) 2.2 (P=0.004); absence of two or more peripheral pulses 3.9 (P<0.001); femoral bruit on auscultation 2.1 (P=0.022); bilateral absence of Achilles tendon reflexes 4.3 (P<0.001); bilateral absence of vibration sense 2.7 (P<0.001). There was a dose-response relationship between plasma glucose or HbA1 and the risk for amputation.

• Litzelman DK, Marriott DJ and Vinicor F: The role of footwear in the prevention of foot lesions in patients with NIDDM, Conventional wisdom or evidence-based practice? Diabetes Care 20:156-162, 1997. Authors' conclusions: "Many variables commonly cited as protective measures in footwear for diabetic patients were not prospectively predictive when controlling for physiologic risk factors. Rigorous analyses are needed to examine the many assumptions regarding footwear recommendations for diabetic patients."Comments: Many a clinician probably says "Hallelujah!" on reading this paper. The authors found that in their inner city indigent NIDDM population, the type and quality of nonprescription footwear made little if any difference in the prevention of foot lesions, even in patients with insensate feet. Indeed, the prescription of specialty shoes was the best overall indicator that a lesion would develop. Again suggesting that the value of special shoes for the diabetic has been overemphasized was the presentation by Gayle Reiber at the American Diabetes Association Meetings on June 24th, 2001 titled: Clinical Trial of Footwear in Patients with Diabetes. They found no benefit of special shoes over properly fitting common everyday shoes in ulcer prevention. In our experience, it seems that the prescription of new shoes seems to be for many patients a sign that they can now walk as far and often as they desire... leading to new lesions. Patients who have had neuropathic ulcers are best advised that they will surely break down again if they walk far enough. As an aside, may I also comment on our recent trip to the Galapagos. While exploring one lava-covered island, our guide advised us to wear thick-soled shoes to protect our feet from the hot and sharp lava. I did. He did not. He went barefooted! When he sat down crossing his legs, I peeped at his feet. They appeared no tougher than mine. How could he do it? Did he know the trail well enough to avoid hazards? Nope! I followed in his footsteps. He left flat imprints. He was not walking heel-toe but flatfooted. The point? Our diabetics are prescribed inserts fitted in an erect standing position to widely distribute their weight across the bottom of their foot. The benefit, however, is greatly reduced the moment they begin to walk heel-toe!

• Litzelman DK, Marriott DJ and Vinicor F: Independent physiological predictors of foot lesions in patients with NIDDM. Diabetes Care 20:1273-1278, 1997. Three hundred fifty-two patients were enrolled in a one year study. Abstract results: "When controlling for intervention effects, only measures of neuropathy (monofilament testing [odds ratio {OR} 2.75, 95%CI 1.55-4.88] and thermal sensitivity testing [2.18, 1.13-4.21] predicted wounds classified 1.2 (minor injury), but investigation of wounds rated at least 1.3 (nonulcerated lesions) indicated baseline wounds (13.41, 3.19-56.26), monofilament abnormalities (5.23, 2.26-12.13), and low HDL (1.63, 1.11-2.39) as predictors. Although fungal dermatitis, dry cracked skin, edema, ingrown nails, microalbuminuria, fasting blood glucose, and hemoglobin A1c were candidates for one or both of the multivariable models (P<0.3), they were not significant multivariate predictors." Comments: The association of lesions with low HDL levels is interesting. HDL, of course, decreases with weight gain. Obesity increases "wear and tear" on the feet. These patients had an average BMI of 33.7(7.3. It may be that these authors are simply telling us that obese patients with neuropathy and NIDDM get foot lesions.

• Maciejewski ML, Reiber GE, Smith DG, Wallace C, Hayes S, Boyko EJ: Effectiveness of diabetic therapeutic footwear in preventing reulceration. Diabetes Care 27:1774-82, 2004. OBJECTIVE-To review the evidence for the effectiveness of therapeutic footwear in preventing foot reulceration in individuals with diabetes and foot risk factors. RESEARCH DESIGN AND METHODS-We conducted a structured literature review based on a Medline search for studies of therapeutic footwear that examined prevention of reulceration. Nine published articles were identified. Characteristics of the study population, components of the intervention, and level of adherence were evaluated. U.S. Preventive Services Task Force criteria for evaluating research were applied to rate each study on study design and internal validity. RESULTS-Risk ratios in all studies assessing the association between therapeutic footwear and reulceration were below 1.0, suggesting some protective footwear benefit. However, in the most rigorous experimental study, no statistically significant benefit was observed between control patients wearing their own footwear and intervention patients wearing study footwear. Annual reulceration in these studies' control groups ranged from 8.4 to 59.3%. In patients with severe foot deformity or prior toe or ray amputation, observational studies suggested a significant protective benefit from therapeutic footwear. CONCLUSIONS-Therapeutic footwear has been used for decades as one of many strategies to prevent reulceration in patients with diabetes and foot risk factors. The findings of several studies reporting statistically significant protective effects from therapeutic footwear may have been influenced by several design issues. When considering the appropriateness of therapeutic footwear recommendations for moderate-risk patients, clinicians and patients should jointly explore individual strategies to decrease events that lead to foot ulcers.

• Maithel SK, Pomposelli FB, Williams M, Sheahan MG, Scovell SD, Campbell DR, LoGerfo FW, Hamdan AD: Creatinine clearance but not serum creatinine alone predicts long-term postoperative survival after lower extremity revascularization. Am J Nephrol 26:612-20, 2006. BACKGROUND: Renal insufficiency is a well-described risk factor for perioperative morbidity and shortened survival after major vascular procedures. Due to the potential inaccuracy of serum creatinine levels alone in measuring kidney function, our aim was to determine whether estimated creatinine clearance more consistently predicted long-term survival. METHODS: A retrospective review of one institution's vascular registry was performed. Logistic regression analysis was conducted to determine independent predictors of 1-, 2- and 3-year postoperative mortality. Creatinine clearance was estimated as [140 - age (years)] x weight (kg)/72 x serum creatinine (mg/dl), multiplied by 0.85 for women. RESULTS: A total of 252 consecutive patients underwent infrainguinal bypass procedures between August 1999 and May 2000. Demographics included average age 68 years, 65% male, 74% diabetic, 12% dialysis-dependent, 23% history of congestive heart failure, 12% history of stroke and 20% serum creatinine >2 mg/dl. One-year mortality was 16% (n = 40), 2-year mortality was 25% (n = 64), and 3-year mortality was 35% (n = 88). There was no difference in serum creatinine values between survivors and non-survivors at 1 year (1.8 vs. 1.9, p = 0.80), 2 years (1.8 vs. 2.0, p = 0.62) or 3 years (1.8 vs. 2.0, p = 0.24), and creatinine >2 mg/dl did not predict long-term adverse outcomes. In contrast, reduced creatinine clearance (< or =60 ml/min) was an independent predictor of mortality regardless of dialysis status (1 year: OR = 2.53, p = 0.014; 2 years: OR = 2.46, p = 0.004; 3 years: OR = 2.45, p = 0.001), and creatinine clearance was higher for survivors versus non-survivors at all 3 time points (1 year: 70.2 vs. 49.5, p = 0.003; 2 years: 72.3 vs. 51.2, p < 0.0001; 3 years: 74.7 vs. 52.6, p < 0.0001). Other independent predictors of mortality included a history of stroke (1 year: OR = 3.28, p = 0.008; 2 years: OR = 2.55, p = 0.025; 3 years: OR = 2.35, p = 0.038) and congestive heart failure (1 year: OR = 2.86, p = 0.006; 2 years: OR = 2.54, p = 0.005; 3 years: OR = 2.13, p = 0.017). CONCLUSIONS: Independent of dialysis status, a decreased creatinine clearance, but not elevated serum creatinine alone, is an independent predictor of mortality after lower extremity arterial reconstruction. Determination of creatinine clearance should replace serum creatinine in the preoperative risk evaluations of patients undergoing major vascular surgical procedures.

• Manam RK and Edelson GW: Lower extremity edema in diabetes mellitus. Practical Diabetology 16: 6-14, 1997. Authors' table summarizing differential diagnosis: I. Diabetes-specific: A. Systemic - nephrotic syndrome and insulin edema; B. Localized - diabetic microangiopathy (neuropathic edema) and muscle infarction. II. Non-Diabetes-Specific: A. Systemic - idiopathic cyclic edema, congestive heart failure, nephrotic syndrome, hepatic cirrhosis, hypoproteinemia, pregnancy, premenstrual water gain, dependent edema and acute glomerulonephritis; B. Localized - primary and secondary lymphedema, ruptured gastrocnemius muscle (medial head), chronic venous insufficiency, thrombophlebitis, deep vein thrombosis, cellulitis, ruptured Baker's cyst, severe arthritis with immobilization, lipedema, angioneurotic edema, retroperitoneal fibrosis, compartment syndrome, severe heat or cold exposure, post vascular surgery, trauma (acute or recurring), inferior vena cava or iliac vein occlusion, pretibial myxedema, rheumatologic disease, allergic response, severe ischemia and drug-induced edema. Comments: In considering the epidemiology of any lower limb problem, one must first have the right diagnosis. This article reminds us that swelling in the leg may have many causes

• Mangano DT, Browner WS, Hollenberg M, London MJ, Tubau JF and Tateo IM: Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. N Engl J Med 323: 1781-1788, 1990. 474 men, 243 with coronary disease and 231 thought to be at high risk for it (eg previous or current vascular surgery, or 2 of the following: age >=65, hypertension, active smoking, cholesterol over 240, and diabetes), followed prospectively before and after noncardiac surgery. 18% had postoperative ischemic cardiac events in the hospital (15 died or had a MI or unstable angina, 30 developed CHF and 38 had ventricular tachycardia). Post-operative myocardial ischemia occurred in 41% of monitored patients and was associated with a 2.8-fold increase in the odds for all adverse cardiac outcomes and a 9.2-fold increase in the odds for an ischemic event. Odds ratio for variables associated with ischemic events: 3.4 for claudication, 5.0 for serum Creatinine over 2mg/dl, 9.2 for post-op ischemic on Holter monitor. Odds ratio for CHF 2.4 in diabetics and 3.5 in patients undergoing vascular surgery.Comment: Boot therapy no risk for these patients.

• Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA: The accuracy of venous leg ulcer prognostic models in a wound care system. Wound Repair Regen 12:163-8, 2004. Venous leg ulcers are among the most common chronic wounds. Treatment is commonly with a limb compression bandage. Previous small, often single-center, studies have shown that it is possible to predict which wounds are likely to respond to compression therapy. We designed this cohort study using a dataset of over 20,000 individuals with a venous leg ulcer to investigate the accuracy of several prognostic models. Creating complex models using logistic regression, as well as simply counting prognostic factors, we show that initial measures of wound size and duration accurately predict, as measured by area under the receiver operator curve and Brier score, who will heal by the 24th week of care. For example, a wound that is less than 10 cm(2) and less than 12 months old at the first visit has a 29 percent chance of not healing by the 24th week of care, while a wound greater than 10 cm(2) and greater than 12 months old has a 78 percent chance of not healing. Ultimately, these models can be applied by a clinician to help determine whom to continue to treat with standard care and perhaps whom to treat with adjuvant therapies. They may also aid in the design of clinical trials. Comments: Essentially, large ulcers with a long history are unlikely to heal with standard therapies. The clinician does well to begin compression boot therapy immediately on presentation with a goal of shortening the pain and disability of the patient. Hopefully, reviewers for insurance carriers and Medicare will not require the boot physician to apply compression bandages and other standard measures for six months if such therapy has already failed in other hands.

• Mayfield JA, Reiber GE, Maynard C, Czerniecki JM, Caps MT, Sangeorzan BJ: Trends in lower limb amputation in the Veterans Health Administration, 1989-1998. J Rehabil Res Dev 37:23-30, 2000. Center of Excellence in Amputation, Prosthetics, and Limb Loss Prevention, Rehabilitation Research and Development, Puget Sound Health Care System, Seattle, WA 98108, USA. OBJECTIVE: To assess trends in lower limb amputation performed in Veterans Health Administration (VHA) facilities. METHODS: All lower limb amputations recorded in the Patient Treatment File for 1989-1998 were analyzed using the hospital discharge as the unit of analysis. Age-specific rates were calculated using the VHA user-population as the denominator. Frequency tables and linear, logistic, and Poisson regression were used respectively to assess trends in amputation numbers, reoperation rates, and age-specific amputation rates. RESULTS: Between 1989-1998, there were 60,324 discharges with amputation in VHA facilities. Over 99.9% of these were in men and constitute 10 percent of all US male amputations. The major indications were diabetes (62.9%) and peripheral vascular disease alone (23.6%). The age-specific rates of major amputation in the VHA are higher than US rates of major amputation. VHA rates of major and minor amputation declined an average of 5% each year, while the number of diabetes-associated amputations remained the same. CONCLUSION: The number and age-specific rates of amputations decreased over 10 years despite an increase in the number of veterans using VHA care.

• Mayfield JA, Reiber GE, Nelson RG and Greene T: A foot risk classification system to predict diabetic amputation in Pima Indians. Diabetes Care 19:704-709, 1996. Sixty one people with amputations (35 toe, 6 transmetatarsal, 1 Symes, 16 below-the-knee and 3 above-the-knee) were identified and compared with 183 control subjects. Men were more likely to suffer amputation than women (odds ratio 6.5)., and people with diabetic eye, renal or cardiovascular disease were more likely to undergo amputation then those without (odds ratio 4.6). The risk of amputation was almost equally associated with these foot risk factors: peripheral neuropathy, peripheral vascular disease, bony deformities, and a history of foot ulcers. After controlling for demographic differences and diabetes severity, the odds ratio for amputation with one risk factor was 2.1; with two risk factors, 4.5; and with three or four risk factors, 9.7. Comments: Toe amputations do count, I suppose, but are far less devastating and costly than leg amputations, which composed only 31% of the study. It would be interesting to see a similar study on a larger number of patients.

• McKitrick LS, McKittrick JB and Risley TS: Transmetatarsal amputation for infection or gangrene in patients with diabetes. Annals of Surg 130: 826-842, 1949. Author's summary: "1. Two hundred and fifteen transmetatarsal amputations have been done from July, 1944, to January 1,, 1949, with two hospital deaths, both due to coronary thrombosis. 2. Thirty-three of these failed to heal, and came to amputation at a higher level. 3. The present condition of the remaining 174 patients who left the hospital with a transmetatarsal amputation is known. One-hundred and thirty-five of these are completely satisfactory. In 32 patients the end result is still undetermined and is regarded as unsatisfactory. Seven patients have come to higher amputation after complete healing for a minimum of one year. 4. The functional result has been excellent in all successful cases. Most patients with unilateral amputations use lamb's wool in the toe of their own shoe. Three patients use an inner sole insert with a rubber toe, which is probably the best, and five patients use a flexible steel bar between the outer and inner sole. 5. Custom-made short shoes are used by all patients with bilateral amputations, and this is regarded as a satisfactory solution. 6. We consider the results very gratifying, and believe amputation at this level to be a major contribution to the management of this group of patients." The authors list their indications for the procedure as (1) gangrene of all or part of one or more toes, providing the gangrene and accompanying infection have become stabilized and the gangrene has not involved the dorsal or plantar aspect of the foot; (2) a stabilized infection or open wound involving the distal portion of the foot, when total excision of the infected area with primary or delayed closure can be accomplished; (3) an open, infected lesion in a neurogenic foot (a) as a curative procedure when the entire area of anesthesia can be excised, or as a delaying procedure when the area of infection can be excised but the line of incision is through the area of anesthesia. In their discussion, they point out that neuropathic ulcers were most disturbing and baffling; they found the blood supply adequate in most patients and usually obtained prompt healing.... with in almost all instances later recurrences in spite of all precautions....unless all of the anesthetic area on the plantar aspect of the foot was excised. They state that probably the most important single factor favoring a successful outcome in patients with borderline circulation is proper timing for the operation: "every effort should be made to do the operation after the gangrene and infection have demarcated." They commonly allowed three weeks in the hospital to prepare the patient for the procedure (antibiotics, diabetes control, bed rest and transfusions). Postoperative care in the hospital was also important. Their average postoperative stay was 30 days. The patients were kept at bedrest for 2-2.5 weeks with the head of the bed elevated to maximize blood flow into the feet. Comments: This paper was an important contribution instructing the general surgeon in the technique of transmetatarsal amputations. The work was done at the beginning of the antibiotic era. Previous attempts at foot surgery were commonly met with sepsis and a significant mortality rate. If more antibiotic resistant organisms develop today, sepsis may again be a major problem promoting both death and a need for higher amputations. Today's HMO should note their usage of hospital days: 21 days preoperatively and 30 days postoperatively. The authors stated these days were crucial for their patients.

• Moulik PK, Mtonga R, Gill GV: Amputation and mortality in new-onset diabetic foot ulcers stratified by etiology. Diabetes Care 26:491-4, 2003. OBJECTIVE: Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. The present study aims to examine the long-term outcome in terms of amputations and mortality in patients with new-onset diabetic foot ulcers in subgroups stratified by etiology. RESEARCH DESIGN AND METHODS: Patients presenting with new ulcers (duration <1 month) to a dedicated diabetic foot clinic between 1994 and 1998 were studied. Outcomes were determined until March 2000 (or death) from podiatry, hospital, and district registers. Baseline clinical examination was done to classify ulcers as neuropathic, ischemic, or neuroischemic. Five-year amputation and mortality rates were derived from Kaplan-Meier survival analysis curves. RESULTS: Of the 185 patients studied, 41% had peripheral vascular disease (PVD) and 61% had neuropathy; 45%, 16%, and 24% of patients had neuropathic, ischemic, and neuroischemic ulcers, respectively. The mean follow-up period was 34 months (range 1-65) including survivors and patients who died during the study period. Five-year amputation rates were higher for ischemic (29%) and neuroischemic (25%) than neuropathic (11%) ulcers. Five-year mortality was 45%, 18%, and 55% for neuropathic, neuroischemic, and ischemic ulcers, respectively. Mortality was higher in ischemic ulcers than neuropathic ulcers. On multivariate regression analysis, only increasing age predicted shorter survival time. CONCLUSIONS: All types of diabetic foot ulcers are associated with high morbidity and mortality. The increased mortality appears to be independent of factors increasing ulcer risk-that is, neuropathy and PVD-in patients with established foot ulcers.

• Mueller MJ, Allen BT and Sinacore DR: Incidence of skin breakdown and higher amputation after transmetatarsal amputation: implications for rehabilitation. Arch Phys Med Rehab 76:50-54, 1995. 120 TMS's on 107 patients aged 62.4+/-13.8. 12% had bilateral TMA. 27% developed skin breakdown (48% within the first 3 months of surgery). 28% required higher amputation (60% within the first month). The amputees had higher incidence of diabetes, hypertension, EKG abnormalities, CHF and prior ipsilateral vascular surgery.

• Nguyen LL, Lipsitz SR, Bandyk DF, Clowes AW, Moneta GL, Belkin M, Conte MS: Resource utilization in the treatment of critical limb ischemia: The effect of tissue loss, comorbidities, and graft-related events. J Vasc Surg 44:971-5,2006. OBJECTIVE: Resource utilization (RU) in the care of patients with critical limb ischemia (CLI) is not well quantified. We present a cohort study to quantify in-hospital RU and analyze the role of tissue loss (TL), comorbidities, and vascular graft-related events (GREs) in patients undergoing peripheral bypass for CLI. METHODS: A retrospective analysis of 1404 patients enrolled in a multicenter clinical trial (PREVENT III) of vein bypass grafting for CLI was performed with analysis of RU during the 1-year follow-up period. Univariate and multivariable linear regressions were performed to determine RU predictors and outcomes. RESULTS: Compared with patients with rest pain, patients presenting with TL as the indication for bypass surgery had a longer index length of stay (mean, 9.8 vs 6.2 days), more rehospitalizations (mean, 1.6 vs 1.2), and a longer cumulative length of stay (mean, 27.7 vs 17.3 days; P < .0001 for all comparisons). Rehospitalizations over the ensuing year were for additional procedures (37.5%), wound infection (14.6%), graft failure (10.7%), and other cardiovascular (10%) and noncardiovascular (26%) reasons. Early GRE (stenosis > or =70%, thrombosis, revision, or major amputation within 30 days) occurred in 162 (11.5%) patients, resulting in a longer index length of stay (mean, 11.8 vs 8.6 days; P = .0002) and cumulative length of stay (mean, 25.9 vs 24.6 days; P = .0043), but no difference in the number of rehospitalizations (mean, 1.6 vs 1.5 days; P = .3272). During the 1-year follow-up, 554 (39.5%) patients had GREs, and this resulted in more rehospitalizations (mean, 2.1 vs 1.1; P < .0001) and a longer cumulative length of stay (mean, 28.2 vs 21.9 days; P < .0001) compared with patients without GRE. Multivariable analysis demonstrated the highly positive association of TL (hazard ratio [HR], 1.75) and early GRE (HR, 1.77) with the index length of stay, whereas comorbidities-namely, dialysis dependency (HR, 1.31), nonsmoking status (HR, 1.29), hypertension (HR, 1.26), and increasing age (HR, 1.01)-also had strong effects. The effect of TL and GRE on later RU (number of rehospitalizations and cumulative length of stay) was present but less pronounced than patient comorbidities (namely, dialysis). CONCLUSIONS: The stage of disease at presentation (TL vs rest pain) and the patency of the bypass graft (freedom from GRE) are critical determinants of RU over the first year after limb-salvage surgery. These effects predominate early (index length of stay) and persist through 1 year. Patient-specific factors, particularly dialysis-dependent renal failure, are also critical comorbidities affecting RU in these patients.

• O'Brien TS, Lamont PM, Crow A, Gray DR, Collin J and Morris PJ: Lower limb ischaemia in the octogenarian: Is limb salvage surgery worthwhile? Annals Royal Col Surg 75:445-447, 1993. 50 patients. 4/6 conservatively treated patients died during initial hospitalization. 2 suitable for angioplasty. 12 (24%) had primary leg amputation with a perioperative mortality of 25%. 5 (10%) had leg amputation with a perioperative mortality of 25%. 5(10%) had iliac bypass, 14 (28%) fem-pop and 11 (22%) distal bypasses with an overall perioperative mortality rate of 12%. Mortality at 6 months was 33% in both the amputation and bypassed groups. Patients with successful bypass were more mobile and had shorter hospitalizations. Conclude patients in their 80's should not be denied bypass.

• Pohjolainen T, Alaranta H: Ten-year survival of Finnish lower limb amputees. Prosthet Orthot Int 22:10-16, 1998. Data on mortality for the ten years following lower limb amputation were obtained from all the 16 surgical units in Southern Finland and the National Social Insurance Institution. In Southern Finland during the period 1984-1985, amputations of the lower limb were performed on 705 patients, of whom 382 (54%) were women and 323 (46%) men. The majority of the amputations, 47% were performed for vascular diseases and 41% were performed for diabetes mellitus. The overall survival was 62% at one year after amputation, 49% at two years, 27% at five years and 15% at ten years. The median survival after amputation was 1 yr 5 mth for the women and 2 yr 8 mth for the men. Of the arteriosclerotics, 43% died within one postoperative year while 43% lived longer than two years and 23% longer than five years. The median survival of arteriosclerotics was 1 yr 6 mth. The corresponding figure for patients with diabetes was 1 yr 11 mth. Of the diabetics, 38% died within one postoperative year while 47% lived longer than two years and 20% longer than five years. Of the trauma patients, 86% lived longer than five years and 71% longer than ten years. Of the trans-femoral amputees, 54% lived longer than one year, 36% over two years, 18% over five years and 8% over ten years. The corresponding figures for trans-tibial amputees were 70%, 53%, 21% and 4%. Many elderly vascular and diabetic patients undergoing amputation have a reduced physiological reserve and high mortality. The more proximal the amputation, the greater the risk that the patient will never be able to walk or that the duration of use of the prosthesis will be short. If a prosthesis seems to be a reasonable option for the elderly amputee, any delays in prosthetic fitting should be avoided in older age groups.

• Pollard J, Hamilton GA, Rush SM, Ford LA: Mortality and morbidity after transmetatarsal amputation: retrospective review of 101 cases. J Foot Ankle Surg 45(2):91-7, 2006. Medical records were reviewed for 90 patients (101 amputations) (mean age 64.3 years, range 39 to 86 years) who underwent transmetatarsal amputation (TMA). The mean follow-up period, excluding those patients who either died or went on to a more proximal amputation less than 6 months after TMA, was 2.1 years. Patients were examined for any postoperative complications associated with TMA. Complications were defined as hospital mortality occurring less than 30 days postoperatively; stump infarction with or without more proximal amputation; postoperative infection; chronic stump ulceration; stump deformity in any of 3 cardinal planes; wound dehiscence; equinus and calcaneus gait. An uncomplicated outcome was defined as the absence of all these complications and an ability to walk on the residuum with a diabetic shoe and filler after a minimum follow-up of 6 months. The chi(2) tests of association were used to determine whether diabetes, a palpable pedal pulse, coronary artery disease, end-stage renal disease, cerebral vascular accident, or hypertension were predictive of or associated with healing. A documented palpable pedal pulse was a predictor of healing (P = .0567) and of not requiring more proximal amputation (P = .03). End-stage renal disease predicted nonhealing (P = .04). A healed stump was achieved in 58 cases (57.4%). Postsurgical complications developed in 88 cases (87.1%). Two patients died within 30 days postoperatively. These data suggest that TMA is associated with high complication rates in a diabetic and vasculopathic population. Comments: Patients with a failing TM amputation may be booted and expected to do well.

• Quebedeaux TL, Lavery LA and Lavery DC: The development of foot deformities and ulcers after great toe amputations in diabetes. Diabetes Care 19:165-167, 1996. Authors followed 25 patients with diabetes, either or both a palpable dorsalis pedis or posterior tibial pulse, a sensory deficit when tested with Semmes-Weinstein monofilaments and a history of an isolated amputation of the great toe and first metatarsal head of at least six months duration. The fate of the other foot served as a control.