Amputation Events Research Articles

PMD104 - COST-EFFECTIVENESS AND COST-UTILITY ANALYSIS OF TREATING DIABETIC FOOT ULCERS WITH URGOSTART COMPARED TO A NEUTRAL DRESSING.

Current National Institute of Health and Care Excellence (NICE) guidance does not indicate a preferred dressing for patients with Diabetic Foot Ulcer (DFU). UrgoStart has recently been shown as superior to a neutral dressing in the double blind randomised controlled Explorer trial. This study examined the cost-effectiveness of UrgoStart compared with a neutral dressing for DFU patients. A Markov-model was designed with seven health states: open, closed, and complicated (pre and post amputation), and deceased. Complicated wounds can cause an amputation event, moving a patient to the post-amputation block. The model took the perspective of the National Health Service (NHS) in the United Kingdom, with a cohort of 1000 patients and base-case time horizon of 1 year. The Explorer trial informed transition probabilities and health-state utility scores; there were no statistically significant differences between the characteristics of the treatment arms at baseline. Both deterministic and probabilistic sensitivity analyses were performed. UrgoStart was the dominant treatment strategy in terms of cost-effectiveness, with a cost saving of £666.51 and a 0.022 gain in quality-adjusted-life years, per patient. Using UrgoStart leads to more wounds healed at 52 weeks than a neutral dressing, 653 and 473 respectively at a cost of £4879.84 per healed wound for UrgoStart compared with £8136.19 for a neutral dressing. The use of UrgoStart also avoided 19 amputations over a year. Sensitivity analysis showed UrgoStart as cost saving, even when a comparator was set at £0. Across 1000 runs of the model, UrgoStart was dominant every time. This analysis showed UrgoStart to be a cost-effective treatment option, with benefits to the patient and the NHS. Primary cost drivers such as community nurse visits and hospital admissions; can be reduced significantly with faster healing. UrgoStart should be considered as a treatment for all patients with a DFU.

The risk of major cardiovascular events for adults with transfemoral amputation

BackgroundIt is well-known that the risk of cardiac disease is increased for those with lower-limb amputations, likely as a result of the etiology of the amputation. Using a longitudinal population-based dataset, we examined the association between transfemoral amputation (TFA) status and the risk of experiencing a major cardiac event for those undergoing either dysvascular or traumatic amputations. The association of receiving a prosthesis with the risk of experiencing a major cardiac event was also examined.MethodsStudy Population: All individuals with TFA (N 162), i.e. knee disarticulation and transfemoral amputation, residing in Olmsted County, MN, between 1987 and 2014. Each was matched (1:10 ratio) with non-TFA adults on age, sex, and duration of residency.Data Analysis: A competing risk Cox proportional hazard model was used to estimate the relative likelihood of an individual with a TFA experiencing a major cardiac event in a given time period as compared to the matched controls. The cohort was divided by amputation etiology: dysvascular vs trauma/cancer. Additional analysis was performed by combining all individuals with a TFA to look at the relationship between prosthesis receipt and major cardiac events.ResultsIndividuals with a dysvascular TFA had an approximately four-fold increased risk of a cardiac event after undergoing an amputation (HR 3.78, 95%CI: 3.07–4.49). These individuals also had an increased risk for non-cardiac mortality (HR 6.27, 95%CI: 6.11–6.58). The risk of a cardiac event was no higher for those with a trauma/cancer TFA relative to the able-bodied controls (HR 1.30, 95%CI: 0.30–5.85). Finally, there was no difference in risk of experiencing a cardiac event for those with or without prosthesis (HR 1.20, 95%CI: 0.55–2.62).ConclusionThe high risk of initial mortality stemming from an amputation event may preclude many amputees from cardiovascular disease progression. Amputation etiology is also an important factor: cardiac events appear to be more likely among patients with a dysvascular TFA. Providing a prosthesis does not appear to be associated with a reduced risk of a major cardiac event following amputation.

The M3 multimorbidity index outperformed both Charlson and Elixhauser indices when predicting adverse outcomes in people with diabetes

ObjectivesMultimorbidity is common among those living with diabetes. The purpose of this manuscript was to assess the performance of the recently developed M3 multimorbidity index within a large, well-defined cohort of patients with diabetes. Study Design and SettingWe compared regression model performance between three morbidity indices (M3, Charlson, and Elixhauser) for important adverse outcomes (hospitalization, amputation, and mortality) among 217,207 patients with diabetes and compared the real-world applied impact of these indices for modeling these diabetes outcomes against two key exposure variables (ethnicity and deprivation). ResultsThe M3 Index outperformed both Charlson and Elixhauser indices in terms of the prediction of hospitalization events, amputation events, and death. When applied to models that were investigating the relationship between (a) ethnicity and (b) deprivation on risk of these outcomes, the M3 Index also explained more confounding due to multimorbidity than either Charlson or Elixhauser (e.g., shift in odds ratio toward the null when predicting hospitalization: M3 Index 60%, Charlson 40%, and Elixhauser 24%). ConclusionThese results give additional support for the utility of the M3 index in clinical populations, adding to previous observations regarding its performance in a general population setting.

The role of preliminary hospitals in the management of a mass burn casualty disaster

PurposeThe Formosa Fun Coast explosion is an internationally-known event that occurred in Taiwan on June 27th, 2015. The blast involved 495 casualties in total, with 253 patients receiving 2nd degree or deeper burns on greater than 40% of the total body surface area (TBSA). Questions were raised regarding whether these victims were sent to the appropriate hospitals or not. Therefore, we analyzed the effect of the initial admission destination in this study. Material and methodsWe retrospectively reviewed all of the victims from the explosion who were sent to the emergency department of Linkou and Keelung Chang Gung Memorial Hospitals. Patients were divided by direct admission and received via transfer. The basic demographics, the efficacy of the initial resuscitation and the clinical outcomes were analyzed. ResultsIn total, forty-six patients were included. Thirty-five of them were primarily admitted, and eleven of them were received via transfer. Between the two groups, there was no significant difference in the resuscitation outcome. The ratio of delaying intubation was similar (14.3% vs 27.3%, p=0.322). The rate of delayed-detected ischemic events was significantly increased in the referral group (0% vs 27.3%, p=0.001). However, there was no amputation event in either group. No difference in mortality was observed between groups (5.7% vs 9.1%, p=0.692). ConclusionOur preliminary findings suggest that local hospitals are capable of providing high-quality acute care to mass casualty burn victims. Our results suggest that patients with suspected limb ischemia should be rapidly transferred to a regional burn center to ensure optimal care. Systemic pre-planning such as employing telemedicine and personnel collaboration, should be considered by the administration to maximize the function of preliminary hospitals in burn care.

Inverse Relationship Between Serum Bilirubin Levels and Diabetic Foot in Chinese Patients with Type 2 Diabetes Mellitus.

BackgroundSeveral studies demonstrated that bilirubin, a potent endogenous antioxidant, is a strong protective factor for many diabetic complications such as nephropathy, retinopathy, neuropathy, and vasculopathy. The purpose of this study was to assess the association between serum bilirubin levels and diabetic foot (DF) in Chinese patients with type 2 diabetes mellitus (T2DM).Material/MethodsThe present cross-sectional study of bilirubin levels in relation to DF was conducted in 1,269 T2DM patients with (n=578) and without (n=691) DF. Blood test results were obtained on hospital admission, including total bilirubin (T-BIL), direct bilirubin (D-BIL), and indirect bilirubin (I-BIL). Data on Wagner classification and amputation procedure in patients with DF were collected by reviewing electronic medical records. Univariate or multivariate analysis were performed to explore the association between bilirubin and DF.ResultsSerum I-BIL levels were shown to play a protective role regarding the presence and severity of DF (OR=0.75, p=0.029 and OR=0.90, p=0.021, respectively). In addition, in a comparison of the lowest and highest tertiles of serum bilirubin concentration, the highest tertile of serum T-BIL (OR=0.51, p=0.011) and I-BIL (OR=0.28, p<0.001) was significantly related with a lower Wagner grade of DF. Patients with DF in the highest tertiles of T-BIL carried a significantly lower risk of amputation events than those in the lowest tertiles (OR=0.47, p=0.025).ConclusionsThe present study provided evidence that decreased serum bilirubin levels were independently associated with the presence and severity of DF and amputation events in patients with DF.

Lived experience of older adults’ adjustment to amputation in the context of wheelchair use

Amputation has a profound psychological impact on recipients. The experience of adjustment to lower limb amputation (LLA) by older adults who use wheelchairs was explored using Interpretative Phenomenological Analysis (IPA). Four men with lower limb amputations due to vascular disease who identified as wheelchair users were interviewed. Participants’ experiences of adjustment to LLA are represented by two themes: “Being an Active Agent” and “Psychosocial Adjustment as an Iterative Process”. Being an Active Agent included three elements: self-reflection, a sense of control over one’s LLA and the belief one is able to take action in decision-making in daily life. The second theme ‘Psychosocial Adjustment as an Iterative Process’ described the ongoing nature of the participants’ narratives of adjustment to LLA. This theme also encompassed participants’ experiences of adjustment to LLA as firmly linked to management of previous life events. Participants’ adjustment did not appear to be directly influenced by the mobility aid they used; rather, the mobility aid provided opportunities for adjustment to occur. Older adults’ adjustment to LLA appears to be influenced by their perception of being an active agent in their adjustment process, particularly in relation to decision-making. Adjustment also appears to be a process which older adults continue to engage in after the amputation event. The findings of this study suggest practical strategies that clinicians can use with older adults undergoing amputation

Predictors of amputation in high-energy forefoot and midfoot injuries

IntroductionHigh energy injuries to the midfoot and forefoot are highly morbid injury groups that are relatively unstudied in the literature. Patients sustaining injuries of this region are challenging to counsel at the time of injury because so little is known about the short and long term results of these injuries. The purpose of this study was to investigate injury specific factors that were predictive of amputation in patients sustaining high energy midfoot and forefoot injuries. Patients and methods137 patients with 146 injured feet [minimum of two fractures located in the forefoot and midfoot, excluding phalanges, talus, calcaneus, with a high energy mechanism]. Results121 of 146 feet (83%) were treated operatively; 27 patients sustained 34 total surgical amputation events. 30-day amputation rate was 13.9% and 1-year amputation rate was 18.9%; 27 of 146 feet ultimately sustained amputation with 23 of 27 sustaining a below the knee amputation (BKA) and 17 of 23 (73.9%) received a BKA as their first amputation. Statistically significant predictors of amputation included the number of bones fractured in the foot (p=0.015), open injury to the plantar or dorsal surfaces of the foot, Gustilo grade, vascular injury, and complete loss of sensation to any surface of the foot (all p<0.001). Specific fracture patterns predictive of any amputation were fracture of all five metatarsals (p<0.001) and fracture of the first metatarsal (p=0.003). Presence of a dislocation or fracture of the distal tibia were not predictive of amputation. Midterm patient-reported-outcomes (N=51) demonstrated no difference in physical function for patients with and without amputations. ConclusionsHigh-energy forefoot and midfoot injuries are associated with a high degree of morbidity; 1/5th of patients sustaining these injuries proceeded to amputation within 1year. Injury characteristics can be used to counsel patients regarding severity and amputation risk.

Lower Extremity Amputation and Mortality Rates in the Reconstructed Diabetic Charcot Foot and Ankle With External Fixation: Data Analysis of 116 Patients.

The aim of this study was to determine the lower extremity amputation and mortality rates of a group of patients who underwent reconstructive surgery using circular external fixation for treatment of diabetic Charcot neuroarthropathy (CN) of the foot and/or ankle. Existing studies regarding lower extremity amputation or mortality rates for diabetic CN of the foot and/or ankle have been performed on mostly conservatively treated patients. The objective of the statistical analysis in this studied population was to understand the difference in overall amputation and mortality rates between the 2 main groups: one with foot and/or ankle ulceration (group 1), and the other without ulceration or osteomyelitis (group 2, control group). Within group 1, 2 subgroups were established: one with osteomyelitis (group 1A) and the other without osteomyelitis (group 1B). Initially, a retrospective analysis of 150 consecutive surgically reconstructed diabetic foot and ankle cases using circular external fixation from January 2005 through December 2012 was conducted. Those which were not supported with the diagnosis of diabetic CN were excluded and the 2 other charts without proper follow-up duration (6 months) for analysis were removed, resulting in the final sample size of N = 116. There were a total of n = 7 (6.0%) below the knee amputations (group 1A = 1, group 1B = 4, and group 2 = 2) with a total of n = 5 mortalities (4.3%) (group 1A = 2, group 1B = 2, and group 2 = 1). The total amount of time for a lower extremity amputation event (n = 7) since the time of surgical reconstruction was 729.43 ± 519.73 days (range 230-1777 days) while for a mortality event (n = 5), it was 1302.00 ± 765.48 days (range 633-2499 days). Prognostic, Level III: Retrospective study.

Abstract 14774: Rescue of Diabetes-related Impairment of Ischemia-mediated Neovascularization With Fenofibrate Treatment

Background: Fenofibrate, a PPARα agonist, reduced amputation events in the Fenofibrate Intervention and Event Lowering in Diabetes study among 9795 patients, the mechanisms of which are unknown. We hypothesised that fenofibrate may attenuate diabetes-related impairment in ischemia-mediated neovascularization. Methods: Hindlimb ischemia was induced in a murine model of streptozotocin induced diabetes mellitus (DM) in wildtype and PPARα receptor knockout mice (KO) with/without fenofibrate (30mg/kg/day in high fat diet). Ischemic recovery was assessed by laser doppler, foot movement and capillary density analysis. Key angiogenic events (tubulogenesis) and expression of thioredoxin-interacting protein (TXNIP) mRNA and protein following normal and high glucose (5 vs 25mM glucose) environments were determined in cultured endothelial cells (ECs), with/without selective PPARα receptor antagonist (10μM MK886) and agonist (10μM WY14643). Results: DM profoundly impaired blood flow recovery following hindlimb ischemia (0.51±0.04[n=5] vs 0.34±0.03[n=5];p&lt;0.001). Fenofibrate (FF) restored DM-related impairment in blood flow recovery (0.53±0.04[n=5] vs 0.34±0.03[n=5];p&lt;0.01), capillary density (1.48±0.03 vs1.20±0.04;p&lt;0.01), foot movement scores to levels of non-diabetic controls. Similar findings for fenofibrate were observed in diabetic PPARα KO mice. In vitro, fenofibric acid (FA) rescued hyperglycemia-induced impairment in EC tubulogenesis (87.8 vs 58.3% of control;p&lt;0.05) by a PPARα-independent mechanism. FA prevented hyperglycemia-induced overexpression of TXNIP (mRNA: 1.20±0.16 vs 1.84±0.28 folds of control;p&lt;0.01) an exquisitely glucose-sensitive regulator of angiogenesis, in a PPARα-independent manner. Furthermore, overexpression of TXNIP abrogated the protective effects of FA. Conclusions: Fenofibrate rescues diabetic impairment in ischemia-mediated angiogenesis via a largely PPARα-independent mechanism. Improved neovascularization may therefore explain in part the reduced amputations seen with fenofibrate in type 2 diabetes. These findings provide a novel mechanistic understanding for fenofibrate action and may provide a platform for new drug targets.

Pre-Operative Anaemia Predicts Poor Outcomes in Patients Undergoing Infra-Inguinal Bypass Surgery

Objectives: Critical limb ischaemia (CLI) requiring infra-inguinal bypass is a common presentation to the vascular surgery service. A significant number of CLI patients also present with anaemia as a comorbidity, the impact of which is unknown. We reviewed the impact of anaemia on mortality and amputation in patients who underwent infra-inguinal bypass surgery. Methods: Demographic data from all patients who underwent infra-inguinal bypass surgery for CLI at the Flinders Medical Centre & Repatriation General Hospital, South Australia between January 2005 and January 2010 were recorded. Haemoglobin (Hb) level, serum creatinine (SCr) level, mortality and amputation events were also recorded for retrospective analysis. Results: 190 patients (141M, 49F) who underwent infra-inguinal bypass surgery over a 5 year period were analyzed. 100 (53%) of these patients had mild anaemia (mean Hb 113 g/L, mean for females 103 g/L, mean for males 116 g/L). Those who presented with anaemia were more likely to have diabetes and renal dysfunction as comorbidities. Anaemia had a significant negative impact on mortality with 30% deaths in those who were anaemic compared to 15.6% deaths in those without anaemia odds ratio (OR) 1.76, 95% CI: 0.90 - 3.48, p < 0.01. This relationship was similar when looking at amputation as an outcome; with the number of amputations in those who were anaemic preoperatively 14% vs 6.7% in those who were not anaemic, OR 2.56, 95% CI: 1.00 - 6.54, p = 0.05. The negative impact of anaemia on mortality 43.5% vs 18.8% was also noted in patients who did not have diabetes or impaired renal function as a comorbidity p < 0.05. Conclusions: Anaemia is a common comorbidity in patients presenting with CLI and it predicts poor outcomes after infra-inguinal bypass. The role of transfusion is debatable, but it is clear that this group of patients requires careful management during the perioperative period to ensure they are medically optimized.

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Bilirubin has antioxidant and anti-inflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation. The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint. Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than threefold risk gradient across levels. Individuals with lower bilirubin concentrations had a higher risk for first amputation (HR 1.38 per 5μmol/l decrease in bilirubin concentration, 95% CI 1.07, 1.79, p = 0.013). The same association persisted after adjustment for baseline variables, including age, height, smoking status, γ-glutamyltransferase level, HbA1c, trial treatment allocation (placebo vs fenofibrate), as well as previous PAD, non-PAD cardiovascular disease, amputation or diabetic skin ulcer, neuropathy, nephropathy and diabetic retinopathy (HR 1.38 per 5μmol/l decrease in bilirubin concentration, 95% CI 1.05, 1.81, p = 0.019). Our results identify a significant inverse relationship between bilirubin levels and total lower-limb amputation, driven by major amputation. Our data raise the hypothesis that bilirubin may protect against amputation in type 2 diabetes.

Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis

The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan-Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.

P109 * Predictive role of erectile dysfunction in the development of coronary heart disease in patients with obstructive sleep apnea syndrome

P109 * Predictive role of erectile dysfunction in the development of coronary heart disease in patients with obstructive sleep apnea syndrome

Skin Perfusion Pressure Is a Prognostic Factor in Hemodialysis Patients

Peripheral arterial disease (PAD) is common in hemodialysis patients and predicts a poor prognosis. We conducted a prospective cohort study to identify risk factors for PAD including skin perfusion pressure (SPP) in hemodialysis patients. The cohort included 373 hemodialysis patients among 548 patients who received hemodialysis at Oyokyo Kidney Research Institute, Hirosaki, Japan from August 2008 to December 2010. The endpoints were lower limb survival (peripheral angioplasty or amputation events) and overall survival of 2 years. Our results showed that <70 mmHg SPP was a poor prognosis for the lower limb survival and overall survival. We also identified age, history of cardiovascular disease, presence of diabetes mellitus, smoking history, and SPP < 70 mmHg as independent risk factors for lower limb survival and overall survival. Then, we constructed risk criteria using the significantly independent risk factors. We can clearly stratify lower limb survival and overall survival of the hemodialysis patients into 3 groups. Although the observation period is short, we conclude that SPP value has the potential to be a risk factor that predicts both lower limb survival and the prognosis of hemodialysis patients.

Abstract 9948: Serum Total Bilirubin Levels Predict Amputation Events in Type 2 Diabetic Mellitus

Objectives: Bilirubin is well known for its antioxidant and anti-inflammatory properties, and may protect against vascular disease. It has previously been demonstrated that higher serum bilirubin levels were associated with reduced peripheral arterial disease (PAD) prevalence. However, the relationship between bilirubin and lower limb amputation, a consequence of PAD, is currently unknown. We hypothesized that bilirubin protects against amputation events in type 2 diabetic patients with PAD. Methods: The relationship between baseline serum total bilirubin level and amputation events was analyzed in 9795 type 2 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study in a pre-specified subsidiary analysis. Lower limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Bilirubin was analyzed continuously using Cox regression techniques. Results: Serum bilirubin level was significantly inversely associated with lower limb amputation rate. When bilirubin was analyzed continuously, patients with lower bilirubin levels had an increased risk of amputation compared with patients with higher bilirubin levels (HR 1.38 per 5 µmol/L decrease in bilirubin, 95% CI 1.07-1.79, p=0.013). The same association persisted after adjustment for baseline variables including age, sex, height, smoking status, alcohol intake, GGT, ALT, HbA1c, and history of hypertension, hypercholesterolemia, previous PAD, prior revascularization, amputation, ulcer, neuropathy, renal dysfunction and diabetic retinopathy (p=0.032), as well as treatment allocation (placebo vs. fenofibrate). Conclusion: Our results identify a highly significant inverse relationship between serum bilirubin level and lower limb amputation rate. Our data is consistent with the hypothesis that bilirubin plays a protective role against amputation in the setting of type 2 diabetes.

Serum Total Bilirubin Levels Predict Amputation Events in Type 2 Diabetic Mellitus

Serum Total Bilirubin Levels Predict Amputation Events in Type 2 Diabetic Mellitus

Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial

SummaryBackgroundAmputations in people with type 2 diabetes mellitus substantially impair their quality of life and impose high costs on health-care systems. Our aim was to assess the effect of fenofibrate on amputation events in a large cohort of patients with type 2 diabetes.MethodsIn the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, 9795 patients aged 50–75 years with type 2 diabetes were randomly assigned by computer-generated randomisation sequence to receive fenofibrate 200 mg per day (n=4895) or matching placebo (n=4900) for 5 years' duration. Information about non-traumatic amputation—a prespecified tertiary endpoint of the study—was routinely gathered. Clinicians who were masked to treatment allocation adjudicated amputations as minor or major (below or above the ankle, respectively). Amputations were also classified on the basis of whether or not large-vessel disease was present in the limb, to distinguish those related to large-artery atherosclerosis from those predominantly related to microvascular disease. Analysis was by intention to treat (ITT). The FIELD study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481.FindingsAll 9795 patients were included in the ITT population. 115 patients had one or more non-traumatic lower-limb amputations due to diabetes. Previous cardiovascular disease, microvascular disease, previous non-traumatic amputation or skin ulcer, smoking, and longer duration of diabetes were more frequent in patients who had amputations during the trial than in those who had other cardiovascular events or in those who had neither event (all p<0·001 for three-way comparison). Mean lipid concentrations differed between patients who had on-study amputations and those who had other cardiovascular events or neither event, but by no more than 0·2 mmol/L. The risks of first amputation (45 vs 70 events; hazard ratio [HR] 0·64, 95% CI 0·44–0·94; p=0·02) and minor amputation events without known large-vessel disease (18 vs 34 events; 0·53, 0·30–0·94; p=0·027) were lower for patients assigned to fenofibrate than for patients assigned to placebo, with no difference between groups in risk of major amputations (24 vs 26 events; 0·93, 0·53–1·62; p=0·79).InterpretationClassic markers of macrovascular and microvascular risk were associated with lower extremity amputations in patients with type 2 diabetes. Treatment with fenofibrate was associated with a lower risk of amputations, particularly minor amputations without known large-vessel disease, probably through non-lipid mechanisms. These findings could lead to a change in standard treatment for the prevention of diabetes-related lower-limb amputations.FundingLaboratoires Fournier SA (now part of Solvay Pharmaceuticals) and National Health and Medical Research Council of Australia.

Alternatives to Heparin Infusion

This article offers an overview of the pathophysiology, diagnosis, and treatment of heparin-induced thrombocytopenia (HIT). This disorder is an immune-mediated reduction of platelets with subsequently increased generation of thrombin and increased risk of arterial and venous thrombosis. Heparin-induced thrombocytopenia can occur as an isolated incident or with acute thrombosis (HIT with thrombosis syndrome [HITTS]). Proper recognition, cessation of all forms of heparin (and compounds that cross-react with heparin), and rapid initiation of nonheparin anticoagulation are essential steps in reducing the risk of death, limb amputation, and new thrombotic events. Current alternatives to heparin are reviewed.

Psychophysiological stress responses in amputees with and without phantom limb pain

The present experiment tested the hypothesis that phantom limb pain amputees show a different pattern of psychophysiological reactivity to stress compared with painfree amputees. Six phantom limb pain (PLP) and five painfree upper-extremity amputees were administered two groups of tasks: stressful and relaxing. The measured dependent variables were skin temperature recorded at both stump and intact site, heart rate, blood pressure, subjective pain and stress ratings. Phantom limb pain patients were characterized by higher stump temperature compared with phantom limb painfree patients. This effect was observed during the whole recording. Consistently with the between-subjects effect, when PLP patients exhibited higher skin temperature (during relaxation, compared with during stressful tasks), they perceived more pain. The experiment showed higher cardiovascular reactivity in PLP patients, specifically to the stressful free-speech task, which focused on recollection of the amputation event. As compared with the painfree patients, during the personal stressor, PLP patients' heart rate and systolic blood pressure increased, indicating a greater sympathetic response. Results indicate that peripheral factors, such as stump temperature reliably differentiate PLP from painfree patients. Moreover, the clear cardiovascular hyperreactivity observed in PLP patients during their report of amputation suggests that PLP is associated with a long-term emotional memory for the painful experience of that event. These results are consistent with most reports in the literature relating phantom pain development to the experience of preamputation pain.