Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow-up.

Background Atopic dermatitis (AD) is a common skin disease that is characterized by recurrent episodes of itching. Filaggrin loss-of-function mutations (FLG null) have been associated with an increased risk of developing AD. Objective To evaluate the effect of individual FLG null mutations on the persistence of AD over time. Methods We evaluated a multiyear prospective cohort study of children with AD with respect to FLG null mutations (R501X, 2282del4, R2447X, and S3247X). We evaluated the association of these mutations with the persistence of AD symptoms over time, with respect to reports of no symptoms of AD and whether topical medication was needed for symptom resolution. Results 857 subjects were followed for 3,684 person-years. One or more FLG null mutations were noted in 16.3% of subjects and specifically in 27.5% of whites and 5.8% of African-Americans. Individuals with a FLG null mutation were less likely [OR: 0.54 (95% CI: 0.41, 0.71)] to report that their skin was symptom-free at any time as compared to those without a FLG null mutation. The effect of these mutations was similar in whites [0.42 (0.31, 0.57) and African-Americans 0.53 (0.25, 1.12) (p=0.62)]. Children with the R501X mutation [0.44 (0.22, 0.88)] were the least responsive to therapy. Conclusions In a US cohort with AD, FLG null mutations were common. Children with FLG null mutations were more likely to have persistent AD. Although, these mutations were more common in those of European ancestry, their effect on persistence was similar in those of African ancestry. Response to therapy was not uniform among children with FLG null mutations.

OBJECTIVE -The goal of this study was to evaluate whether simple risk factors can be identified that successfully characterize who will heal and who will not heal among patients who have received standard therapy for diabetic neuropathic foot ulcers.RESEARCH DESIGN AND METHODS -For this cohort study, we evaluated Ͼ31,000 individuals with a diabetic neuropathic foot ulcer seen in the Curative Health Services System. Using multivariate logistic regression, we evaluated the association between wound size, wound duration, wound grade, and other variables and their effect on whether a patient would heal by the 20th week of care.RESULTS -We demonstrated that wound size, wound duration, and wound grade are all significantly associated with the likelihood of a wound healing by the 20th week of care. In addition, we noted that these associations were not significantly affected by the treating wound care center, whether the unit of analysis was one wound on a patient or all of their wounds, or current adjuvant therapies.CONCLUSIONS -We have shown that three easy-to-measure risk factors are associated with a wound healing. These results should help clinicians understand the likelihood that a wound will heal and help those conducting clinical investigations to design better trials. Diabetes Care 25:1835-1839, 2002L ower-extremity ulcers are a serious complication of diabetes. More than 16 million people in the U.S. have diabetes, and 15% of them can expect to develop a foot ulcer at some point in their lives (1-3). Diabetic patients admitted to the hospital with lower-extremity ulcers were hospitalized longer on average than those who were hospitalized and did not have ulcers (1,3). Whereas only 4% of the population has diabetes, 46% of those admitted to a hospital with a foot ulcer had diabetes, and half of all lower-extremity amputations in hospitalized patients occurred in diabetic patients (1,3). Those with a lower-extremity amputation have a diminished quality of life and increased health costs, often have many concomitant medical ailments, are more likely to have the contralateral limb amputated, and are more likely to die within the next 5 years than those with no amputation (4,5).There are many pathways for the development of a diabetic foot ulcer. In general, they include a combination of lowerlimb arterial insufficiency, lower-limb diabetic neuropathy, and local trauma (6). About 20% of diabetic patients with foot ulcers will primarily have inadequate arterial blood flow, ϳ50% will primarily have diabetic neuropathy, and ϳ30% will be afflicted with both conditions (1,6). Inadequate arterial blood flow is usually treated by a variety of surgical techniques that improve blood flow (7). For this study, foot ulcers on individuals with diabetes who lack protective sensation and have adequate arterial blood flow to their foot are termed diabetic neuropathic foot ulcers (DNFUs) (8 -10).The treatment of a DNFU usually consists of debridement of necrotic tissue, use of a moist wound dressing, and the use of a device that p...

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.

Importance Atopic dermatitis (AD) is a common illness of childhood Objective The goal of this study was to evaluate the natural history of AD and determine the persistence of symptoms over time. Design A cross-sectional and cohort study. Setting A nation-wide long-term registry of children with AD. Participants Children enrolled in the Pediatric Eczema Elective Registry (PEER). Main outcome Self-reported outcome of whether or not a child’s skin was AD symptom-free for 6 months at 6 month intervals. Results 7,157 subjects were enrolled in the PEER study for a total of 22, 550 person-years. At least 2 years of follow-up was observed for 4,248 and at least 5 years of follow-up was observed for 2,416 children. Multiple demographic and exposure variables were associated with more persistent AD. At every age (i.e. 2 to 26 years), more than 80% of PEER subjects had symptoms of AD and/or were using medication to treat their AD. It was not until age 20 years that 50% of subjects had at least one lifetime six-month symptom and treatment free period. Conclusions and Relevance Based on this large longitudinal cohort study, symptoms associated with AD appear to persist well into the second decade of a child’s life and likely longer. AD is likely a life-long illness.

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OBJECTIVELower-extremity amputation (LEA) is common among persons with diabetes. The goal of this study was to identify geographic variation and the influence of location on the incidence of LEA among U.S. Medicare beneficiaries with diabetes.RESEARCH DESIGN AND METHODSWe conducted a cohort study of beneficiaries of Medicare. The geographic unit of analysis was hospital referral regions (HRRs). Tests of spatial autocorrelation and geographically weighted regression were used to evaluate the incidence of LEA by HRRs as a function of geographic location in the U.S. Evaluated covariates covered sociodemographic factors, risk factors for LEA, diabetes severity, provider access, and cost of care.RESULTSAmong persons with diabetes, the annual incidence per 1,000 of LEA was 5.0 in 2006, 4.6 in 2007, and 4.5 in 2008 and varied by the HRR. The incidence of LEA was highly concentrated in neighboring HRRs. High rates of LEA clustered in contiguous portions of Texas, Oklahoma, Louisiana, Arkansas, and Mississippi. Accounting for geographic location greatly improved our ability to understand the variability in LEA. Additionally, covariates associated with LEA per HRR included socioeconomic status, prevalence of African Americans, age, diabetes, and mortality rate associated with having a foot ulcer.CONCLUSIONSThere is profound “region-correlated” variation in the rate of LEA among Medicare beneficiaries with diabetes. In other words, location matters and whereas the likelihood of an amputation varies dramatically across the U.S. overall, neighboring locations have unexpectedly similar amputation rates, some being uniformly high and others uniformly low.

OBJECTIVE -The goal of this study was to determine whether surrogate markers based primarily on changes in the size of a wound can be used to correctly predict which individuals with diabetic neuropathic foot ulcers will heal after 12 or 20 weeks of care. RESEARCH DESIGN AND METHODS-This is a retrospective cohort study using the Curative Health Services database. As many as 39,918 neuropathic wounds on 20,213 individuals with diabetes were evaluated. Seven surrogates based on changes in wound size were evaluated.RESULTS -Surrogates measured after 2, 4, or 8 weeks of care and based on percentage change in area, log healing rate, and log area ratio discriminated well with respect to differentiating between those wounds that healed and those that did not heal by the 12th or 20th week of care. For example, after 4 weeks of care, the percentage change in area can be used to correctly discriminate 76% of the time between those that healed and those that did not by the 20th week of care.CONCLUSIONS -The surrogate markers can be used in clinical trials such that shorter and smaller trials can be conducted with reasonable accuracy in order to determine which potential new therapeutics should be studied in larger, longer trials. In addition, the surrogates may also benefit clinicians when they are trying to decide whether a wound care therapy will ultimately be successful. Diabetes Care 26:1696 -1700, 2003C linical trials of therapies for individual patients with diabetic neuropathic foot ulcers are limited by the prolonged time period needed to reach the ultimate outcome, a healed wound. In fact, randomized clinical trials usually follow subjects for between 12 and 20 weeks. As a result, the trials are very expensive and patients may be exposed to potentially nonefficacious experimental agents for prolonged periods of time. A valid surrogate marker of complete wound healing would minimize the number of subjects exposed to a potentially unsuccessful treatment and minimize the time required to develop a successful new treatment, thereby improving the efficiency with respect to cost and design needed to successfully screen potential therapeutic agents. Finally, a valid surrogate marker allows for the identification of patients who are not likely to heal by standard methods early in the patient's course of treatment, thereby expediting referral to specialty centers or expediting initiation of stepped treatment algorithms.More than 10 years ago, the rate of healing for patients with diabetic foot ulcers was shown by Pecoraro et al.(1) to statistically differentiate between those patients who eventually healed and those who did not. Studies have also shown that for other chronic wounds, the percent change in the wound area over the initial 4 weeks of therapy, as well as the rate of healing over the initial 4 weeks of therapy, may predict who will ultimately heal (2-8). However, most of these studies were small and did not evaluate diabetic foot ulcers. Surrogate markers require extensive epidemiologic testing to ensure validit...