Alejandra C. Vivas

High mortality in patients with chronic wounds

To the Editor: Chronic wounds have become a major public health issue in the United States and abroad. Patients with chronic wounds are often elderly, have cardiovascular disease and other comorbid conditions, and are at additional risk for further complications. This results in additional health care expenditures; for example, the United States alone spends

Evidence-based management of common chronic lower extremity ulcers

25 billion annually related to chronic wounds and the demand for wound care is increasing. Specifically, diabetic foot ulcer complications have 5-year mortality rates similar to common types of cancer. A recent study from the Netherlands reported patients with diabetes mellitus who had foot ulcers to be at an increased risk for mortality compared with diabetics without foot ulceration (49% mortality over 10 years compared with 35.2% mortality—R 1.49). However, little is known about mortality for patients with other chronic wounds. We evaluated mortality in patients with chronic wounds to understand this better. We performed a retrospective cohort study of patients with chronic wounds treated in wound care centers and patients not treated in wound centers (matched by age, gender, and state of residence) using Centers for Medicare and Medicaid Services (CMS) data. Wound etiologies included venous leg ulcers, diabetic foot ulcers, and pressure ulcers. Using administrative data patients were followed for a 2-year period. We examined the incidence of wound-related deaths over a 2-year period. One thousand eight hundred fifteen patients with diabetic foot ulcers (DFU), pressure ulcers (PU) and venous leg ulcers (VLU) were included, 854 were treated at outpatient wound centers and 961 were treated in community practices. Fiftythree (52.6%) percent were men and the mean age of the group was 78 years old. Pressure ulcers accounted for 44% of the wounds and 84% were lower limb ulcers (Table 1). Comorbidities were common as two-thirds had cardiovascular disease, over half of patients had diabetes mellitus (DM), over 40% had peripheral arterial disease (PAD), one-quarter had either renal disease or neuropathy, and 4% had suffered a hip fracture. A higher frequency of comorbidities existed in patients treated in wound centers (Table 2). Of 1,815 patients, 28% (504 patients) died during the 2-year follow-up. Forty-six (2.5%) died in the hospital from a wound-related diagnosis (Table 3). No difference in death rate was noted in the different sites (Table 3), nor differences in the frequency of comorbidities or wound infection between deceased and surviving patients but differences existed in gangrene (RR51.93 95%, CI51.56–2.39); amputation (RR5 1.74 95%, CI51.35–2.25); and hospitalization for a woundrelated condition (RR51.95 95%, CI51.52–2.50) (Table 4). In summary we found that over one-quarter (28%) of wounded patients seen as outpatients died during a 2-year period. Drawn from both outpatient wound centers and community-based practices, they likely represent outpatients with wounds that are seen in the United States. As subjects of this study were outpatients and the majority of wounds were on the lower extremity, inpatients might have a different or even higher mortality with a greater percentage of sacral or ischial wounds. The population’s mean age was 75 years old and compared with similarly aged patients, death rates were much higher than the reported death rate for 75–79 year olds (4%), suggesting a higher risk of death in the wounded population. As expected patients studied had a high frequency of diseases that impede normal healing or may contribute to the

Epidermal Grafting Using a Novel Suction Blister–Harvesting System for the Treatment of Pyoderma Gangrenosum

Chronic lower extremity ulcers are a significant burden on patients and health care systems worldwide. Although relatively common, these wounds can be difficult to treat and present a challenge to physicians. Treatment has often been based on anecdotal accounts; however, there is a growing emphasis on using evidence‐based conclusions to guide clinical decisions. In this review article, the standard of care and adjuvant therapies of venous leg ulcers and diabetic foot ulcers are presented from an evidence‐based perspective.

Neuropathy and Ankle Mobility Abnormalities in Patients With Chronic Venous Disease

Patient 1 A woman in her 40s without other significant medical history presented in 2013with an 8-month history of an exquisitely painful ulcer on thedistal left lateral leg. Shenoted that the lesionbeganas “a small red bump” that she believedtobean insectbite.Aphysician at another institutionperformedan incision anddrainage to treat a suspected abscess andprescribedoral antibiotics, but the lesiondeteriorated. Abiopsyperformed in 2012hadnonspecific results and Gram, acid-fast, and Fite stains were negative for organisms. Venous and arterial insufficiencywere excludedby lower limb duplexultrasound.She receivedadiagnosisofpyodermagangrenosum(PG)andwasprescribedprednisone60mgdailyandtopical clobetasol propionate ointment, 0.05%, to the wound edges. On referral,physicalexaminationrevealedasharplydemarcatedulcerwith purple undermined borders, consistent with the PG diagnosis. The prednisonedosagewas taperedbecauseof adverse effects, and cyclosporine 400 mg daily and weekly leg compression were initiated. Although the inflamed undermined borders improved, the wound failed to reduce in size after 2months of therapy (Figure 1).

A prospective pilot study of ultrasound therapy effectiveness in refractory venous leg ulcers

IMPORTANCE How complications associated with chronic venous insufficiency (CVI) develop is not clear. The central source of the complications is likely a dysfunction of the calf muscle pump, which includes veins and their valves, the gastrocnemius and other lower leg and foot muscles as well as the nerves supplying the muscles, and ankle mobility limitations. The least well-studied source of complications is the relationship between range of ankle movement (ROAM), neuropathy, and the clinical severity of the disease. OBJECTIVE To study sensory neuropathic changes and ankle mobility in patients with CVI to help elucidate the pathophysiologic development of venous ulcers. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study took place from August 2011 to August 2012 at the outpatient wound clinic and the wound healing research clinic at the University of Miami Hospital. Sixty-four limbs from 42 individuals were evaluated and individually classified according to the clinical aspect of the clinical-etiology-anatomy-pathophysiology classification for CVI. MAIN OUTCOMES AND MEASURES Range of ankle movement was measured using goniometry, measuring active ankle combined plantarflexion and dorsiflexion and combined inversion and eversion. Peripheral neuropathy was measured subjectively through the Neuropathy Symptom Score and objectively through the Neuropathy Disability Score scales. RESULTS More patients with severe CVI had reduced plantarflexion-dorsiflexion ROAM compared with patients with mild CVI (25 [89%] vs 11 [31%]; P < .001) and reduced inversion-eversion ROAM (22 [79%] vs 4 [11%]; P < .001). Patients with worse CVI had significantly worse neuropathy with higher Neuropathy Symptom Score and Neuropathy Disability Score values compared with patients with less severe CVI. CONCLUSIONS AND RELEVANCE We found a relationship between reduced ROAM and worse neuropathy with increased severity of CVI. Management in patients with CVI should include testing for neuropathy and improving ankle mobility.

US-National Institutes of Health-funded research for cutaneous wounds in 2012.

Venous insufficiency is the most common cause of leg ulcers in the United States. Venous leg ulcers cost the health care system billions of dollars annually, and healing rates are less than 70% with standard of care; therefore, new therapies are needed to increase healing times and minimize associated costs. Non contact ultrasound therapy has been used to treat a variety of chronic wounds including venous leg ulcers, and it is thought that ultrasound has an effect on decreasing the bacterial count in wounds, although the exact mechanism of action of ultrasound is yet to be determined. We conducted an open labelled pilot study of 10 refractory venous ulcers of large size to determine the effect of non contact ultrasound on wound closure, bacterial counts, expression of inflammatory cytokines and pain reduction. We lacked a sham control group but we compared the baseline and end of treatment assessments and noted the differences. We found a significant reduction in wound area (P = 0·0039) over the 4‐week treatment period. We also found a decline in individual and total bacterial counts; however, these differences were not significant. For all patients, there was also a trend toward reduced inflammatory cytokine expression compared with baseline levels; however, this reduction did not reach statistical significance. Interestingly, there was a correlation between healing and change in cytokine expression, which showed statistically significance for tumour necrosis factor (TNF)‐αP = 0·0395, IL‐1a P = 0·0351, IL‐6 P = 0·0508, IL‐8 P = 0·0990. Pain as measured by the visual analogue scale (VAS) was reduced from 4 at the baseline to 2·7 by the end of the study. In conclusion, we found that patients treated with ultrasound therapy and compression therapy show clinical improvement over the course of 4 weeks and had a decrease in inflammatory cytokines, bacterial counts and pain.

The FDA and designing clinical trials for chronic cutaneous ulcers

Chronic cutaneous wounds are a major burden on patients, healthcare providers, and the US healthcare system. This study, carried out in part by the Wound Healing Societys Government Regulatory Committee, aimed to evaluate the current state of National Institutes of Health funding of cutaneous wound healing–related research projects. National Institutes of Health Research Portfolio Online Reporting Tools Expenditures & Results system was used to identify wound healing projects funded by the National Institutes of Health in the 2012 fiscal year. Research projects focusing on cutaneous wound prevention/education, mechanisms, complications, treatment, or imaging/monitoring were included in the analysis. Ninety‐one projects were identified, totaling a collective funding of

Topical and Biologic Therapies for Diabetic Foot Ulcers

29,798,991 and median funding of

Primary nonadherence (failure to obtain prescribed medicines) among dermatology patients

308,941. Thirteen institutes/centers from the National Institutes of Health were responsible for awarding funds; three of which (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases) accounted for 60.4% of the grant funding. The predominant funding mechanisms included R01 (48.3%), R43 (14.3%), and R21 (9.9%). New applications and pre‐existing applications accounted for 39.6 and 55.0% of the awarded grants, respectively. Grants awarded to investigators affiliated with universities accounted for 68.1% of grants and 25.3% were to investigators in the private sector. This analysis of current National Institutes of Health funding may facilitate more transparency of National Institutes of Health‐allocated research funds and serve as an impetus to procure additional support for the field of wound healing.

Quality assessment of tissue specimens for studies of diabetic foot ulcers

Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade. This is in part due to unsuccessful clinical trials and subsequent lack of Food and Drug Administration (FDA) approval. In this article, we discuss the FDA approval process, how it relates to chronic wound trials, common issues that arise, and how best to manage them. Additionally, problems encountered specific to diabetic foot ulcers (DFU) and venous leg ulcers (VLU) are addressed. Careful construction of a clinical trial is necessary in order to achieve the best possible efficacy outcomes and thereby, gain FDA approval. How to design an optimal trial is outlined.