The Cost-effectiveness of Treating Diabetic Lower Extremity Ulcers with Becaplermin (Regranex): A Core Model with an Application Using Swedish Cost Data

AbstractObjectivesThe objective of this study was to develop a model capable of assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower extremity ulcers with becaplermin gel (Regranex) plus good wound care (GWC) relative to treating them with GWC alone.MethodsA Markov simulation model was developed that includes six health states: Uninfected Ulcer, Infected Ulcer, Gangrene, Healed Ulcer, Healed Ulcer-History of Amputation, and Deceased. To predict clinical outcomes, information was taken from a specially designed prospective 9-month follow-up study of 183 neuropathic patients in the US treated with GWC. Cost of treatment data were taken primarily from a study of a cohort of 314 patients in Sweden. The efficacy of becaplermin was assumed equal to that achieved in a pooled analysis of four randomized clinical trials. A model application provides expected clinical outcomes for a cohort of patients. Annual treatment costs per patient were estimated using treatment practice and unit prices from Sweden.ResultsDue to a higher rate of healing and a shorter average healing time, treatment with becaplermin gel was predicted to increase the average number of months spent in the healed state over the first year following development of an ulcer by 24% relative to GWC alone. In addition, the corresponding number of amputations was 9% lower for the becaplermin-treated cohort. The average expected cost of $12,078 US for an individual treated with GWC alone declines to$11,708 US for one treated with becaplermin, in spite of $1262 becaplermin costs. Expenses related to topical treatment and inpatient care account for 83% of the resources conserved.ConclusionOur results suggest that in Sweden treatment with becaplermin in conjunction with GWC consumes fewer resources and generates better outcomes than treatment with GWC alone for diabetic neuropathic ulcers. In light of the high and increasing incidence of such ulcers, the potential savings in costs and suffering may be important. Results are difficult to extrapolate internationally because they are strongly related to country-specific treatment practices and price levels

Increased Urine IgM and IgG2 Levels, Indicating Decreased Glomerular Size Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2 Diabetes

Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were randomised to treatment with 5000 IU of dalteparin, (n = 28), or physiological saline, (n = 26), once daily until ulcer healing or for a maximum of 6 months. Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary levels of IgM and IgG2 were elevated in 47 and 50 patients, respectively. Elevated urinary levels of IgM and IgG2 indicate decreased glomerular size selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1 levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P < 0.001) and serum IGFBP-1 (P < 0.05) while no significant effects were seen in any of the other studied parameters. In conclusion, dalteparin therapy in patients with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG2 despite significantly increased glycosaminoglycans in urine. Elevated urinary levels of IgM and IgG2 might be more sensitive markers of renal disease than albuminuria in patients with type 2 diabetes and antihypertensive therapy

Standards for the development and methodology of the 2019 International Working Group on the Diabetic Foot guidelines

Diabetic foot disease is a source of major patient suffering and societal costs. Investing in evidence-based international guidelines on diabetic foot disease is likely among the most cost-effective forms of health care expenditure, provided the guidelines are outcome focused, evidence based, and properly implemented. The International Working Group on the Diabetic Foot (IWGDF) has published and updated international guidelines since 1999. The 2019 updates are based on formulating relevant clinical questions and outcomes, rigorous systematic reviews of the literature, and recommendations that are specific, and unambiguous along with their transparent rationale, all using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework. We herein describe the development of the 2019 IWGDF guidelines on the prevention and management of diabetic foot disease, which consists of six chapters, each prepared by a separate working group of international experts. These documents provide guidelines related to diabetic foot disease on prevention; offloading; peripheral artery disease; infection; wound healing interventions; and classification of diabetic foot ulcers. Based on these six chapters, the IWGDF Editorial Board also produced a set of practical guidelines. Each guideline underwent extensive review by the members of the IWGDF Editorial Board as well as independent international experts in each field. We believe that adoption and implementation of the 2019 IWGDF guidelines by health care providers, public health agencies, and policymakers will result in improved prevention and management of diabetic foot disease and a subsequent worldwide reduction in the patient and societal burden this disease causes

Effectiveness of revascularisation of the ulcerated foot in patients with diabetes and peripheral artery disease: A systematic review

In patients with diabetes, foot ulceration and peripheral artery disease (PAD), it is often difficult to determine whether, when and how to revascularise the affected lower extremity. The presence of PAD is a major risk factor for non-healing and yet clinical outcomes of revascularisation are not necessarily related to technical success. The International Working Group of the Diabetic Foot updated systematic review on the effectiveness of revascularisation of the ulcerated foot in patients with diabetes and PAD is comprised of 64 studies describing >13000 patients. Amongst 60 case series and 4 non-randomised controlled studies, we summarised clinically relevant outcomes and found them to be broadly similar between patients treated with open vs endovascular therapy. Following endovascular revascularisation, the 1 year and 2 year limb salvage rates were 80% (IQR 78-82%) and 78% (IQR 75-83%), whereas open therapy was associated with rates of 85% (IQR 80-90%) at 1 year and 87% (IQR 85-88%) at 2years, however these results were based on a varying combination of studies and cannot therefore be interpreted as cumulative. Overall, wound healing was achieved in a median of 60% of patients (IQR 50-69%) at 1 year in those treated by endovascular or surgical therapy, and the major amputation rate of endovascular vs open therapy was 2% vs 5% at 30days, 10% vs 9% at 1 year and 13% vs 9% at 2years. For both strategies, overall mortality was found to be high, with 2% (1-6%) perioperative (or 30day) mortality, rising sharply to 13% (9-23%) at 1 year, 29% (19-48%) at 2years and 47% (39-71%) at 5years. Both the angiosome concept (revascularisation directly to the area of tissue loss via its main feeding artery) or indirect revascularisation through collaterals, appear to be equally effective strategies for restoring perfusion. Overall, the available data do not allow us to recommend one method of revascularisation over the other and more studies are required to determine the best revascularisation approach in diabetic foot ulceration.Peer reviewe

Diagnostics and treatment of the diabetic foot.

Every 30 s, a lower limb is amputated due to diabetes. Of all amputations in diabetic patients 85% are preceded by a foot ulcer which subsequently deteriorates to a severe infection or gangrene. There is a complexity of factors related to healing of foot ulcers including strategies for treatment of decreased perfusion, oedema, pain, infection, metabolic disturbances, malnutrition, non-weight bearing, wound treatment, foot surgery, and management of intercurrent disease. Patients with diabetic foot ulcer and decreased perfusion do often not have rest pain or claudication and as a consequence non-invasive vascular testing is recommended for early recognition of ulcers in need of revascularisation to achieve healing. A diabetic foot infection is a potentially limb-threatening condition. Infection is diagnosed by the presence or increased rate of signs inflammation. Often these signs are less marked than expected. Imaging studies can diagnose or better define deep, soft tissue purulent collections and are frequently needed to detect pathological findings in bone. The initial antimicrobial treatment as well as duration of treatment is empiric. There is a substantial delay in wound healing in diabetic foot ulcer which has been related to various abnormalities. Several new treatments related to these abnormalities have been explored in wound healing with various successes. An essential part of the strategy to achieve healing is an effective offloading. Many interventions with advanced wound management have failed due to not recognizing the need for effective offloading. A multidisciplinary approach to wounds and foot ulcer has been successfully implemented in different centres with a substantial decrease in amputation rate

The Diabetic Foot Syndrome Today : A Pandemic Uprise

Diabetes mellitus is growing at epidemic proportions worldwide; currently 415 million adults are estimated to have diabetes and by 2040, this number is estimated to increase to 642 million. As a consequence, the prevalence of diabetes-related complications is bound to increase. Diabetic foot disorders are common throughout the world, resulting in major medical, social and economic consequences for the patients, and a public health problem. The risk for ulceration and amputation is much higher in individuals with diabetes compared to that of the non-diabetic population: it is estimated that every 20 s an amputation is performed on an individual with diabetes somewhere in the world. Foot ulceration is the commonest major end point among diabetic complications. More than 5% of diabetic patients have a history of foot ulceration and the cumulative lifetime incidence may be as high as 25%. Incidence and prevalence figures related to both foot ulcerations and lower extremity amputations have been reported worldwide. There is a substantial global variation in the incidence and prevalence of amputation and diabetic foot ulcer (DFU). The variation may be partially explained by differences in the measurement of amputation and DFU, as well as the ascertainment of diabetes, demographic factors, setting or other confounders. There is an urgent need to determine a standardized way to report the incidence and prevalence of diabetes-related amputation and foot ulcer in order to be able to be used as a marker of quality of care

Ren- och viltåtgärder E10 sträckan V Svartbyn–Stenbron : Fördjupad utredning avseende behov av stängsel och faunapassager

Målet med den här studien är att identifiera åtgärder som leder till en ökad trafiksäkerhet och minskning av antalet ren- och viltolyckor längs väg E10 mellan Västra Svartbyn och Stenbron i Norrbotten. Aktuella åtgärdsförslag har tagits fram i dialogmöten tillsammans med berörda samebyar. Även jakt- och viltvårdsintressenter har bidragit med information till studien