Importance of factors determining the low health-related quality of life in people presenting with a diabetic foot ulcer: the Eurodiale study.

AIM: To identify the factors responsible for the low health-related quality of life associated with foot ulcers and the relative importance of these factors. METHODS: A total of 1232 patients with a new foot ulcer, who presented at one of the 14 centres in 10 European countries participating in the Eurodiale study, were included in this cross-sectional study. Patient and ulcer characteristics were obtained as well as results from the Euro-Qol-5D questionnaire, a health-related quality of life instrument with five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). To analyse the relative importance of comorbidities and ulcer- and patient-related factors for health-related quality of life, linear regression models were used to calculate the relative contributions of each factor to the fit (R(2) ) of the model. RESULTS: Patients reported poor overall health-related quality of life, with problems primarily in the mobility and pain/discomfort domains. Among the comorbidities, the inability to stand or walk without help was the most important determinant of decreased health-related quality of life in all five domains. Among ulcer-related factors, ulcer size, limb-threatening ischaemia and elevated C-reactive protein concentration also had high importance in all domains. The clinical diagnosis of infection, peripheral arterial disease and polyneuropathy were only important in the pain/discomfort domain. CONCLUSIONS: The factors that determine health-related quality of life are diverse and to an extent not disease-specific. To improve health-related quality of life, treatment should not only be focused on ulcer healing but a multifactorial approach by a specialized multidisciplinary team is also important.

Differences in minor amputation rate in diabetic foot disease throughout Europe are in part explained by differences in disease severity at presentation.

OBJECTIVES: The incidence of minor amputation may vary significantly, and determinants of minor amputation have not been studied systematically. We evaluated minor amputation rate, the determinants of minor amputation and differences in amputation rate between European centres. METHODS: In the Eurodiale study, a prospective cohort study of 1232 patients (1088 followed until end-point) with a new diabetic foot ulcer were followed on a monthly basis until healing, death, major amputation or up to a maximum of 1 year. Ulcers were treated according to international guidelines. Baseline characteristics independently associated with minor amputation were examined using multiple logistic regression modelling. Based on the results of the multivariable analysis, a disease severity score was calculated for each patient. RESULTS: One hundred and ninety-four (18%) patients underwent a minor amputation. Predictors of minor amputation were depth of the ulcer (odds ratio 6.08, confidence interval 4.10-9.03), peripheral arterial disease (odds ratio 1.84, confidence interval 1.30-2.60), infection (odds ratio 1.56, confidence interval 1.05-2.30) and male sex (odds ratio 1.42, confidence interval 0.99-2.04). Minor amputation rate varied between 2.4 and 34% in the centres. Minor amputation rate in centres correlated strongly with disease severity score at the moment of presentation to the foot clinic (r=0.75). CONCLUSIONS: Minor amputation is performed frequently in diabetic foot centres throughout Europe and is determined by depth of the ulcer, peripheral arterial disease, infection and male sex. There are important differences in amputation rate between the European centres, which can be explained in part by severity of disease at presentation. This may suggest that early referral to foot clinics can prevent minor amputations.

Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale Study.

AIMS/HYPOTHESIS: The aim of the present study was to investigate resource utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in resource utilisation between individuals with or without peripheral arterial disease (PAD) and/or infection. METHODS: Data on resource utilisation were collected prospectively in a European multicentre study. Data on 1,088 patients were available for the analysis of resource use, and data on 821 patients were included in the costing analysis. Costs were calculated for each patient by multiplying the country-specific direct and indirect unit costs by the number of resources used from inclusion into the study up to a defined endpoint. Country-specific costs were converted into purchasing power standards. RESULTS: Resource use and costs varied between outcome groups and between disease severity groups. The highest costs per patient were for hospitalisation, antibiotics, amputations and other surgery. All types of resource utilisation and costs increased with the severity of disease. The total cost per patient was more than four times higher for patients with infection and PAD at inclusion than for patients in the least severe group, who had neither. CONCLUSIONS/INTERPRETATION: Important differences in resource use and costs were found between different patient groups. The costs are highest for individuals with both peripheral arterial disease and infection, and these are mainly related to substantial costs for hospitalisation. In view of the magnitude of the costs associated with in-hospital stay, reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease.

Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study.

AIMS/HYPOTHESIS: Outcome data on individuals with diabetic foot ulcers are scarce, especially in those with peripheral arterial disease (PAD). We therefore examined the clinical characteristics that best predict poor outcome in a large population of diabetic foot ulcer patients and examined whether such predictors differ between patients with and without PAD. METHODS: Analyses were conducted within the EURODIALE Study, a prospective cohort study of 1,088 diabetic foot ulcer patients across 14 centres in Europe. Multiple logistic regression modelling was used to identify independent predictors of outcome (i.e. non-healing of the foot ulcer). RESULTS: After 1 year of follow-up, 23% of the patients had not healed. Independent baseline predictors of non-healing in the whole study population were older age, male sex, heart failure, the inability to stand or walk without help, end-stage renal disease, larger ulcer size, peripheral neuropathy and PAD. When analyses were performed according to PAD status, infection emerged as a specific predictor of non-healing in PAD patients only. CONCLUSIONS/INTERPRETATION: Predictors of healing differ between patients with and without PAD, suggesting that diabetic foot ulcers with or without concomitant PAD should be defined as two separate disease states. The observed negative impact of infection on healing that was confined to patients with PAD needs further investigation.

Cost-effectiveness of tacrolimus ointment vs. standard treatment in patients with moderate and severe atopic dermatitis: a health-economic model simulation based on a patient survey and clinical trial data.

BACKGROUND: Atopic dermatitis (AD) affects health and quality of life (QoL) and also has great impact on both healthcare costs and costs to society. OBJECTIVES: The aim of the study was to analyse the cost-effectiveness of treatment with tacrolimus ointment vs. standard treatment in patients with moderate to severe AD. METHODS: A Markov simulation model was constructed capturing several key features of AD and its treatment: disease severity, treatment alternatives, and QoL. The model was populated with data from three sources: (i) efficacy data from a randomized controlled trial including patients with moderate to severe AD treated with either tacrolimus ointment or standard treatment (corticosteroids), (ii) resource utilization and QoL data from a patient survey including 161 Swedish patients with AD, and (iii) official price lists. Costs were calculated according to disease severity for the two treatment alternatives using the perspective of the Swedish healthcare sector. Two analyses were performed, one based on the quantity of medication used in the trial and one based on the survey data. The relationship between effectiveness of tacrolimus ointment and the amount of medication used was tested in sensitivity analyses. RESULTS: In the model simulations patients with severe AD treated with tacrolimus ointment experienced on average 4.6 more AD-free weeks per year than patients given standard treatment. The corresponding figure for patients with moderate AD was 6.5 more AD-free weeks per year. The cost-effectiveness ratios [cost per Quality Adjusted Life Year (QALY) gained] for treatment with tacrolimus ointment vs. standard treatment were 2,334 British pound for moderate AD and 3,875 British pound for severe AD when treatment patterns from the survey were assumed, and 8,269 British pound for moderate AD and 12,304 British pound for severe AD when treatment patterns from the clinical trial were assumed. The results of sensitivity analyses were all well within limits to be considered cost-effective. CONCLUSIONS: Estimates of the incremental cost-effectiveness ratio are far below the currently discussed threshold in Sweden, corresponding to approximately 48,700 British pound per QALY gained, and equivalent thresholds in other countries. Treatment with tacrolimus ointment in patients with moderate and severe AD can therefore be considered cost-effective.

High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study.

AIMS/HYPOTHESIS: Large clinical studies describing the typical clinical presentation of diabetic foot ulcers are limited and most studies were performed in single centres with the possibility of selection of specific subgroups. The aim of this study was to investigate the characteristics of diabetic patients with a foot ulcer in 14 European hospitals in ten countries. METHODS: The study population included 1,229 consecutive patients presenting with a new foot ulcer between 1 September 2003 and 1 October 2004. Standardised data on patient characteristics, as well as foot and ulcer characteristics, were obtained. Foot disease was categorised into four stages according to the presence or absence of peripheral arterial disease (PAD) and infection: A: PAD -, infection -; B: PAD -, infection +; C: PAD +, infection -; D: PAD +, infection +. RESULTS: PAD was diagnosed in 49% of the subjects, infection in 58%. The majority of ulcers (52%) were located on the non-plantar surface of the foot. With regard to severity, 24% had stage A, 27% had stage B, 18% had stage C and 31% had stage D foot disease. Patients in the latter group had a distinct profile: they were older, had more non-plantar ulcers, greater tissue loss and more serious comorbidity. CONCLUSIONS/INTERPRETATION: According to our results in this European cohort, the severity of diabetic foot ulcers at presentation is greater than previously reported, as one-third had both PAD and infection. Non-plantar foot ulcers were more common than plantar ulcers, especially in patients with severe disease, and serious comorbidity increased significantly with increasing severity of foot disease. Further research is needed to obtain insight into the clinical outcome of these patients.

Accurate diagnosis and effective treatment of leg ulcers reduce prevalence, care time and costs.

OBJECTIVE: This long-term follow-up recorded the prevalence, aetiology and treatment of hard-to-heal leg and foot ulcers, and an estimated nurses' time spent providing care, for the years 1994-2005. METHOD: A questionnaire was sent to all district and community nurses in the county of Blekinge, Sweden, during one week in 1994, 1998, 2004 and 2005. Calculating the costs of hard-to-heal leg and foot ulcer care was not a primary aim, but the reduction in prevalence and time spent on wound management suggested it was important to illustrate the economic consequences of these changes over time. RESULTS: Estimated prevalence of hard-to-heal leg and foot ulcers reduced from 0.22% in 1994 to 0.15% in 2005. Treatment time decreased from 1.7 hours per patient per week in 1994 to 1.3 hours in 2005. Annual costs of leg and foot ulcer care reduced by SEK 6.96 million in the study area from 1994 to 2005. CONCLUSION: Improved wound management was demonstrated; leg and foot ulcer prevalence and treatment time were reduced. The results could be attributed to an increased interest in leg and foot ulcer care among staff, which was maintained by repeated questionnaires, continuous education, establishment of a wound healing centre in primary care and wound management recommendations from a multidisciplinary group. The improved ulcer care reduced considerably the annual costs of wound management in the area.

Prevention of diabetes-related foot ulcers and amputations: a cost-utility analysis based on Markov model simulations.

AIMS/HYPOTHESIS: We analysed the cost-effectiveness of intensified prevention in diabetic patients with different risks for foot ulcers and lower extremity amputations. Specifically, we examined whether the additional prevention costs associated with present recommendations would be offset by reduced costs of future foot ulcers and amputations. METHODS: Markov-based 5-year cost-utility simulations of current versus optimal prevention were done for hypothetical cohorts of diabetic patients older than 24 years. The model included eight possible health states for four risk groups. A population of 1677 diabetes patients provided data on present foot ulcer prevention and general mortality. Optimal prevention was defined according to the International Consensus on the Diabetic Foot. Model assumptions, transition probabilities and other data included in the model were based on published literature. The main outcome measures were cumulative incidences of foot ulcers, amputations and deaths, costs, cost-effectiveness, and quality-adjusted life years. RESULTS: An intensified prevention strategy including patient education, foot care and footwear is cost-effective if the risk for foot ulcers and lower extremity amputations can be reduced by 25 %. This is valid for all patients with diabetes except those with no specific risk factors. CONCLUSION/INTERPRETATION: Providing all diabetic patients at risk or high risk for foot ulcers and amputations with adequate prevention would be a cost-effective or even cost-saving strategy.

Health-related quality of life in patients with diabetes mellitus and foot ulcers.

To investigate health-related quality of life (HRQL) in diabetes patients separately for those with current foot ulcers, those with primary healed ulcers, and those who have undergone minor or major amputations. The EuroQol quality of life (QoL) questionnaire including a visual analogue scale (VAS) was sent to 457 patients treated for foot ulcers by a multidisciplinary team between 1995 and 1998. Patients who never had undergone any lower extremity amputation (LEA) were classified according to whether an ulcer was present at time of the survey or if they had healed primarily. Patients who had undergone any amputation were classified into a minor or a major amputation group according to their maximal amputation status. Patient characteristics and ulcer status at time of the survey were collected using patient records and pre-set forms used to follow-up of foot ulcer patients specifically. A response rate of 70% was obtained. Completion rates on single items were high. There were no differences in patient characteristics between respondents and non-respondents. Patients with current foot ulcers rated their HRQL significantly lower than patients who had healed primarily without amputation. Major amputation reduced the EuroQol index value, while the VAS value was reduced by other diabetic complications and increased by living with a healthy partner. Both values were reduced by a current foot ulcer. EuroQol can be used to investigate HRQL in diabetic patients with foot complications. Patients with current foot ulcers value their QoL lower than primary healed patients. QoL is reduced after major amputations.

Treatment of locally advanced pancreatic carcinoma in Sweden. A health economic comparison of palliative treatment with best supportive care versus palliative treatment with gemcitabine in combination with best supportive care.

OBJECTIVE: Patients with pancreatic cancer have only short survival after diagnosis, irrespective of treatment. The aim of this study was to perform a health economic evaluation of present standard treatment (in most cases, palliative treatment in combination with best supportive care) versus palliative treatment with gemcitabine in combination with best supportive care in patients with locally advanced pancreatic carcinoma. DESIGN: The use of resources and associated costs according to present treatment practice were estimated and calculated retrospectively. Costs were calculated from diagnosis until death. Actual costs and treatment effects for the patient population were compared with expected treatment costs for the same population if they additionally received gemcitabine. SETTING: This economic analysis is based on a hypothetical comparison and was performed from a societal point of view. PATIENTS AND PARTICIPANTS: The study population consisted of all patients diagnosed with pancreatic cancer during the year April 1994 to March 1995 and resident in Stockholm County, Sweden. After exclusions, 184 patients were included in the economic analysis. INTERVENTIONS: The effects of gemcitabine treatment on survival and disease-related symptoms were extrapolated from the results of a recent randomised clinical trial in North America. MAIN OUTCOME MEASURES AND RESULTS: The estimated additional costs for chemotherapy, treatment of adverse effects and in- and outpatient care associated with gemcitabine treatment were approximately 132,000 Swedish kronor (SEK) per life-year gained. This result is comparable with costs per life-year gained for other accepted treatments, for example those of home dialysis and kidney transplants for chronic renal failure. CONCLUSIONS: Treatment with gemcitabine in patients with pancreatic cancer may be a cost-effective alternative, but the results need to be confirmed in future randomised trials.

Cancer treatment in Sweden--costs of drugs, inpatient and outpatient care from 1985 to 1996 and cost effectiveness of new drugs.

This study was carried out to investigate the direct costs for treatment of patients with cancer from 1985 to 1996 in Sweden, and to examine health economic effects of changes in treatment pattern. Material for the study was collected from official statistics and from published health economic evaluations of cancer treatment. Costs for inpatient care decreased during the period, while costs for outpatient care and drugs increased. In total, the direct health care costs for cancer treatment decreased from 1985 to 1996. New drugs registered on the market are often more expensive than the drugs they replace. From a health economic perspective it is not clear, however, that higher drug costs necessarily increase total costs. Further health economic research is needed because many treatment alternatives have not yet been evaluated, and furthermore, because a treatment option can be cost effective in one specific indication but not in another.

Cost-effective management of diabetic foot ulcers. A review.

Foot lesions are common and serious complications in patients with diabetes mellitus. In recent years, several authors have, in addition to the medical aspects, focused on the high costs for treatment of this complication. However, few studies have performed a complete health-economic comparison and analysis of different treatments. This is probably related to the complexity of the problem and ethical difficulties in performing randomised clinical trials on these patients. Despite the lack of comparative health-economic studies, most authors conclude that amputations should be avoided if there is any possibility of saving the limb. This is not only because of the economic consequences-high costs for repeated hospitalisations, rehabilitation, home care and social-service support-associated with amputations, but also the quality-of-life aspects. Alternative treatment options might seem costly in the short term, but most cost-effectiveness analyses that also consider the long term perspective have concluded that treatment alternatives in which the limb is saved are more cost effective. Methodological aspects, such as the perspective of a study, may cause difficulties in comparing results between countries and settings. By using the societal perspective in economic studies, incentives to push costs from one sector to another might be avoided.

Cavity foot ulcers in diabetic patients: a comparative study of cadexomer iodine ointment and standard treatment. An economic analysis alongside a clinical trial.

Diabetic foot ulcers with exposure of tendon, muscle, or bone imply a high probability for deep infections and amputations. Delayed healing times are often described. The aim of this study was to compare the clinical effect and economic cost of cadexomer iodine with standard treatment in diabetic feet with cavity ulcers. Patients with deep, exudative foot ulcers were included in a 12-week open, randomised, comparative study. When ulcers stopped exudating, vaseline gauze was used in both groups until the end of the study. Costs were estimated for dressing material, staff and transportation. Clinically relevant improvement was seen in 12 patients treated with cadexomer iodine and in 13 patients treated with standard treatment. The average weekly cost was SEK 903 and SEK 1,421, respectively, of which the major part was costs for staff and transportation related to frequency of dressing changes. Treatment with cadexomer iodine ointment (Iodosorb) showed no clinical difference compared to topical treatment consisting of gentamicin solution, streptodornase/streptokinase, or dry saline gauze but was associated with considerably lower weekly treatment costs.

Long-term costs for foot ulcers in diabetic patients in a multidisciplinary setting.

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 3 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, costs related to recurrence of ulcer, and costs for prevention of new ulcers. Expected total present value cost per patient during 3 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 the need for increased home care and social service, but also due to costs for recurrent ulcers and new amputations.

Topical treatment of diabetic foot ulcers: an economic analysis of treatment alternatives and strategies.

In a prospective study, 314 patients with diabetic foot ulcers were followed and 40 patients died before healing occurred. In those patients who healed, a retrospective economic analysis of the costs for topical treatment was performed. The aim of the study was to analyse the costs and discuss how different treatment strategies influence total costs. Data collected for each patient were total time to healing, treatment time for each type of dressing, and the frequency of dressing changes. Material costs for the dressings, labour, and travelling costs were calculated separately. A formula for simulation of economic consequences of different treatment strategies including the introduction of new strategies was designed. The cost for topical treatment was strongly related to the severity of the ulcer and wound healing time. The average weekly cost per patient for topical treatment varied between 40.3 pounds and 385 pounds. The dominating costs for topical treatment were expenses for staff and transportation. The most important factor to reduce costs is the frequency of dressing changes. The study emphasizes the need for prospective comparative studies of cost effectiveness in topical treatment strategies.

Diabetic foot ulcers in a multidisciplinary setting. An economic analysis of primary healing and healing with amputation.

OBJECTIVES: To perform an economic analysis of primary healing and healing with amputation in diabetic patients with foot ulcers. DESIGN: A retrospective economic analysis based on a prospective study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer. SETTING: A multidisciplinary foot-care team. SUBJECTS: A total of 314 consecutively presenting diabetic patients with foot ulcers. Forty patients died before healing occurred. In those patients who healed primarily (n = 197) or after amputation (n = 77), a retrospective economic analysis was performed. INTERVENTIONS: All patients were treated by a multidisciplinary foot care team consisting of diabetologist, orthopaedic surgeon, diabetes nurse, podiatrist and orthotist both as in- and out-patients. The patients were followed by the team from admittance until final outcome, i.e. primary healing or healing with amputation or death. MAIN OUTCOME MEASURES: Data from both the prospectively collected patient material and from patient records were used to estimate the cost for hospital care, antibiotics, surgery, out-patient care, staff attendance, drugs and material for ulcer dressings, and orthopaedic appliances. RESULTS: The total costs were SEK 51,000 (3000-808,000) for patients with primary healing and SEK 344,000 (27,000-992,000) for healing with amputation. Costs for in-patient care were 37% of total average costs for primary healing and 82% for patients with amputation. The costs for topical treatment of the ulcers in out-patient care were 45% of the total average cost for primary healed and 13% for patients who healed with amputation. The costs for products used for ulcer dressings were 21% of total costs for topical treatment, i.e. 9% and 3% of total average costs for primary healing and healing with amputation, respectively. Costs for visits to the foot care team, antibiotics and orthopaedic appliances were low in relation to total costs. CONCLUSION: Treatment of diabetic patients with foot ulcers in a multidisciplinary system was associated with relatively low costs. Healing with amputation was associated with high costs mainly due to multiple and extended hospitalization. These findings indicate the potential cost savings of preventive and multidisciplinary foot care.

Self-treatment with desmopressin intranasal spray in patients with bleeding disorders: effect on bleeding symptoms and socioeconomic factors.

Desmopressin (1-desamino-8-D-arginine vasopressin), an established hemostatic agent for the treatment of bleeding in mild hemophilia A, von Willebrand's disease, or platelet disorders, has mostly been given parenterally as intravenous or subcutaneous injections. Intranasal administration by spray has been shown to yield significant and highly reproducible increases in the plasma concentrations of factor VIII and von Willebrand factor and platelet adhesiveness, and to be suitable for self-administration at home, as it is easy to handle and does not involve the use of needles. This paper presents data from a questionnaire answered by 78 patients with mild hemophilia A, von Willebrand's disease, or platelet disorders, who had used the spray at home to treat bleeding symptoms. The patients experienced decreased blood loss and shortened duration of epistaxis, menorrhagia, tissue bleeding, and bleeding in connection with minor surgery or tooth extraction. The use of factor VIII concentrates was diminished, as were the number of visits to outpatient care and absence from school or work.