I fear COVID but diabetic foot (DF) is worse: a survey on patients' perception of a telemedicine service for DF during lockdown.

AIMS: To evaluate the patients' perceptions of telemedicine visits during COVID-19 lockdown and their level of anxiety about COVID and diabetic foot (DF). METHODS: In May 2020, we contacted by phone all the patients who underwent in March and April to remote monitoring visits for DF during the lockdown for COVID-19, with a structured interview, focusing on their perceptions about telemedicine service for DF and on the anxiety toward COVID and DF. RESULTS: We analyzed 257 remote monitoring visits in 211 patients. Two hundred and six patients answered the follow-up interview; 177 patients (85.9%) remembered the monitoring visit, 140 (67.9%) the health care professional and 181 patients (87.9%) the reason of contact; 169 patients were alone during the visit, 37 with a relative. Patients judged useful both the monitoring during pandemic (4.35 ± 0.28 on a maximum of five) and the possibility to continue after the lockdown (4.34 ± 0.23 on a maximum of five). Eventually, we observed that DF patients were more worried by DF than by COVID on a scale from 0 (not fear at all) to 5 (terrified) (4.79 ± 0.05 vs. 3.27 ± 1.03, p < 0.05). This difference was higher in previously ulcerated patients (4.84 ± 0.03 vs. 3.03 ± 1.13, p < 0.05) and even more in amputees (4.93 ± 0.03 vs. 2.73 ± 1.21, p < 0.05). CONCLUSIONS: DF patients appreciated televisits during lockdown and the continuation of this service after its end. In this context DF prevails on COVID in the worries of patients, especially if they are recurrent ones.

Minor amputation does not negatively affect health-related quality of life as compared with conservative treatment in patients with a diabetic foot ulcer: An observational study.

BACKGROUND: Health-related quality of life (HRQoL) is poor in patients with persistent diabetic foot ulcers and poor HRQoL predicts worse outcomes in these patients. Amputation is often considered a treatment failure, which is why conservative treatment is generally preferred over amputation. However, it is unclear whether minor amputation negatively affects HRQoL compared with conservative treatment in patients with diabetic foot ulcers. METHODS: In the cohort of the multicenter, prospective, observational Eurodiale study, we determined difference in change of HRQoL measured by EQ-5D between patients with a diabetic foot ulcers that healed after conservative treatment (n = 676) and after minor amputation (n = 145). Propensity score was used to adjust for known confounders, attempting to overcome lack of randomization. RESULTS: Baseline HRQoL was not significantly different between patients treated conservatively and undergoing minor amputation. In addition, there was no difference in the change of HRQoL between these groups. In patients who healed 6 to 12 months after the first visit, HRQoL on the anxiety/depression subscale even appeared to improve more in those who underwent minor amputation. CONCLUSIONS: Minor amputation was not associated with a negative impact on HRQoL in patients with a diabetic foot ulcers. It may therefore not be considered treatment failure in terms of HRQoL but rather a viable treatment option. A randomized controlled trial is warranted to further examine the influence of minor amputations on health-related quality of life.

Safety and effectiveness of therapeutic magnetic resonance in diabetic foot ulcers: a prospective randomised controlled trial.

OBJECTIVE: To test the efficacy and safety of therapeutic magnetic resonance (TMR) in the management of diabetic foot ulcers (DFU), the authors designed a prospective randomised controlled trial in three highly specialised diabetic foot clinics. METHOD: All the patients consecutively visited in a period of 18 months were screened according to the inclusion (presence of an ulcer >1 cm2 in the foot lasting at least 6 weeks; ABPI>0.6; consent to participate in the study) and exclusion (Charcot's foot; local or systemic infections; chronic renal failure; any wearable electrically-driven life-supporting device) criteria. Patients, who were treated according to international guideline protocols, were randomised into two groups: group A received for four weeks the sham application of TMR, while group B received the active TMR for the same period. People were followed-up to 10 weeks and healing rate (HR), healing time (HT), rate of granulation tissue on wound bed (% GT), reduction of the area of the lesion (∆AL) and a score (0-3) evaluating erythema, oedema, pain and tenderness, respectively, were measured. Adverse events (AE) were registered and monitored throughout the study. RESULTS: No differences were observed in HR, HT and ∆AL between the two groups during follow-up, while % GT and the scores for erythema, oedema and pain at 10 weeks showed significant (p<0.05) improvements in group B compared with group A and versus baseline. When restricted to non-ischaemic patients (ABPI>0.8), ∆AL was significantly (p<0.05) more pronounced in group B than in group A. No difference in AE occurrence was observed between the two groups. CONCLUSION: Our study, despite not being able to demonstrate the effectiveness of TMR on healing rate at 10 weeks, with 4 weeks of active treatment in neuro-ischaemic DFUs, shows positive effects on clinical aspects of the DFU and is associated with a significant increase of GT in the wound bed. DECLARATION OF INTEREST: The study has been fully sponsored by Thereson S.p.A., manufacturer of TMR devices.

KPC-producing Klebsiella pneumoniae rectal colonization is a risk factor for mortality in patients with diabetic foot infections.

To evaluate the relationship between carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) gut colonization and mortality in diabetic patients with a foot infection (DFI) we performed a single-centre, retrospective, matched case-control study. In the study period, we identified 21 patients with DFI who had KPC-Kp gut colonization and 21 controls. The 90-day mortality rate was significantly higher in patients with colonized guts (47%) than the controls (4%) (p 0.013). A multivariate analysis demonstrated that gut colonization with KPC-Kp was the only independent predictor of mortality: odds ratio 13.33, 95% CI 1.90-272.80, p 0.024. In patients with DFI, KPC-Kp gut colonization appears to be an important risk factor for mortality.

An updated overview and clarification of the principle role of debridement.

Routine care of non-healing acute and chronic wounds often comprises either cleaning or debridement. Consequently, debridement is a basic necessity to induce the functional process of tissue repair, which makes it a central medical intervention in the management of acute and chronic, non-healing wounds.

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.

Iloprost in the management of peripheral arterial disease in patients with diabetes mellitus.

Diabetic complications in the lower extremities, especially those secondary to diabetic macroangiopathy, have increasingly become a clinical emergency, given the high prevalence and progression of the disease. Until recently, the only approach to treating advanced stage disease was medical therapy and major amputation; however, the advent of revascularization procedures has radically improved the prognosis of patients with critical lower limb ischemia. In this setting, iloprost holds a dual position: as first-choice therapy in patients ineligible for revascularization and as complementary therapy in candidates for surgical or endovascular revascularization.

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.

A randomized controlled trial to examine the efficacy and safety of a new super-oxidized solution for the management of wide postsurgical lesions of the diabetic foot.

This randomized trial was done to test the effectiveness and safety of using a novel antiseptic solution (Dermacyn(R) Wound Care [DWC], Oculus Innovative Sciences, Petaluma, CA) in the management of the postoperative lesions on the infected diabetic foot. 40 patients with postsurgical lesions wider than 5 cm2 left open to heal by secondary intention were randomized into 2 groups. Group A was locally treated with DWC, whereas group B received povidone iodine as local medication, both in adjunct to systemic antibiotic therapy and surgical debridement if needed. Ischemia, renal failure, bilateral lesions, or immunodepression were considered as exclusion criteria. Patients were followed up weekly for 6 months. The primary endpoint was healing rate at 6 months, while secondary endpoints were healing time, time to achieve negative cultures, duration of antibiotic therapy, number of reinterventions, and adverse events. Healing rates at 6 months were significantly shorter in group A (90%) than in group B (55%; P < .01). The time taken for cultures to become negative and duration of antibiotic therapy were also significantly (P < .05) shorter in group A than in group B, whereas the number of reinterventions was significantly higher in group B (P < .05). No difference was noted in the adverse events except that for reinfections, which were more frequent in group B than in group A (P < .01). DWC is as safe as and more effective than standard local antiseptics in the management of wide postsurgical lesions in the infected diabetic foot.

Effectiveness and safety of a novel gel dressing in the management of neuropathic leg ulcers in diabetic patients: a prospective double-blind randomized trial.

Neuropathic leg ulcers (NLUs) affect more than 10% of diabetic patients with peripheral neuropathy and represent the most common cause of ulceration of the leg in these patients. Though their pathogenesis is well known, related to the chronic neuropathic edema, the management of NLUs, mainly based on elastocompression, is still controversial, with lower healing rates than nondiabetic venous leg ulcers. The authors tested if a novel gel formulation, containing amino acids and hyaluronic acid (Vulnamin)gel; Errekappa, Milan, Italy), will improve the outcomes of NLUs when used together with elastocompression. Thirty patients affected by NLU were randomized into 2 groups, both treated with 4-layer elastocompressive bandaging: patients in group A were topically treated with the application of Vulnamin) gel, whereas patients in group B received only the inert gel vehicle. The healing rate at 3 months was evaluated as the primary endpoint, whereas the secondary endpoints were healing time, reduction in ulcer area and ulceration score in 4 weeks, number of infective complications, and overall satisfaction of patients. Healing rate was significantly (P < .05) higher in patients in group A when compared with those in group B; healing time, patients' satisfaction, and reduction in ulcer area and ulceration score in 4 weeks were also higher in patients in group A. However, no significant differences were found in the prevalence of infections and other adverse events. The use of Vulnamin) gel with elastocompression is safe and effective in the management of NLUs of diabetic patients.

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.

Delivery of care to diabetic patients with foot ulcers in daily practice: results of the Eurodiale Study, a prospective cohort study.

AIMS: To determine current management and to identify patient-related factors and barriers that influence management strategies in diabetic foot disease. METHODS: The Eurodiale Study is a prospective cohort study of 1232 consecutive individuals presenting with a new diabetic foot ulcer in 14 centres across Europe. We determined the use of management strategies: referral, use of offloading, vascular imaging and revascularization. RESULTS: Twenty-seven percent of the patients had been treated for > 3 months before referral to a foot clinic. This varied considerably between countries (6-55%). At study entry, 77% of the patients had no or inadequate offloading. During follow-up, casting was used in 35% (0-68%) of the plantar fore- or midfoot ulcers. Predictors of use of casting were male gender, large ulcer size and being employed. Vascular imaging was performed in 56% (14-86%) of patients with severe limb ischaemia; revascularization was performed in 43%. Predictors of use of vascular imaging were the presence of infection and ischaemic rest pain. CONCLUSION: Treatment of many patients is not in line with current guidelines and there are large differences between countries and centres. Our data suggest that current guidelines are too general and that healthcare organizational barriers and personal beliefs result in underuse of recommended therapies. Action should be undertaken to overcome these barriers and to guarantee the delivery of optimal care for the many individuals with 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.

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.

Clinical and microbiological efficacy of colistin therapy in combination with rifampin and imipenem in multidrug-resistant Pseudomonas aeruginosa diabetic foot infection with osteomyelitis.

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Clinical and microbiological efficacy of colistin therapy alone or in combination as treatment for multidrug resistant Pseudomonas aeruginosa diabetic foot infections with or without osteomyelitis.

We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 +/- 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Screening for peripheral arterial disease by means of the ankle-brachial index in newly diagnosed Type 2 diabetic patients.

AIM: To evaluate the prevalence of peripheral arterial disease (PAD) with the ankle-brachial index (ABI) in newly diagnosed Type 2 diabetic subjects. METHODS: Between autumn 2002 and spring 2003, 2559 newly diagnosed Type 2 diabetic subjects (about 15% of the cases/year in Italy) were enrolled in 265 diabetology centres. Family history of diabetes, smoking, height, weight, waistline, fasting glycaemia, glycosylated haemoglobin, total and HDL-cholesterol and triglyceride values were collected. Claudication, cyanosis, cold foot, foot hair anomalies, skin thinning and femoral, popliteal, posterior tibial and dorsalis pedis pulses were assessed. The ABI was measured with a portable Doppler continuous-wave instrument. RESULTS: An ABI < 0.9 was found in 539 (21.1%) patients. Claudication was present in 187 (7.3%). Femoral pulse was absent in 218 (8.5%), popliteal in 316 (12.3%), tibial in 563 (22.0%) and dorsalis pedis in 578 (22.6%). Foot cyanosis was observed in 88 (3.4%), cold foot in 359 (13.9%), skin thinning in 468 (18.3%) and hair anomalies in 857 (33.5%). Multivariate analysis of the variables associated with ABI < 0.9 in the univariate analysis confirmed the independent role of age [relative risk (RR) 1.02, P < 0.001, confidence interval (CI) 1.01, 1.04], claudication (RR 4.53, P < 0.001, CI 2.97, 6.93), absence of tibial pulse (RR 3.45, P < or = 0.001. CI 2.54, 4.68) and pedis pulse (RR 1.96, P < or = 0.001, CI 1.4, 2.68). CONCLUSIONS: PAD, as represented by ABI < 0.9, is common in newly diagnosed Type 2 diabetic patients.

Biochemical and ultrasound tests for early diagnosis of active neuro-osteoarthropathy (NOA) of the diabetic foot.

OBJECTIVES: To test the effectiveness of a combined approach to an early diagnosis of neuro-osteoarthropathy (NOA) of the diabetic foot, we studied a group of outpatients with active NOA, presenting for the first time to our Diabetic Foot Clinic in 1998, by means of an integrated approach designed to assess bone turnover. PATIENTS AND METHODS: Fifteen consecutive diabetic patients (five Type 1 and ten Type 2 diabetic individuals, age 61.9+/-12.2 years, diabetes duration 18.7+/-8.9 years, HbA(1c) 8.4+/-1.5%) with active NOA (Group 1) were compared to nine diabetic patients with chronic stable NOA (Group 2), 14 neuropathic diabetic patients without NOA (Group 3), 13 non-neuropathic diabetic patients (Group 4) and 15 healthy controls (Group 5). Determination of serum carboxy-terminal collagen telopeptide (ICTP), bone alkaline phosphatase isoenzyme (B-ALP), osteocalcin (BGP) concentrations, as well as urinary excretion of deoxypyridinoline (DPD) were obtained in all individuals for assessment of bone reabsorption and new bone formation. Moreover in all individuals quantitative ultrasound (QUS) of the calcaneal bone was performed and mass density of lumbar spine and femur bone was determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: QUS was significantly lower in the active NOA patients as compared with other groups (P<0.01), while ICTP was higher in both NOA groups (P<0.01). Urinary DPD was higher in the neuropathic non-NOA group (P<0.01) than the other groups, and osteocalcin was higher in healthy controls compared to diabetic patients without NOA. QUS and ICTP were inversely correlated (r=0.44, P=0.000). QUS in the active NOA group was significantly (P<0.01) lower in the affected compared to the unaffected foot. CONCLUSION: Our results indicate a possible role for an integrated approach to the diagnosis and monitoring of NOA involving the diabetic foot. DPD may identify patients at-risk for NOA, ICTP could be tested as a marker for NOA in asymptomatic cases. Finally, QUS of the calcaneal bone may be useful in discriminating active versus quiescent phases.