A new diabetic foot risk assessment tool: DIAFORA.

AIMS: This study aimed to derive a new model to classify subjects with diabetes and active diabetic foot ulcer by their risk of lower extremity amputation. METHODS: A prospective cohort study was conducted that included all subjects with diabetic foot ulcer attending our Hospital Diabetic Foot Clinic from 2010 to 2013. Variables were collected at baseline. Subjects were followed up until healing, lower extremity amputation, death or for at least 3 months. Logistic regression was used to derive the new model, and the area under the receiver operating characteristic curve was assessed to propose the model with the greatest discrimination. RESULTS: A total of 293 participants were included and followed for a median of 91 days. In 23.2% amputation was required, 5.1% died and 3.1% were lost. Our final model included the variables most commonly used in clinical practice for diabetic foot risk assessment (presence of neuropathy, foot deformity, peripheral arterial disease and previous foot complications) in addition to multiple diabetic foot ulcer, infection, gangrene and bone involvement. This model had an area under the receiver operating characteristic curve of 0.91 [95% confidence interval (CI) 0.87-0.95] and as classification of 0.89 (95% CI 0.84-0.93) for lower extremity amputation prediction. The high-risk group presented a positive likelihood ratio of 5 (95% CI 3-8) and predictive value of 58 (46-71). Only one minor lower extremity amputation occurred in the low-risk group. CONCLUSIONS: We propose a new classification: diabetic foot risk assessment (DIAFORA). This classification was equally or more accurate for lower extremity amputation prediction in diabetic foot ulcer patients when compared with the existing ones.

Prevention of foot ulcers in the at-risk patient with diabetes: a systematic review.

BACKGROUND: Prevention of foot ulcers in patients with diabetes is extremely important to help reduce the enormous burden of foot ulceration on both patient and health resources. A comprehensive analysis of reported interventions is not currently available, but is needed to better inform caregivers about effective prevention. The aim of this systematic review is to investigate the effectiveness of interventions to prevent first and recurrent foot ulcers in persons with diabetes who are at risk for ulceration. METHODS: The available medical scientific literature in PubMed, EMBASE, CINAHL and the Cochrane database was searched for original research studies on preventative interventions. Both controlled and non-controlled studies were selected. Data from controlled studies were assessed for methodological quality by two independent reviewers. RESULTS: From the identified records, a total of 30 controlled studies (of which 19 RCTs) and another 44 non-controlled studies were assessed and described. Few controlled studies, of generally low to moderate quality, were identified on the prevention of a first foot ulcer. For the prevention of recurrent plantar foot ulcers, multiple RCTs with low risk of bias show the benefit for the use of daily foot skin temperature measurements and consequent preventative actions, as well as for therapeutic footwear that demonstrates to relieve plantar pressure and that is worn by the patient. To prevent recurrence, some evidence exists for integrated foot care when it includes a combination of professional foot treatment, therapeutic footwear and patient education; for just a single session of patient education, no evidence exists. Surgical interventions can be effective in selected patients, but the evidence base is small. CONCLUSION: The evidence base to support the use of specific self-management and footwear interventions for the prevention of recurrent plantar foot ulcers is quite strong, but is small for the use of other, sometimes widely applied, interventions and is practically nonexistent for the prevention of a first foot ulcer and non-plantar foot ulcer.

Classification systems for lower extremity amputation prediction in subjects with active diabetic foot ulcer: a systematic review and meta-analysis.

AIM: We systematically review the available systems used to classify diabetic foot ulcers in order to synthesize their methodological qualitative issues and accuracy to predict lower extremity amputation, as this may represent a critical point in these patients' care. MATERIAL AND METHODS: Two investigators searched, in EBSCO, ISI, PubMed and SCOPUS databases, and independently selected studies published until May 2013 and reporting prognostic accuracy and/or reliability of specific systems for patients with diabetic foot ulcer in order to predict lower extremity amputation. RESULTS: We included 25 studies reporting a prevalence of lower extremity amputation between 6% and 78%. Eight different diabetic foot ulcer descriptions and seven prognostic stratification classification systems were addressed with a variable (1-9) number of factors included, specially peripheral arterial disease (n = 12) or infection at the ulcer site (n = 10) or ulcer depth (n = 10). The Meggitt-Wagner, S(AD)SAD and Texas University Classification systems were the most extensively validated, whereas ten classifications were derived or validated only once. Reliability was reported in a single study, and accuracy measures were reported in five studies with another eight allowing their calculation. Pooled accuracy ranged from 0.65 (for gangrene) to 0.74 (for infection). CONCLUSION: There are numerous classification systems for diabetic foot ulcer outcome prediction, but only few studies evaluated their reliability or external validity. Studies rarely validated several systems simultaneously and only a few reported accuracy measures. Further studies assessing reliability and accuracy of the available systems and their composing variables are needed.

Anti-biofilm activity of low-molecular weight chitosan hydrogel against Candida species.

Candida invasive infections have increased in frequency during the last decades. Such infections are often associated to medical indwelling devices like central venous catheter. The recurrent nature and difficulties in the treatment of these infections are often related to biofilm formation. The objective of this study was to investigate the anti-biofilm activity of low-molecular weight chitosan hydrogel (LMWCH), a natural biopolymer obtained from the N-deacylation of crustacean chitin, upon clinical relevant Candida species. The in vitro ability of LMWCH to impair biofilm formation and to disorganize a preformed biofilm was tested in polystyrene microplates and quantified by the semi quantitative XTT assay and by the crystal violet assay. LMWCH in vivo efficacy as a coating for medical indwelling devices was evaluated for the first time for Candida parapsilosis, using a mouse subcutaneous foreign body model using polyurethane catheter segments. Scanning electron microscopy was used to access biofilm architecture after LMWCH treatment. We found that LMWCH efficiently impaired biofilm formation of all Candida species, also promoting biofilm disaggregation. Most importantly, LMWCH was able to significantly inhibit biofilm formation by C. parapsilosis in an in vivo catheter mouse model. SEM images showed biofilm collapsed cells compatible with membrane damage, suggesting that this could be one of the possible mechanisms underlying biofilm impairment. LMWCH revealed to be a promising compound for treatment of candidiasis or its prevention through medical device coating.

Novel method for evaluating in vitro activity of anidulafungin in combination with amphotericin B or azoles.

A combination of drugs possessing different targets has been used as salvage therapy, although without scientific support. In vitro studies validating such combinations are scarce, and the methodology is very laborious and time-consuming. This study proposes a flow cytometric (FC) protocol as an alternative to evaluate the effect of the combination of anidulafungin (AND) with amphotericin B (AMB) and azoles (fluconazole and voriconazole), tested upon 39 and 36 Candida strains, respectively. The concentration assayed in the combination was 0.5× MIC of each drug. The membrane potential marker DiBAC(4)(3) [Bis-(1,3-dibutylbarbituric acid) trimethine oxonol] was used for AND-AMB, and the metabolic marker FUN-1 was used for AND-azoles. Drug interaction was determined by calculating a staining index (SI): the sum of the percentage of depolarized cells (DC) after treatment with drug combinations divided by the DC of the drug alone, and the sum of the mean intensity of fluorescence (MIF) displayed by cells treated with drug combinations divided by the MIF of the drug alone for FUN-1. An SI of <1 means antagonism, an SI between 1 and 4 means no interaction, and an SI of >4 means synergism. The combination of AND and AMB by FC and checkerboard was synergistic for 46 and 43% of isolates and antagonistic for 5 and 8%, respectively. For the combination of AND and azoles, it was synergistic for 36% and antagonistic for 3% by FC and synergistic for 44% and antagonistic for 3% by checkerboard. When the FC method was compared to the gold standard checkerboard method, the agreement was 0.91 (95% confidence interval [95% CI] of 0.88 to 0.94), sensitivity was 0.88 (95% CI of 0.73 to 0.95), and specificity was 0.95 (95% CI of 0.84 to 1). Thus, FC is a rapid and reliable method (<2 h) to assess the effect of antifungal combinations.

A novel flow cytometric protocol for assessment of yeast cell adhesion.

Microbial adhesion is a field of recognized relevance and, as such, an impressive array of tools has been developed to understand its molecular mechanisms and ultimately for its quantification. Some of the major limitations found within these methodologies concern the incubation time, the small number of cells analyzed, and the operator's subjectivity. To overcome these aspects, we have developed a quantitative method to measure yeast cells' adhesion through flow cytometry. In this methodology, a suspension of yeast cells is mixed with green fluorescent polystyrene microspheres (uncoated or coated with host proteins). Within 2 h, an adhesion profile is obtained based on two parameters: percentage and cells-microsphere population's distribution pattern. This flow cytometry protocol represents a useful tool to quantify yeast adhesion to different substrata in a large scale, providing manifold data in a speedy and informative manner.

Predictive factors for diabetic foot ulceration: a systematic review.

Improving ability to predict and prevent diabetic foot ulceration is imperative because of the high personal and financial costs of this complication. We therefore conducted a systematic review in order to identify all studies of factors associated with DFU and assess whether available DFU risk stratification systems incorporate those factors of highest potential value. We performed a search in PubMed for studies published through April 2011 that analysed the association between independent variables and DFU. Articles were selected by two investigators-independently and blind to each other. Divergences were solved by a third investigator. A total of 71 studies were included that evaluated the association between diabetic foot ulceration and more than 100 independent variables. The variables most frequently assessed were age, gender, diabetes duration, BMI, HbA(1c) and neuropathy. Diabetic foot ulceration prevalence varied greatly among studies. The majority of the identified variables were assessed by only two or fewer studies. Diabetic neuropathy, peripheral vascular disease, foot deformity and previous diabetic foot ulceration or lower extremity amputation - which are the most common variables included in risk stratification systems - were consistently associated with diabetic foot ulceration development. Existing diabetic foot ulceration risk stratification systems often include variables shown repeatedly in the literature to be strongly predictive of this outcome. Improvement of these risk classification systems though is impaired because of deficiencies noted, including a great lack of standardization in outcome definition and variable selection and measurement.

Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).

Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter Study Group (EHSG), the European Society of Pathology (ESP) and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach (termed MAPS). A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia, and the need for adequate staging in the case of high grade dysplasia, and they focus on treatment and surveillance indications and methods.

Risk stratification systems for diabetic foot ulcers: a systematic review.

AIMS/HYPOTHESIS: Several risk stratification systems have been proposed for predicting development of diabetic foot ulcer. However, little has been published that assesses their similarities and disparities, diagnostic accuracy and evidence level. Consequently, we conducted a systematic review of the existing stratification systems. METHODS: We searched the MEDLINE database for studies (published until April 2010) describing the creation and validation of risk stratification systems for prediction of diabetic foot ulcer development. RESULTS: We included 13 studies describing or evaluating the following different risk degree stratification systems: University of Texas; International Working Group on Diabetic Foot; Scottish Intercollegiate Guideline Network (SIGN); American Diabetes Association; and Boyko and colleagues. We confirmed that five variables were included in almost all the systems: diabetic neuropathy, peripheral vascular disease, foot deformity, and previous foot ulcer and amputation. The number of variables included ranged from four to eight and the number of risk groups from two to six. Only four studies reported or allowed the calculation of diagnostic accuracy measures. The SIGN system showed some higher diagnostic accuracy values, particularly positive likelihood ratio, while predictive ability was confirmed through external validation only in the system of Boyko et al. CONCLUSIONS/INTERPRETATION: Foot ulcer risk stratification systems are a much needed tool for screening patients with diabetes. The core variables of various systems are very similar, but the number of included variables in each model and risk groups varied greatly. Overall, the quality of evidence for these systems is low, as little validation of their predictive ability has been done.

External validation and optimisation of a model for predicting foot ulcers in patients with diabetes.

AIMS/HYPOTHESIS: In 2006 a risk stratification model was developed by Boyko et al. to predict foot ulceration in patients with diabetes, using seven commonly available clinical variables. We sought to validate and optimise this clinical prediction rule in a different setting. METHODS: A retrospective cohort study was conducted on all patients with diabetes attending the podiatry section of a diabetic foot clinic at a tertiary hospital in Portugal (n = 360). Assessment at baseline included variables evaluated in the previous study and other relevant variables. RESULTS: Type 2 diabetes was present in 98% of patients, 45% were men and (at baseline) the median age was 65 years. Median follow-up was 25 months (range 3-86), during which 94 patients (26%) developed a foot ulcer. Boyko's model had an area under the receiver operating curve of 0.83 (95% CI 0.78-0.88). The corresponding value for the optimised model, which included the footwear risk variable, was 0.88 (95% CI 0.84-0.91). Both models had high classification accuracy for prediction of foot ulceration. However, the optimised model tended to produce higher specificity and positive likelihood ratio values at all levels. CONCLUSIONS/INTERPRETATION: This study confirmed that Boyko's proposed model has a high capacity to predict foot ulceration in diabetes patients of both sexes. Our results suggest that the inclusion of a further footwear variable could improve the model. Nevertheless, prospective validation in a larger population is still necessary.

Diabetic foot ulcer development risk classifications' validation: A multicentre prospective cohort study.

AIMS: To prospectively validate the existing classifications to stratify subjects with diabetes mellitus (DM) by their risk of diabetic foot ulcer (DFU), in high and low risk settings. METHODS: A prospective multicentre cohort study was conducted, including 446 subjects with DM without active DFU followed in the hospital or primary care setting. Demographic, clinical characterization variables, and those included in the classifications were collected at baseline. Subjects were followed for 1year, until DFU or death. RESULTS: In our sample, with a mean age of 65years, 52% were male; 32 developed a DFU, 7 required an amputation and 18 died. Differences were found between participants' characteristics and classifications' accuracy according to the setting. The great majority of the variables were associated with higher DFU risk. Globally, classifications were highly and equally valid, positive predictive values (PV) were inferior to 40%, negative PV superior to 90% and area under the receiver operating characteristic curve superior to 0.75. DISCUSSION: All the existing classifications are valid to be applied in high risk clinical context and have a very high capacity to categorize as low risk those subjects that will not develop a DFU. Further research is needed in the primary care setting.

Portugal meets Eurodiale: better late than never.

Understanding the quality of diabetic foot care delivery is essential. The Eurodiale consortium addressed subjects' characteristics, diabetic foot ulcer prognostic predictors and clinical outcomes, in 10 European countries. We analyzed the results of a specialized Portuguese diabetic foot clinic at the light of the ones from Eurodiale.

Validation and comparison of currently available stratification systems for patients with diabetes by risk of foot ulcer development.

AIMS/HYPOTHESIS: There are five systems to stratify the risk for the development of a diabetic foot ulcer (DFU). This study aimed to prospectively validate all of them in the same cohort of participants to allow their direct comparison. METHODS: A retrospective cohort study was conducted on all patients with diabetes but without an active DFU attending our podiatry section (n=364) from January 2008 to December 2010. Participants' characteristics and all variables composing the stratification systems were assessed at baseline. Follow-up was performed for 1 year or until DFU occurred. RESULTS: Participants had a mean age of 64 years; 99.7% had type 2 diabetes and 48.6% were male. Median follow-up was 12 months (1-12) during which 33 subjects (9.1%) developed a DFU. Age, diabetes duration, foot deformity, peripheral vascular disease, diabetic peripheral neuropathy, previous DFU, and previous lower extremity amputation were associated with DFU occurrence. All systems presented greater DFU occurrence frequency as the risk group was higher (χ(2), P<0.001) and showed good diagnostic accuracy values, especially negative predictive value (≥ 95%) and area under the receiver operating curve (≥ 0.73). The lowest performance concerned positive predictive value (≤ 29.5%). CONCLUSIONS/INTERPRETATION: All the currently available stratification systems show high accuracy to detect which patients will develop a DFU with no significant differences among them. Therefore, for diabetic foot screening and resource allocation, it would be desirable to have a single unified system, combining the available systems, prospectively validated in a multicenter context and testing the inclusion of novel predictive variables' pertinence.

Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).

Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy, the European Helicobacter Study Group, the European Society of Pathology, and the Sociedade Portuguesa de Endoscopia Digestiva have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach. A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia and the need for adequate staging in the case of high-grade dysplasia, and they focus on treatment and surveillance indications and methods.