The antecedents and outcomes of persistent and remitting adolescent depressive symptom trajectories: a longitudinal, population-based English study.

BACKGROUND: Depression often first emerges in adolescence and, for many, is a lifelong disorder. The long-term clinical course of depression is highly variable. We aimed to examine the adult outcomes of adolescent-onset trajectories of clinically significant depressive symptoms and to identify factors differentiating trajectories that persist and desist in adulthood. METHODS: We included participants from the English population-based Avon Longitudinal Study of Parents and Children with data on depressive symptoms. Self-reported depression symptoms were assessed on ten occasions when participants were age 10·5-25 years using the short Mood and Feelings Questionnaire, and major depressive disorder episodes were assessed at age 13·0 years, 15·0 years, 17·5 years, and 25·0 years. We characterised trajectories of depression symptoms using latent class growth analysis, for which we required depression data at least once from each of three key phases: ages 10·5-13·5 years; 16·5-18·5 years; and 21-25 years. We examined adult outcomes by assessing lifetime suicidal self-harm and functional impairment at age 24·0 years, and employment, education, and the self-reported Strengths and Difficulties Questionnaire at age 25·0 years. FINDINGS: We studied 4234 participants: 2651 (63%) female, 1582 (37%) male, and one individual with missing sex data. The mean age was 10·6 years (SD 0·2) at baseline and 25·8 years (SD 0·5) at the final timepoint. Data on ethnicity were not available in our data set. We identified four depression trajectory classes: adolescent-persistent depression with onset early in adolescence (7%, n≈279), adolescent-limited depression with onset later in adolescence and remittance by adult life (14%, n≈592), adult-increasing depression (25%, n≈1056), and stable-low levels of depression (54%, n≈2307). The adolescent-persistent class was associated with poor adult outcomes for functional impairment (62%), suicidal self-harm (27%), mental health difficulties (25%), and not being in education, employment, or training (16%). Adolescent-limited depression was associated with transient adolescent stress, but by early adulthood functional impairment and mental health difficulties were similar to the stable-low group. Major depressive disorder polygenic score (odds ratio [OR] 1·36, 95% CI 1·04-1·79), adolescent educational attainment (OR 0·47, 0·30-0·74), and any early childhood adversity (OR 2·60, 1·42-4·78), that persisted into adulthood (OR 1·60, 1·38-1·87) distinguished the adolescent-persistent and adolescent-limited groups. INTERPRETATION: The future course of adolescent depression can be differentiated by age at onset during adolescence, adolescent academic attainment, early and persistent adversity, and genetic loading. A detailed social and educational history could be helpful in making clinical decisions about the intensity of interventions for young people with clinically elevated depressive symptoms who seek help. FUNDING: Medical Research Council, Wolfson Centre for Young People's Mental Health, Wolfson Foundation.

Comparative analyses of all FDA EUA-approved rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation

BackgroundRapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies. MethodsFor 18 RA tests with emergency use authorization from the United States of America FDA and an RT-PCR test, we conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data. ResultsWe demonstrate that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting. ConclusionsThese RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease. Plain language summaryPrevious research has determined optimal timing for testing in quarantine and the utility of different frequencies of testing for disease surveillance using RT-PCR and generalized rapid antigen tests. However, these strategies can depend on the specific rapid antigen test used. By examining 18 rapid antigen tests, we demonstrate that a single rapid antigen test performs better than RT-PCR when quarantines are two days or less in duration. In the context of disease surveillance, the ability of a rapid antigen test to provide results quickly counteracts its lower sensitivity with potentially more false positives. These analytical results based on highly controlled test validation were consistent with real-world data obtained from quarantine and serial testing in an industrial setting.

The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses.

BACKGROUND: There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. METHODS: In a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year program to collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center. RESULTS: Over 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children's or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the focus is on sequencing complete trios. ASC sequencing for the first 1,000 samples (all from whole-blood DNA) is complete and data will be released in 2014. Data is being made available through NIH databases (database of Genotypes and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA released in Dist 11.0. Primary funding for the collection, genotyping, sequencing and distribution of TASC samples was provided by Autism Speaks and the NIH, including the National Institute of Mental Health (NIMH) and the National Human Genetics Research Institute (NHGRI). CONCLUSIONS: TASC represents an important sample set that leverages expert sites. Similar approaches, leveraging expert sites and ongoing studies, represent an important path towards further enhancing available ASD samples.

Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE): a promising tool to diagnose bacterial infections in diabetic foot ulcers.

AIM: The diagnosis of diabetic foot infections is difficult due to limitations of conventional culture-based techniques. The objective of this study was to evaluate the contribution of denaturing gradient gel electrophoresis (DGGE) in the microbiological diagnosis of diabetic foot ulcers in comparison to conventional techniques, and also to evaluate the need to perform a biopsy sample for this diagnosis. METHODS: Twenty diabetic patients (types 1 and 2) with foot ulcers (grades 1-4) were included. After debridement of their wounds, samples were taken in duplicate by surface swabbing and deep-tissue biopsy. The samples were analyzed by conventional culture and by a new molecular biology tool, DGGE technology. RESULTS: Polymerase chain reaction (PCR)-DGGE led to the identification of more bacteria than did conventional cultures (mean: 2.35 vs 0.80, respectively). In 11 cases, the technology detected pathogenic species not isolated by classical cultures. PCR-DGGE also identified significantly more pathogenic species at deep levels compared with species detected at superficial levels (87% vs 58%, respectively; P = 0.03). In 9/20 cases, pathogenic bacteria were detected only in deep samples, revealing the need to perform tissue biopsy sampling. CONCLUSION: DGGE, achievable in 48h, could be a useful technique for the bacteriological diagnosis of diabetic foot infections. It may help to identify pathogenic bacteria in deeply infected ulcers, thereby contributing to a more appropriate use of antibiotics.

First report of the predominance of clonal complex 398 Staphylococcus aureus strains in osteomyelitis complicating diabetic foot ulcers: a national French study.

Staphylococcus aureus is the most common pathogen cultured from diabetic foot infection including diabetic foot osteomyelitis. This French multicentre study determined the genetic content of S. aureus isolated from 157 consecutive cases admitted to 12 diabetic foot centres between 2008 and 2011. We describe for the first time the emergence of the CC398 methicillin-susceptible S. aureus clone, the main clone in diabetic foot osteomyelitis, and its tropism for bone. This clone spreads to humans from an animal source through its intrinsic virulence. This adaptation of S. aureus isolates looks to be a worrisome problem and should be carefully monitored.

[Switzerland eliminates measles. National Strategy for the Elimination of Measles 2011-2015]. / Die Schweiz eliminiert die Masern. Nationale Strategie zur Masernelimination 2011-2015.

The measles virus circulates within Switzerland in an endemic way leading to sporadic outbreaks. The most recent outbreak occurred in 2011. It lasted 9 months and had 687 reported cases. This is in contrast to 2012 when there were 66 cases,corresponding to an incidence of 8 cases per million inhabitants. During 2008-2010, the average national vaccination coverage for one or two doses of measles vaccine amounted to 92 and 83 % for 2-year-olds, 95 and 85 % for 8-year-olds, and 95 and 85 % for 16-year-olds, respectively. To improve the national vaccination coverage, the Federal Council adopted the National Strategy for the Elimination of Measles 2011-2015 in 2011.The strategy was drawn up in a participative process led by the Federal Office for Public Health.The cantons as key partners were represented by the Conference of the Cantonal Directors for Public Health and the Association of Cantonal Health Officers. The strategy pursues the vision of eliminating measles in Switzerland in order to protect the population against measles and its complications, including all persons who may not be vaccinated for medical reasons. The strategy comprises six axes of intervention:(1)political engagement and support by all stakeholders, (2)a targeted ≥ 95 % two-dose vaccination coverage for all 2-year-olds, (3)easier access and incentives for the booster vaccination for everyone in the 2-year-old age group up to those born in 1964, (4)communication and promotion, (5)uniform national outbreak control, and (6)targeted surveillance.

Molecular epidemiology of Staphylococcus aureus strains isolated from inpatients with infected diabetic foot ulcers in an Algerian University Hospital.

Staphylococcus aureus is the most common pathogen cultured from diabetic foot infection (DFI). The consequence of its spread to soft tissue and bony structures is a major causal factor for lower-limb amputation. The objective of the study was to explore ecological data and epidemiological characteristics of S. aureus strains isolated from DFI in an Algerian hospital setting. Patients were included if they were admitted for DFI in the Department of Diabetology at the Annaba University Hospital from April 2011 to March 2012. Ulcers were classified according to the Infectious Diseases Society of America/International Working Group on the Diabetic Foot classification system. All S. aureus isolates were analysed. Using oligonucleotide arrays, S. aureus resistance and virulence genes were determined and each isolate was affiliated to a clonal complex. Among the 128 patients, 277 strains were isolated from 183 samples (1.51 isolate per sample). Aerobic Gram-negative bacilli were the most common isolated organisms (54.9% of all isolates). The study of ecological data highlighted the extremely high rate of multidrug-resistant organisms (MDROs) (58.5% of all isolates). The situation was especially striking for S. aureus [(85.9% were methicillin-resistant S. aureus (MRSA)], Klebsiella pneumonia (83.8%) and Escherichia coli (60%). Among the S. aureus isolates, 82.2% of MRSA belonged to ST239, one of the most worldwide disseminated clones. Ten strains (13.7%) belonged to the European clone PVL+ ST80. ermA, aacA-aphD, aphA, tetM, fosB, sek, seq, lukDE, fnbB, cap8 and agr group 1 genes were significantly associated with MRSA strains (p <0.01). The study shows for the first time the alarming prevalence of MDROs in DFI in Algeria.

Distribution of edin in Staphylococcus aureus isolated from diabetic foot ulcers.

Staphylococcus aureus is both a common colonizer of human skin and the most frequently isolated pathogen in diabetes foot infections (DFIs). The spread of DFI to soft tissue and bony structures is a major causal factor for lower-limb amputation. It is therefore of great importance to differentiate colonizing from infecting strains of S. aureus. Epidermal cell differentiation inhibitors known as EDIN and EDIN-like factors, a group of toxins targeting RhoA master regulator of the actin cytoskeleton, may confer virulence properties on S. aureus. In this study, for the first time, analysis of S. aureus strains, recovered in DFIs at an initial stage and during the follow-up, showed that 71.4% of edin-positive strains were associated with moderate-to-severe infections (grades 3 and 4 of the IDSA/IWGDF classification) compared with 28.6% of edin-positive strains associated with low-grade infections. Most of these strains were edin-B positive (86.7%) and belonged to CC25/28-MSSA (n = 10). One edin-B-positive ST152-MSSA strain was negative for the two highly prevalent predictive markers of infecting strains (lukDE and hlgv). Collectively, this points towards the edin-B encoding gene as a bonafide subsidiary predictive risk marker of DFI.

Treatment of acute Charcot foot with bisphosphonates: a systematic review of the literature.

AIM/HYPOTHESIS: We undertook a systematic review of the literature concerning the efficacy and safety of bisphosphonates in acute Charcot neuropathic osteoarthropathy. METHODS: MEDLINE, PubMed, the Cochrane Database of Systematic Reviews, and abstracts presented during the meetings of the American Diabetes Association and the European Association of Diabetes were searched for relevant publications from the period January 1990 to September 2011. RESULTS: A total of ten studies on the treatment of acute Charcot osteoarthropathy with bisphosphonates were identified and included in the analysis. Only four clinical trials were published, three of which were randomised. Bisphosphonates appeared to induce significant reductions in skin temperature and bone turnover markers compared with placebo, without serious adverse events. Nevertheless, bisphosphonates did not shorten the immobilisation time. Moreover, no data were available regarding their long-term effects. CONCLUSIONS/INTERPRETATIONS: Bisphosphonates have been shown to be effective for reducing bone turnover markers and skin temperature in some studies. Nevertheless, the long-term efficacy, specifically that regarding the occurrence of deformities and ulcerations, remains to be demonstrated as no follow-up studies have been published. Moreover, some studies have suggested that bisphosphonates may lengthen the resolution phase of the disease. In our opinion, the data are too weak to support the use of bisphosphonates as a routine treatment for acute Charcot neuroarthropathy.

Painful diabetic neuropathy: diagnosis and management.

The prevalence of painful diabetic peripheral neuropathy (PDN) is about 20% in patients with type 2 diabetes and 5% in those with type 1. Patients should be systematically questioned concerning suggestive symptoms, as they are not usually volunteers. As PDN is due to small-fibre injury, the 10 g monofilament pressure test as well as the standard electrophysiological procedures may be normal. Diagnosis is based on clinical findings: type of pain (burning discomfort, electric shock-like sensation, aching coldness in the lower limbs); time of occurrence (mostly at rest and at night); and abnormal sensations (such as tingling or numbness). The DN4 questionnaire is an easy-to-use validated diagnostic tool. Three classes of drugs are of equal value in treating PDN: tricyclic antidepressants; anticonvulsants; and selective serotonin-reuptake inhibitors. These compounds may be prescribed as first-line therapy following pain assessment using a visual analogue scale. If the initial drug at its maximum tolerated dose does not lead to a decrease in pain of at least 30%, another drug class should be prescribed; if the pain is decreased by 30% but remains greater than 3/10, a drug from a different class may be given in association.

Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism.

BACKGROUND: Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5'-flanking region of AVPR1A in variable gene expression and social behaviour. METHODS: We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. RESULTS: The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. CONCLUSIONS: These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

Management of patients hospitalized for diabetic foot infection: results of the French OPIDIA study.

AIM: This study was an analysis of how diabetic patients with infected foot wounds are managed in hospital by departments specializing in diabetic foot pathology, including an evaluation of the outcome 1 year after discharge. METHODS: This was a prospective study of a cohort of patients hospitalized for diabetic foot infection at 38 hospital centres in France and followed-up for 1 year after discharge. RESULTS: Altogether, 291 patients were included (73% male; 85% type 2 diabetes; mean age: 64.3±11.7 years). Most of the wounds were located on the toes and forefoot, and infection was most often graded as moderate; nevertheless, in about 50% of patients, osteomyelitis was suspected. Also, 87% of patients had peripheral neuropathy and 50-62% had peripheral artery disease. Gram-positive cocci, and Staphylococcus aureus in particular, were by far the most frequently isolated microorganisms. During hospitalization, lower-limb amputation was performed in 35% of patients; in 52%, the wound healed or had a favourable outcome. A year after discharge, 150 non-amputated patients were examined: at this time, 19% had to undergo amputation, whereas 79% had healed their wounds with no relapse. Risk factors for amputation were location (toes), severity of the wound and presence of osteomyelitis. Peripheral artery disease was associated with a poor prognosis, yet was very often neglected. CONCLUSION: In spite of being managed at specialized centres that were, in general, following the agreed-upon published guidelines, the prognosis for diabetic foot infection remains poor, with a high rate (48%) of lower-limb amputation.

Beneficial effects of implementing guidelines on microbiology and costs of infected diabetic foot ulcers.

AIMS/HYPOTHESIS: In 2003, guidelines for management of diabetic foot infection (DFI) were written by the authors' team according to the guidelines of the International Working Group on the Diabetic Foot. The effects of implementing these guidelines on the microbiology and costs of infected diabetic foot ulcers were assessed. METHODS: From 2003 to 2007, potential beneficial effects of implementing these guidelines were assessed by comparison over time of bacteriological data (number of bacterial samples, number of microorganisms isolated in cultures, prevalence of multidrug-resistant organisms [MDRO] and colonising flora), and costs related to use of antimicrobial agents and microbiology laboratory workload. RESULTS: The study included 405 consecutive diabetic patients referred to the Diabetic Foot Unit for a suspected DFI. From 2003 to 2007, a significant decrease was observed in the median number of bacteria species per sample (from 4.1 to 1.6), prevalence of MDRO (35.2% vs 16.3%) and methicillin-resistant Staphylococcus aureus (52.2% vs 18.9%) (p < 0.001). Moreover, prevalence of pathogens considered as colonisers dramatically fell from 23.1% to 5.8% of all isolates (p < 0.001). In parallel, implementation of guidelines was associated with a saving of euro14,914 (US$20,046) related to a reduced microbiology laboratory workload and euro109,305 (US$147,536) due to reduced prescription of extended-spectrum antibiotic agents. CONCLUSIONS/INTERPRETATION: Implementation of guidelines for obtaining specimens for culture from patients with DFI is cost-saving and provides interesting quality indicators in the global management of DFI.

[In vitro activity of daptomycin against strains isolated from diabetic foot ulcers]. / Activité in vitro de la daptomycine vis-à-vis de souches cliniques isolées de plaies du pied chez des diabétiques.

PURPOSE OF THE STUDY: The aim of this study was to evaluate the in vitro activity of daptomycin and other comparator agents against bacterial strains isolated from diabetic foot infections (DFI). PATIENTS AND METHODS: All diabetic patients hospitalized for a first episode of DFI (stage 2 to 4, according to the International Working Group of Diabetic Foot classification) were selected in Nîmes University hospital between June 2006 to August 2007. MIC were determined using E-test strip (AB Biodisk) and custom broth microdilution panels against bacterial strains isolated from foot samples. RESULTS: Two hundred strains were studied. Daptomycin was active against 99.5% of all the strains especially Streptococcus sp. (100%), Enterococcus sp. (100%), coagulase-negative Staphylococcus (100%) and methicillin-susceptible Staphylococcus aureus (100%). Exclusively, one methicillin-resistant S. aureus strain was not covered by this antibiotic. CONCLUSIONS: Daptomycin, a new broad spectrum antimicrobial agent against Gram-positive cocci, is qualified to belong to the therapeutic arsenal package of complicated skin and soft tissue infections in diabetic patients after microbial documentation.

The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD): Findings from a family-based association test (FBAT) analysis.

BACKGROUND: Low serotonergic (5-HT) activity correlates with increased impulsive-aggressive behavior, while the opposite association may apply to cognitive impulsiveness. Both types of impulsivity are associated with attention-deficit/hyperactivity disorder (ADHD), and genes of functional significance for the 5-HT system are implicated in this disorder. Here we demonstrate the separation of aggressive and cognitive components of impulsivity from symptom ratings and test their association with 5-HT and functionally related genes using a family-based association test (FBAT-PC). METHODS: Our sample consisted of 1180 offspring from 607 families from the International Multicenter ADHD Genetics (IMAGE) study. Impulsive symptoms were assessed using the long forms of the Conners and the Strengths and Difficulties parent and teacher questionnaires. Factor analysis showed that the symptoms aggregated into parent- and teacher-rated behavioral and cognitive impulsivity. We then selected 582 single nucleotide polymorphisms (SNPs) from 14 genes directly or indirectly related to 5-HT function. Associations between these SNPs and the behavioral/cognitive groupings of impulsive symptoms were evaluated using the FBAT-PC approach. RESULTS: In the FBAT-PC analysis for cognitive impulsivity 2 SNPs from the gene encoding phenylethanolamine N-methyltransferase (PNMT, the rate-limiting enzyme for adrenalin synthesis) attained corrected gene-wide significance. Nominal significance was shown for 12 SNPs from BDNF, DRD1, HTR1E, HTR2A, HTR3B, DAT1/SLC6A3, and TPH2 genes replicating reported associations with ADHD. For overt aggressive impulsivity nominal significance was shown for 6 SNPs from BDNF, DRD4, HTR1E, PNMT, and TPH2 genes that have also been reported to be associated with ADHD. Associations for cognitive impulsivity with a SERT/SLC6A4 variant (STin2: 12 repeats) and aggressive behavioral impulsivity with a DRD4 variant (exon 3: 3 repeats) are also described. DISCUSSION: A genetic influence on monoaminergic involvement in impulsivity shown by children with ADHD was found. There were trends for separate and overlapping influences on impulsive-aggressive behavior and cognitive impulsivity, where an association with PNMT (and arousal mechanisms affected by its activity) was more clearly involved in the latter. Serotonergic and dopaminergic mechanisms were implicated in both forms of impulsivity with a wider range of serotonergic mechanisms (each with a small effect) potentially influencing cognitive impulsivity. These preliminary results should be followed up with an examination of environmental influences and associations with performance on tests of impulsivity in the laboratory.

[Epidemiology of diabetic foot problems]. / Epidémiologie du pied diabétique.

Since diabetes mellitus is growing at epidemic proportions worldwide, the prevalence of diabetes-related complications is bound to increase. Diabetic foot disorders, a major source of disability and morbidity, are a significant burden for the community and a true public health problem. Many epidemiological data have been published on the diabetic foot but they are difficult to interpret because of variability in the methodology and in the definitions used in these studies. Moreover, there is a lack of consistency in population characteristics (ethnicity, social level, accessibility to care) and how results are expressed. In westernized countries, two of 100 diabetic patients are estimated to suffer from a foot ulcer every year. Amputation rates vary considerably: incidence ranges from 1 per thousand in the Madrid area and in Japan to up to 20 per thousand in some Indian tribes in North America. In metropolitan France, the incidence of lower-limb amputation is approximately 2 per thousand but with marked regional differences, and in French overseas territories, the incidence rate is much higher. Nevertheless, the risk for ulceration and amputation is much higher in diabetics compared to the nondiabetic population: the lifetime risk of a diabetic individual developing an ulcer is as high as 25% and it is estimated that every 30s an amputation is performed for a diabetic somewhere in the world. As reviewed in this paper, peripheral neuropathy, arterial disease, and foot deformities are the main factors accounting for this increased risk. Age and sex as well as social and cultural status are contributing factors. Knowing these factors is essential to classify every diabetic using a risk grading system and to take preventive measures accordingly.

Risk factors and healing impact of multidrug-resistant bacteria in diabetic foot ulcers.

AIM: To determine the risk factors for acquiring multidrug-resistant organisms (MDRO) and their impact on outcome in infected diabetic foot ulcers. METHODS: Patients hospitalized in our diabetic foot unit for an episode of infected foot ulcer were prospectively included. Diagnosis of infection was based on clinical findings using the International Working Group on the Diabetic Foot-Infectious Diseases Society of America (IWGDF-ISDA) system, and wound specimens were obtained for bacterial cultures. Each patient was followed-up for 1 year. Univariate analysis was performed to compare infected ulcers according to the presence or absence of MDRO; logistic regression was used to identify explanatory variables for MDRO presence. Factors related to healing time were evaluated by univariate and multivariate survival analyses. RESULTS: MDRO were isolated in 45 (23.9%) of the 188 patients studied. Deep and recurrent ulcer, previous hospitalization, HbA(1c) level, nephropathy and retinopathy were significantly associated with MDRO-infected ulceration. By multivariate analysis, previous hospitalization (OR=99.6, 95% CI=[19.9-499.0]) and proliferative retinopathy (OR=7.4, 95% CI=[1.6-33.7]) significantly increased the risk of MDRO infection. Superficial ulcers were associated with a significant decrease in healing time, whereas neuroischaemic ulcer, proliferative retinopathy and high HbA(1c) level were associated with an increased healing time. In the multivariate analysis, presence of MDRO had no significant influence on healing time. CONCLUSION: MDRO are pathogens frequently isolated from diabetic foot infection in our foot clinic. Nevertheless, their presence appears to have no significant impact on healing time if early aggressive treatment, as in the present study, is given, including empirical broad-spectrum antibiotic treatment, later adjusted according to microbiological findings.

[In vitro activity of ertapenem against strains isolated from diabetic foot infections]. / Activité in vitro de l'ertapénème vis-à-vis de souches bactériennes isolées de plaies infectées du pied chez des patients diabétiques.

OBJECTIVE: The authors aimed to evaluate the in vitro activity of ertapenem against bacterial strains isolated from diabetic foot infections (DFI). METHODOLOGY: All diabetic patients hospitalized for a first episode of DFI (stages 2 to 4, according to the International Working Group of Diabetic Foot Classification) were selected in the Nîmes University hospital between January 2005 to December 2005. MICs were determined using both E-test strips and dilution methods on bacterial strains isolated from foot samples. RESULTS: Two hundred and fifty-two bacteria (154 Gram-positive cocci including 94 Staphylococcus aureus, 80 Gram-negative bacilli with 56 Enterobacteriaceae, and 18 anaerobes) were studied. Ertapenem was active against all Streptococcus spp., Enterobacteriaceae, anaerobes, and also against 89.8% of methicillin-susceptible S. aureus isolates. However, this antibiotic was active only against 31.5% of Staphylococcus epidermidis, 21.8% of Enterococcus faecalis, and 15.8% of Pseudomonas aeruginosa. CONCLUSION: Our results indicate that ertapenem may be a useful agent to treat patients suffering from DFI after bacterial identification.

Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study.

AIMS/HYPOTHESIS: Infection of diabetic foot ulcers is common; at early stages it is difficult to differentiate between non-infected ulcers (or those colonised with normal flora) and ulcers infected with virulent bacteria that lead to deterioration. This pilot study aimed to assess the diagnostic accuracy of inflammatory markers as an aid to making this distinction. METHODS: We included 93 diabetic patients who had an episode of foot ulcer and had not received antibiotics during the 6 months preceding the study. Ulcers were classified as infected or uninfected, according to the Infectious Diseases Society of America-International Working Group on the Diabetic Foot classification. Diabetic patients without ulcers (n=102) served as controls. C-reactive protein (CRP), orosomucoid, haptoglobin and procalcitonin were measured together with white blood cell and neutrophil counts. The diagnostic performance of each marker, in combination (using logistic regression) or alone, was assessed. RESULTS: As a single marker, CRP was the most informative for differentiating grade 1 from grade 2 ulcers (sensitivity 0.727, specificity 1.000, positive predictive value 1.000, negative predictive value 0.793) with an optimal cut-off value of 17 mg/l. In contrast, white blood cell and neutrophil counts were not predictive. The most relevant combination derived from the logistic regression was the association of CRP and procalcitonin (AUC 0.947), which resulted in a significantly more effective determination of ulcer grades, as shown by comparing receiver operating characteristic curves. CONCLUSIONS/INTERPRETATION: Measurement of only two inflammatory markers, CRP and procalcitonin, might be of value for distinguishing between infected and non-infected foot ulcers in subgroups of diabetic patients, to help ensure the appropriate allocation of antibiotic treatment. Nevertheless, external validation of the diagnostic value of procalcitonin and CRP in diabetic foot ulcers is needed before routine use can be recommended.