Effect on total microbial load and community composition with two vs six-week topical Cadexomer Iodine for treating chronic biofilm infections in diabetic foot ulcers.

This study compares two vs six weeks of topical antimicrobial therapy with Cadexomer Iodine in patients with diabetic foot ulcers (DFUs) complicated by chronic biofilm infections. Patients with non-healing DFUs with suspected chronic biofilm infections were eligible for enrolment. Patients were randomised to receive either two or six weeks of treatment with topical Cadexomer Iodine. Tissue biopsies from the ulcers were obtained pre-and-post treatment and underwent DNA sequencing and real-time quantitative polymerase chain reaction (PCR) to determine the total microbial load, community composition, and diversity of bacteria. Scanning electron microscopy confirmed biofilm in all 18 ulcers with suspected chronic biofilm infections. Cadexomer Iodine resulted in 14 of 18 (78%) samples achieving a mean 0.5 log10 reduction in microbial load. Regardless of treatment duration, there was no statistical difference in the reduction of total microbial loads. No difference in the rate of wound healing in the two groups was seen at 6 weeks. Cadexomer Iodine reduces the total microbial load in DFUs with chronic biofilm infections and affects microbial community composition and diversity. All ulcers in both groups showed an initial reduction in wound size with application of Cadexomer Iodine, which might reflect its effect on biofilms.

Microscopy visualisation confirms multi-species biofilms are ubiquitous in diabetic foot ulcers.

Increasing evidence within the literature has identified the presence of biofilms in chronic wounds and proposed that they contribute to delayed wound healing. This research aimed to investigate the presence of biofilm in diabetic foot ulcers (DFUs) using microscopy and molecular approaches and define if these are predominantly mono- or multi-species. Secondary objectives were to correlate wound observations against microscopy results in ascertaining if clinical cues are useful in detecting wound biofilm. DFU tissue specimens were obtained from 65 subjects. Scanning electron microscopy (SEM) and peptide nucleic acid fluorescent in situ hybridisation (PNA-FISH) techniques with confocal laser scanning microscopy (CLSM) were used to visualise biofilm structures. Next-generation DNA sequencing was performed to explore the microbial diversity. Clinical cues that included the presence of slough, excessive exudate, a gel material on the wound bed that reforms quickly following debridement, poor granulation and pyocyanin were correlated to microscopy results. Of the 65 DFU specimens evaluated by microscopy, all were characterised as containing biofilm (100%, P < 0·001). The presence of both mono-species and multi-species biofilms within the same tissue sections were detected, even when DNA sequencing analysis of DFU specimens revealed diverse polymicrobial communities. No clinical correlations were identified to aid clinicians in identifying wound biofilm. Microscopy visualisation, when combined with molecular approaches, confirms biofilms are ubiquitous in DFUs and form either mono- or multi-species biofilms. Clinical cues to aid clinicians in detecting wound biofilm are not accurate for use in DFUs. A paradigm shift of managing DFUs needs to consider anti-biofilm strategies.

The pulling power of chocolate: Effects of approach-avoidance training on approach bias and consumption.

Previous research has shown that action tendencies to approach alcohol may be modified using computerized Approach-Avoidance Task (AAT), and that this impacted on subsequent consumption. A recent paper in this journal (Becker, Jostman, Wiers, & Holland, 2015) failed to show significant training effects for food in three studies: Nor did it find effects on subsequent consumption. However, avoidance training to high calorie foods was tested against a control rather than Approach training. The present study used a more comparable paradigm to the alcohol studies. It randomly assigned 90 participants to 'approach' or 'avoid' chocolate images on the AAT, and then asked them to taste and rate chocolates. A significant interaction of condition and time showed that training to avoid chocolate resulted in faster avoidance responses to chocolate images, compared with training to approach it. Consistent with Becker et al.'s Study 3, no effect was found on amounts of chocolate consumed, although a newly published study in this journal (Schumacher, Kemps, & Tiggemann, 2016) did do so. The collective evidence does not as yet provide solid basis for the application of AAT training to reduction of problematic food consumption, although clinical trials have yet to be conducted.

Outcomes and cost minimisation associated with outpatient parenteral antimicrobial therapy (OPAT) for foot infections in people with diabetes.

OBJECTIVE: To determine clinical outcomes in patients with diabetic foot infections receiving outpatient parenteral antimicrobial therapy (OPAT), to evaluate cost savings from the use of OPAT and to analyse demographic, clinical and laboratory data that may predict OPAT failure. RESEARCH DESIGN AND METHODOLOGY: A retrospective cohort analysis was conducted between 1 January 2007 and 7 July 2012 at a tertiary referral hospital in metropolitan Sydney. Patients with diabetic foot infection were identified from the outpatient parenteral antimicrobial therapy database. Demographic, clinical, laboratory and operative report data were obtained from patient charts and electronic medical records. Potential cost savings were calculated on the estimated cost of expenditure versus the expected savings. Linear regression was used to explore outcomes associated with outpatient parenteral antimicrobial therapy failure. RESULTS: Fifty-nine patients were identified over the 5-year study period. The outpatient parenteral antimicrobial therapy success rate for diabetic foot infections was 88%. Following the resolution of the primary episode of infection, new infective episodes within the study period were high (n = 26, 44%). Regression analysis of variables for OPAT failure failed to indicate any factors reaching statistical significance. A total of 1569 days were saved by using outpatient parenteral antimicrobial therapy for an estimated total cost saving of $983,645 or $16,672 per patient. CONCLUSION: Outpatient intravenous therapy for diabetic foot infections is an effective mode of treatment that can contribute to significant healthcare savings. High re-infection rates associated with diabetes foot ulceration in this population underline the need for close monitoring and management of these patients in multidisciplinary high-risk foot setting.

Clinical outcomes in people with diabetes-related foot infections: Analysis from a limb preservation service infection database.

BACKGROUND: Diabetes-related foot infections are common and represent a significant clinical challenge. There are scant data about outcomes from large cohorts. The purpose of this study was to report clinical outcomes from a large cohort of people with diabetes-related foot infections. METHODS: A tertiary referral hospital limb preservation service database was established in 2018, and all new episodes of foot infections were captured prospectively using an electronic database (REDCap). People with foot infections between January 2018 and May 2023, for whom complete data were available on infection episodes, were included. Infection outcomes were compared between skin and soft tissue infections (SST-DFI) and osteomyelitis (OM) using chi-square tests. RESULTS: Data extraction identified 647 complete DFI episodes in 397 patients. The data set was divided into two cohorts identifying each infection episode and its severity as either SST-DFI (N = 326, 50%) or OM (N = 321, 50%). Most infection presentations were classified as being moderate (PEDIS 3 = 327, 51%), with 36% mild (PEDIS 2 = 239) and 13% severe (PEDIS 4 = 81). Infection resolution occurred in 69% (n = 449) of episodes with failure in 31% (n = 198). Infection failures were more common with OM than SST-DFI (OM = 140, 71% vs. SST-DFI = 58, 29%, p < 0.00001). In patients with SST-DFI a greater number of infection failures were observed in the presence of peripheral arterial disease (PAD) compared to the patients without PAD (failure occurred in 30% (31/103) of episodes with PAD and 12% (27/223) of episodes without PAD; p < 0.001). In contrast, the number of observed infection failures in OM episodes were similar in patients with and without PAD (failure occurred in 45% (57/128) of episodes with PAD and 55% (83/193) of episodes without PAD; p = 0.78). CONCLUSIONS: This study provides important epidemiological data on the risk of poor outcomes for DFI and factors associated with poor outcomes in an Australian setting. It highlights the association of PAD and treatment failure, reinforcing the need for early intervention to improve PAD in patients with DFI. Future randomised trials should assess the benefits of revascularisation and surgery in people with DFI and particularly those with OM where outcomes are worse.

A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

Cellular mechanisms and/or microbiological interactions which contribute to chronic diabetes related foot ulcers (DRFUs) were explored using serially collected tissue specimens from chronic DRFUs and control healthy foot skin. Total RNA was isolated for next-generation sequencing. We found differentially expressed genes (DEGs) and enriched hallmark gene ontology biological processes upregulated in chronic DRFUs which primarily functioned in the host immune response including: (i) Inflammatory response; (ii) TNF signalling via NFKB; (iii) IL6 JAK-STAT3 signalling; (iv) IL2 STAT5 signalling and (v) Reactive oxygen species. A temporal analysis identified RN7SL1 signal recognition protein and IGHG4 immunoglobulin protein coding genes as being the most upregulated genes after the onset of treatment. Testing relative temporal changes between healing and non-healing DRFUs identified progressive upregulation in healed wounds of CXCR5 and MS4A1 (CD20), both canonical markers of lymphocytes (follicular B cells/follicular T helper cells and B cells, respectively). Collectively, our RNA-seq data provides insights into chronic DRFU pathogenesis.

Host-microbe metatranscriptome reveals differences between acute and chronic infections in diabetes-related foot ulcers.

Virtually all diabetes-related foot ulcers (DRFUs) will become colonized by microorganisms that may increase the risk of developing an infection. The reasons why some ulcerations develop acute clinical infections (AI-DRFUs) whilst others develop chronic infection (CI-DRFUs) and the preceding host-microbe interactions in vivo remain largely unknown. Establishing that acute and chronic infections are distinct processes requires demonstrating that these are two different strategies employed by microbes when interacting with a host. In this study, dual-RNA seq was employed to differentiate the host-microbe metatranscriptome between DRFUs that had localized chronic infection or acute clinical infection. Comparison of the host metatranscriptome in AI-DRFUs relative to CI-DRFUs identified upregulated differentially expressed genes (DEGs) that functioned as regulators of vascular lymphatic inflammatory responses, T-cell signalling and olfactory receptors. Conversely, CI-DRFUs upregulated DEGs responsible for cellular homeostasis. Gene set enrichment analysis using Hallmark annotations revealed enrichment of immune and inflammatory profiles in CI-DRFUs relative to AI-DRFUs. Analysis of the microbial metatranscriptome identified the DEGs being enriched within AI-DRFUs relative to CI-DRFUs included several toxins, two-component systems, bacterial motility, secretion systems and genes encoding for energy metabolism. Functions relevant to DRFU pathology were further explored, including biofilm and bacterial pathogenesis. This identified that the expression of biofilm-associated genes was higher within CI-DRFUs compared to that of AI-DRFUs, with mucR being the most highly expressed gene. Collectively, these data provide insights into the host-microbe function in two clinically-distinct infective phenotypes that affect DRFUs. The data reveal that bacteria in acutely infected DRFUs prioritize motility over biofilm and demonstrate greater pathogenicity and mechanisms, which likely subvert host cellular and immune pathways to establish infection. Upregulation of genes for key vascular inflammatory mediators in acutely infected ulcers may contribute, in part, to the clinical picture of a red, hot, swollen foot, which differentiates an acutely infected ulcer from that of a chronic infection.

Metatranscriptome sequencing identifies Escherichia are major contributors to pathogenic functions and biofilm formation in diabetes related foot osteomyelitis.

Osteomyelitis in the feet of persons with diabetes is clinically challenging and is associated with high rates of amputation. In this study RNA-sequencing was employed to explore microbial metatranscriptomes with a view to understand the relative activity and functions of the pathogen/s responsible for diabetes foot osteomyelitis (DFO). We obtained 25 intraoperative bone specimens from persons with confirmed DFO, observing that Escherichia spp. (7%), Streptomyces spp. (7%), Staphylococcus spp. (6%), Klebsiella spp. (5%) and Proteus spp. (5%) are the most active taxa on average. Data was then subset to examine functions associated with pathogenesis (virulence and toxins), biofilm formation and antimicrobial/multi-drug resistance. Analysis revealed Escherichia spp. are the most active taxa relative to pathogenic functions with K06218 (mRNA interferase relE), K03699 (membrane damaging toxin tlyC) and K03980 (putative peptidoglycan lipid II flippase murJ), K01114 (membrane damaging toxin plc) and K19168 (toxin cptA) being the most prevalent pathogenic associated transcripts. The most abundant transcripts associated with biofilm pathways included components of the biofilm EPS matrix including glycogen synthesis, cellulose synthesis, colonic acid synthesis and flagella synthesis. We further observed enrichment of a key enzyme involved in the biosynthesis of L-rhamnose (K01710 -dTDP-glucose 4,6-dehydratase rfbB, rmlB, rffG) which was present in all but four patients with DFO.

Subacute casemix classification for stroke rehabilitation in Australia. How well does AN-SNAP v2 explain variance in outcomes?

OBJECTIVE: We sought the best predictors for length of stay, discharge destination and functional improvement for inpatients undergoing rehabilitation following a stroke and compared these predictors against AN-SNAP v2. METHOD: The Oxfordshire classification subgroup, sociodemographic data and functional data were collected for patients admitted between 1997 and 2007, with a diagnosis of recent stroke. The data were factor analysed using Principal Components Analysis for categorical data (CATPCA). Categorical regression analyses was performed to determine the best predictors of length of stay, discharge destination, and functional improvement. RESULTS: A total of 1154 patients were included in the study. Principal components analysis indicated that the data were effectively unidimensional, with length of stay being the most important component. Regression analysis demonstrated that the best predictor was the admission motor FIM score, explaining 38.9% of variance for length of stay, 37.4%.of variance for functional improvement and 16% of variance for discharge destination. CONCLUSION: The best explanatory variable in our inpatient rehabilitation service is the admission motor FIM. AN- SNAP v2 classification is a less effective explanatory variable. This needs to be taken into account when using AN-SNAP v2 classification for clinical or funding purposes.

Utilisation of the 2019 IWGDF diabetic foot infection guidelines to benchmark practice and improve the delivery of care in persons with diabetic foot infections.

AIMS: To utilise the 2019 International Working Group on the Diabetic Foot (IWGDF) - diabetic foot infection (DFI) guidelines as an audit tool for clinical practice in patients with diabetes attending a High-Risk Foot Service. METHODS: Data from 93 consecutive patients were collected over a 19-month period in patients attending a High-Risk Foot Service. The diagnosis and management of each patient in the sample were compared against the 2019 IWGDF DFI guidelines, grouped into four categories: Diagnosis, Microbiology, Treatment of soft tissue infection, and Surgical treatment and osteomyelitis. Deficits in performance were recorded using the recommendations as a benchmark standard. RESULTS: There were 109 DFI events. Nineteen (63%) of the recommendations were met, 7 (24%) were partially met, and four (13%) recommendations were not met. Fourteen of the sample had no documented requests for full blood counts. Tissue was obtained for culture in 32 (29%) of the sample. No percutaneous bone biopsies were performed. Only 13 (28%) patients had intraoperative bone specimens sent for culture and sensitivities, with no bone specimens sent for histopathology. Modification of antibiotic therapy following available culture results was low, occurring in 12 out of 63 possible occasions (19%). The duration of antibiotic regimens in PEDIS 2 infections and osteomyelitis was greater than that recommended. CONCLUSIONS: Utilising the IWGDF DFI guidelines to benchmark clinical practice is a useful tool to identify gaps in clinical performance or service delivery and may help to improve patient care.

A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot infections: a pilot study.

Diabetic foot infections (DFIs) are a major cause of hospitalization and can lead to lower extremity amputation. In this pilot study, we used a multiomics approach to explore the host-microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however Staphylococcus aureus and Streptococcus genera were abundant and highly active in most mild to moderate DFIs. Further, we identified the significant enrichment of several virulence factors associated with infection pathogenicity belonging to both Staphylococcus aureus and Streptococcus. In severe DFIs, patients demonstrated a greater microbial diversity and differential gene expression demonstrated the enrichment of multispecies virulence genes suggestive of a complex polymicrobial infection. The host response in patients with severe DFIs was also significantly different as compared to mild to moderate DFIs. This was attributed to the enrichment of host genes associated with inflammation, acute phase response, cell stress and broad immune-related responses, while those associated with wound healing and myogenesis were significantly depleted.

Interrater reliability of functional status scores for patients transferred from one rehabilitation setting to another.

OBJECTIVE: To report the interrater reliability of FIM total score, FIM motor subscore, and FIM cognitive subscore from scoring that occurred in routine clinical practice in 2 closely linked inpatient rehabilitation services in Sydney, Australia. DESIGN: A natural-experiment blind clinical interrater reliability cohort study of the FIM across 2 rehabilitation units. SETTING: This study is set in 2 inpatient rehabilitation units immediately adjacent to each other in southwestern Sydney, New South Wales, Australia. PARTICIPANTS: All patients (N=143) who were transferred between the 2 rehabilitation units between August 2006 and October 2007 were included in the study. INTERVENTION: Discharge FIMs were scored by the first unit and an admission FIM was scored independently by the second unit within a few days. The FIM scores were analyzed for agreement and systematic bias. MAIN OUTCOME MEASURE: Intraclass correlation coefficients, kappa statistic, weighted kappa statistic, and Bland-Altman plots were used. RESULTS: There were 143 sets of scores identified. The range of differences between the 2 FIM totals was -32 to 50, between the FIM motor subscores was -22 to 43, and between the FIM cognitive subscores was -14 to 21. Bland-Altman plots demonstrated poor agreement. Few FIM totals were perfectly matched. The intraclass correlation coefficients ranged from .872 for the FIM total to .830 for the cognitive subscales. Values for kappa ranged from -.007 (FIM motor subscore) to .123 (FIM cognitive subscore). Values for weighted kappa ranged from .465 (FIM cognitive subscore) to .521 (FIM total). CONCLUSIONS: There was no systematic scoring bias evident. Intraclass correlation coefficients were high, but tests of agreement demonstrated poor agreement. These findings have implications for the use of the FIM and any patient classification or funding system based on the FIM, especially if poor levels of agreement were found in the presence of all staff being FIM credentialed and standardization of methods of assessment. This study indicates that further investigation of agreement of both FIM totals and FIM item scores in the clinical setting is warranted.

Representations and coverage of non-English-speaking immigrants and multicultural issues in three major Australian health care publications.

BACKGROUND: No recent Australian studies or literature, provide evidence of the extent of coverage of multicultural health issues in Australian healthcare research. A series of systematic literature reviews in three major Australian healthcare journals were undertaken to discover the level, content, coverage and overall quality of research on multicultural health. Australian healthcare journals selected for the study were The Medical Journal of Australia (MJA), The Australian Health Review (AHR), and The Australian and New Zealand Journal of Public Health (ANZPH). Reviews were undertaken of the last twelve (12) years (1996-August 2008) of journal articles using six standard search terms: 'non-English-speaking', 'ethnic', 'migrant', 'immigrant', 'refugee' and 'multicultural'. RESULTS: In total there were 4,146 articles published in these journals over the 12-year period. A total of 90 or 2.2% of the total articles were articles primarily based on multicultural issues. A further 62 articles contained a major or a moderate level of consideration of multicultural issues, and 107 had a minor mention. CONCLUSIONS: The quantum and range of multicultural health research and evidence required for equity in policy, services, interventions and implementation is limited and uneven. Most of the original multicultural health research articles focused on newly arrived refugees, asylum seekers, Vietnamese or South East Asian communities. While there is some seminal research in respect of these represented groups, there are other communities and health issues that are essentially invisible or unrepresented in research. The limited coverage and representation of multicultural populations in research studies has implications for evidence-based health and human services policy.

Monitoring wound progression to healing in diabetic foot ulcers using three-dimensional wound imaging.

AIM: 3D wound imaging has provided clinicians with even greater wound measurement options. No data is available to guide clinicians as to which 3D measurements may yield the most reflective marker of wound progression to healing. METHOD: A prospective pilot study was undertaken to assess the accuracy of five 3D wound measurements that best reflect metrics of interest to clinicians. Twenty-one diabetic foot ulcers were enrolled from initial ulcer presentation, through to healing. The relationship between mean wound healing measurement variables was examined using linear regression and Pearsons correlation coefficient, in addition to assessing clinician inter-rater reliability of measurements using Intra-class correlation coefficients (ICC). RESULTS: Statistical analysis demonstrated a linear healing slope for each wound measurement as having a value greater than R 0.70 and a statistical significance of p = 0.0001. This suggests that all five wound measurements are useful prognostic markers of wound progression to healing. Low variability of measurements between users indicates good inter-observer reliability. CONCLUSION: 3D wound measurements demonstrate a linear correlation between the measurement and time to healing. This suggests they could be effective prognostic markers of a wounds progression to healing and closure. It may also provide important early identification of wounds not responding to standard care. Larger studies are required to validate our results.

A Cluster of Failures of Midline Catheters in a Hospital in the Home Program: A Retrospective Analysis.

A cluster of 11 midline catheter failures occurred during a 2-week period in a Hospital in the Home program in an urban tertiary hospital in Australia. These failures prompted a 4-month retrospective audit of patients receiving outpatient antimicrobial therapy between December 1, 2016 and March 1, 2017. Primary outcomes were dwell time and catheter failure. Peripherally inserted central catheters had significantly fewer failures and significantly longer dwell times compared with midline catheters. Women experienced higher rates of midline catheter failure than men. The proportion of patients with midline catheters receiving continuous infusions who experienced a failure was markedly higher than those receiving bolus doses. Suggestions for further related research are discussed.

Analysis of proximal bone margins in diabetic foot osteomyelitis by conventional culture, DNA sequencing and microscopy.

Multiple approaches were employed to detect pathogens from bone margins associated with Diabetic Foot Osteomyelitis (DFO). Intra-operative bone specimens of 14 consecutive subjects with suspected DFO were collected over a six-month study period from Liverpool Hospital. Infected bone and a proximal bone margins presumed to be 'clean/non-infected' were collected. Bone material was subjected to conventional culture, DNA sequencing and microscopy. In total, eight of 14 (57%) proximal bone margins had no growth by conventional culture but were identified in all proximal bone specimens by DNA sequencing. Proximal margins had lower median total microbial counts than infected specimens, but these differences were not statistically significant. Pathogens identified by sequencing in infected specimens were identified in proximal margins and the microbiomes were similar (ANOSIM = 0.02, p = 0.59). Using a combination of SEM and/or PNA-FISH, we visualized the presence of microorganisms in infected bone specimens and their corresponding proximal margins of seven patients (50%) with DFO. We identify that bacteria can still reside in what seems to be proximal 'clean' margins. The significance and implications of clinical outcomes requires further analysis from a larger sample size that incorporates differences in surgical and post-operative approaches, correlating any outcomes back to culture-sequence findings.

Analysis of draft Australian rehabilitation service standards: comparison with international standards.

BACKGROUND: Following her review of health systems and structures Dwyer 1 suggested that there is a need to evaluate models of care for individuals with chronic diseases. Rehabilitation services aim to optimise the activity and participation of individuals with restrictions due to both acute and chronic conditions. Assessing and optimising the standard of these services is one method of assuring the quality of service delivered to these individuals. Knowledge of baseline standards allows evaluation of the impact of health care reforms in this area of need. The aim of this article is to compare the currently available rehabilitation service standards in Australia with those used in the USA and the UK. RESULTS: The mixed method qualitative analysis performed on the three sets of standards demonstrated repeatability and convergence via the use of triangulation. Australian Faculty of Rehabilitation Medicine (AFRM) standards were found to be consistent and concise, to provide definitions, and to cover the majority of clinically relevant issues to an extent similar to the other rehabilitation service standards. Inclusion of standards for business practices, the rehabilitation process for the person served, and outpatient and community-based rehabilitation services should be considered by the AFRM. CONCLUSION: The AFRM standards are an appropriate way of assessing rehabilitation services in Australia. As suggested by other workers 23 there should be ongoing review and field testing of the standards to maximise the relevance and utilisation of the standards.

How are language barriers bridged in acute hospital care? The tale of two methods of data collection.

OBJECTIVE: To explore language service provision in a pilot hospital study with two methods of data collection. METHODS: This mixed mode study design comprises a multilingual telephone survey followed by a medical records audit, undertaken at Liverpool Hospital in 2004-05. RESULTS: Two hundred and fifty-eight patients responded from 360 patients representing nine language groups. About a third of patients with limited English proficiency had used a professional interpreter in hospital. Concordance between the multilingual telephone survey and the medical records audit was apparent, although the telephone survey mostly showed non-significant, higher rates than the audit. While the methods showed high agreement (76%) for frequency of interpreter usage, kappa indicated only fair agreement (PABAK 0.40). Forty-eight percent of the patients preferred relatives as interpreters and 51% felt that their inability to speak English negatively affected their hospital stay. CONCLUSIONS: Professional interpreter usage is lower than desirable in the hospital, especially in the Emergency Department. Relatives frequently interpret. Under-reporting on the medical record is suggested, implying a need for improved documentation, while possible over-reporting in the telephone survey may relate to recall bias and social acquiescence.