Guidelines on the classification of foot ulcers in people with diabetes (IWGDF 2023 update).

BACKGROUND: This publication represents a scheduled update of the 2019 guidelines of the International Working Group of the Diabetic Foot (IWGDF) addressing the use of systems to classify foot ulcers in people with diabetes in routine clinical practice. The guidelines are based on a systematic review of the available literature that identified 28 classifications addressed in 149 articles and, subsequently, expert opinion using the GRADE methodology. METHODS: First, we have developed a list of classification systems considered as being potentially adequate for use in a clinical setting, through the summary of judgements for diagnostic tests, focussing on the usability, accuracy and reliability of each system to predict ulcer-related complications as well as use of resources. Second, we have determined, following group debate and consensus, which of them should be used in specific clinical scenarios. Following this process, in a person with diabetes and a foot ulcer we recommend: (a) for communication among healthcare professionals: to use the SINBAD (Site, Ischaemia, Bacterial infection, Area and Depth) system (first option) or consider using WIfI (Wound, Ischaemia, foot Infection) system (alternative option, when the required equipment and level of expertise is available and it is considered feasible) and in each case the individual variables that compose the systems should be described rather than a total score; (b) for predicting the outcome of an ulcer in a specific individual: no existing system could be recommended; (c) for characterising a person with an infected ulcer: the use of the IDSA/IWGDF classification (first option) or consider using the WIfI system (alternative option, when the required equipment and level of expertise is available and it is considered as feasible); (d) for characterising a person with peripheral artery disease: consider using the WIfI system as a means to stratify healing likelihood and amputation risk; (e) for the audit of outcome(s) of populations: the use of the SINBAD score. CONCLUSIONS: For all recommendations made using GRADE, the certainty of evidence was judged, at best, as being low. Nevertheless, based on the rational application of current data this approach allowed the proposal of recommendations, which are likely to have clinical utility.

Classification of foot ulcers in people with diabetes: A systematic review.

BACKGROUND: Classification and scoring systems can help both clinical management and audit the outcomes of routine care. AIM: This study aimed to assess published systems used to characterise ulcers in people with diabetes to determine which should be recommended to (a) aid communication between health professionals, (b) predict clinical outcome of individual ulcers, (c) characterise people with infection and/or peripheral arterial disease, and (d) audit to compare outcomes in different populations. This systematic review is part of the process of developing the 2023 guidelines to classify foot ulcers from the International Working Group on Diabetic Foot. METHODS: We searched PubMed, Scopus and Web of Science for articles published up to December 2021 which evaluated the association, accuracy or reliability of systems used to classify ulcers in people with diabetes. Published classifications had to have been validated in populations of >80% of people with diabetes and a foot ulcer. RESULTS: We found 28 systems addressed in 149 studies. Overall, the certainty of the evidence for each classification was low or very low, with 19 (68%) of the classifications being assessed by ≤ 3 studies. The most frequently validated system was the one from Meggitt-Wagner, but the articles validating this system focused mainly on the association between the different grades and amputation. Clinical outcomes were not standardized but included ulcer-free survival, ulcer healing, hospitalisation, limb amputation, mortality, and cost. CONCLUSION: Despite the limitations, this systematic review provided sufficient evidence to support recommendations on the use of six particular systems in specific clinical scenarios.

Management of diabetes-related foot disease in the outpatient setting during the COVID-19 pandemic.

The use of telephone and/or video consultation in routine management of acute diabetes-related foot disease (DFD) before the coronavirus disease 2019 (COVID-19) pandemic at a tertiary hospital is unprecedented. In March 2020, the Diabetes Feet Australia (DFA) released a national guideline to inform DFD management during the COVID-19 pandemic. The present study aimed to describe the adherence to the DFA guideline of managing acute DFD using telephone and/or video consultation at a Western Australian tertiary hospital during this period. We found >80% adherence rate to the DFA guideline and the management of active DFD using telephone and/or video consultations was feasible and acceptable in carefully selected patients.

Prevalence and prognosis of a low serum testosterone in men with type 2 diabetes: the Fremantle Diabetes Study Phase II.

BACKGROUND: Because published studies have usually involved imprecise assays and selected patients with limited additional data and follow-up, the consequences of a low serum testosterone in diabetes are unclear. This study assessed the prevalence, associates and prognosis of a low testosterone in community-dwelling men with type 2 diabetes. DESIGN: Longitudinal observational study. PATIENTS: 788 men (mean ± SD age: 65·8 ± 11·3 years) followed for 4·0 ± 1·1 years. MEASUREMENTS: Serum testosterone, SHBG, erectile dysfunction (ED; Sexual Health Inventory for Men score <22), anaemia (haemoglobin <130 g/l), all-cause mortality. RESULTS: The mean ± SD total serum testosterone by liquid chromatography/mass spectrometry was 13·1 ± 5·9 nmol/l (30·6% <10 nmol/l). Most men with a total testosterone <10 nmol/l (67·0%) had a normal/low serum LH. Serum testosterone was independently associated with anaemia (P < 0·001), but not ED (P = 0·80), in logistic regression models. The optimal cut-point (Youden Index) for anaemia was 9·8 nmol/l (sensitivity 53·6%, specificity 75·4%). During the follow-up, 102 men (12·9%) died. There was a U-shaped relationship between total serum testosterone quintiles and death (P = 0·003, log rank test). The middle quintile (>11·1 to ≤13·7 nmol/l) had the lowest risk and there was a 78% increased risk for highest (>16·9 nmol/l) vs lowest (≤8·6 nmol/l) quintile in Cox proportional hazards modelling (P = 0·036). Free serum testosterone and SHBG quintiles were not associated with death. CONCLUSIONS: These data provide some support for the general conventional serum testosterone <10 nmol/l cut-point in identifying an increased risk of anaemia and the subsequent death in men with type 2 diabetes, but indicate that high-normal levels are also an adverse prognostic indicator.

Effect of continuous positive airway pressure therapy on sexual function and serum testosterone in males with type 2 diabetes and obstructive sleep apnoea.

OBJECTIVE: There have been no studies of the effect of continuous positive airway pressure (CPAP) therapy on erectile dysfunction (ED) and serum testosterone in men with type 2 diabetes and obstructive sleep apnoea (OSA), a patient group at increased risk of ED and hypogonadism. The aim of this study was to determine whether CPAP improves sexual and gonadal function in males with type 2 diabetes and a pre-CPAP apnoea-hypopnoea index >15/h. DESIGN: Substudy of a trial assessing the effect of 3 months of CPAP on cardiovascular risk in type 2 diabetes. PATIENTS: Of 35 males starting CPAP, 27 (mean ± SD age 65.4 ± 9.6 years, median [interquartile range] diabetes duration 12.1 [5.2-15.3] years) completed the trial. MEASUREMENTS: Serum total and free testosterone, responses to the Androgen Deficiency in the Aging Aale (ADAM) and Sexual Health Inventory for Men (SHIM) questionnaires. RESULTS: There were no significant changes in mean total or free testosterone (baseline concentrations 12.7 ± 4.5 nm and 0.26 ± 0.07 pm, respectively), or SHIM score (baseline 13 [5-17]), after 3 months of CPAP (P > 0.20). The ADAM score (baseline 6.2 ± 2.1) fell after 1 month (to 5.0 ± 2.6) and was maintained at this level at 3 months (P = 0.015). The Epworth Sleepiness Scale score decreased and self-reported physical activity increased over 3 months (P ≤ 0.017) without a change in body mass index (P = 1.00). CONCLUSIONS: These findings imply that CPAP therapy improves somnolence and promotes exercise in men with type 2 diabetes, but that there is no direct benefit for gonadal or sexual function.

Measuring thyroid peroxidase antibodies on the day nulliparous women present for management of miscarriage: a descriptive cohort study.

BACKGROUND: There has been recent evidence suggesting the presence of anti-thyroid peroxidase antibodies (TPOAb) increases the risk of miscarriage, and levothyroxine can rescue miscarriages associated with TPOAb. We propose the most clinically pragmatic cohort to screen for TPOAb are women presenting for management of a missed miscarriage and have never birthed a liveborn. We measured serum TPOAb among nulliparous women presenting for management of miscarriage, and compared levels with women who have had 2 or more livebirths (and never miscarried). Given its potential role in immunomodulation, we also measured Vitamin D levels. METHODS: We performed a prospective descriptive cohort study at a tertiary hospital (Mercy Hospital for Women, Victoria, Australia). We measured TPOAb and Vitamin D levels in serum obtained from 118 nulliparous women presenting for management of miscarriage, and 162 controls with 2 or more livebirths (and no miscarriages). Controls were selected from a serum biobank prospectively collected in the first trimester at the same hospital. RESULTS: Nulliparous women with 1 or more miscarriages had higher thyroid peroxidase antibody (TPOAb) levels than those with 2 or more livebirths; TPOAb in miscarriage group was 0.3 mIU/L (interquartile range [IR]: 0.2-0.7) vs 0.2 mIU/L among controls (IR 0.0-0.5; p < 0.0001). We confirmed TPOAb levels were not correlated with serum human chorionic gonadotrophin (hCG) concentrations in either the miscarriage or control groups. In contrast, thyroid stimulating hormone, fT3 and fT4 levels (thyroid hormones) either trended towards a correlation, or were significantly correlated with serum hCG levels in the two groups. Of the entire cohort that was predominantly caucasian, only 12% were Vitamin D sufficient. Low Vitamin D levels were not associated with miscarriage. CONCLUSIONS: We have confirmed the association between miscarriage and increased TPOAb levels. Furthermore, it appears TPOAb levels in maternal blood are not influenced by serum hCG levels. Therefore, we propose the day nulliparous women present for management for miscarriage is a clinically relevant, and pragmatic time to screen for TPOAb.

Diabetes-related foot disease: new insights with an antipodean focus.

Diabetes-related foot disease (DFD), defined as ulceration, infection or destruction of tissues of the foot in a person with current or previously diagnosed diabetes mellitus, is associated with a heavy burden for both patients and the healthcare system with high morbidity, mortality and costs. Improved outcomes for people with DFD are achieved with an interdisciplinary approach and adherence to best practice clinical guidelines; however, in the Australian context, the vastness of the country presents unique challenges in achieving optimal outcomes for all people with DFD, with variation in service delivery, availability and accessibility between metropolitan, rural and remote areas. Aboriginal and Torres Strait Islander Australians and people with diabetes living in rural and remote areas experience higher rates of lower-extremity amputation, and further efforts and resources are required to improve outcomes for these high-risk groups. In recent years, there have been advances in knowledge, including the understanding of the pathogenesis of diabetes-related peripheral neuropathy, genetic polymorphisms and mechanisms of disease associated with acute Charcot neuroarthropathy, biomarkers and potential mediators of diabetes-related foot ulcer (DFU) healing, the microbiology and microbiome profile of DFUs, pressure assessment and management as well as an expanded understanding of DFU sequelae and comorbidities. In this review, we describe new insights into pathophysiology, sequelae and comorbidities of DFD with a focus on basic and translational aspects and contributions to the field from Australian and New Zealand DFD researchers.

Temporal trends in minor and major lower extremity amputation in people with type 2 diabetes: The Fremantle Diabetes Study.

AIMS: To determine whether incident minor and major lower extremity amputations (LEAs) have declined in recent decades in type 2 diabetes. METHODS: Participants with type 2 diabetes from the community-based Fremantle Diabetes Study Phases I (FDS1; n = 1,296, mean age 64.0 years, recruited 1993-1996) and II (FDS2; n = 1,509, mean age 65.4 years, recruited 2008-2011) were followed from entry to incident minor/major LEA, death or five years. Cox regression determined hazard ratios (HRs) for each outcome for FDS2 versus FDS1 and independent predictors of incident minor and major LEA in the combined cohort. RESULTS: Age- and sex-adjusted HRs (95% CIs) in FDS2 versus FDS1 for incident minor and major LEA were, respectively, 0.60 (0.27, 1.35) and 0.59 (0.22, 1.59). Higher glycated haemoglobin, urine albumin: creatinine (uACR) ratio and peripheral sensory neuropathy (PSN) were independent predictors of incident minor LEA. Higher fasting serum glucose, peripheral arterial disease (PAD), end-stage kidney disease and prior diabetes-related minor LEA were associated with incident major LEA. CONCLUSIONS: There were non-significant reductions of approximately 40% in incident minor and major LEA in community-based people with type 2 diabetes during the 15 years between FDS Phases. Predictors of minor/major LEA confirm distinct high-risk patient groups with implications for clinical management.

Exercise in adults admitted to hospital with diabetes-related foot ulcers: a pilot study of feasibility and safety.

BACKGROUND: Diabetes-related foot ulcers result in significant mortality, morbidity and economic costs. Pressure offloading is important for ulcer healing, but patients with diabetes-related foot ulcers are presented with a dilemma, because whilst they are often advised to minimise standing and walking, there are also clear guidelines which encourage regular, sustained exercise for patients with diabetes. To overcome these apparently conflicting recommendations, we explored the feasibility, acceptability and safety of a tailored exercise program for adults admitted to hospital with diabetes-related foot ulcers. METHODS: Patients with diabetes-related foot ulcers were recruited from an inpatient hospital setting. Baseline demographics and ulcer characteristics were collected, and participants undertook a supervised exercise training session comprising aerobic and resistance exercises followed by prescription of a home exercise programme. Exercises were tailored to ulcer location, which complied with podiatric recommendations for pressure offloading. Feasibility and safety were assessed via recruitment rate, retention rate, adherence to inpatient and outpatient follow up, adherence to home exercise completion, and recording of adverse events. RESULTS: Twenty participants were recruited to the study. The retention rate (95%), adherence to inpatient and outpatient follow up (75%) and adherence to home exercise (50.0%) were all acceptable. No adverse events occurred. CONCLUSIONS: Targeted exercise appears safe to be undertaken by patients with diabetes-related foot ulcers during and after an acute hospital admission. Recruitment in this cohort may prove challenging, but adherence, retention and satisfaction with participation in exercise were high. TRIAL REGISTRATION: The trial is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12622001370796).

Routine bacterial culture of proximal bone specimens during minor amputation in patients with diabetes-related foot infections has little clinical utility in predicting re-operation or ulcer healing.

BACKGROUND: Trans-phalangeal and trans-metatarsal amputation, collectively termed 'minor amputations' are important procedures for managing infections of diabetes-related foot ulcers (DFU). Following minor amputation, international guidelines recommend a prolonged course of antibiotics if residual infected bone on intra-operative bone samples are identified, but the quality of the evidence underpinning these guidelines is low. In this study, we examined the concordance of microbiological results from proximal bone cultures compared to results from superficial wound swabs in relation to patient outcomes; with the aim of determining the utility of routinely obtaining marginal bone specimens. METHODS: Data was retrospectively collected on 144 individuals who underwent minor amputations for infected DFU at a large Australian tertiary hospital. Concordance was identified for patients with both superficial wound swabs and intra-operative bone samples available. Patient outcomes were monitored up to 6 months post-amputation. The primary outcome was complete healing at 6 months; and secondary outcome measures included further surgery and death. Mann Whitney U testing was performed for bivariate analyses of continuous variables, Chi-Squared testing used for categorical variables and a logistic regression was performed with healing as the dependent variable. RESULTS: A moderate-high degree of concordance was observed between microbiological samples, with 38/111 (35%) of patients having discordant wound swab and bone sample microbiology. Discordant results were not associated with adverse outcomes (67.2% with concordant results achieved complete healing compared with 68.6% patients with discordant results; P = 0.89). Revascularisation during admission (0.37 [0.13-0.96], P = 0.04) and amputation of the 5th ray (0.45 [0.21-0.94], P = 0.03) were independent risk factors for non-healing. CONCLUSION: There was a moderate-high degree of concordance between superficial wound swab results and intra-operative bone sample microbiology in this patient cohort. Discordance was not associated with adverse outcomes. These results suggest there is little clinical utility in routinely collecting proximal bone as an adjunct to routine wound swabs for culture during minor amputation for an infected DFU.

Bone and metabolic health in patients with non-metastatic prostate cancer who are receiving androgen deprivation therapy.

Androgen deprivation therapy (ADT) in men with prostate cancer increases the risk of osteoporotic fractures, type 2 diabetes and, possibly, cardiovascular events. There is considerable uncertainty about the risk-benefit ratio of ADT in non-palliative treatment; the benefits of ADT in treating non-metastatic prostate cancer need to be carefully weighed against the risks of ADT-induced adverse events. Baseline assessment of bone health at the initiation of ADT should include measurement of bone mineral density (BMD) by dual energy x-ray absorptiometry and, in men with osteopaenia, a thoracolumbar spine x-ray. General measures to prevent bone loss, including regular physical activity, as well as ensuring calcium and vitamin D sufficiency, should be instituted routinely. All men with a previous minimal trauma fracture should receive pharmacological therapy unless contraindicated; for those who have not sustained a minimal trauma fracture, treatment is advised if the BMD T score is ≤ - 2.0, or if the 10-year risk of a major osteoporotic fracture exceeds 20%. Men with prostate cancer who are receiving ADT should be closely monitored for weight gain and diabetes; intensive lifestyle intervention is recommended to prevent ADT-induced weight gain and insulin resistance. Management of the metabolic sequelae of ADT includes optimal reduction of cardiovascular risk factors, with particular attention to weight, blood pressure, lipid profile, smoking cessation, and glycaemic control.

Temporal Trends in Incident Hospitalization for Diabetes-Related Foot Ulcer in Type 2 Diabetes: The Fremantle Diabetes Study.

OBJECTIVE: To determine whether, reflecting trends in other chronic complications, incident hospitalization for diabetes-related foot ulcer (DFU) has declined over recent decades in type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants with type 2 diabetes from the community-based Fremantle Diabetes Study phases I (FDS1; 1,296 participants, mean age 64.0 years, 48.6% males, recruited 1993-1996) and II (FDS2; 1,509 participants, mean age 65.4 years, 51.8% males, recruited 2008-2011) were followed from entry to first hospitalization for/with DFU, death, or 5 years (whichever came first). Incident rate ratios (IRRs) and incident rate differences (IRDs) were calculated for FDS2 versus FDS1 overall and in 10-year age-groups. Cox proportional hazards modeling determined independent predictors of first DFU hospitalization in the combined cohort. RESULTS: Incident DFU hospitalization (95% CI) was 1.9 (0.9-3.3)/1,000 person-years in FDS1 during 5,879 person-years of follow-up and 4.5 (3.0-6.4)/1,000 person-years in FDS2 during 6,915 person-years of follow-up. The crude IRR (95% CI) was 2.40 (1.17-5.28) (P = 0.013) and IRD 2.6 (0.7-4.5)/1,000 person-years (P = 0.010). The highest IR for any age-group was 23.6/1,000 person-years in FDS2 participants aged 31-40 years. Age at diabetes diagnosis (inverse), HbA1c, insulin use, height, ln(urinary albumin/creatinine), absence of any foot pulse, previous peripheral revascularization, and peripheral sensory neuropathy (PSN) were independent predictors of incident hospitalization for/with DFU. CONCLUSIONS: Incident DFU hospitalizations complicating type 2 diabetes increased between FDS phases, especially in younger participants, and were more likely in those with PSN, peripheral arterial disease, and suboptimal glycemic control at baseline.

Australian guideline on wound classification of diabetes-related foot ulcers: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease.

BACKGROUND: Wound classification systems are useful tools to characterise diabetes-related foot ulcers (DFU) and are utilised for the purpose of clinical assessment, to promote effective communication between health professionals, and to support clinical audit and benchmarking. Australian guidelines regarding wound classification in patients with DFU are outdated. We aimed to adapt existing international guidelines for wound classification to develop new evidence-based Australian guidelines for wound classification in people with diabetes and DFU. METHODS: Recommended NHRMC procedures were followed to adapt suitable International Working Group on the Diabetic Foot (IWGDF) guidelines on wound classification to the Australian health context. Five IWGDF wound classification recommendations were evaluated and assessed according to the ADAPTE and GRADE systems. We compared our judgements with IWGDF judgements to decide if recommendations should be adopted, adapted or excluded in an Australian context. We re-evaluated the quality of evidence and strength of recommendation ratings, provided justifications for the recommendation and outlined any special considerations for implementation, subgroups, monitoring and future research in an Australian setting. RESULTS: After the five recommendations from the IWGDF 2019 guidelines on the classification of DFUs were evaluated by the panel, two were adopted and three were adapted to be more suitable for Australia. The main reasons for adapting, were to align the recommendations to existing Australian standards of care, especially in specialist settings, to maintain consistency with existing recommendations for documentation, audit and benchmarking and to be more appropriate, acceptable and applicable to an Australian context. In Australia, we recommend the use of the SINBAD system as a minimum standard to document the characteristics of a DFU for the purposes of communication among health professionals and for regional/national/international audit. In contrast to the IWGDF who recommend against usage, in Australia we recommend caution in the use of existing wound classification systems to provide an individual prognosis for a person with diabetes and a foot ulcer. CONCLUSIONS: We have developed new guidelines for wound classification for people with diabetes and a foot ulcer that are appropriate and applicable for use across diverse care settings and geographical locations in Australia.

Establishing the national top 10 priority research questions to improve diabetes-related foot health and disease: a Delphi study of Australian stakeholders.

INTRODUCTION: Diabetes-related foot disease is a large cause of the global disease burden yet receives very little research funding to address this large burden. To help address this gap, it is recommended to first identify the consensus priority research questions of relevant stakeholders, yet this has not been performed for diabetes-related foot disease. The aim of this study was to determine the national top 10 priority research questions for diabetes-related foot health and disease from relevant Australian stakeholders. RESEARCH DESIGN AND METHODS: A modified three-round Delphi online survey design was used to seek opinions from relevant Australian stakeholders including those with diabetes or diabetes-related foot disease or their carers (consumers), health professionals, researchers and industry. Participants were recruited via multiple public invitations and invited to propose three research questions of most importance to them (Round 1), prioritize their 10 most important questions from all proposed questions (Round 2), and then rank questions in order of importance (Round 3). RESULTS: After Round 1, a total of 226 unique questions were proposed by 210 participants (including 121 health professionals and 72 consumers). Of those participants, 95 completed Round 2 and 69 completed Round 3. The top 10 priority research questions covered a range of topics, including health economics, peripheral neuropathy, education, infection, technology, exercise, and nutrition. Consumers prioritized peripheral neuropathy and prevention-related questions. Health professionals prioritized management-related questions including Australia's First Peoples foot health, health economics and infection questions. CONCLUSIONS: These priority research questions should guide future national research agendas, funding and projects to improve diabetes-related foot disease burdens in Australia and globally. Future research should focus on consumer priority research questions to improve the burden of diabetes-related foot disease on patients and nations. Further research should also investigate reasons for different priorities between consumers and health professionals.

Reduction in femoral neck and total hip bone mineral density following hospitalisation for diabetes-related foot ulceration.

Management of diabetes-related foot ulceration (DFU) includes pressure offloading resulting in a period of reduced activity. The metabolic effects of this are unknown. This study aims to investigate changes in bone mineral density (BMD) and body composition 12 weeks after hospitalisation for DFU. A longitudinal, prospective, observational study of 22 people hospitalised for DFU was conducted. Total body, lumbar spine, hip and forearm BMD, and total lean and fat mass were measured by dual-energy X-ray absorptiometry (DXA) during and 12 weeks after hospitalisation for DFU. Significant losses in total hip BMD of the ipsilateral limb (- 1.7%, p < 0.001), total hip BMD of the contralateral limb (- 1.4%, p = 0.005), femoral neck BMD of the ipsilateral limb (- 2.8%, p < 0.001) and femoral neck BMD of the contralateral limb (- 2.2%, p = 0.008) were observed after 12 weeks. Lumbar spine and forearm BMD were unchanged. HbA1c improved from 75 mmol/mol (9.2%) to 64 mmol/mol (8.0%) (p = 0.002). No significant changes to lean and fat mass were demonstrated. Total hip and femoral neck BMD decreased bilaterally 12 weeks after hospitalisation for DFU. Future research is required to confirm the persistence and clinical implications of these losses.

Cognitive Impairment in People with Diabetes-Related Foot Ulceration.

AIMS: To determine whether there is an excess of cognitive impairment in patients with type 2 diabetes and foot ulceration. METHODS: 55 patients with type 2 diabetes and foot ulcers attending Multidisciplinary Diabetes Foot Ulcer clinics (MDFU cohort) were compared with 56 patients with type 2 diabetes attending Complex Diabetes clinics (CDC cohort) using commonly used screening tests for cognitive impairment (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA)), as well as foot self-care, mood and health literacy. MMSE was also compared between the MDFU cohort and a historical community-based cohort of patients with type 2 diabetes (FDS2 cohort). RESULTS: Median MMSE scores were the same in all three groups (28/30). Median MOCA scores did not differ between the MDFU and CDC cohorts (25/30). There were no significant differences in the percentages of patients with MMSE ≤ 24 or MOCA ≤ 25 between MDFU and CDC cohorts (3.6% versus 10.7%, p = 0.27 and 56.4% versus 51.8%, p = 0.71, respectively), findings that did not change after adjustment for age, sex, education, diabetes duration, and random blood glucose. CONCLUSIONS: Using conventionally applied instruments, patients with type 2 diabetes and foot ulceration have similar cognition compared with patients without, from either hospital-based clinic or community settings.

Thyroid function and autoantibody status among women who spontaneously deliver under 35 weeks of gestation.

OBJECTIVE: Recent studies report an association between maternal thyroid auto-antibodies and preterm birth. None have made the important distinction between spontaneous and iatrogenic preterm birth. We investigated the association between spontaneous preterm birth before 35-week gestation and both thyroid function and auto-antibody status. DESIGN: Retrospective nested case-control study, samples retrieved from a biobank of around 8000 samples. PATIENTS: Forty-six cases of spontaneous preterm birth <35-weeks gestation compared with 124 cases who delivered at 40 weeks gestation, matched for maternal age and duration of serum storage. All resulted in a singleton liveborn. MEASUREMENTS: First trimester serum levels of TSH, free T4, free T3, anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies. RESULTS: Women who had a preterm birth delivered at a median gestational age of 33 (+1 day) weeks gestation (controls 40 + 3 weeks) and had significantly lower birthweight infants [mean (range) weight 1965 (581-3117) grams compared with controls 3526 (2685-4760) grams]. Median levels of anti-thyroglobulin and anti-TPO antibodies were similar in the two groups (Anti-Tg: 3 IU/ml (Range 1-316) v 3 IU/ml (1-691); Anti-TPO 8 IU/ml (3-73) v 9 IU/ml (3-499); P >/= 0.18 for both comparisons, compared using three statistical models). In the preterm group, the median TSH level was 0.70 mIU/l (range 0.04-3.84), similar to controls (0.88 (0.01-2.87), P = 0.1). Free T3 and T4 levels were also similar in both groups. CONCLUSIONS: Thyroid function and thyroid autoantibody status among women who have a spontaneous preterm delivery before 35 weeks gestation are not different from women delivering at term.

Development and Validation of a Simple Hip Fracture Risk Prediction Tool for Type 2 Diabetes: The Fremantle Diabetes Study Phase I.

OBJECTIVE: To develop a type 2 diabetes hip fracture risk tool in community-based patients, to validate it in an independent cohort, and to compare its performance against the only published prediction equation to include type 2 diabetes as a risk factor (QFracture). RESEARCH DESIGN AND METHODS: Hip fracture hospitalizations in 1,251 participants with type 2 diabetes aged 40-89 years from the longitudinal Fremantle Diabetes Study Phase I (FDS1) were ascertained between entry (1993-1996) and end-2012. Competing risk regression modeling determined independent predictors of time to first fracture over 10 years and the coefficients incorporated in a risk model. The model was validated in 286 participants with type 2 diabetes from the Busselton Health Study (BHS). RESULTS: Fifty FDS1 participants (4.0%) experienced a first hip fracture during 10,306 person-years of follow-up. Independent predictors of fracture were older age, female sex, lower BMI, peripheral sensory neuropathy, and estimated glomerular filtration rate <45 mL/min/1.73 m2. The model-predicted mean 10-year incident fracture risk was 3.3% with good discrimination, calibration, and accuracy. For a 3% cutoff, sensitivity was 76.0%, specificity 71.9%, positive predictive value (PPV) 10.1%, and negative predictive value (NPV) 98.6%. Model performance in the small BHS sample was also good (sensitivity 66.7%, specificity 79.8%, PPV 6.2%, and NPV 99.2%). QFracture performed well in FDS1 but required availability of 25 variables. CONCLUSIONS: The FDS1 hip fracture risk equation is a simple validated adjunct to type 2 diabetes management that uses variables that are readily available in routine care.

Spray on skin for diabetic foot ulcers: an open label randomised controlled trial.

BACKGROUND: One Australian loses a limb every 3 h as a result of infected diabetic foot ulcers (DFU). This common condition accounts for substantial morbidity and mortality for affected individuals and heavy economic costs for the health sector and the community. There is an urgent need to test interventions that improve wound healing time, prevent amputations and recurrent ulceration in patients presenting with DFU whilst improving quality of life and reducing health care costs. METHODS: One hundred and fifty eligible participants will be randomised to receive an autologous skin cell suspension, also termed 'spray-on' skin (ReCell®) or standard care interventions for their DFU. The primary outcome is complete wound healing at 6 months, but participants will be followed up for a total of 12 months to enable secondary outcomes including total overall costs, ulcer free days at 12 months and quality of life to be assessed. DISCUSSION: Outpatient costs for dressings, home nursing visits and outpatient appointments are key cost drivers for DFU. If spray-on skin is effective, large cost savings to WA Health will be realised immediately through a shortened time to healing, and through a higher proportion of patients achieving complete healing. Shortened healing times may enable participants to return to work earlier. Any economic benefits are likely to be amplified across Australia and other similar demographic settings where aging populations with increased diabetes rates are considered major future challenges. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000511235. Registered on 9 April 2018.