Effectiveness of psychosocial interventions for the prevention and treatment of foot ulcers in people with diabetes: a systematic review.

AIM: To identify and synthesize the evidence for the effectiveness of psychosocial interventions to promote the healing, and/or reduce the occurrence of, foot ulceration in people with diabetes. METHODS: In March 2019 we searched CENTRAL, Medline, Embase and PsycInfo for randomized controlled trials of interventions with psychosocial components for people with diabetes. The primary outcomes of this review were foot ulceration and healing. We assessed studies using the Cochrane risk-of-bias tool, the TIDieR checklist and GRADE. We conducted narrative synthesis and random-effects meta-analysis. RESULTS: We included 31 randomized controlled trials (4511 participants), of which most (24 randomized controlled trials, 4093 participants) were prevention studies. Most interventions were educational with a modest psychosocial component. Ulceration and healing were not reported in most studies; secondary outcomes varied. Evidence was of low or very low quality because of high risks of bias and imprecision, and few studies reported adherence or fidelity. In groups where participants had prior ulceration, educational interventions had no clear effect on new ulceration (low-quality evidence). Two treatment studies, assessing continuous pharmacist support and an intervention to promote understanding of well-being, reported healing but their evidence was also of very low quality. CONCLUSION: Most psychosocial intervention randomized controlled trials assessing foot ulcer outcomes in people with diabetes were prevention studies, and most interventions were primarily educational. Ulcer healing and development were not well reported. There is a need for better understanding of psychological and behavioural influences on ulcer incidence, healing and recurrence in people with diabetes. Randomized controlled trials of theoretically informed interventions, which assess clinical outcomes, are urgently required. (PROSPERO registration: CRD42016052960).

Psychosocial and behavioural prognostic factors for diabetic foot ulcer development and healing: a systematic review.

AIM: To investigate whether ulceration, amputation and healing of foot ulcers in people living with diabetes are associated with psychosocial and behavioural factors. METHODS: We searched MEDLINE, Embase, PsychINFO, CINAHL and The Cochrane Library to March 2019 for longitudinal studies with multivariable analyses investigating independent associations. Two reviewers extracted data and assessed risk of bias. RESULTS: We identified 15 eligible studies involving over 12 000 participants. Clinical and methodological heterogeneity precluded meta-analysis, so we summarize narratively. Risk of bias was moderate or high. For ulceration, we found significantly different results for people with and without an ulcer history. For those with no ulcer history, moderate quality evidence suggests depression increases ulcer risk [three studies; e.g. hazard ratio (HR) 1.68 (1.20, 2.35) per Hospital Anxiety and Depression Scale (HADS) standard unit]. Better foot self-care behaviour reduces ulcer risk [HR 0.61 (0.40, 0.93) per Summary of Diabetes Self-Care Activities scale standard unit; one study]. For people with diabetes and previous ulcers, low- or very low-quality evidence suggests little discernible association between ulcer recurrence and depression [e.g. HR 0.88 (0.61, 1.27) per HADS standard unit], foot self-care, footwear adherence or exercise. Low-quality evidence suggests incomplete clinic attendance is strongly associated with amputation [odds ratio (OR) 3.84 (1.54, 9.52); one study]. Evidence for the effects of other psychosocial or behavioural factors on ulcer healing and amputation is very low quality and inconclusive. CONCLUSIONS: Psychosocial and behavioural factors may influence the development of first ulcers. More high quality research is needed on ulcer recurrence and healing. (Open Science Framework Registration: https://osf.io/ej689).

Prevalence of active Charcot disease in the East Midlands of England.

AIMS: To undertake a prospective point prevalence study of the prevalence of active Charcot neuro-inflammatory osteoarthropathy (Charcot disease) in a circumscribed part of England and to audit the time elapsing between disease onset and first diagnosis. METHODS: The prevalence of active Charcot disease of the foot during a single month was assessed by specialist foot care teams at seven secondary care services in the East Midlands region of England. RESULTS: A total of 90 cases were identified, representing 4.3 per 10 000 of the 205 033 total diabetes population of the region. The time elapsed from first presentation to any healthcare professional until diagnosis was also assessed. While the diagnosis was suspected or confirmed in one-third of patients within 2 weeks, it was not made for 2 months or more in 23 patients (24%). CONCLUSIONS: Non-specialist professionals should have greater awareness of the existence of this uncommon complication of diabetes in the hope that earlier diagnosis will lead to lesser degrees of deformity.

Management of adults with diabetes on the haemodialysis unit: summary of guidance from the Joint British Diabetes Societies and the Renal Association.

Diabetic nephropathy remains the principal cause of end-stage renal failure in the UK and its prevalence is set to increase. People with diabetes and end-stage renal failure on maintenance haemodialysis are highly vulnerable, with complex comorbidities, and are at high risk of adverse cardiovascular outcomes, the leading cause of mortality in this population. The management of people with diabetes receiving maintenance haemodialysis is shared between diabetes and renal specialist teams and the primary care team, with input from additional healthcare professionals providing foot care, dietary support and other aspects of multidisciplinary care. In this setting, one specialty may assume that key aspects of care are being provided elsewhere, which can lead to important components of care being overlooked. People with diabetes and end-stage renal failure require improved delivery of care to overcome organizational difficulties and barriers to communication between healthcare teams. No comprehensive guidance on the management of this population has previously been produced. These national guidelines, the first in this area, bring together in one document the disparate needs of people with diabetes on maintenance haemodialysis. The guidelines are based on the best available evidence, or on expert opinion where there is no clear evidence to inform practice. We aim to provide clear advice to clinicians caring for this vulnerable population and to encourage and improve education for clinicians and people with diabetes to promote empowerment and self-management.

New horizons in the understanding of the causes and management of diabetic foot disease: report from the 2017 Diabetes UK Annual Professional Conference Symposium.

Diabetes-related foot disease remains a common problem. For wounds, classic teaching recommends the treatment of any infection, offloading the wound and ensuring a good blood supply, as well as ensuring that the other modifiable risk factors are addressed and optimized. There remain, however, several questions about these and other aspects of the care of diabetes-related foot disease. Some of these questions are addressed in the present report; in particular, the impact of newer technologies in the identification of any organisms present in a wound, as well as the use of novel approaches to treat infections. The use of new remote sensing technology to identify people at risk of developing foot ulceration is also considered, in an attempt to allow early intervention and prevention of foot ulcers. The psychological impact of foot disease is often overlooked, but with an increasing number of publications on the subject, the cause-and-effect role that psychology plays in foot disease, such as ulcers and Charcot neuroarthropathy, is considered. Finally, because of heterogeneity in diabetic foot studies, comparing results is difficult. A recently published document focusing on ensuring a standardized way of reporting foot disease trials is discussed.

Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review.

The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality.

Use of HSI to measure oxygen saturation in the lower limb and its correlation with healing of foot ulcers in diabetes.

AIM: To explore the use of hyperspectral imaging (HSI) to predict healing of diabetic foot ulcers in patients with diabetes. METHODS: We used a HSI technique that incorporated novel software to account for tissue scattering of light, and was validated using blood samples of varying oxygen saturation assessed by blood gas analysis. HSI was then performed on a population newly presenting with diabetic foot ulcers to a specialist clinic, and associations were sought with healing at 12 and 24 weeks. RESULTS: The correlation between the results of HSI and blood gas analysis was strong (r = 0.994). A total of 43 patients (mean ± sd age 62.7 ± 12.2 years; 31 men, 12 women; 37 with Type 2 diabetes, six with Type 1 diabetes) with foot ulcers were included in the prospective clinical study and underwent HSI within 16 days of presentation. In all, 26 ulcers healed within 12 weeks and 28 within 24 weeks. There was a negative association between tissue oxygenation assessed by HSI at baseline and healing by 12 weeks (P = 0.009), and this was observed in both infected and non-infected ulcers. There was a significant positive correlation between oxygenation assessed by HSI and time to healing (P = 0.03). No correlations were observed at 24 weeks. CONCLUSIONS: These findings suggest that HSI may predict healing in routine practice. The fact that the correlation between HSI and healing was negative could be explained by HSI being a measure of oxygenation of haemoglobin and there may be an inverse relationship between this and the oxygenation of extravascular tissue in people with neuropathy and/or microvascular disease.

Chronic kidney disease and the foot in diabetes--is inflammation the missing link?

Diabetes is commonly complicated by the development of chronic kidney disease (CKD). Equally prevalent is the development of diabetic foot disease and it is now recognised that there is a higher risk of the development of foot disease and major amputation in those patients with CKD. This is particularly marked in those patients with end-stage kidney disease receiving renal replacement therapy for which there are many possible mechanisms, including the effect of dialysis on tissue hypoxia. What has been recognised recently is that the risk of the development of foot disease appears to start prior to the onset of renal replacement therapy. Whilst this may be due to the fact that the emphasis of care shifts towards the requirements of the patients' renal disease, here we discuss the possibility that the presence of a foot ulcer itself may contribute to the development or progression of CKD through repeated episodes of sepsis or chronic inflammation, or both.

Audit of acute Charcot's disease in the UK: the CDUK study.

AIMS/HYPOTHESIS: We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. METHODS: Clinicians managing cases of acute Charcot foot in the UK and Ireland between June 2005 and February 2007 were invited to register anonymised details on a secure website. RESULTS: A total of 288 cases (age 57.0 ± 11.3 years [mean ± SD]; 71.2% male) were registered from 76 centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder (p = 0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p = 0.005). CONCLUSIONS/INTERPRETATION: The median time to resolution was longer than in earlier series. Although limited by being observational and non-randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial.

A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes.

The outcome of management of diabetic foot ulcers is poor, and there is continuing uncertainty concerning optimal approaches to management. It was for these reasons that in 2006 the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing undertook a systematic review of the evidence to inform protocols for routine care and to highlight areas which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between December 2006 and June 2010. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae and hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; hyperbaric oxygen therapy (HBOT); compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound; other systemic therapies which did not fit in the above categories. Heterogeneity of studies prevented pooled analysis of results. Of the 1322 papers identified, 43 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic review, but the conclusion is similar: that with the exception of HBOT and, possibly, negative pressure wound therapy, there is little published evidence to justify the use of newer therapies. This echoes the conclusion of a recent Cochrane review and the systematic review undertaken by the National Institute for Health and Clinical Excellence Guidelines Committee in the UK. Analysis of evidence presents considerable difficulties in this field particularly as controlled studies are few and the majority are of poor methodological quality.

Clinical evaluation of a new device in the assessment of peripheral sensory neuropathy in diabetes.

AIMS: Current National Institute for Health and Clinical Excellence guidelines state that patients with diabetes should have annual examination of their feet to exclude signs of sensory impairment. The VibraTip is a new disposable device producing a vibratory stimulus, which has been developed in order to screen for peripheral sensory neuropathy in diabetes. This study was designed to evaluate the device by assessing intra-rater reliability and comparing the ability of the VibraTip to detect or exclude peripheral sensory neuropathy with other bedside methods. METHODS: One hundred and forty-one patients with diabetes (Type 1 or Type 2) were examined for diabetic peripheral sensory neuropathy using a Neurothesiometer, 10-g monofilament, a 128-Hz tuning fork, a Neurotip™ and a VibraTip. The failure to perceive the Neurosthesiometer stimulus at ≥ 25 V in either foot was considered the reference method for the presence of peripheral sensory neuropathy. Receiver operating characteristic curves were produced for each device and the sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of peripheral sensory neuropathy were calculated. Repeat testing with the VibraTip was performed in 18 patients and intra-rater reliability assessed using Cronbach alpha. RESULTS: Analysis of the area under the receiver operating characteristic curves showed that the 10-g monofilament was significantly better than the 128-Hz tuning fork (P = 0.0056) and the Neurotip (P = 0.0022), but was no different from the VibraTip (P = 0.3214). The alpha coefficient for the VibraTip was calculated to be 0.882, indicating good reliability. CONCLUSIONS: The VibraTip is a device comparable with the 10-g monofilament and therefore could be considered a useful tool for screening for peripheral sensory neuropathy in diabetes.

Recurrence of the acute Charcot foot in diabetes.

BACKGROUND: The acute Charcot foot is thought to occur in people who have a number of predisposing factors, of which distal neuropathy is the most important. But while occurrence in the contralateral foot is not infrequent, recurrence in the same foot seems to be very rare. CASE REPORT: A case is described in which discrete episodes of inflammation of the midfoot occurred in the same foot over a period of 14 years, and were attributed to acute Charcot neuroarthropathy (Charcot foot). There was coincidental evidence of osteomyelitis of the 4(th) toe but there was no suspicion that the inflammatory episodes of the midfoot were the result of bone infection and they settled without treatment with antibiotics. CONCLUSION: This case had clinically diagnosed recurrences of inflammation and destruction typical of the acute Charcot foot over an extended period, and this is most unusual. The implications of the rarity of such recurrences are discussed.

Foot care education in patients with diabetes at low risk of complications: a consensus statement.

AIMS: To define and agree a practical educational framework for delivery by all healthcare professionals managing patients with diabetes, particularly those at low risk of developing foot complications. METHODS: A consensus meeting of a multidisciplinary expert panel. Prior to the meeting, relevant clinical papers were disseminated to the panel for review. The consensus was largely based upon the experts' clinical experience and judgement. RESULTS: Four main health behaviours were identified for those at low risk of developing foot complications, namely: control of blood glucose levels; attendance at annual foot screening examination; reporting of any changes in foot health immediately; and the engagement in a simple daily foot care routine. CONCLUSION: There is currently little evidence-based literature to support specific foot care practices. Patients with diabetes at low risk of developing complications should be encouraged to undertake a basic foot care regimen to reduce their likelihood of developing complications.

Medial arterial calcification in diabetes and its relationship to neuropathy.

Calcification of the media of arterial walls is common in diabetes and is particularly associated with distal symmetrical neuropathy. Arterial calcification also complicates chronic kidney disease and is an independent risk factor for cardiovascular and all-cause mortality. The term calcification is not strictly accurate because the morphological changes incorporate those of new bone formation, i.e. ossification. The processes are complex, but are closely related to those involved in bone homeostasis, and it is relevant that calcification of the arterial wall and osteopenia often co-exist. One particular factor linked to the development of arterial calcification is distal symmetrical neuropathy; indeed, it has been suggested that neuropathy explains the distal distribution of arterial calcification in diabetes. It has also been suggested that the link with neuropathy results from loss of neuropeptides, such as calcitonin gene-related peptide, which are inherently protective. The association between distal symmetrical neuropathy and calcification of the arterial wall highlights the fact that neuropathy may be an independent risk factor for cardiovascular mortality.

Comparison of four systems of classification of diabetic foot ulcers in Tanzania.

AIMS: The aim was to compare the use of four different systems of foot ulcer classification in a consecutive population with diabetes presenting to a specialist clinic in Dar es Salaam, Tanzania. METHODS: Clinical data were collected prospectively in all patients presenting with foot ulcers between 3 January 2003 and 30 September 2005, and were used retrospectively to classify their ulcers using the Meggitt/Wagner, University of Texas (UT), Size (Area and Depth), Sepsis, Arteriopathy, and Denervation [S(AD)SAD] and Perfusion, Extent/size, Depth/tissue loss, Infection and Sensation (PEDIS) systems. Comparison was made between the strength of the associations between baseline characteristics of each system and outcome determined at 5 December 2005, using linear by linear association. RESULTS: The strongest statistical associations (P < 0.001) were observed between percent healing and Wagner score (chi(2)= 85.923), depth [S(AD)SAD, PEDIS and UT grade, 70.558], infection [S(AD)SAD, 61.774; PEDIS, 37.924] and UT stage (32.929). Weaker but significant (P < 0.001) associations were observed between percent healing and neuropathy [S(AD)SAD, PEDIS 12.475] and peripheral arterial disease [S(AD)SAD, PEDIS 10.799], as well as cross-sectional area [S(AD)SAD 4.387, P = 0.036]. CONCLUSION: The strength of the statistical association between outcome and both neuropathy and infection contrasts with findings in series previously reported from the USA and UK, and highlights the differences which may be found in different populations. These differences have implications for any system of classification chosen to compare the effectiveness of management in different centres in different countries.

Altered composition of high density lipoproteins in women with the polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) appear at increased cardiovascular risk due in part to a dyslipidemia characterized by increased plasma triglyceride and reduced high density lipoprotein (HDL) cholesterol levels. This is a detailed exploratory study of HDL composition in 35 obese [body mass index (BMI), > 27] and 22 nonobese subjects with PCOS and in 14 healthy obese and 18 nonobese women. Although we found reduced levels of total and HDL2 cholesterol in obese women with PCOS, HDL composition was modified by depletion of lipid relative to protein, with reduced ratios of HDL total cholesterol and HDL phospholipids to apolipoprotein A-I (apoA-I) compared to those in obese controls (P = 0.008 and P = 0.012, respectively). This was explained by reduced cholesterol (P = 0.004) and phospholipid (although not significant, P = 0.07) in HDL with no change in the content of apoA-I, its major protein. Obesity, insulin resistance, and hyperandrogenemia are features of PCOS and potentially affect lipid metabolism. Insulin sensitivity was assessed by the reduction in endogenous glucose concentration after exogenous insulin; the insulin, glucose, and fatty acid responses to oral glucose; and the fasting insulin concentration. When age, BMI, free androgen index, insulin sensitivity determined by all methods, and the presence of PCOS were subjected to stepwise multivariate regression analysis, the presence of PCOS was the most consistent predictor of lipid-depleted HDL (HDL total cholesterol/apoA-I and HDL phospholipids/apoA-I). We speculate that altered activity of hepatic lipase or lipid transfer protein could explain this aspect of the dyslipidemia. Obesity has an important influence on the lipid profile. Obese PCOS and control subjects had higher levels of cholesterol, triglyceride, apoB, and fatty acids than their lean counterparts, and BMI proved the best predictor of blood levels on multiple regression analysis. In contrast, lean PCOS patients had normal sensitivity to insulin and lipid profiles similar to those of the lean controls and did not manifest the HDL abnormalities. Although in PCOS, correlations were obtained between the free androgen index and cholesterol, triglyceride, and apoB levels and between the integrated glucose and insulin responses after oral glucose and fasting fatty acid and triglyceride levels, when age and adiposity were included as covariates only fatty acids and the integrated glucose response remained significantly correlated. Among the controls, total, low density lipoprotein cholesterol, triglycerides, and apoB were related to aspects of insulin sensitivity independent of age and BMI. Lipid metabolism in PCOS is dependent on several related factors, but subjects with PCOS who are obese show a specific reduction in HDL lipid, suggesting a reduced capacity for cholesterol removal from tissues with diminished antiatherogenic potential. Efforts should be directed toward reducing obesity in PCOS to improve the metabolic disturbance in addition to ameliorating the presenting symptoms.

Reduced serum lipoprotein(a) levels in patients with primary biliary cirrhosis.

Lipoprotein(a) (Lp(a)) is a unique lipoprotein, elevated serum levels of which are independently associated with an increased risk of coronary heart disease (CHD). Primary biliary cirrhosis (PBC) is often associated with high serum cholesterol, itself a risk factor for CHD. Despite this, patients with PBC are thought to have a lower than expected incidence of CHD. We hypothesised that this may be related to low serum levels of Lp(a) in PBC patients. This was investigated by collecting fasting blood samples from 42 patients with PBC, 39 age- and sex-matched subjects with non-PBC liver disease and 432 community control subjects. Serum was analysed for total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and apolipoproteins A1 and B (apo A1 and apo B). Lp(a) was measured by an enzyme-linked immunosorbent assay (ELISA) technique. There was a significant reduction of Lp(a) concentrations in the PBC group compared with the healthy controls (median value 28.5 mg/l vs. 75.0 mg/l, P < 0.005) and between the non-PBC liver disease group (median value 52.0 mg/l) and control group (P = 0.001). Within both the liver disease and PBC patient groups there were significant negative correlations between Lp(a) levels and bilirubin (R = -0.564, P < 0.001 and R = -0.395, P = 0.010 respectively). This preliminary study has demonstrated reduced Lp(a) levels in PBC patients which may be a contributory factor to explain a possible cardioprotective effect in such patients, despite elevated LDL cholesterol levels.

A simple, sensitive technique for classification of apolipoprotein(a) isoforms by sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

Lipoprotein(a) (Lp(a)) is a lipoprotein containing a unique glycoprotein, apolipoprotein(a) (apo(a)), which shows considerable heterogeneity of apparent molecular mass on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). A unifying classification of isoform has been lacking. A simple sensitive procedure for classifying apo(a) isoforms was developed in which the relative mobility of apo(a) on SDS-PAGE was related to that of apolipoprotein (apo) B-100 (Rf vs B). After Western blotting apo(a) bands were visualised by a sensitive double antibody technique employing commercial polyclonal antibodies (sheep antihuman Lp(a) antibody, alkaline phosphatase-linked donkey antisheep antibody). The technique was sensitive (lower limit of detection 0.02 micrograms apo(a)) and had good reproducibility (coefficient of variation 0.9-6.4%). Ten isoform mobilities are described (less than 0.35, 0.40, 0.50, 0.60, 0.70, 0.80, 1.0, 1.10, greater than 1.15). Individuals may have single or double band phenotypes. This classification is compatible with those previously described and the method is suitable for many laboratories, as it employs standard equipment and commercially available materials.