Can the introduction of a 12-lead ECG help reduce mortality in those presenting with foot ulceration to multidisciplinary diabetic foot clinics? An observational evaluation of a real-world implementation pilot in England.

AIMS/HYPOTHESIS: The risk of dying within 2 years of presentation with diabetic foot ulceration is over six times the risk of amputation, with CVD the major contributor. Using an observational evaluation of a real-world implementation pilot, we aimed to assess whether for those presenting with diabetic foot ulceration in England, introducing a 12-lead ECG into routine care followed by appropriate clinical action was associated with reduced mortality. METHODS: Between July 2014 and December 2017, ten multidisciplinary diabetic foot services in England participated in a pilot project introducing 12-lead ECGs for new attendees with foot ulceration. Inception coincided with launch of the National Diabetes Footcare Audit (NDFA), whereby all diabetic footcare services in England were invited to enter data on new attendees with foot ulceration. Poisson regression models assessed the mortality RR at 2 and 5 years following first assessment of those receiving care in a participating pilot unit vs those receiving care in any other unit in England, adjusting for age, sex, ethnicity, deprivation, type and duration of diabetes, ulcer severity, and morbidity in the year prior to first assessment. RESULTS: Of the 3110 people recorded in the NDFA at a participating unit during the pilot, 33% (1015) were recorded as having received an ECG. A further 25,195 people recorded in the NDFA had attended another English footcare service. Unadjusted mortality in the pilot units was 16.3% (165) at 2 years and 37.4% (380) at 5 years for those who received an ECG, and 20.5% (430) and 45.2% (950), respectively, for those who did not receive an ECG. For people included in the NDFA at other units, unadjusted mortality was 20.1% (5075) and 42.6% (10,745), respectively. In the fully adjusted model, mortality was not significantly lower for those attending participating units at 2 (RR 0.93 [95% CI 0.85, 1.01]) or 5 years (RR 0.95 [95% CI 0.90, 1.01]). At participating units, mortality in those who received an ECG vs those who did not was lower at 5 years (RR 0.86 [95% CI 0.76, 0.97]), but not at 2 years (RR 0.87 [95% CI 0.72, 1.04]). Comparing just those that received an ECG with attendees at all other centres in England, mortality was lower at 5 years (RR 0.87 [95% CI 0.78, 0.96]), but not at 2 years (RR 0.86 [95% CI 0.74, 1.01]). CONCLUSIONS/INTERPRETATION: The evaluation confirms the high mortality seen in those presenting with diabetic foot ulceration. Overall mortality at the participating units was not significantly reduced at 2 or 5 years, with confidence intervals just crossing parity. Implementation of the 12-lead ECG into the routine care pathway proved challenging for clinical teams-overall a third of attendees had one, although some units delivered the intervention to over 60% of attendees-and the evaluation was therefore underpowered. Nonetheless, the signals of potential mortality benefit among those who had an ECG suggest that units in a position to operationalise implementation may wish to consider this. DATA AVAILABILITY: Data from the National Diabetes Audit can be requested through the National Health Service Digital Data Access Request Service process at: https://digital.nhs.uk/services/data-access-request-service-dars/dars-products-and-services/data-set-catalogue/national-diabetes-audit-nda.

The foot in diabetes - a reminder of an ever-present risk.

The term 'diabetic foot disease' (DFD) often signifies the presence of foot ulceration and infection, but one must also be wary of the rarer occurrence of Charcot foot disease. The worldwide prevalence of DFD is 6.3% (95%CI: 5.4-7.3%). Foot complications present a major challenge to both patients and healthcare systems, with increased rates of hospitalisation and an almost trebled 5-year mortality. The Charcot foot often occurs in patients with long-standing diabetes, presenting as an inflamed or swollen foot or ankle, following unrecognised minor trauma. This review focuses on the prevention and early identification of the 'at-risk' foot. DFD is best managed by a multi-disciplinary foot clinic team consisting of podiatrists and healthcare professionals. This ensures a combination of expertise and provision of a multi-faceted evidence-based treatment plan. Current research using endothelial progenitor cells (EPC) and mesenchymal stem cells (MSC) offers a new dimension in wound management.

The pressure time integral: An underused, clinically significant parameter as a determinant of neuropathic ulceration in diabetes.

BACKGROUND: The purpose of this study was to evaluate plantar pressure dynamics in the occurrence of active diabetic neuropathic ulceration (DNU) and any changes in loadings occurring in individuals with a history of diabetic neuropathic ulceration (DHNU). Since current gold standard offloading strategies are not producing desirable healing outcomes and optimum ulcer prevention, this study aimed to better understand the effect of diabetic peripheral neuropathy (DPN) and ulceration on mean peak plantar pressure (MPPP) and pressure-time integral (PTI) changes. RESEARCH QUESTION: Is there a redistribution of plantar pressure during gait in the presence of active and history of diabetic neuropathic ulceration? METHODS: A prospective, cross-sectional study was conducted, in which, eighty adult participants were divided into four groups, namely, the DM, DPN, DNU and DHNU groups. Participants were instructed to walk barefoot over a Tekscan HR Mat™ at self-selected speed. MPPP and PTI data were analysed under five forefoot anatomical landmarks and compared between individuals with and without active neuropathic ulceration. RESULTS: Minimal MPPP significant changes were observed between ulcerated and non-ulcerated groups, however, PTI values were significantly increased in the ulcerated groups under all plantar ulceration regions. No significant plantar pressure differences were observed between the DNU and DHNU groups. Logistic regression tests demonstrated that as PTIs under the hallux increase, the likelihood of an individual living with DPN developing ulceration increases. SIGNIFICANCE: A significant increase in PTI values in the presence of ulceration highlights the importance of evaluating the duration of loads under forefoot regions during gait rather than just focusing on the magnitude of pressures during ulcer management and prevention. Moreover, results show that PTI values remain high in the presence of a history of neuropathic ulceration, possibly demonstrating the value of PTI as a clinical tool over MPPP in the assessment of the high-risk diabetic foot.

Predicting Diabetic Neuropathy Risk Level Using Artificial Neural Network and Clinical Parameters of Subjects With Diabetes.

BACKGROUND: A risk assessment tool has been developed for automated estimation of level of neuropathy based on the clinical characteristics of patients. The smart tool is based on risk factors for diabetic neuropathy, which utilizes vibration perception threshold (VPT) and a set of clinical variables as potential predictors. METHODS: Significant risk factors included age, height, weight, urine albumin-to-creatinine ratio, glycated hemoglobin, total cholesterol, and duration of diabetes. The continuous-scale VPT was recorded using a neurothesiometer and classified into three categories based on the clinical thresholds in volts (V): low risk (0-20.99 V), medium risk (21-30.99 V), and high risk (≥31 V). RESULTS: The initial study had shown that by just using patient data (n = 5088) an accuracy of 54% was achievable. Having established the effectiveness of the "classical" method, a special Neural Network based on a Proportional Odds Model was developed, which provided the highest level of prediction accuracy (>70%) using the simulated patient data (n = 4158). CONCLUSION: In the absence of any assessment devices or trained personnel, it is possible to establish with reasonable accuracy a diagnosis of diabetic neuropathy by means of the clinical parameters of the patient alone.

The effect of induced joint restriction on plantar pressure during gait - a pilot study.

BACKGROUND: The aim of this study was to analyse the effect of induced lower limb joint restriction on plantar pressures during gait. Focusing on restricting a single joint, without the effect of other co-morbidities, would provide better understanding as to the resultant plantar loadings during gait, which would be especially beneficial in patients requiring offloading procedures. RESEARCH QUESTION: Does induced lower limb joint restriction affect plantar pressure distribution during gait? METHODS: A prospective, quasi-experimental study was conducted, recruiting ten healthy, adult participants who were instructed to walk barefoot over a Tekscan HR Mat™. This procedure was repeated after separately inducing restriction of the hip, knee and ankle joints. Mean peak plantar pressure (MPP) and pressure-time integral (PTI) data were analysed to compare between unrestricted and restricted data. RESULTS: Significant plantar pressure changes were observed in the heel and first metatarsal regions. Rearfoot PTIs were increased with restriction of the contralateral hip (left p <0.001) (right p =0.02) and knee joints (left p =0.01) (right p =0.04). Both MPPs (left p =0.01; right p =0.01) and PTIs (left p =0.004; right p =0.03) were increased in the first metatarsal when restricting the hip joint of the same limb. MPP was decreased in the left first metatarsal with induced knee (left p =0.01; right p =0.04) and ankle (left and right p <0.001) joint restriction. Finally, MPP was decreased in the right first metatarsal with knee (left and right p =0.01) and ankle (left p =0.04; right p =0.01) joint restriction. SIGNIFICANCE: Limited joint mobility may have a direct effect on plantar pressure, particularly with restriction in the hip and knee joints, hence careful attention should be given especially in patients with conditions involving plantar loadings. Results in this study also show that PTI changes during gait should be equally evaluated clinically along with peak plantar pressure analysis.

A brown tumor secondary to hyperparathyroidism in the maxilla, skull, scapula, and femora.

Primary hyperparathyroidism presenting with diffuse skeletal involvement, such as discrete osteoclastic bone lesions, is rare. We describe a 35-year-old woman who presented with a left mandibular mass that rapidly enlarged over 3 weeks. Radiological, histological, and biochemical investigations led to the diagnosis of brown tumor secondary to primary hyperparathyroidism. A neck ultrasound revealed a 1.5 × 2.3 × 4.6 cm mass at the lower pole of the left thyroid lobe, suggestive of a parathyroid adenoma. Bone scan showed additional abnormal foci of increased uptake in the maxilla, both femora, skull, and scapula. Brown tumors are treated primarily by correcting the underlying endocrine disorder, and a parathyroidectomy was performed.

Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life.

OBJECTIVE: Chronic diabetic peripheral neuropathic pain (DPNP) is difficult to treat, with treatment regimens often inadequate at controlling pain and limited by side effects and drug tolerance. Secondary parameters, such as quality of sleep and mood, may also be important for successful DPNP management. The objectives of this study were to compare the analgesic efficacy of pregabalin, amitriptyline, and duloxetine, and their effect on polysomnographic sleep, daytime functioning, and quality of life in patients with DPNP. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, parallel group investigation of type 1 and 2 diabetic subjects with DPNP. Each treatment group had a single-blind, 8-day, placebo run-in followed by 14 days of lower-dose and 14 days of higher-dose medication. At the end of each dose titration period, subjective pain, sleep, and daytime functioning were assessed during a 2-day residential period. RESULTS: All medications reduced pain when compared with placebo, but no one treatment was superior to any other. For sleep, pregabalin improved sleep continuity (P < 0.001), whereas duloxetine increased wake and reduced total sleep time (P < 0.01 and P < 0.001). Despite negative effects on sleep, duloxetine enhanced central nervous system arousal and performance on sensory motor tasks. There were no significant safety findings; however, there was a significantly higher number of adverse events in the pregabalin treatment group. CONCLUSIONS: There was no significant difference in analgesic efficacy between amitriptyline, duloxetine, and pregabalin. However, there were significant differences in the secondary parameters, which may be of relevance when deciding the optimal treatment for DPNP.

Acute hypoglycemia decreases myocardial blood flow reserve in patients with type 1 diabetes mellitus and in healthy humans.

BACKGROUND: Hypoglycemia is associated with increased cardiovascular mortality, but the reason for this association is poorly understood. We tested the hypothesis that the myocardial blood flow reserve (MBFR) is decreased during hypoglycemia using myocardial contrast echocardiography in patients with type 1 diabetes mellitus (DM) and in healthy control subjects. METHODS AND RESULTS: Twenty-eight volunteers with DM and 19 control subjects underwent hyperinsulinemic clamps with maintained sequential hyperinsulinemic euglycemia (plasma glucose, 90 mg/dL [5.0 mmol/L]) followed by hyperinsulinemic hypoglycemia (plasma glucose, 50 mg/dL [2.8 mmol/L]) for 60 minutes each. Low-power real-time myocardial contrast echocardiography was performed with flash impulse imaging using low-dose dipyridamole stress at baseline and during hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia. In control subjects, MBFR increased during hyperinsulinemic euglycemia by 0.57 U (22%) above baseline (B coefficient, 0.57; 95% confidence interval, 0.38 to 0.75; P<0.0001) and decreased during hyperinsulinemic hypoglycemia by 0.36 U (14%) below baseline values (B coefficient, -0.36; 95% confidence interval, -0.50 to -0.23; P<0.0001). Although MBFR was lower in patients with DM at baseline by 0.37 U (14%; B coefficient, -0.37; 95% confidence interval, -0.55 to -0.19; P=0.0002) compared with control subjects at baseline, the subsequent changes in MBFR during hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia in DM patients were similar to that observed in control subjects. Finally, the presence of microvascular complications in the patients with DM was associated with a reduction in MBFR of 0.52 U (24%; B coefficient, -0.52; 95% confidence interval, -0.70 to -0.34; P<0.0001). CONCLUSIONS: Hypoglycemia decreases MBFR in both healthy humans and patients with DM. This finding may explain the association between hypoglycemia and increased cardiovascular mortality in susceptible individuals.