Monitoring of Charcot neuroarthropathy. A mixed methods, feasibility study

Background: Charcot neuroarthropathy (CN) is a serious complication of diabetes neuropathy which affects the lower limb. The best method to monitor disease progression and, diagnose remission is unknown. Magnetic resonance imaging (MRI) may be useful for monitoring disease, but this has not been evaluated. Furthermore, there is a lack of understanding about people’s experiences of living with CN and receiving treatment. Aim: To investigate the feasibility of using serial MRI to monitor and diagnose remission in CN and to understand people’s experiences of living with CN. Methods: A mixed methods approach was used: 1) a systematic review to assess the effectiveness of techniques for monitoring response to treatment in acute CN; 2) a multicentre, randomised, prospective, two arm, open feasibility study of using serial MRI to monitor CN; 3) a qualitative study to understand people’s experiences of CN. Results: The systematic review showed multiple techniques to monitor response to treatment, but uncertainty remains about their effectiveness. Five sites participated in the feasibility study. Two-thirds of eligible participants agreed to take part. Forty-three participants were recruited. The main reason for ineligibility was a previous episode of CN. Thirteen participants were withdrawn post-randomisation due to an alternative diagnosis. Nineteen participates achieved remission, six did not. This study found that the intervention, serial MRI was achievable, safe, and acceptable. The qualitative study showed that receiving treatment for CN has physical, socio-economic, and psychological consequences, for the individual and their family which extend beyond the burden of wearing an offloading device. Conclusion: The rates of recruitment, retention, data, and MRI completeness show that a definitive study to evaluate the effectiveness of MRI in disease monitoring in CN is justified and feasible. Healthcare professionals should use a more holistic and person-centred approach to supporting individuals with C

Predictors of outcomes in diabetic foot osteomyelitis treated initially with conservative (nonsurgical) medical management: A retrospective study

The optimal way to manage diabetic foot osteomyelitis remains uncertain, with debate in the literature as to whether it should be managed conservatively (ie, nonsurgically) or surgically. We aimed to identify clinical variables that influence outcomes of nonsurgical management in diabetic foot osteomyelitis. We conducted a retrospective study of consecutive patients with diabetes presenting to a tertiary center between 2007 and 2011 with foot osteomyelitis initially treated with nonsurgical management. Remission was defined as wound healing with no clinical or radiological signs of osteomyelitis at the initial or contiguous sites 12 months after clinical and/or radiological resolution. Nine demographic and clinical variables including osteomyelitis site and presence of foot pulses were analyzed. We identified 100 cases, of which 85 fulfilled the criteria for analysis. After a 12-month follow-up period, 54 (63.5%) had achieved remission with nonsurgical management alone with a median (interquartile range) duration of antibiotic treatment of 10.8 (10.1) weeks. Of these, 14 (26%) were admitted for intravenous antibiotics. The absence of pedal pulses in the affected foot (n = 34) was associated with a significantly longer duration of antibiotic therapy to achieve remission, 8.7 (7.1) versus 15.9 (13.3) weeks (P = .003). Osteomyelitis affecting the metatarsal was more likely to be amputated than other sites of the foot (P = .016). In line with previous data, we have shown that almost two thirds of patients presenting with osteomyelitis healed without undergoing surgical bone resection

Systematic review of techniques to monitor remission of acute Charcot-neuroarthropathy in people with diabetes

Aim: The management of acute Charcot neuroarthropathy relies on off-loading which is costly and time-consuming. Published studies have used monitoring techniques with unknown diagnostic precision to detect remission. We performed a systematic review of techniques for monitoring response to offloading in acute Charcot neuroarthropathy. Materials and Methods: We included studies of off-loading which evaluated or described monitoring techniques in acute Charcot neuroarthropathy. PubMed, EMBASE, CINAHL and Cochrane databases were searched (January1993-July 2018). We extracted data from papers including study design, setting, population, monitoring techniques and treatment outcomes. We also extracted information on the cost, clinical applicability, sensitivity and specificity, safety and participant acceptability of the monitoring techniques. Results: We screened 1205 titles, 140 abstracts and 45 full-texts, and included 29 studies. All studies were of low quality and at high risk of bias. In seven studies, the primary aim was to evaluate monitoring techniques: three evaluated magnetic resonance imaging, two thermography monitoring, one three-phase bone scanning and one Doppler spectrum analysis. The remaining 22 observational studies reported treatment outcomes and described the monitoring techniques used to assess the Charcot neuroarthropathy. Heterogeneity prevented the pooling of data. Very few studies included data on cost, clinical applicability, sensitivity and specificity, safety and patient acceptability of the monitoring techniques used. Conclusion: Multiple techniques have been used to evaluate remission in acute Charcot neuroathropathy but uncertainty remains about their effectiveness. We recommend further research into the influences of different monitoring techniques on treatment outcomes

Mitochondrial dysfunction is the cause of one of the earliest changes seen on magnetic resonance imaging in Charcot neuroarthopathy – Oedema of the small muscles in the foot

The hypothesis laid out in this thesis states that the early changes seen on an MR imaging in those with early Charcot neuroarthopathy may be due to mitochondrial dysfunction. In a Charcot foot, there is movement between bones. In an attempt to prevent this movement, the small muscles of the foot contract continuously when the foot is weight bearing. This contraction takes energy in the form of ATP. However, the reduction of glucose transport into the muscle cells due to insulin resistance / insufficiency, leads to reduction in the ATP producing capacity of the mitochondria. The ATP depletion affects the cell membrane gradient leading to mitochondrial and cellular swelling. These early cellular changes could then be picked up with MR imaging as muscle oedema

A qualitative study to understand people’s experiences of living with Charcot neuroarthropathy

Aims: Charcot neuroarthropathy (CN) is a complication of neuropathy, in people with diabetes. Treatment requires the prolonged wearing of an offloading device, which can be challenging. The importance of understanding people’s perspectives for promoting their engagement in self-management is well known. However, no such studies have been done in CN. This qualitative study aimed to understand people’s experiences of CN. Methods: Semi-structured interviews with a purposive sample of 14 participants with CN, recruited from a randomised controlled trial. We gathered opinions, thoughts, and the meanings participants attributed to their experiences of CN and its physical, socio-economic, and physiological effects and how this affected their families, and relationships. We analysed the interviews using Inductive Thematic Analysis. Results: Four analytic themes were identified: 1) ‘Trapped at home isolated and missing social life and daily life routines’; 2) ‘Disruption to people’s roles, responsibilities, relationships, and mobility, which people adapted to try and address and manage’; 3) ‘Pain which participants related to the direct or indirect consequences of wearing the cast or boot’; 4) ‘Blame for developing CN, attributed to themselves and healthcare professionals’. Participants described guilt about needing more support, expressing frustration, low mood, and low self-esteem. Conclusion: This study highlights experiential aspects of the previously unrecognised burden of CN. Its physical, social, and emotional impact on participants and their families is substantial and sustained. There is a need to raise clinical awareness of CN and its wider effects

The impact of glycaemic variability on wound healing in the diabetic foot – a retrospective study of new ulcers presenting to a specialist multidisciplinary foot clinic

Aims: Glycaemic variability – the visit-to-visit variation in HbA1c – plays a possible role in the development of micro and macrovascular disease in patients with diabetes. Whether HbA1c variability is a factor determining wound healing in diabetic foot ulcers remains unknown. We aimed to determine whether HbA1c variability is associated with foot ulcer healing time. Methods: A retrospective analysis of patients presenting to our specialist multidisciplinary foot clinic between July 2013 and March 2015, with at least three HbA1c measurements within five years of presentation and more than two follow-up reviews. HbA1c variation was measured by magnitude of standard deviation. Results: 629 new referrals were seen between July 2013 and March 2015. Of these, 172 patients had their number of days to healing recorded and sufficient numbers of HbA1c values to determine variability. The overall geometric mean days to heal was 91.1 days (SD 80.8 to 102.7). In the low HbA1c variability group the geometric mean days to heal was 78.0 days (60.2 to 101.2) vs 126.9 days (102.0 to 158.0) in the high Hb1Ac variability group (p=0.032). Those with low HbA1c (< 58 mmol/mol) and low variability healed faster than those with high HbA1c and high variability (73.5 days [59.5 to 90.8] vs 111.0 days [92.0 to 134.0], p=0.007). Additionally, our results show that time to healing is more dependent on the mean HbA1c than the variability in HbA1c (p=0.007). Conclusions/interpretation: Our data suggest that there was a significant association between HbA1c variability and healing time in diabetic foot ulcers

Controversies in the management of active Charcot neuroarthropathy

Charcot neuroarthropathy (CN) was first described over 150 years ago. Despite this there remains uncertanity around the factors that contribute to its development, and progression. This article will discuss the current controversies around the pathogenesis, epidemiology, diagnosis, assessment and management of the condition. The exact pathogenesis of CN is not fully understood, and it is likely to be multifactorial, with perhaps currently unknown mechanisms contributing to its development. Further studies are needed to examine opportunities to help screen for and diagnose CN. As a result of many of these factors, the true prevalence of CN is still largely unknown. Almost all of the recommendations for the assessment and treatment of CN are based on low-quality level III and IV evidence. Despite recommendations to offer people with CN nonremovable devices, currently only 40–50% people are treated with this type of device. Evidence is also lacking about the optimal duration of treatment; reported outcomes range from 3 months to more than a year. The reason for this variation is not entirely clear. A lack of standardised definitions for diagnosis, remission and relapse, heterogeneity of populations, different management approaches, monitoring techniques with unknown diagnostic precision and variation in follow-up times prevent meaningful comparison of outcome data. If people can be better supported to manage the emotional and physical consequences of CN, then this could improve people’s quality of life and well-being. Finally, we highlight the need for an internationally coordinated approach to research in CN

IWGDF Guideline on Offloading Foot Ulcers in Persons with Diabetes: Part of the 2019 IWGDF Guidelineson the Prevention and Managementof Diabetic Foot Disease

The International Working Group on the Diabetic Foot (IWGDF) has published evidence - based guideline s on the prevention and management of diabetic foot disease since 1999. This guideline is on the use of offloading interventions to promote healing foot ulcers in persons with diabetes and updates the previous IWGDF guideline . We followed the GRADE methodology to devise clinical questions and critically important outcomes in the PICO format , to conduct a systematic review of the medical - scientific literature , and to write recommendations and the irrationale. The recommendations are based on the quality of evidence found in the systematic review , expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. For healing a neuropathic plantar forefoot or midfoot ulcer in a person with diabetes, w e recommend that a non - removable knee - high offloading device is the first - choice of offloading treatment . A removable knee - high and removable ankle - high offloading device are to be considered as the second - and third - choice offloading treatment , respectively , if contraindications or patient intolerance to non - removable offloading exist . Appropriately fitting footwear combine d with felted foam can be considered as the fourth - choice offloading treatment. If non - surgical offloading fails, we recommend to consider surgical offloading interventions for healing metatarsal head and digital ulcers. We have added new recommendations for the use of offloading treatment for healing ulcers that are complicated with infection or ischemia, and for healing plantar heel ulcers. Offloading is arguably the most important of multiple interventions needed to heal a neuropathic plantar foot ulcer in a person with diabetes . Following these recommendations will help health care professionals and teams provide better care for diabetic patients who have a foot ulcer and are at risk for infection, hospitalisation and amputation