Cost-effectiveness of temperature monitoring to help prevent foot ulcer recurrence in people with diabetes: A multicenter randomized controlled trial.

AIMS: Diabetes-related foot ulcers are common, costly, and frequently recur. Multiple interventions help prevent these ulcers. However, none of these have been prospectively investigated for cost-effectiveness. Our aim was to evaluate the cost-effectiveness of at-home skin temperature monitoring to help prevent diabetes-related foot ulcer recurrence. MATERIALS AND METHODS: Multicenter randomized controlled trial. We randomized 304 persons at high diabetes-related foot ulcer risk to either usual foot care plus daily at-home foot skin temperature monitoring (intervention) or usual care alone (control). Primary outcome was cost-effectiveness based on foot care costs and quality-adjusted life years (QALY) during 18 months follow-up. Foot care costs included costs for ulcer prevention (e.g., footwear, podiatry) and for ulcer treatment when required (e.g., consultation, hospitalisation, amputation). Incremental cost-effectiveness ratios were calculated for intervention versus usual care using probabilistic sensitivity analysis for willingness-to-pay/accept levels up to €100,000. RESULTS: The intervention had a 45% probability of being cost-effective at a willingness-to-accept of €50,000 per QALY lost. This resulted from (non-significantly) lower foot care costs in the intervention group (€6067 vs. €7376; p = 0.45) because of (significantly) fewer participants with ulcer recurrence(s) in 18 months (36% vs. 47%; p = 0.045); however, QALYs were (non-significantly) lower in the intervention group (1.09 vs. 1.12; p = 0.35), especially in those without foot ulcer recurrence (1.09 vs. 1.17; p = 0.10). CONCLUSIONS: At-home skin temperature monitoring for diabetes-related foot ulcer prevention compared with usual care is at best equally cost-effective. The intervention resulted in cost-savings due to preventing foot ulcer recurrence and related costs, but this came at the expense of QALY loss, potentially from self-monitoring burdens.

Does the skin heat up before it breaks down in diabetic foot ulceration?

AIMS: Most diabetic foot ulcers are caused by tissue stress from being ambulatory in people without protective sensation. These ulcers are suggested to be preceded by local skin temperature increase due to inflammation of the underlying tissue, a so-called hotspot. Evidence to support this mechanism of ulcer development is meagre at best. We investigated if foot ulcers are preceded by increased skin temperature in people with diabetes and foot ulcer history. MATERIAL AND METHODS: Participants measured temperature at 6-8 plantar foot locations each day for 18 months and identified a hotspot with a temperature difference >2.2°C between corresponding foot locations for two consecutive days. RESULTS: Twenty-nine of 151 participants developed a non-traumatic ulcer while adhering to temperature measurements. In the 2 months prior to ulceration, 8 (28%) had a true hotspot (i.e. at/adjacent to the ulcer location) and the hotspot was on average no longer present 9 days before ulceration. Seven (24%) participants had a false hotspot (i.e. at another location) and 14 (48%) had no hotspot. CONCLUSIONS: The skin of the majority of the ulcers does not heat up before it breaks down or, when it does, not directly before breakdown, questioning the foot temperature increase-uslcer association.

Health-related quality of life and associated factors in people with diabetes at high risk of foot ulceration.

BACKGROUND: The health-related quality of life (HRQoL) of people with diabetes-related foot complications has been increasingly reported, mostly from studies of people with a foot ulcer. The aim of this study was to assess HRQoL and determine factors associated with HRQoL in people with diabetes at high risk of foot ulceration. METHODS: In all, 304 participants enrolled in the Diabetic Foot Temperature Trial (DIATEMP) were included in the cross-sectional analysis. HRQoL was measured by the RAND® 36-Item Short Form Health Survey (SF-36) at baseline. Potential factors associated with HRQoL were analysed using multiple linear regression analyses for the eight domains of the SF-36. RESULTS: Participants were predominantly male (72%), mean age 64.6 (±10.5) years, 77% type 2 diabetes and mean duration of diabetes 20 (±14) years. Mean SF-36 domain scores for the General Health (49.2 ± 20.1), Role Physical (50.9 ± 44.7), Physical Function (58.5 ± 27.9) and Vitality domains (59.8 ± 21.6) were lower compared to the Mental Health (78.4 ± 18.0), Social Functioning (75.3 ± 24.2), Role Emotional (73.5 ± 38.9) and Bodily Pain (67.0 ± 27.0) domains. HRQoL was lower than Dutch population-based and general diabetes samples, but higher than in samples with an ulcer. Use of a walking aid was associated with lower HRQoL across all 8 SF-36 domains (ß range - 0.20 to - 0.50), non-Caucasian descent was associated with lower HRQoL in 5 domains (ß range - 0.13 to - 0.17). Not working, higher BMI and younger age were associated with lower HRQoL in 3 domains. CONCLUSIONS: People at high risk of diabetes-related foot ulceration have reduced HRQoL that varies across domains, with the physical domains most affected. Assessing mobility, ethnicity, BMI and job status may be useful in daily practice to screen for people who might benefit from interventions targeting HRQoL. TRIAL REGISTRATION: Netherlands Trial Registration: NTR5403. Registered on 8 September 2015.

Efficacy of at home monitoring of foot temperature for risk reduction of diabetes-related foot ulcer: A meta-analysis.

AIMS: To perform an updated systematic review of randomised controlled trials examining the efficacy of at-home foot temperature monitoring in reducing the risk of a diabetes-related foot ulcer (DFU). METHODS: Systematic review performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Risk-of-bias was assessed using version 2 of the Cochrane risk-of-bias tool. Meta-analyses were performed using random effect models. Leave-one-out sensitivity analyses and a sub-analysis excluding trials considered at high risk-of-bias assessed the consistency of the findings. The certainty of the evidence was assessed with GRADE. RESULTS: Five randomised controlled trials involving 772 participants meeting the International Working Group on the Diabetic Foot (IWGDF) risk category 2 or 3 were included. All trials reported instructing participants to measure skin temperature at-home at six or more sites on each foot using a hand-held infra-red thermometer at least daily and reduce ambulatory activity in response to hotspots (temperature differences >2.2°C on two consecutive days between similar locations in both feet). One, one, and three trials were considered at low, moderate and high risk-of-bias, respectively. Participants allocated to at-home foot temperature monitoring had a reduced risk of developing a DFU (relative risk 0.51, 95% CI 0.31-0.84) compared to controls. Sensitivity and sub-analyses suggested that the significance of this finding was consistent. The GRADE assessment suggested a low degree of certainty in the finding. CONCLUSIONS: At-home daily foot temperature monitoring and reduction of ambulatory activity in response to hotspots reduce the risk of a DFU in moderate or high risk people with a low level of certainty.

Effectiveness of at-home skin temperature monitoring in reducing the incidence of foot ulcer recurrence in people with diabetes: a multicenter randomized controlled trial (DIATEMP).

INTRODUCTION: The skin of people with diabetic foot disease is thought to heat up from ambulatory activity before it breaks down into ulceration. This allows for early recognition of imminent ulcers. We assessed whether at-home monitoring of plantar foot skin temperature can help prevent ulcer recurrence in diabetes. RESEARCH DESIGN AND METHODS: In this parallel-group outcome-assessor-blinded multicenter randomized controlled trial (7 hospitals, 4 podiatry practices), we randomly assigned people with diabetes, neuropathy, foot ulcer history (<4 years, n=295), or Charcot's neuro-arthropathy (n=9) to usual care (ie, podiatric treatment, education, and therapeutic footwear) or usual care plus measuring skin temperatures at 6-8 plantar sites per foot each day (enhanced therapy). If ∆T>2.2°C between corresponding sites on the left and right foot for two consecutive days, participants were instructed to reduce ambulatory activity until this hotspot disappeared and contact their podiatrist. Primary outcome was ulcer recurrence in 18 months on the plantar foot, interdigital, or medial/lateral/anterior forefoot surfaces; secondary outcome was ulcer recurrence at any foot site. RESULTS: On the basis of intention-to-treat, 44 of 151 (29.1%) participants in enhanced therapy and 57 of 153 (37.3%) in usual care had ulcer recurrence at a primary outcome site (RR: 0.782 (95%CI 0.566 to 1.080), p=0.133). Of the 83 participants in enhanced therapy who measured a hotspot, the 24 subsequently reducing their ambulatory activity had significantly fewer ulcer recurrences (n=3) than those in usual care (RR: 0.336 (95% CI 0.114 to 0.986), p=0.017). Enhanced therapy was effective over usual care for ulcer recurrence at any foot site (RR: 0.760 (95% CI 0.579 to 0.997), p=0.046). CONCLUSIONS: At-home foot temperature monitoring does not significantly reduce incidence of diabetic foot ulcer recurrence at or adjacent to measurement sites over usual care, unless participants reduce ambulatory activity when hotspots are found, or when aiming to prevent ulcers at any foot site. TRIAL REGISTRATION NUMBER: NTR5403.

Development of a prediction model for foot ulcer recurrence in people with diabetes using easy-to-obtain clinical variables.

INTRODUCTION: We aimed to develop a prediction model for foot ulcer recurrence in people with diabetes using easy-to-obtain clinical variables and to validate its predictive performance in order to help risk assessment in this high-risk group. RESEARCH DESIGN AND METHODS: We used data from a prospective analysis of 304 people with foot ulcer history who had 18-month follow-up for ulcer outcome. Demographic, disease-related and organization-of-care variables were included as potential predictors. Two logistic regression prediction models were created: model 1 for all recurrent foot ulcers (n=126 events) and model 2 for recurrent plantar foot ulcers (n=70 events). We used 10-fold cross-validation, each including five multiple imputation sets for internal validation. Performance was assessed in terms of discrimination using area under the receiver operating characteristic curve (AUC) (0-1, 1=perfect discrimination), and calibration with the Brier Score (0-1, 0=complete concordance predicted vs observed values) and calibration graphs. RESULTS: Predictors in model 1 were: a younger age, more severe peripheral sensory neuropathy, fewer months since healing of previous ulcer, presence of a minor lesion, use of a walking aid and not monitoring foot temperatures at home. Mean AUC for model 1 was 0.69 (2SD 0.040) and mean Brier Score was 0.22 (2SD 0.011). Predictors in model 2 were: a younger age, plantar location of previous ulcer, fewer months since healing of previous ulcer, presence of a minor lesion, consumption of alcohol, use of a walking aid, and foot care received in a university medical center. Mean AUC for model 2 was 0.66 (2SD 0.023) and mean Brier Score was 0.16 (2SD 0.0048). CONCLUSIONS: These internally validated prediction models predict with reasonable to good calibration and fair discrimination who is at highest risk of ulcer recurrence. The people at highest risk should be monitored more carefully and treated more intensively than others. TRIAL REGISTRATION NUMBER: NTR5403.

Surgical Treatment of Diabetic Foot Ulcers Complicated by Osteomyelitis with Gentamicin-Loaded Calcium Sulphate-Hydroxyapatite Biocomposite.

Diabetic foot ulcers, complicated by osteomyelitis, can be treated by surgical resection, dead space filling with gentamicin-loaded calcium sulphate-hydroxyapatite (CaS-HA) biocomposite, and closure of soft tissues and skin. To assess the feasibility of this treatment regimen, we conducted a multicenter retrospective cohort study of patients after failed conventional treatments. From 13 hospitals we included 64 patients with forefoot (n = 41 (64%)), midfoot (n = 14 (22%)), or hindfoot (n = 9 (14%)) ulcers complicated by osteomyelitis. Median follow-up was 43 (interquartile range, 20-61) weeks. We observed wound healing in 54 patients (84%) and treatment success (wound healing without ulcer recurrence) in 42 patients (66%). Treatment failures (no wound healing or ulcer recurrence) led to minor amputations in four patients (6%) and major amputations in seven patients (11%). Factors associated with treatment failures in univariable Cox regression analysis were gentamicin-resistant osteomyelitis (hazard ratio (HR), 3.847; 95%-confidence interval (CI), 1.065-13.899), hindfoot ulcers (HR, 3.624; 95%-CI, 1.187-11.060) and surgical procedures with gentamicin-loaded CaS-HA biocomposite that involved minor amputations (HR, 3.965; 95%-CI, 1.608-9.777). In this study of patients with diabetic foot ulcers, complicated by osteomyelitis, surgical treatment with gentamicin-loaded CaS-HA biocomposite was feasible and successful in 66% of patients. A prospective trial of this treatment regimen, based on a uniform treatment protocol, is required.

Infrared thermography for monitoring severity and treatment of diabetic foot infections.

Monitoring of diabetic foot infections is largely based on clinical assessment, which is limited by moderate reliability. We conducted a prospective study to explore monitoring of thermal asymmetry (difference between mean plantar temperature of the affected and unaffected foot) for the assessment of severity of diabetic foot infections. In patients with moderate or severe diabetic foot infections (International Working Group on the Diabetic Foot infection-grades 3 or 4) we measured thermal asymmetry with an advanced infrared thermography setup during the first 4-5 days of in-hospital treatment, in addition to clinical assessments and tests of serum inflammatory markers (white blood cell counts and C-reactive protein levels). We assessed the change in thermal asymmetry from baseline to final assessment, and investigated its association with infection-grades and serum inflammatory markers. In seven included patients, thermal asymmetry decreased from median 1.8°C (range: -0.6 to 8.4) at baseline to 1.5°C (range: -0.1 to 5.1) at final assessment (P = 0.515). In three patients who improved to infection-grade 2, thermal asymmetry at baseline (median 1.6°C (range: -0.6 to 1.6)) and final assessment (1.5°C (range: 0.4 to 5.1)) remained similar (P = 0.302). In four patients who did not improve to infection-grade 2, thermal asymmetry decreased from median 4.3°C (range: 1.8 to 8.4) to 1.9°C (range: -0.1 to 4.4; P = 0.221). No correlations were found between thermal asymmetry and infection-grades (r = -0.347; P = 0.445), CRP-levels (r = 0.321; P = 0.482) or WBC (r = -0.250; P = 0.589) during the first 4-5 days of hospitalization. Based on these explorative findings we suggest that infrared thermography is of no value for monitoring diabetic foot infections during in-hospital treatment.

Development of a multivariable prediction model for plantar foot ulcer recurrence in high-risk people with diabetes.

INTRODUCTION: Forty per cent of people with diabetes who heal from a foot ulcer recur within 1 year. The aim was to develop a prediction model for plantar foot ulcer recurrence and to validate its predictive performance. RESEARCH DESIGN AND METHODS: Data were retrieved from a prospective analysis of 171 high-risk patients with 18 months follow-up. Demographic, disease-related, biomechanical and behavioral factors were included as potential predictors. Two logistic regression models were created. Model 1 for all recurrent plantar foot ulcers (71 cases) and model 2 for those ulcers indicated to be the result of unrecognized repetitive stress (41 cases). Ten-fold cross-validation, each including five multiple imputation sets, was used to internally validate the prediction strategy; model performance was assessed in terms of discrimination and calibration. RESULTS: The presence of a minor lesion, living alone, increased barefoot peak plantar pressure, longer duration of having a previous foot ulcer and less variation in daily stride count were predictors of the first model. The area under the receiver operating curve was 0.68 (IQR 0.61-0.80) and the Brier score was 0.24 (IQR 0.20-0.28). The predictors of the second model were presence of a minor lesion, longer duration of having a previous foot ulcer and location of the previous foot ulcer. The area under the receiver operating curve was 0.76 (IQR 0.66-0.87) and the Brier score was 0.17 (IQR 0.15-0.18). CONCLUSIONS: These validated prediction models help identify those patients that are at increased risk of plantar foot ulcer recurrence and for that reason should be monitored more carefully and treated more intensively.

Telehealth and telemedicine applications for the diabetic foot: A systematic review.

The aim of this systematic review is to assess the peer-reviewed literature on the psychometric properties, feasibility, effectiveness, costs, and current limitations of using telehealth and telemedicine approaches for prevention and management of diabetic foot disease. MEDLINE/PubMed was searched for peer-reviewed studies on telehealth and telemedicine approaches for assessing, monitoring, preventing, or treating diabetic foot disease. Four modalities were formulated: dermal thermography, hyperspectral imaging, digital photographic imaging, and audio/video/online communication. Outcome measures were: validity, reliability, feasibility, effectiveness, and costs. Sixty-one studies were eligible for analysis. Three randomized controlled trials showed that handheld infrared dermal thermography as home-monitoring tool is effective in reducing ulcer recurrence risk, while one small trial showed no effect. Hyperspectral imaging has been tested in clinical settings to assess and monitor foot disease and conflicting results on its diagnostic use show that this method is still in an experimental stage. Digital photography is used to assess and monitor foot ulcers and pre-ulcerative lesions and was found to be a valid, reliable, and feasible method for telehealth purposes. Audio/video/online communication is mainly used for foot ulcer monitoring. Two randomized controlled trials show similar healing efficacy compared with regular outpatient clinic visits, but no benefit in costs. In conclusion, several technologies with good psychometric properties are available that may be of benefit in helping to assess, monitor, prevent, or treat diabetic foot disease, but in most cases, feasibility, effectiveness, and cost savings still need to be demonstrated to become accepted and used modalities in diabetic foot care.

The cost-effectiveness and cost-utility of at-home infrared temperature monitoring in reducing the incidence of foot ulcer recurrence in patients with diabetes (DIATEMP): study protocol for a randomized controlled trial.

BACKGROUND: Home monitoring of foot temperatures in high-risk diabetes patients proves to be a promising approach for early recognition and treatment of pre-signs of ulceration, and thereby ulcer prevention. Despite previous studies demonstrating its efficacy, it is currently not widely applied in (Dutch) health care. METHODS: In a multicenter, outcome-assessor-blinded, randomized controlled trial, 304 patients with diabetes mellitus types I or II, loss of protective sensation based on peripheral neuropathy, and a history of foot ulceration in the preceding 4 years or a diagnosis of Charcot neuro-osteoarthropathy will be included. Enhanced therapy will consist of usual care and additional at-home daily measurement of foot temperatures at six to eight predefined locations on the foot. If a contralateral foot temperature difference of > 2.2 °C is found on two consecutive days, the participant is instructed to contact their podiatrist for further foot diagnosis or treatment, and to reduce ambulatory activity by 50% until temperatures are normalized. Enhanced therapy will be compared to usual care. The primary outcomes are the cost (savings) per patient without a foot ulcer (i.e., cost-effectiveness) and per quality-adjusted life year gained (i.e., cost-utility). The primary clinical outcome in the study is the proportion of patients with foot ulcer recurrence on the plantar foot, apical surfaces of the toes, the interdigital spaces or medial and lateral forefoot surfaces during 18-month follow-up. DISCUSSION: Confirmation of the efficacy of at-home foot temperature monitoring in ulcer prevention, together with assessing its usability, cost-effectiveness and cost-utility, could lead to implementation in Dutch health care, and in many settings across the world. TRIAL REGISTRATION: Netherlands Trial Registration: NTR5403 . Registered on 8 September 2015.

Risk factors for postoperative delirium after colorectal operation.

BACKGROUND: A clear understanding of risk factors for postoperative delirium helps in the selection of individuals who might benefit from targeted perioperative intervention. The aim of this study was to identify risk factors for postoperative delirium after colorectal operation for malignancy. METHODS: All consecutive patients who underwent elective or emergency operation because of malignancy of the colon, sigmoid, or rectum between 2009 and 2012 were included in this study. Potential risk factors for postoperative delirium were selected based on previous studies. These candidate factors were analyzed using univariate and multivariate logistic regression analysis. Based on this analysis, odds ratios and 95% confidence intervals were estimated. RESULTS: A total of 436 patients underwent an oncologic resection of the colon, sigmoid, or rectum. Postoperative delirium was observed in 45 (10.3%) patients. Patients with a delirium had a greater in-hospital mortality rate (8.9% vs 3.6%, P = .09), spent more days in the intensive care unit, and had a longer total hospital stay. Variables associated with postoperative delirium in univariate analyses were age, American Society of Anesthesiologists classification, blood transfusion, history of psychiatric disease, history of cerebrovascular disease, postoperative pain management, postoperative renal impairment, C-reactive protein levels, leukocyte blood count, and postoperative complications. Independent risk factors were history of psychiatric disease (odds ratio 8.38, 95% confidence interval: 1.50-46.82), age (odds ratio 4.01, 95% confidence interval; 1.55-10.37), and perioperative blood transfusion (odds ratio 2.37, 95% confidence interval; 1.11-5.06). CONCLUSION: This study shows that postoperative delirium is a frequently encountered complication after colorectal operation. Three independent risk factors for postoperative delirium were identified (history of psychiatric disease, age, and perioperative transfusion) that may contribute to risk estimation in this patient population.

The Evaluation of More Lymph Nodes in Colon Cancer Is Associated with Improved Survival in Patients of All Ages.

BACKGROUND: Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of ≥ 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer. METHODS: In a population-based cohort study, all patients (N = 41,074) diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as < 66, 66-75 and > 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival. RESULTS: Over an eight years time period there was a 41.2% increase in patients with ≥ 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%). After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which ≥ 12 lymph nodes were removed compared to patients with < 12 lymph nodes removed, there was a statistically significant higher overall survival (< 66: HR: 0.858 (95% CI, 0.789-0.933); 66-75: HR: 0.763 (95% CI, 0.714-0.814); > 75: HR: 0.734 (95% CI, 0.700-0.771)) and relative survival (< 66: RER: 0.783 (95% CI, 0.708-0.865); 66-75: RER: 0.672 (95% CI, 0.611-0.739); > 75: RER: 0.621 (95% CI, 0.567-0.681)) in all three age groups. CONCLUSIONS: The removal of ≥ 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification.