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Journal of Vascular Surgery Feb 2016The objective of this review was to synthesize the available randomized controlled trials (RCTs) estimating the relative efficacy and safety of intensive vs less... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this review was to synthesize the available randomized controlled trials (RCTs) estimating the relative efficacy and safety of intensive vs less intensive glycemic control in preventing diabetic foot syndrome.
METHODS
We used the umbrella design (systematic review of systematic reviews) to identify eligible RCTs. Two reviewers determined RCT eligibility and extracted descriptive, methodologic, and diabetic foot outcome data. Random-effects meta-analysis was used to pool outcome data across studies, and the I(2) statistic was used to quantify heterogeneity.
RESULTS
Nine RCTs enrolling 10,897 patients with type 2 diabetes were included and deemed to be at moderate risk of bias. Compared with less intensive glycemic control, intensive control (hemoglobin A1c, 6%-7.5%) was associated with a significant decrease in risk of amputation (relative risk [RR], 0.65; 95% confidence interval [CI], 0.45-0.94; I(2) = 0%). Intensive control was significantly associated with slower decline in sensory vibration threshold (mean difference, -8.27; 95% CI, -9.75 to -6.79). There was no effect on other neuropathic changes (RR, 0.89; 95% CI, 0.75-1.05; I(2) = 32%) or ischemic changes (RR, 0.92; 95% CI, 0.67-1.26; I(2) = 0%). The quality of evidence is likely moderate.
CONCLUSIONS
Compared with less intensive glycemic control therapy, intensive control may decrease the risk of amputation in patients with diabetic foot syndrome. The reported risk reduction is likely overestimated because the trials were open and the decision to proceed with amputation could be influenced by glycemic control.
Topics: Adult; Aged; Blood Glucose; Diabetic Foot; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Syndrome; Treatment Outcome
PubMed: 26804364
DOI: 10.1016/j.jvs.2015.10.005 -
Systematic Reviews Mar 2023Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN.
METHODS
Following the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients' quality of life.
RESULTS
We reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] - 0.89; 95% confidence interval [CI] - 1.09 to - 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients' quality of life, which was assessed using the Clinical Global Impression severity subscale (MD - 0.48; 95% CI - 0.61 to - 0.36; P < .00001), Patient Global Impression of Improvement scale (MD - 0.50; 95% CI - 0.64 to - 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms.
CONCLUSIONS
Duloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021225451.
Topics: Humans; Duloxetine Hydrochloride; Diabetic Neuropathies; Quality of Life; Randomized Controlled Trials as Topic; Pain; Diabetes Mellitus
PubMed: 36945033
DOI: 10.1186/s13643-023-02185-6 -
Journal of Vascular Surgery Feb 2016Increased plantar foot pressure is one of several key factors that lead to diabetic foot ulcers. Multiple methods have been proposed to relieve this pressure and thus... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Increased plantar foot pressure is one of several key factors that lead to diabetic foot ulcers. Multiple methods have been proposed to relieve this pressure and thus enhance wound healing and potentially prevent relapse. We aimed in this systematic review to find the best available evidence for off-loading methods.
METHODS
We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest included complete wound healing, time to complete wound healing, amputation, infection, and relapse rates.
RESULTS
We identified 19 interventional studies, of which 13 were randomized controlled trials, including data from 1605 patients with diabetic foot ulcers using an off-loading method. The risk of bias in the included studies was moderate. This analysis demonstrated improved wound healing with total contact casting over removable cast walker, therapeutic shoes, and conventional therapy. There was no advantage of irremovable cast walkers over total contact casting. There was improved healing with half-shoe compared with conventional wound care. Therapeutic shoes and insoles reduced relapse rate in comparison with regular footwear. Data were sparse regarding other off-loading methods.
CONCLUSIONS
Although based on low-quality evidence (ie, evidence warranting lower certainty), benefits are demonstrated for use of total contact casting and irremovable cast walkers in the treatment of diabetic foot ulcers. Reduced relapse rate is demonstrated with various therapeutic shoes and insoles in comparison with regular footwear.
Topics: Aged; Casts, Surgical; Diabetic Foot; Female; Humans; Male; Middle Aged; Research Design; Shoes
PubMed: 26804369
DOI: 10.1016/j.jvs.2015.10.006 -
The Cochrane Database of Systematic... Dec 2017Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of a review published in 2013.
OBJECTIVES
To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain.
SEARCH METHODS
On 21 November 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We searched the Chinese Biomedical Retrieval System (January 1978 to November 2016). We searched the US National Institutes of Health (NIH) databases and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials in January 2017, and we wrote to the companies who make oxcarbazepine and to pain experts requesting additional information.
SELECTION CRITERIA
All RCTs and randomised cross-over studies of oxcarbazepine for the treatment of people of any age or sex with any neuropathic pain were eligible. We planned to include trials of oxcarbazepine compared with placebo or any other intervention with a treatment duration of at least six weeks, regardless of administration route and dose.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Five multicentre, randomised, placebo-controlled, double-blind trials with a total of 862 participants were eligible for inclusion in this updated review. Three trials involved participants with painful diabetic peripheral neuropathy (DPN) (n = 634), one included people with neuropathic pain due to radiculopathy (n = 145), and one, which was newly identified at this update, involved participants with peripheral neuropathic pain of mixed origin (polyneuropathy, peripheral nerve injury or postherpetic neuralgia) (n = 83). Some studies did not report all outcomes of interest. For painful DPN, compared to the baseline, the proportion of participants who reported at least a 50% or 30% reduction of pain scores after 16 weeks of treatment in the oxcarbazepine group versus the placebo group were: at least 50% reduction: 34.8% with oxcarbazepine versus 18.2% with placebo (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.08 to 3.39, number of people needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 41); and at least 30% reduction: 44.9% with oxcarbazepine versus 28.6% with placebo (RR 1.57, 95% CI 1.01 to 2.44; NNTB 6, 95% CI 3 to 114; n = 146). Both results were based on data from a single trial, since two trials that found little or no benefit did not provide data that could be included in a meta-analysis. Although these trials were well designed, incomplete outcome data and possible unblinding of participants due to obvious adverse effects placed the results at a high risk of bias. There was also serious imprecision and a high risk of publication bias. The radiculopathy trial reported no benefit for the outcome 'at least 50% pain relief' from oxcarbazepine. In mixed neuropathies, 19.3% of people receiving oxcarbazepine versus 4.8% receiving placebo had at least 50% pain relief. These small trials had low event rates and provided, at best, low-quality evidence for any outcome. The proportion of people with 'improved' or 'very much improved' pain was 45.9% with oxcarbazepine versus 30.1% with placebo in DPN (RR 1.46, 95% CI 1.13 to 1.88; n = 493; 2 trials; very-low-quality evidence) and 23.9% with oxcarbazepine versus 14.9% with placebo in radiculopathy (RR 1.61, 95% CI 0.81 to 3.20; n = 145).We found no trials in other types of neuropathic pain such as trigeminal neuralgia.Trial reports stated that most adverse effects were mild to moderate in severity. Based on moderate-quality evidence from the three DPN trials, serious adverse effects occurred in 8.3% with oxcarbazepine and 2.5% with placebo (RR 3.65, 95% CI 1.45 to 9.20; n = 634; moderate-quality evidence). The number needed to treat for an additional harmful (serious adverse effect) outcome (NNTH) was 17 (95% CI 11 to 42). The RR for serious adverse effects in the radiculopathy trial was 3.13 (95% CI 0.65 to 14.98, n = 145). The fifth trial did not provide data.More people withdrew because of adverse effects with oxcarbazepine than with placebo (DPN: 25.6% with oxcarbazepine versus 6.8% with placebo; RR 3.83, 95% CI 2.29 to 6.40; radiculopathy: 42.3% with oxcarbazepine versus 14.9% with placebo; RR 2.84, 95% CI 1.55 to 5.23; mixed neuropathic pain: 13.5% with oxcarbazepine versus 1.2% with placebo; RR 11.51, 95% CI 1.54 to 86.15).
AUTHORS' CONCLUSIONS
This review found little evidence to support the effectiveness of oxcarbazepine in painful diabetic neuropathy, neuropathic pain from radiculopathy and a mixture of neuropathies. Some very-low-quality evidence suggests efficacy but small trials, low event rates, heterogeneity in some measures and a high risk of publication bias means that we have very low confidence in the measures of effect. Adverse effects, serious adverse effects and adverse effects leading to discontinuation are probably more common with oxcarbazepine than placebo; however, the numbers of participants and event rates are low. More well-designed, multicentre RCTs investigating oxcarbazepine for various types of neuropathic pain are needed, and selective publication of studies or data should be avoided.
Topics: Analgesics, Non-Narcotic; Carbamazepine; Diabetic Neuropathies; Humans; Neuralgia; Numbers Needed To Treat; Oxcarbazepine; Radiculopathy; Randomized Controlled Trials as Topic
PubMed: 29199767
DOI: 10.1002/14651858.CD007963.pub3 -
Association of arterial stiffness and neuropathy in diabetes: a systematic review and meta-analysis.BMJ Open Diabetes Research & Care Feb 2023Evidence is still emerging on the relationships of arterial stiffness with cardiac autonomic neuropathy (CAN) and peripheral neuropathy (PN). To our knowledge no... (Meta-Analysis)
Meta-Analysis
Evidence is still emerging on the relationships of arterial stiffness with cardiac autonomic neuropathy (CAN) and peripheral neuropathy (PN). To our knowledge no systematic reviews or meta-analyses of these associations have been published. The purpose of our review was to assess the association of arterial stiffness with each type of neuropathy. Medline and Embase were systematically searched for observational studies of arterial stiffness and neuropathy.The systematic review of 60 studies (25 for CAN and 37 for PN), 59 including people with diabetes, showed arterial stiffness overall was higher in people with neuropathy than people without neuropathy. Forty-three studies were included in the meta-analysis. For CAN (19 studies), arterial stiffness was increased in people with neuropathy compared with without, as measured by pulse wave velocity (PWV) (mean difference: 1.32 m/s, 95% CI 0.82 to 1.81, p<0.00001), pulse pressure (PP) (mean difference: 6.25 mmHg, 95% CI 4.51 to 7.99, p<0.00001) or augmentation index (mean difference: 5.52%, 95% CI 3.46 to 7.58, p<0.0001). For PN (26 studies), arterial stiffness was increased in people with neuropathy compared with those without, as measured by PWV (mean difference: 1.22 m/s, 95% CI 0.87 to 1.58, p<0.00001) or PP (mean difference: 4.59 mmHg, 95% CI 2.96 to 6.22, p<0.00001). Only two cohort studies were located so the temporality of the association between arterial stiffness and neuropathy remains unclear. Increased arterial stiffness is associated with CAN and PN.PROSPERO registration number: CRD42019129563.
Topics: Humans; Vascular Stiffness; Pulse Wave Analysis; Diabetes Mellitus; Peripheral Nervous System Diseases; Blood Pressure
PubMed: 36746528
DOI: 10.1136/bmjdrc-2022-003140 -
EBioMedicine Dec 2023Diabetic foot ulcers (DFUs) are a common complication of diabetes, associated with important morbidity. Appropriate animal models of DFUs may improve drug development,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic foot ulcers (DFUs) are a common complication of diabetes, associated with important morbidity. Appropriate animal models of DFUs may improve drug development, and subsequently the success rate of clinical trials. However, while many models have been proposed, they are extremely heterogeneous, and no standard has emerged. We thus propose a systematic review with a network meta-analysis (NMA) to gather direct and indirect evidence, and compare the different mouse models of diabetes-related ulcers.
METHODS
The systematic search was performed in Pubmed and Embase. The main outcomes were wound size measurement at days 3, 7, 11 and 15 (±1 day). The risk of bias and methodological quality of all included studies was assessed by using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool. Meta-regressions were done on prespecified variables, including mouse strain, type of ulcer, sex, age, and use of a splint.
FINDINGS
We included 295 studies. Among all models, only db/db, ob/ob, streptozotocin (STZ), and STZ + high fat diet mice showed a significantly delayed wound healing, compared with controls, at each time point. Age, sex and ulcer type had influence on wound healing, although not at all time points.
INTERPRETATION
In conclusion, the db/db model is associated with the largest delay in wound healing The STZ model also exhibits significantly decreased wound healing. STZ + high fat diet and ob/ob mice may also be relevant models of diabetes-related ulcers, although the results rely on a more limited number of studies.
FUNDING
This work was funded by the Agence Nationale de la Recherche (grant ANR-18-CE17-0017).
Topics: Animals; Mice; Network Meta-Analysis; Disease Models, Animal; Diabetic Foot; Animal Experimentation; Diet, High-Fat; Streptozocin; Diabetes Mellitus
PubMed: 38251464
DOI: 10.1016/j.ebiom.2023.104856 -
International Wound Journal Feb 2017Diabetic foot ulcerations may determine minor or major amputation, with a high impact on patients' life expectation and quality of life and on economic burden. Among... (Review)
Review
Diabetic foot ulcerations may determine minor or major amputation, with a high impact on patients' life expectation and quality of life and on economic burden. Among minor amputations, transmetatarsal amputation (TMA) appears to be the most effective in terms of limb salvage rates and in maintaining foot and ankle biomechanics. In spite of this, TMA needs particular pre- and postoperative management in order to avoid the frequent failure rates. A systematic review was undertaken of studies concerning TMA and its care in diabetic foot gangrene. Studies were identified by searching the MEDLINE, Scopus and Science Direct databases until 13 January 2016. All studies were assessed using the Downs and Black quality checklist. Of the 348 records found, 86 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 35 manuscripts because of the following reasons: (1) no innovative or important content, (2) no multivariable analysis, (3) insufficient data, (4) no clear potential biases or strategies to solve them, (5) no clear endpoints and (6) inconsistent or arbitrary conclusions. The final set included 51 articles. In the current literature, there are less data about TMA, indication for the selection of patients, outcomes and complications. Generally, the judgment of an experienced physician is one of the best indicators of subsequent healing. Ankle brachial indices, toe pressures, laser Doppler skin perfusion pressures, angiography and Doppler assessment of foot vasculature may help physicians in this decision. In any case, despite the presumed lower healing rate, it is reasonable to pursue a TMA in a patient with a higher likelihood of continued ambulation. Furthermore, tailored wound closure, adjuvant local treatments and the choice of the most appropriate antibiotic therapy, when infection occurs, are pivotal elements for the success of TMA procedures. TMA is a valuable option for diabetic foot gangrene that can prevent major limb loss and minimise loss of function, thus improving the quality of life for diabetic patients.
Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Diabetic Foot; Female; Gangrene; Humans; Male; Metatarsal Bones; Middle Aged
PubMed: 27696694
DOI: 10.1111/iwj.12682 -
Journal of Vascular Surgery Feb 2016Several methods of débridement of diabetic foot ulcers are currently used. The relative efficacy of these methods is not well established. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several methods of débridement of diabetic foot ulcers are currently used. The relative efficacy of these methods is not well established.
METHODS
This systematic review and meta-analysis was conducted to find the best available evidence for the effect of débridement on diabetic foot wound outcomes. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011 for randomized controlled studies (RCTs) and observational comparative studies.
RESULTS
We identified 11 RCTs and three nonrandomized studies reporting on 800 patients. The risk of bias was moderate overall. Meta-analysis of three RCTs showed that autolytic débridement significantly increased the healing rate (relative risk [RR], 1.89; 95% confidence interval [CI] 1.35-2.64). Meta-analysis of four studies (one RCT) showed that larval débridement reduced amputation (RR, 0.43; 95% CI, 0.21-0.88) but did not increase complete healing (RR, 1.27; 95% CI, 0.84-1.91). Surgical débridement was associated with shorter healing time compared with conventional wound care (one RCT). Insufficient evidence was found for comparisons between autolytic and larval débridement (one RCT), between ultrasound-guided and surgical débridement, and between hydrosurgical and surgical débridement.
CONCLUSIONS
The available literature supports the efficacy of several débridement methods, including surgical, autolytic, and larval débridement. Comparative effectiveness evidence between these methods and supportive evidence for other methods is of low quality due to methodologic limitations and imprecision. Hence, the choice of débridement method at the present time should be based on the available expertise, patient preferences, the clinical context and cost.
Topics: Adult; Aged; Debridement; Diabetic Foot; Female; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 26804366
DOI: 10.1016/j.jvs.2015.10.002 -
Journal of Diabetes and Metabolic... Jun 2022Diabetes mellitus can cause several long-term macrovascular and microvascular complications including nephropathy, neuropathy, and retinopathy (DR). Several studies have... (Review)
Review
BACKGROUND
Diabetes mellitus can cause several long-term macrovascular and microvascular complications including nephropathy, neuropathy, and retinopathy (DR). Several studies have reported positive associations between eating pathologies and DR; however, these studies have not been aggregated and sub-grouped into type of pathological eating behaviour, and the differences in risk according to type of eating behaviour is unknown. The aim of this review, therefore, was to aggregate risks of DR in populations with and without pathological eating behaviours, stratified according to eating behaviour.
METHODS
A systematic review and meta-analysis was conducted. Major databases and grey literature were search from inception until 1/6/2021. Studies reporting the prevalence of pathological eating behaviours (against a control group with no pathological eating behaviours) in diabetic people with and without DR were included. Odds ratios were calculated from primary data.
RESULTS
Seven studies with eight independent outcomes with a total of 1162 participants were included. The odds ratio of DR in the total pooled analysis was 2.94 (95%CI 1.86-4.64; = <0.001; I = 29.59). Two types of eating behaviour yielded enough data for sub-group analysis. Eating disorder not otherwise specified yielded an odds ratio of 2.73 (95%CI 1.81-4.10; = <0.001; I = 0.00), and binge eating disorder yielded an non-significant odds ratio of 0.92 (95%CI 0.31-2.77; = 0.887;I = 0.00).
DISCUSSION
The likelihood of DR increases almost three times in the presence of pathological eating behaviours. More studies are required to confirm this in clinical populations stratified by eating disorder. Practitioners working with people with diabetes should closely monitor eating behaviours to preclude this risk.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-022-00980-x.
PubMed: 35673454
DOI: 10.1007/s40200-022-00980-x -
Diabetology & Metabolic Syndrome May 2023Diabetes is one of the chronic conditions with a high burden all around the world. Macrovascular and microvascular involvement are among the common mechanisms by which...
BACKGROUND
Diabetes is one of the chronic conditions with a high burden all around the world. Macrovascular and microvascular involvement are among the common mechanisms by which diabetes can impact patients' lives. Endocan as an inflammatory endothelial biomarker has been shown to increase in several communicable and non-communicable diseases. Herein, we aim to investigate the role of endocan as a biomarker in diabetes as a systematic review and meta-analysis.
METHODS
International databases, including PubMed, Web of Science, Scopus, and Embase were searched for relevant studies assessing blood endocan in diabetic patients. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of circulating endocan levels between diabetic patients and non-diabetic controls were conducted through random-effect meta-analysis.
RESULTS
Totally, 24 studies were included, assessing 3354 cases with a mean age of 57.4 ± 8.4 years. Meta-analysis indicated that serum endocan levels were significantly higher in diabetic patients in comparison with healthy controls (SMD 1.00, 95% CI 0.81 to 1.19, p-value < 0.01). Moreover, in the analysis of studies with only type-2 diabetes, the same result showing higher endocan was obtained (SMD 1.01, 95% CI 0.78 to 1.24, p-value < 0.01). Higher endocan levels were also reported in chronic diabetes complications such as diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy.
CONCLUSION
Based on our study's findings, endocan levels are increased in diabetes, however, further studies are needed for assessing this association. In addition, higher endocan levels were detected in chronic complications of diabetes. This can help researchers and clinicians in recognizing disease endothelial dysfunction and potential complications.
PubMed: 37189201
DOI: 10.1186/s13098-023-01076-z