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European Review For Medical and... Apr 2019Septic arthritis and osteomyelitis are rare in children, but they are difficult to treat and are associated with a high rate of sequelae. This paper addresses the main...
OBJECTIVE
Septic arthritis and osteomyelitis are rare in children, but they are difficult to treat and are associated with a high rate of sequelae. This paper addresses the main clinical issues related to septic arthritis and osteomyelitis by means of a systematic review of systematic reviews.
MATERIALS AND METHODS
The major electronic databases were searched for systematic reviews/meta-analyses septic arthritis and osteomyelitis. The papers that fulfilled the inclusion/exclusion criteria were selected.
RESULTS
There were four systematic reviews on septic arthritis and four on osteomyelitis. Independent assessment of their methodological quality by two reviewers using AMSTAR 2 indicated that its criteria were not consistently followed.
CONCLUSIONS
Collectively, these works provide strong evidence regarding a large number of issues including classification, epidemiology and risk factors, causative organisms, clinical presentation, laboratory markers, imaging, diagnostic needle aspiration, antibiotic therapy, surgical therapy, and prognosis. A clinical summary based on the best evidence is supplied.
Topics: Acute Disease; Arthritis, Infectious; Child; Humans; Osteomyelitis
PubMed: 30977881
DOI: 10.26355/eurrev_201904_17484 -
The American Journal of Medicine Mar 2022We sought to determine if controlled, prospective clinical data validate the long-standing belief that intravenous (IV) antibiotic therapy is required for the full...
BACKGROUND
We sought to determine if controlled, prospective clinical data validate the long-standing belief that intravenous (IV) antibiotic therapy is required for the full duration of treatment for 3 invasive bacterial infections: osteomyelitis, bacteremia, and infective endocarditis.
METHODS
We performed a systematic review of published, prospective, controlled trials that compared IV-only to oral stepdown regimens in the treatment of these diseases. Using the PubMed database, we identified 7 relevant randomized controlled trials (RCTs) of osteomyelitis, 9 of bacteremia, 1 including both osteomyelitis and bacteremia, and 3 of endocarditis, as well as one quasi-experimental endocarditis study. Study results were synthesized via forest plots and funnel charts (for risk of study bias), using RevMan 5.4.1 and Meta-Essentials freeware, respectively.
RESULTS
The 21 studies demonstrated either no difference in clinical efficacy, or superiority of oral versus IV-only antimicrobial therapy, including for mortality; in no study was IV-only treatment superior in efficacy. The frequency of catheter-related adverse events and duration of inpatient hospitalization were both greater in IV-only groups.
DISCUSSION
Numerous prospective, controlled investigations demonstrate that oral antibiotics are at least as effective, safer, and lead to shorter hospitalizations than IV-only therapy; no contrary data were identified. Treatment guidelines should be modified to indicate that oral therapy is appropriate for reasonably selected patients with osteomyelitis, bacteremia, and endocarditis.
Topics: Anti-Bacterial Agents; Bacteremia; Endocarditis; Endocarditis, Bacterial; Humans; Osteomyelitis
PubMed: 34715060
DOI: 10.1016/j.amjmed.2021.10.007 -
European Review For Medical and... Apr 2019Chronic osteomyelitis is a difficult to treat infection of the bone, which requires a combined medical and surgical approach and often persists intermittently for years,...
Chronic osteomyelitis is a difficult to treat infection of the bone, which requires a combined medical and surgical approach and often persists intermittently for years, with relapses and failures. The optimal type, route of administration, and duration of antibiotic treatment remain controversial, and the emergence of multi-drug resistant organisms poses major therapeutic challenges. Identification of the causative agent and subsequent targeted antibiotic treatment has a major impact on patients' outcome. In this review, we summarize which intravenous and oral antibiotics are the best options available for the treatment of chronic osteomyelitis, according to specific aetiologies.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Chronic Disease; Humans; Osteomyelitis
PubMed: 30977893
DOI: 10.26355/eurrev_201904_17500 -
Clinical Infectious Diseases : An... Jan 2019The treatment of osteomyelitis in patients with stage IV sacral pressure ulcers is controversial. We conducted a systematic literature review and did not find evidence...
The treatment of osteomyelitis in patients with stage IV sacral pressure ulcers is controversial. We conducted a systematic literature review and did not find evidence of benefit of antibacterial therapy in this setting without concomitant surgical debridement and wound coverage. Furthermore, many patients with chronically exposed bone do not have evidence of osteomyelitis when biopsied, and magnetic resonance imaging may not accurately distinguish osteomyelitis from bone remodeling. The goal of therapy should be local wound care and assessment for the potential of wound closure. If the wound can be closed and osteomyelitis is present on bone biopsy, appropriate antibiotic therapy is reasonable. We find no data to support antibiotic durations of >6 weeks in this setting, and some authors recommend 2 weeks of therapy if the osteomyelitis is limited to cortical bone. If the wound will not be closed, we find no clear evidence supporting a role for antibiotic therapy.
Topics: Aged; Humans; Male; Anti-Bacterial Agents; Osteomyelitis; Pressure Ulcer; Sacrum
PubMed: 29986022
DOI: 10.1093/cid/ciy559 -
The Cochrane Database of Systematic... May 2021Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality....
BACKGROUND
Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis.
SEARCH METHODS
We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.
Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Aztreonam; Bias; Cefazolin; Clavulanic Acid; Drug Therapy, Combination; Floxacillin; Gentamicins; Humans; Infant, Newborn; Neonatal Sepsis; Randomized Controlled Trials as Topic; Ticarcillin; Vancomycin
PubMed: 33998665
DOI: 10.1002/14651858.CD013836.pub2 -
Health Technology Assessment... Oct 2019Osteomyelitis is an infection of the bone. Medical imaging tests, such as radiography, ultrasound, magnetic resonance imaging (MRI), single-photon emission computed...
BACKGROUND
Osteomyelitis is an infection of the bone. Medical imaging tests, such as radiography, ultrasound, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET), are often used to diagnose osteomyelitis.
OBJECTIVES
To systematically review the evidence on the diagnostic accuracy, inter-rater reliability and implementation of imaging tests to diagnose osteomyelitis.
DATA SOURCES
We conducted a systematic review of imaging tests to diagnose osteomyelitis. We searched MEDLINE and other databases from inception to July 2018.
REVIEW METHODS
Risk of bias was assessed with QUADAS-2 [quality assessment of diagnostic accuracy studies (version 2)]. Diagnostic accuracy was assessed using bivariate regression models. Imaging tests were compared. Subgroup analyses were performed based on the location and nature of the suspected osteomyelitis. Studies of children, inter-rater reliability and implementation outcomes were synthesised narratively.
RESULTS
Eighty-one studies were included (diagnostic accuracy: 77 studies; inter-rater reliability: 11 studies; implementation: one study; some studies were included in two reviews). One-quarter of diagnostic accuracy studies were rated as being at a high risk of bias. In adults, MRI had high diagnostic accuracy [95.6% sensitivity, 95% confidence interval (CI) 92.4% to 97.5%; 80.7% specificity, 95% CI 70.8% to 87.8%]. PET also had high accuracy (85.1% sensitivity, 95% CI 71.5% to 92.9%; 92.8% specificity, 95% CI 83.0% to 97.1%), as did SPECT (95.1% sensitivity, 95% CI 87.8% to 98.1%; 82.0% specificity, 95% CI 61.5% to 92.8%). There was similar diagnostic performance with MRI, PET and SPECT. Scintigraphy (83.6% sensitivity, 95% CI 71.8% to 91.1%; 70.6% specificity, 57.7% to 80.8%), computed tomography (69.7% sensitivity, 95% CI 40.1% to 88.7%; 90.2% specificity, 95% CI 57.6% to 98.4%) and radiography (70.4% sensitivity, 95% CI 61.6% to 77.8%; 81.5% specificity, 95% CI 69.6% to 89.5%) all had generally inferior diagnostic accuracy. Technetium-99m hexamethylpropyleneamine oxime white blood cell scintigraphy (87.3% sensitivity, 95% CI 75.1% to 94.0%; 94.7% specificity, 95% CI 84.9% to 98.3%) had higher diagnostic accuracy, similar to that of PET or MRI. There was no evidence that diagnostic accuracy varied by scan location or cause of osteomyelitis, although data on many scan locations were limited. Diagnostic accuracy in diabetic foot patients was similar to the overall results. Only three studies in children were identified; results were too limited to draw any conclusions. Eleven studies evaluated inter-rater reliability. MRI had acceptable inter-rater reliability. We found only one study on test implementation and no evidence on patient preferences or cost-effectiveness of imaging tests for osteomyelitis.
LIMITATIONS
Most studies included < 50 participants and were poorly reported. There was limited evidence for children, ultrasonography and on clinical factors other than diagnostic accuracy.
CONCLUSIONS
Osteomyelitis is reliably diagnosed by MRI, PET and SPECT. No clear reason to prefer one test over the other in terms of diagnostic accuracy was identified. The wider availability of MRI machines, and the fact that MRI does not expose patients to harmful ionising radiation, may mean that MRI is preferable in most cases. Diagnostic accuracy does not appear to vary with the potential cause of osteomyelitis or with the body part scanned. Considerable uncertainty remains over the diagnostic accuracy of imaging tests in children. Studies of diagnostic accuracy in children, particularly using MRI and ultrasound, are needed.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42017068511.
FUNDING
This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 61. See the NIHR Journals Library website for further project information.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cost-Benefit Analysis; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Middle Aged; Osteomyelitis; Positron-Emission Tomography; Reproducibility of Results; Technology Assessment, Biomedical; Ultrasonography; Young Adult
PubMed: 31670644
DOI: 10.3310/hta23610 -
Diving and Hyperbaric Medicine Mar 2017The tenth European Consensus Conference on Hyperbaric Medicine took place in April 2016, attended by a large delegation of experts from Europe and elsewhere. The focus...
Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment.
The tenth European Consensus Conference on Hyperbaric Medicine took place in April 2016, attended by a large delegation of experts from Europe and elsewhere. The focus of the meeting was the revision of the European Committee on Hyperbaric Medicine (ECHM) list of accepted indications for hyperbaric oxygen treatment (HBOT), based on a thorough review of the best available research and evidence-based medicine (EBM). For this scope, the modified GRADE system for evidence analysis, together with the DELPHI system for consensus evaluation, were adopted. The indications for HBOT, including those promulgated by the ECHM previously, were analysed by selected experts, based on an extensive review of the literature and of the available EBM studies. The indications were divided as follows: Type 1, where HBOT is strongly indicated as a primary treatment method, as it is supported by sufficiently strong evidence; Type 2, where HBOT is suggested as it is supported by acceptable levels of evidence; Type 3, where HBOT can be considered as a possible/optional measure, but it is not yet supported by sufficiently strong evidence. For each type, three levels of evidence were considered: A, when the number of randomised controlled trials (RCTs) is considered sufficient; B, when there are some RCTs in favour of the indication and there is ample expert consensus; C, when the conditions do not allow for proper RCTs but there is ample and international expert consensus. For the first time, the conference also issued 'negative' recommendations for those conditions where there is Type 1 evidence that HBOT is not indicated. The conference also gave consensus-agreed recommendations for the standard of practice of HBOT.
Topics: Bacterial Infections; Biomedical Research; Brain Injuries; Burns; Carbon Monoxide Poisoning; Crush Injuries; Decompression Sickness; Embolism, Air; Europe; Evidence-Based Medicine; Femur Head Necrosis; Fractures, Open; Hearing Loss, Sudden; Humans; Hyperbaric Oxygenation; Osteomyelitis; Radiation Injuries; Skin Transplantation; Wound Healing
PubMed: 28357821
DOI: 10.28920/dhm47.1.24-32 -
The Cochrane Database of Systematic... Apr 2018Percutaneous vertebroplasty remains widely used to treat osteoporotic vertebral fractures although our 2015 Cochrane review did not support its role in routine practice. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Percutaneous vertebroplasty remains widely used to treat osteoporotic vertebral fractures although our 2015 Cochrane review did not support its role in routine practice.
OBJECTIVES
To update the available evidence of the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures.
SEARCH METHODS
We updated the search of CENTRAL, MEDLINE and Embase and trial registries to 15 November 2017.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials (RCTs) of adults with painful osteoporotic vertebral fractures, comparing vertebroplasty with placebo (sham), usual care, or another intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events.
DATA COLLECTION AND ANALYSIS
We used standard methodologic procedures expected by Cochrane.
MAIN RESULTS
Twenty-one trials were included: five compared vertebroplasty with placebo (541 randomised participants), eight with usual care (1136 randomised participants), seven with kyphoplasty (968 randomised participants) and one compared vertebroplasty with facet joint glucocorticoid injection (217 randomised participants). Trial size varied from 46 to 404 participants, most participants were female, mean age ranged between 62.6 and 81 years, and mean symptom duration varied from a week to more than six months.Three placebo-controlled trials were at low risk of bias and two were possibly susceptible to performance and detection bias. Other trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding.Compared with placebo, high- to moderate-quality evidence from five trials (one with incomplete data reported) indicates that vertebroplasty provides no clinically important benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success at one month. Evidence for quality of life and treatment success was downgraded due to possible imprecision. Evidence was not downgraded for potential publication bias as only one placebo-controlled trial remains unreported. Mean pain (on a scale zero to 10, higher scores indicate more pain) was five points with placebo and 0.6 points better (0.2 better to 1 better) with vertebroplasty, an absolute pain reduction of 6% (2% better to 10% better, minimal clinical important difference is 15%) and relative reduction of 9% (3% better to14% better) (five trials, 535 participants). Mean disability measured by the Roland-Morris Disability Questionnaire (scale range zero to 23, higher scores indicate worse disability) was 14.2 points in the placebo group and 1.7 points better (0.3 better to 3.1 better) in the vertebroplasty group, absolute improvement 7% (1% to 14% better), relative improvement 10% better (3% to 18% better) (three trials, 296 participants).Disease-specific quality of life measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) (scale zero to 100, higher scores indicating worse quality of life) was 62 points in the placebo group and 2.75 points (3.53 worse to 9.02 better) in the vertebroplasty group, absolute change: 3% better (4% worse to 9% better), relative change: 5% better (6% worse to 15% better (two trials, 175 participants). Overall quality of life (European Quality of Life (EQ5D), zero = death to 1 = perfect health, higher scores indicate greater quality of life) was 0.38 points in the placebo group and 0.05 points better (0.01 better to 0.09 better) in the vertebroplasty group, absolute improvement: 5% (1% to 9% better), relative improvement: 18% (4% to 32% better) (three trials, 285 participants). In one trial (78 participants), 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; 95% CI 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute difference: 9% more reported success (11% fewer to 29% more); relative change: 40% more reported success (33% fewer to 195% more).Moderate-quality evidence (low number of events) from seven trials (four placebo, three usual care, 1020 participants), up to 24 months follow-up, indicates we are uncertain whether vertebroplasty increases the risk of new symptomatic vertebral fractures (70/509 (or 130 per 1000; range 60 to 247) observed in the vertebroplasty group compared with 59/511 (120 per 1000) in the control group; RR 1.08 (95% CI 0.62 to 1.87)).Similarly, moderate-quality evidence (low number of events) from five trials (three placebo, two usual care, 821 participants), indicates uncertainty around the risk of other serious adverse events (18/408 or 76 per 1000, range 6 to 156) in the vertebroplasty group compared with 26/413 (or 106 per 1000) in the control group; RR 0.64 (95% CI 0.36 to 1.12). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses indicate that the effects did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks. Including data from the eight trials that compared vertebroplasty with usual care in a sensitivity analyses altered the primary results, with all combined analyses displaying considerable heterogeneity.
AUTHORS' CONCLUSIONS
Based upon high- to moderate-quality evidence, our updated review does not support a role for vertebroplasty for treating acute or subacute osteoporotic vertebral fractures in routine practice. We found no demonstrable clinically important benefits compared with placebo (sham procedure) and subgroup analyses indicated that the results did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks.Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the high- to moderate-quality evidence that shows no important benefit of vertebroplasty and its potential for harm.
Topics: Aged; Aged, 80 and over; Bone Cements; Female; Fractures, Compression; Glucocorticoids; Humans; Male; Middle Aged; Osteoporotic Fractures; Pain Measurement; Pain, Postoperative; Quality of Life; Randomized Controlled Trials as Topic; Spinal Fractures; Vertebroplasty
PubMed: 29618171
DOI: 10.1002/14651858.CD006349.pub3 -
Infectious Diseases and Therapy Dec 2021A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with... (Review)
Review
INTRODUCTION
A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options.
METHODS
Literature searches retrieved peer-reviewed publications and abstracts from major international infectious disease congresses from January 2015 to February 2021. Results were screened using pre-defined criteria to limit the dataset to relevant publications (notable exclusions were paediatric data and outcomes data for bacteria intrinsically resistant to ceftazidime-avibactam). Data for included publications were subjected to qualitative synthesis.
RESULTS
Seventy-three relevant publications (62 peer-reviewed articles; 10 abstracts) comprising 1926 patients treated with ceftazidime-avibactam (either alone or combined with other antimicrobials) and 1114 comparator/control patients were identified. All patients were hospitalised for serious illness and most had multiple comorbidities. The most common infections were pneumonia, bacteraemia, and skin/soft tissue, urinary tract, or abdominal infections; smaller numbers of patients with meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n = 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.
CONCLUSION
This review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.
PubMed: 34379310
DOI: 10.1007/s40121-021-00507-6 -
The Cochrane Database of Systematic... Jul 2020Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage and cause significant morbidity and mortality. The presence of a wound has an impact on nutritional status because of the metabolic cost of repairing tissue damage, in addition to the nutrient losses via wound fluid. Nutritional interventions may improve wound healing of foot ulcers in people with diabetes.
OBJECTIVES
To evaluate the effects of nutritional interventions on the healing of foot ulcers in people with diabetes.
SEARCH METHODS
In March 2020 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated the effect of nutritional interventions on the healing of foot ulcers in people with diabetes.
DATA COLLECTION AND ANALYSIS
Two review authors, working independently, assessed included RCTs for their risk of bias and rated the certainty of evidence using GRADE methodology, using pre-determined inclusion and quality criteria.
MAIN RESULTS
We identified nine RCTs (629 participants). Studies explored oral nutritional interventions as follows: a protein (20 g protein per 200 mL bottle), 1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals and trace elements; arginine, glutamine and β-hydroxy-β-methylbutyrate supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements; 1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus 300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000 IU vitamin D supplements. The comparator in eight studies was placebo, and in one study a different dose of vitamin D. Eight studies reported the primary outcome measure of ulcer healing; only two studies reported a measure of complete healing. Six further studies reported measures of change in ulcer dimension, these studies reported only individual parameters of ulcer dimensions (i.e. length, width and depth) and not change in ulcer volume. All of the evidence identified was very low certainty. We downgraded it for risks of bias, indirectness and imprecision. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, increases the proportion of ulcers healed at six months more than placebo (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.42 to 1.53). It is also uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases the proportion of ulcers healed at 16 weeks compared with placebo (RR 1.09, 95% CI 0.85 to 1.40). It is uncertain whether the following interventions change parameters of ulcer dimensions over time when compared with placebo; 220 mg zinc sulphate supplement containing 50 mg elemental zinc, 250 mg magnesium oxide supplement, 1000 mg/day omega-3 fatty acid from flaxseed oil supplement, magnesium and vitamin E co-supplementation and vitamin D supplementation. It is also uncertain whether 150,000 IU of vitamin D, impacts ulcer dimensions when compared with 300,000 IU of vitamin D. Two studies explored some of the secondary outcomes of interest for this review. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, reduces the number of deaths (RR 0.96, 95% CI 0.06 to 14.60) or amputations (RR 4.82, 95% CI 0.24 to 95.88) more than placebo. It is uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases health-related quality of life at 16 weeks more than placebo (MD -0.03, 95% CI -0.09 to 0.03). It is also uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement reduces the numbers of new ulcers (RR 1.04, 95% CI 0.71 to 1.51), or amputations (RR 0.66, 95% CI 0.16 to 2.69) more than placebo. None of the included studies reported the secondary outcomes cost of intervention, acceptability of the intervention (or satisfaction) with respect to patient comfort, length of patient hospital stay, surgical interventions, or osteomyelitis incidence. One study exploring the impact of arginine, glutamine and β-hydroxy-β-methylbutyrate supplement versus placebo did not report on any relevant outcomes.
AUTHORS' CONCLUSIONS
Evidence for the impact of nutritional interventions on the healing of foot ulcers in people with diabetes compared with no nutritional supplementation, or compared with a different dose of nutritional supplementation, remains uncertain, with eight studies showing no clear benefit or harm. It is also uncertain whether there is a difference in rates of adverse events, amputation rate, development of new foot ulcers, or quality of life, between nutritional interventions and placebo. More research is needed to clarify the impact of nutritional interventions on the healing of foot ulcers in people with diabetes.
Topics: Arginine; Diabetic Foot; Dietary Proteins; Dietary Supplements; Fatty Acids, Omega-3; Female; Glutamine; Humans; Magnesium; Magnesium Oxide; Male; Middle Aged; Minerals; Randomized Controlled Trials as Topic; Trace Elements; Valerates; Vitamins; Wound Healing; Zinc Sulfate
PubMed: 32677037
DOI: 10.1002/14651858.CD011378.pub2