Dataset Information

Preclinical therapies to prevent or treat fracture non-union: A systematic review.

ABSTRACT:

Background

Non-union affects up to 10% of fractures and is associated with substantial morbidity. There is currently no single effective therapy for the treatment or prevention of non-union. Potential treatments are currently selected for clinical trials based on results from limited animal studies, with no attempt to compare results between therapies to determine which have the greatest potential to treat non-union.

Aim

The aim of this systematic review was to define the range of therapies under investigation at the preclinical stage for the prevention or treatment of fracture non-union. Additionally, through meta-analysis, it aimed to identify the most promising therapies for progression to clinical investigation.

Methods

MEDLINE and Embase were searched from 1St January 2004 to 10th April 2017 for controlled trials evaluating an intervention to prevent or treat fracture non-union. Data regarding the model used, study intervention and outcome measures were extracted, and risk of bias assessed.

Results

Of 5,171 records identified, 197 papers describing 204 therapies were included. Of these, the majority were only evaluated once (179/204, 88%), with chitosan tested most commonly (6/204, 3%). Substantial variation existed in model design, length of survival and duration of treatment, with results poorly reported. These factors, as well as a lack of consistently used objective outcome measures, precluded meta-analysis.

Conclusion

This review highlights the variability and poor methodological reporting of current non-union research. The authors call for a consensus on the standardisation of animal models investigating non-union, and suggest journals apply stringent criteria when considering animal work for publication.

SUBMITTER: Bennett PM

PROVIDER: S-EPMC6070249 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preclinical therapies to prevent or treat fracture non-union: A systematic review.

Bennett Philippa M PM Stewart Sarah K SK Dretzke Janine J Bem Danai D Penn-Barwell Jowan G JG

PloS one 20180801 8

<h4>Background</h4>Non-union affects up to 10% of fractures and is associated with substantial morbidity. There is currently no single effective therapy for the treatment or prevention of non-union. Potential treatments are currently selected for clinical trials based on results from limited animal studies, with no attempt to compare results between therapies to determine which have the greatest potential to treat non-union.<h4>Aim</h4>The aim of this systematic review was to define the range of ...[more]

PMID: 30067783

Similar Datasets

Project description:BACKGROUND:Hyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than one atmosphere absolute (ATA) in a pressure vessel. This technology has been used to treat a variety of diseases and has been described as helping patients who have delayed healing or established non-union of bony fractures. This is an update of a Cochrane Review first published in 2005, and previously updated in 2008. OBJECTIVES:The aim of this review is to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of delayed bony healing and established non-union of bony fractures. SEARCH METHODS:We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2012), the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1946 to July Week 1 2012), EMBASE (1974 to 2012 July 16), CINAHL (1937 to 17 July 2012), the Database of Randomised Controlled Trials in Hyperbaric Medicine (accessed July 2012), the WHO International Clinical Trials Registry Platform (17 July 2012) and reference lists of articles. SELECTION CRITERIA:We aimed to include all randomised controlled trials comparing the clinical effects of HBOT with no HBOT (no treatment or sham) for healing of bony fractures and fracture non-unions. DATA COLLECTION AND ANALYSIS:Two review authors independently screened electronic search results, and all three authors independently performed study selection. We planned independent data collection and risk of bias assessment by two authors using standardised forms. MAIN RESULTS:No trials met the inclusion criteria. In this update, we identified three ongoing randomised controlled trials. Among the eight excluded studies were three randomised trials comparing HBOT with no treatment that included patients with fractures. One of these trials had been abandoned and the other two did not report on fracture healing outcomes. AUTHORS' CONCLUSIONS:This systematic review failed to locate any relevant clinical evidence to support or refute the effectiveness of HBOT for the management of delayed union or established non-union of bony fractures. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of these injuries. There are three randomised controlled trials underway and we anticipate these will help provide some relevant clinical evidence to address this issue in the future.

Project description:Background: Dementia has a significant impact on quality of life of older individuals. Impaired proteostasis has been implicated as a potential cause of dementia, that can be therapeutically targeted to improve patient outcomes. This review aimed to collate all current evidence of the potential for targeting proteostasis with repurposed drugs as an intervention for age-related dementia and cognitive decline. Methods: PubMed, Web of Science and Embase databases were searched from inception until 4th July 2017 for studies published in English. Interventional studies of repurposed proteostasis-modifying drugs in Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body disease, vascular dementia, and cognitive aging, in either animal models or humans with change in cognition as the outcome were included. The SYRCLE and Cochrane tools were used to assess risk of bias for included studies. Results: Overall 47 trials, 38 animal and 9 human, were isolated for inclusion in this review. Drugs tested in animals and humans included lithium, rapamycin, rifampicin, and tyrosine kinase inhibitors. Drugs tested only in animals included Macrophage and Granulocyte-Macrophage Colony Stimulating Factors, methylene blue, dantrolene, geranylgeranylacetone, minocycline and phenylbutyric acid. Lithium (n = 10 animal, n = 6 human) and rapamycin (n = 12 animal, n = 1 human) were the most studied proteostasis modifying drugs influencing cognition. Nine of ten animal studies of lithium showed a statistically significant benefit in Alzheimer's models. Rapamycin demonstrated a significant benefit in models of vascular dementia, aging, and Alzheimer's, but may not be effective in treating established Alzheimer's pathology. Lithium and nilotinib had positive outcomes in human studies including Alzheimer's and Parkinson's patients respectively, while a human study of rifampicin in Alzheimer's failed to demonstrate benefit. Microdose lithium showed a strongly significant benefit in both animals and humans. While the risk of bias was relatively low in human studies, the risk of bias in animal studies was largely unclear. Conclusion: Overall, the collective findings support the hypothesis that targeting proteostasis for treatment of dementia may be beneficial, and therefore future studies in humans with repurposed proteostasis modifying drugs are warranted. Larger human clinical trials focusing on safety, efficacy, tolerability, and reproducibility are required to translate these therapeutics into clinical practice.

Project description:BackgroundMāori and Pacific Islander people are a priority population originating from Australasia. Māori and Pacific Islander children exhibit greater risk of obesity and associated morbidities compared to children of other descent, secondary to unique cultural practices and socioeconomic disadvantage. Despite these known risk factors, there is limited synthesised evidence for preventing and treating childhood obesity in this unique population. The objective of this systematic review was to identify and evaluate global prevention or treatment interventions for overweight or obesity that targeted Māori and Pacific Islander children and adolescents (aged 2-17 years).MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The databases PubMed, EMBASE, Scopus, Web of Science and CINAHL were searched from inception to August 2018. Study quality and risk of bias was assessed using a modified Downs and Black Quality Checklist for Health Care Intervention Studies. Studies were included if RCT/intervention/case control/ or prevention study designs. The study group was defined under the search term 'Oceanic Ancestry Group'.ResultsOf the initial 94 articles identified, six were included describing two prevention and three treatment interventions. Interventions were heterogenous in setting, design, length and outcomes. Four interventions were implemented in New Zealand. Most studies were of 'fair' quality. One study recruited an exclusive population of Māori and Pacific Islander participants. In the five studies that recruited mixed populations, one performed sub-group analysis on Māori and Pacific Islander participants. No study reported an improvement in anthropometric outcomes post-intervention in complete or sub-group analysis. Improvements in cardiometabolic or psychological secondary outcomes were inconsistent across all studies.ConclusionsThere is a lack of evidence to recommend specific intervention characteristics to optimise obesity prevention or treatment outcomes for Māori and Pacific Islander children. Future research requires greater consideration of cultural values and beliefs, community engagement, exclusive targeting of Māori and Pacific Islander children and families, and sub-group analyses for mixed-population studies. Incorporating co-design principles during study design and implementation can maximise the cultural specificity of interventions and may contribute to improved health and weight-related outcomes for this at-risk, priority population.Trial registrationPROSPERO CRD42019121790 (26 March 2019).

Project description:The aim of this systematic review was to summarize the results of trials evaluating interventions for the reduction of sarcopenia in patients undergoing surgery. Searches were conducted using the Cochrane Central Register of Controlled Trials, MEDLINE and Embase. RCTs evaluating exercise, dietary or pharmacological interventions to address sarcopenia in the perioperative period were included. Treatment effect estimates were expressed as standardized mean differences (MDs) with confidence intervals, and heterogeneity was expressed as I2 values. Seventy trials including 3402 participants were selected for the data synthesis. Exercise interventions significantly increased muscle mass (MD 0.62, 95 per cent c.i. 0.34 to 0.90; P < 0.001), muscle strength (MD 0.55, 0.39 to 0.71; P < 0.001), measures of gait speed (MD 0.42, 0.05 to 0.79; P = 0.03), and reduced time for completion of set exercises (MD -0.76, -1.12 to -0.40; P < 0.001) compared with controls. Subgroup analysis showed that interventions in the early postoperative period were more likely to have a positive effect on muscle mass (MD 0.71, 0.35 to 1.07; P < 0.001) and timed tests (MD -0.70, -1.10 to -0.30; P = 0.005) than preoperative interventions. Treatment effects on muscle mass (MD 0.09, -0.31 to 0.49; P = 0.66) and strength (MD 0.46, -0.01 to 0.92; P = 0.05) were attenuated by the presence of cancer. Results of analyses restricted to nine trials at low risk of allocation concealment bias and fourteen trials at low risk of attrition bias were comparable to those of the primary analysis. Risk-of-bias assessment showed that most trials were at high risk of incomplete outcome and attrition bias, thus reducing the estimate of certainty of the evidence according to the GRADE assessment tool. Exercise interventions appear beneficial in reducing the impact of sarcopenia. Because of the high risk of bias and low certainty of the current evidence, large RCTs using standardized measures of muscle mass should be undertaken.

Dataset Information

Preclinical therapies to prevent or treat fracture non-union: A systematic review.

Background

Aim

Methods

Results

Conclusion

Publications

Preclinical therapies to prevent or treat fracture non-union: A systematic review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets