Transitivity, coherence, and reliability of network meta-analyses comparing proximal humerus fracture treatments: a meta-epidemiological study.

BACKGROUND: Network meta-analyses can be valuable for decision-makers in guiding clinical practice. However, for network meta-analysis results to be reliable, the assumptions of both transitivity and coherence must be met, and the methodology should adhere to current best practices. We aimed to assess whether network meta-analyses of randomized controlled trials (RCTs) comparing interventions for proximal humerus fractures provide reliable estimates of intervention effects. METHODS: We searched PubMed, EMBASE, The Cochrane Library, and Web of Science for network meta-analyses comparing interventions for proximal humerus fractures. We critically assessed the methodology regarding the development of a protocol, search strategy, trial inclusion, outcome extraction, and the methods used to conduct the network meta-analyses. We assessed the transitivity and coherence of the network graphs for the Constant score (CS), Disabilities of the Arm, Shoulder, and Hand score (DASH), and additional surgery. Transitivity was assessed by comparing probable effect modifiers (age, gender, fracture morphology, and comorbidities) across intervention comparisons. Coherence was assessed using Separating Indirect from Direct Evidence (SIDE) (Separating Indirect from Direct Evidence) and the design-by-treatment interaction test. We used CINeMA (Confidence in Network Meta-analyses) to assess the confidence in the results. RESULTS: None of the three included network meta-analyses had a publicly available protocol or data-analysis plan, and they all had methodological flaws that could threaten the validity of their results. Although we did not detect incoherence for most comparisons, the transitivity assumption was violated for CS, DASH, and additional surgery in all three network meta-analyses. Additionally, the confidence in the results was 'very low' primarily due to within-study bias, reporting bias, intransitivity, imprecision, and heterogeneity. CONCLUSIONS: Current network meta-analyses of RCTs comparing interventions for proximal humerus fractures do not provide reliable estimates of intervention effects. We advise caution in using these network meta-analyses to guide clinical practice. To improve the utility of network meta-analyses to guide clinical practice, journal editors should require that network meta-analyses are done according to a predefined analysis plan in a publicly available protocol and that both coherence and transitivity have been adequately assessed and reported.

A meta-epidemiological study found that meta-analyses of the same trials may obtain drastically conflicting results.

OBJECTIVES: To assess how much protocols reduce methodological flexibility and variation of results in meta-analyses comparing operative with nonoperative treatments for proximal humerus fractures. STUDY DESIGN AND SETTING: A meta-epidemiological study. We searched four bibliographic databases for eligible meta-analyses. We contacted the authors of the meta-analyses, requesting a copy of their protocol. We identified the included studies and extracted intervention effect data for functional outcome, quality of life, and adverse events. Using the same intervention effect data for each outcome domain, we conducted multiple meta-analyses using differing combinations of methodological choices (analytical scenarios) without restricting the available methodological choices (as if no protocol was used). For each protocol, we repeated this process but restricted the available choices to those listed in the protocol. We then compared the distributions of effect estimates with and without protocols. Methodological flexibility was estimated as the difference in number of possible meta-analyses and the variation of results as the difference between the most conflicting effect estimates. RESULTS: We identified 23 meta-analyses, included 24 primary studies, and obtained three protocols. The protocols markedly reduced methodological flexibility (range for functional outcomes 94%-99%; quality of life 58%-76%; adverse events 87%-91%). The corresponding reduction in the variation of the results varied (range for functional outcomes; 33%-78%, quality of life; 10%-24%; adverse events 10%-13%). CONCLUSION: Although the protocols consistently reduced methodological flexibility, the reduction in the variation (bias) of results varied. Consequently, review authors may obtain conflicting results based on the same data. We advise caution when interpreting the conclusions of meta-analyses with absent or imprecise protocols.

A 12-Week Supervised Exercise Therapy Program for Patients with Diabetic Foot Ulcers: Program Development and Preliminary Feasibility.

Exercise therapy helps improve glycaemic control and insulin sensitivity and may be relevant in treating patients with diabetic foot ulcers (DFUs). This study describes the development of a 12-week exercise therapy program for patients with DFUs and the preliminary feasibility of the program focusing on the program's inclusion, adherence, and safety. The development process is built on knowledge from a published systematic review on exercise for people with DFUs and a grounded theory study on the main concerns of people with DFUs regarding physical activity. The development involved doctors, wound care nurses, podiatrists, and feedback from patients and physical therapists using semi-structured interviews. The program was designed as a combination of aerobic and resistance training exercises. The aerobic exercise phase on the stationary bike of 30-minute duration was aimed at a moderate intensity. Resistance exercises were conducted with a 15-repetition maximum approach (four to five sets per trial) throughout the 12-week period. Three patients were included and received the exercise intervention. Except for recruitment and retention rates, acceptance levels were met for all other research progression criteria. Patients found the intervention relevant, wanted further guidance on continuing exercising, and would have liked the intervention closer to their home for example, a municipality setting. Although the exercise therapy program for patients with DFUs was developed in a thorough process with the inclusion of available evidence and the involvement of patients and other stakeholders conclusions on feasibility are limited due to the low recruitment rate. A reconsideration of the setting is needed in future exercise intervention studies.

Inforatio technique to promote wound healing of diabetic foot ulcers: study protocol for a parallel-group, evaluator-blinded, randomised clinical trial.

INTRODUCTION: Diabetic foot ulcers (DFUs) are associated with extensive consequences for the affected patients and treatment of these hard-to-heal ulcers is known for being challenging. New treatment methods to supplement the current standard care may improve the prognosis for these patients.A preceding feasibility trial with promising results, facilitated this trial that aims to study the effect of a novel simple treatment, called inforatio technique, which may promote healing of DFUs. The inforatio technique is a minimally invasive procedure where small cuts are made on wound beds with punch biopsy tools. METHODS AND ANALYSIS: This multicentre randomised clinical trial will be conducted at outpatient clinics at Zealand University Hospital, Herlev University Hospital, Slagelse Hospital and Nykoebing Falster Hospital. 100 participants will be included and randomised in a 1:1 ratio to either a control group that receives usual care or an intervention group that receives both usual care and the inforatio technique.The primary outcome is complete healing evaluated on digital images by blinded observers. It is not possible to blind participants or the outpatient clinic staff because the inforatio technique is visible in wound beds after application. Change in EQ-5D-5L (EuroQoL-5 Dimension- 5 Level) Visual Analogue Scale Score and Wound-QoL Global Score from baseline to end of follow-up are secondary outcomes. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Danish National Committee on Health Research Ethics on 15 December 2021 (approval ID: SJ-904). Trial results are planned to be published in a high-impact peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05189470.

Benefits and Harms of Exercise Therapy for Patients With Diabetic Foot Ulcers: A Systematic Review.

AIM: Exercise therapy is a core element in the treatment of diabetes, but the benefits and harms for patients with a diabetic foot ulcer (DFU) are unknown. We therefore aimed to systematically review the benefits on health-related quality of life (HRQoL) and harms of exercise therapy for patients with DFU. METHODS: We searched 6 major databases. We performed citation and reference searches of included studies and contacted authors of ongoing trials. We included randomized controlled trials (RCTs) to assess potential benefits on HRQoL and harms of exercise therapy. Observational studies were included to identify potential harms of exercise therapy. RESULTS: We included 10 published publications of 9 trials and results from 2 unpublished trials including a total of 281 individuals with DFUs receiving various forms of exercise therapy. Due to lack of HRQoL measurements and high heterogeneity, it was not possible to perform meta-analyses. Results on HRQoL was present in one unpublished study. Harms reported ranged from musculoskeletal problems, increased wound size, to amputation; however, no safe conclusions could be drawn from the available data due to high heterogeneity and risk of bias in the trials. CONCLUSIONS/INTERPRETATION: Protective strategies are often preferred over therapeutic exercise that might have unforeseen consequences for patients over time. Based on the current literature, no evidence-based recommendations can be provided on the benefits and harms of exercise therapy for patients with DFUs. Well-conducted RCTs are needed to guide rehabilitation including detailed description of adverse events and an exercise program in a semisupervised or fully supervised setting.