A Network Meta-Analysis of Randomized Controlled Trials Directed at Treating Lateral Epicondylalgia

Background: Lateral epicondylosis is the most prevalent cause of lateral elbow pain, occurring in 4 per 1000 patients. The aim of most treatments is to reduce inflammation even with histological evidence demonstrating that lateral epicondylosis is a non-inflammatory condition. Objective: To determine the relative merits of the different regimens used to diminish lateral epicondylosis pain using a mixed treatment comparison/network meta-analysis (NMA). Methods: A thorough literature search was performed. The eligibility criteria for this mixed treatment comparison were: randomized controlled clinical trials; human subjects; working age population (16 to 70 years); the outcome measure was an objective pain assessment; measured at a 1- to 3-month follow-up. The NMA were performed using the GeMTC user interface for automated NMA utilizing a Bayesian Hierarchical Model of random effects. The evaluation of confidence in the findings from NMA was performed using a semi-automated platform called CINeMA (Confidence in Network Meta-Analysis). Results: The model suggests that articulation technique is the most effective measure for decreasing lateral epicondylalgia followed by topical nitrates, acupuncture, kinesiology taping and low-level laser therapy, respectively. Muscle energy technique, local corticosteroid injection, prolotherapy and counterforce bracing displayed a trend toward being less effective than placebo. Conclusions: The results suggest that the most effective modalities for improving lateral epicondylalgia are those that decrease muscle tone and those that improve circulation, while measures meant to decrease inflammation appear to be of no or limited benefit.

A method for assessing robustness of the results of a star-shaped network meta-analysis under the unidentifiable consistency assumption

Background In a star-shaped network, pairwise comparisons link treatments with a reference treatment (often placebo or standard care), but not with each other. Thus, comparisons between non-reference treatments rely on indirect evidence, and are based on the unidentifiable consistency assumption, limiting the reliability of the results. We suggest a method of performing a sensitivity analysis through data imputation to assess the robustness of results with an unknown degree of inconsistency. Methods The method involves imputation of data for randomized controlled trials comparing non-reference treatments, to produce a complete network. The imputed data simulate a situation that would allow mixed treatment comparison, with a statistically acceptable extent of inconsistency. By comparing the agreement between the results obtained from the original star-shaped network meta-analysis and the results after incorporating the imputed data, the robustness of the results of the original star-shaped network meta-analysis can be quantified and assessed. To illustrate this method, we applied it to two real datasets and some simulated datasets. Results Applying the method to the star-shaped network formed by discarding all comparisons between non-reference treatments from a real complete network, 33% of the results from the analysis incorporating imputed data under acceptable inconsistency indicated that the treatment ranking would be different from the ranking obtained from the star-shaped network. Through a simulation study, we demonstrated the sensitivity of the results after data imputation for a star-shaped network with different levels of within- and between-study variability. An extended usability of the method was also demonstrated by another example where some head-to-head comparisons were incorporated. Conclusions Our method will serve as a practical technique to assess the reliability of results from a star-shaped network meta-analysis under the unverifiable consistency assumption.

Improving Glycemic Control in Type 2 Diabetes Using Mobile Applications and e-Coaching: A Mixed Treatment Comparison Network Meta-Analysis

Objectives: This study compared the effectiveness of glycemic control among usual care, care management using a mobile application (app), and management using an app with additional e-coaching for patients with type 2 diabetes mellitus (T2DM) using a mixed treatment comparison (MTC) network meta-analysis (NMA). Methods: A systematic search for published randomized controlled trials (RCTs) was conducted, which included Pubmed, Web of Science, Cochrane Central Register of Controlled Trials, CINAL, Koreamed, KMbase, and ScienceOn, until October 2020. Among the 10,391 studies identified after removing duplicates, 14 RCTs were finally included in the MTC NMA. Data extraction and methodological quality assessment using version 2 of the Cochrane tool for assessing the risk-of-bias in randomized trials (RoB 2) was performed. The comparative efficacy was analyzed using the random-effects NMA based on a frequentist model by the intervention group and main outcome variables. Results: At the 3-month follow-up after each intervention, a comparison of the P-scores revealed the app plus e-coaching intervention to be the most effective method for reducing the HbA1c level in a homogeneous gender ratio group (P-score 0.92). At the 6-month follow-up period, app intervention was the best in reducing the HbA1c level in the homogeneous gender ratio and under 60 years of age group (P-score 1.00). Conclusions: Based on MTC analysis using the data from published RCTs, mobile apps or apps with e-coaching interventions for T2DM patients were more effective in improving the HbA1c values, FBS, and hypoglycemia frequency than usual care. Nevertheless, further research will be needed to clarify the effects of adding e-coaching to the app. Study registration: Research Registry UIN (reviewregistry780)

Comparison of Different Stenting Techniques of Coronary Bifurcation Lesions: A Network Meta-Analysis of 7601 Patients

IntroductionIntervention on coronary bifurcations lesions (CBL) is challenging. While provisional side branch (PS) stenting is the recommended method in most cases, there is no consensus on the preferred 2-stent technique.Material and methodsWe performed a network meta-analysis including randomized controlled trials (RCT) and observational studies comparing stenting techniques in CBL with reported clinical outcomes. A mixed treatment comparison model generation was performed to compare culotte, T and protrusion (TAP), crush and provisional techniques.ResultsWe included 14 RCT and 14 observational studies comprising 7,601 patients among whom 2,516 were treated with PS, 792 with TAP, 1,493 with culotte and 2,808 with crush. A Bayesian network meta-analysis showed a significant rate reduction of major adverse cardiovascular events (OR=0.73; 95%CI 0.52-0.99) and a trend for reduction in lesion revascularization (OR=0.72; 95%CI 0.48-1.11) and myocardial infarction (OR=0.62; 95%CI 0.3-1.08) with the crush technique, mainly driven by the double kissing (DK) crush, compared with all other stenting techniques. Other clinical outcomes, including mortality and stent thrombosis (ST) did not differ significantly between methods.ConclusionsThe crush technique, and especially DKcrush, is associated with improved outcomes compared to culotte, T and protrusion (TAP) and provisional techniques for CBL treatment. Further research is required to determine the optimal stenting technique for CBL.

A mixed treatment comparison of selected osteopathic techniques used to treat acute nonspecific low back pain: a proof of concept and plan for further research

Context Back injuries have a high prevalence in the United States and can be costly for both patients and the healthcare system at large. While previous guidelines from the American College of Physicians for the management of acute nonspecific low back pain (ANLBP) have encouraged nonpharmacologic management, those treatment recommendations involved only superficial heat, massage, acupuncture, and spinal manipulation. Investigation about the efficacy of spinal manipulation in the management of ANLBP is warranted. Objectives To compare the results in previously-published literature documenting the outcomes of osteopathic manipulative treatment (OMT) techniques used to treat ANLBP. The secondary objective of this study was to demonstrate the utility of using Bayesian network meta-analysis (NMA) to perform a mixed treatment comparison (MTC) of a variety of osteopathic techniques. Methods A literature search for randomized controlled trials (RCTs) of ANLBP treatments was performed in April 2020 according to PRISMA guidelines by searching MEDLINE/PubMed, OVID, Cochrane Central, PEDro, and OSTMED.Dr databases; scanning the reference lists of articles; and using the Canadian Agency for Drugs and Technologies in Health grey literature checklist. Each database was searched from inception to April 1, 2020. The following search terms were used: acute low back pain, acute low back pain plus physical therapy, acute low back pain plus spinal manipulation, and acute low back pain plus osteopathic manipulation. The validity of eligible trials was assessed by the single author using an adapted National Institute for Health and Care Excellence methodology checklist for randomized, controlled trials and an extraction form based on that checklist. The outcome measure chosen for this NMA was the Visual Analogue Scale of pain. The NMA were performed using the GeMTC user interface for automated NMA utilizing a Bayesian hierarchical model of random effects. Results The literature search initially found 483 unduplicated records. After screening and full text assessment, five RCTs were eligible for the MTC, yielding a total of 430 participants. Results of the MTC model suggested that there was no statistically significant decrease in reported pain when exercise, high-velocity low-amplitude (HVLA), counterstrain, muscle energy technique, or a mix of techniques were added to conventional treatment to treat ANLBP. However, the rank probabilities assessment determined that HVLA and the OMT mixed treatment protocol plus conventional care were ranked superior to conventional care alone for improving ANLBP. Conclusions While this study failed to provide definitive evidence upon which clinical recommendations can be based, it does demonstrate the utility of performing NMA for MTCs of osteopathic modalities used to treat ANLBP. However, to take full advantage of this statistical technique, future studies should be designed with consideration for the methodological shortcomings found in past osteopathic research.

Comparison of coronary bifurcation lesions stenting techniques- a network meta-analysis

Background Coronary bifurcations lesions (CBL) are account for 15–20% of all percutaneous coronary interventions (PCI) and constitute a major challenge for interventionists in terms of procedural success rate and long-term cardiac events. Based on data from multiple randomized trials and registries, current guidelines advocate the use of provisional side branch (SB) stenting strategy for the majority of CBL's. However, for true or complex CBL's (long side branches lesions, difficult side branches access or high risk of side branches compromise), which account for up to 25% of CBL's, this strategy may by unsafe and ineffective due to a potential risk of intraprocedural or long-term occlusion of a significant side branch and a two-stenting technique may be needed in order to achieve optimal results. Up to date, the optimal two- stenting technic for CBL remains in debate. Accordingly, our aim was to compare different stenting techniques in coronary bifurcation lesions. Methods We performed a MEDLINE search for randomized controlled trials (RCT) and observational studies comparing stenting techniques in CBL's with reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare culotte, T and protrusion (TAP), crush and provisional techniques Results A total of 13 RCT and 12 observational studies were identified including 6806 patients, among whom 1,201 were treated with cullotte, 2,731 with crush, 797 with TAP and 2077 with provisional stenting. The Bayesian hierarchical random-effects model demonstrated a significant reduction in target lesion revascularization (TLR) rate with crush techniques compared with provisional technique (OR 0.64 95% CI 0.42–0.97) along with a trend for reduction in major adverse cardiovascular (MACE) events (OR 0.75, 95% CI 0.55–1.02). TAP and culotte techniques did not show similar results. Equality of other endpoints, including mortality, myocardial infarction and re-stenosis was found between all CBL's techniques (Figure 1). Discussion Our findings suggest improved outcomes with crush technique compared to other double stenting techniques in terms of TLR with a trend towards MACE reduction. Further research is required to determine the optimal stenting technique for coronary bifurcations lesions along with the utility of imaging and physiology in this complex subset. Figure 1. Comparison of double stentin techniques Funding Acknowledgement Type of funding source: None

Drug Therapies for Patients with IgA Nephropathy: A Network Meta-analysis of Randomized Clinical Trials

Background: Several drugs are used for treating IgA nephropathy (IgAN). We carried out a network meta-analysis evaluating these drugs. Methods: Electronic databases were searched for appropriate randomized clinical trials carried out in patients with IgAN. The primary outcome was proteinuria remission rates and there were several other secondary outcome measures. The risk of bias was assessed. Mixed treatment comparison estimates were modelled from direct and indirect comparison estimates. Grading of the evidence for key comparisons was carried out. Results: Fifty-seven clinical trials were included in the systematic review and 51 in the metaanalysis. Polyunsaturated fatty acids, corticosteroids/angiotensin receptor blockers (ARB), ARB, angiotensin converting enzyme inhibitors (ACEI), ARB/ACEI, corticosteroids/ACEI and hypolipidemics/ ARB were observed with significantly higher rates of proteinuria remission than the standard of care. Several benefits were observed with other drugs on the secondary outcome measures. A very low grade was observed for the interventions. Conclusion: We observed a few interventions to perform better in the management of IgAN. The results of this study will aid in further evaluation of such drugs that may assist in saving the resources and time. However, the readers should interpret the findings with great caution as the results might change with the advent of future head-to-head clinical trials.

SAT-662 Effects of SGLT Inhibitors or GLP1 Analogues on Glucose Homeostasis and Body Weight in Patients with Type 1 Diabetes: A Network Meta-Analysis

Objective: Despite intensive insulin treatment in patients with type 1 diabetes (T1D), many of them do not reach the glycemic target goal. We performed a network meta-analysis to evaluate the efficacy and safety of additional therapy to insulin in patients with T1D. Methods: We searched CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded from January 1970 until September 2019 to identify randomized controlled trials (RCTs) in T1D patients treated with insulin and metformin, sodium-glucose cotransporter (SGLT) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). We performed direct and indirect network meta-analysis using Bayesian models and generated rankings of the different hypoglycemia agents by generating mixed treatment comparison. Results: With 23 RCTs (n = 5,151), we performed the network meta-analysis using eight groups; 1) insulin alone, 2) insulin and metformin, 3) insulin and canagliflozin, 4) insulin and dapagliflozin, 5) insulin and empagliflozin, 6) insulin and sotagliflozin, 7) insulin and liraglutide, and 8) insulin and exenatide. Compared with insulin alone, HbA1c was significantly lower in the group treated with insulin and sotagliflozin (mean difference: -0.43%; 95% credible intervals: -0.62 to -0.23). Total daily insulin dose was significantly lower in the insulin and sotagliflozin group by 6.3 U/day than in insulin alone group. Compared with insulin alone, body weight was significantly decreased in the group treated with canagliflozin by 4.5kg, sotagliflozin by 2.8kg, and exenatide by 5.1 kg, respectively. Severe hypoglycemic episodes did not differ between the groups. Conclusions: In patients with T1D, sotagliflozin add-on to insulin decreased HbA1c levels, daily insulin dose, and body weight without hypoglycemia compared to insulin monotherapy. Combined treatment of canagliflozin or exenatide with insulin was effective in weight loss compared with insulin alone in these patients.