Clinical efficacy of botulinum toxin in lateral elbow tendinopathy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin injections for lateral elbow tendinopathy have been used as an alternative therapeutic option. However, few studies have quantitatively summarized the effect of botulinum toxin as well as its clinical significance. We aimed to evaluate the clinical efficacy (based on pain and grip strength) and adverse events of botulinum toxin on lateral elbow tendinopathy. PATIENTS AND METHODS: The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched until March 2023 for randomized controlled trials reporting the effects of botulinum toxin injections on lateral elbow tendinopathy. A random- or fixed-effects model (depending of inter-study variability) and generic inverse variance method were used to pool quantitative data from outcomes. The risk of bias was assessed with the Cochrane Risk of Bias 2.0 tool. RESULTS: A total of 8 clinical trials recruiting 438 subjects were included for meta-analysis. Pooled analysis revealed that botulinum toxin significantly reduced pain (mean difference [MD] -0.95, 95% CI [-1.63, -0.26], p=0.007) but it was not clinically relevant. No significant effect was detected for grip strength (MD-0.62kg, 95% CI [-2.25, 1.02], p=0.46) or in the risk for adverse events (odds ratio [OR] 0.41, 95% CI [0.05, 3.56], p=0.42) between botulinum toxin injection and control interventions. DISCUSSION: The use of botulinum toxin reached greater pain relief than control interventions and normal saline after a period of 12 to 24 weeks. However, changes in pain relief did not reach clinical significance. The studies that had the greatest reduction in pain used higher doses of botulinum toxin (60 U). Additionally, differences in grip strength and adverse events did not reach statistical or clinical importance. A subanalysis indicated that botulinum toxin outperformed corticosteroid injections in terms of improving grip strength. Botulinum toxin only causes local and minimal side effects such as irritation, ecchymosis, and paralysis. LEVEL OF EVIDENCE: I.

Association of GLP1R Polymorphisms With the Incretin Response.

CONTEXT: Polymorphisms in the gene encoding the glucagon-like peptide-1 receptor (GLP1R) are associated with type 2 diabetes but their effects on incretin levels remain unclear. OBJECTIVE: We evaluated the physiologic and hormonal effects of GLP1R genotypes before and after interventions that influence glucose physiology. DESIGN: Pharmacogenetic study conducted at 3 academic centers in Boston, Massachusetts. PARTICIPANTS: A total of 868 antidiabetic drug-naïve participants with type 2 diabetes or at risk for developing diabetes. INTERVENTIONS: We analyzed 5 variants within GLP1R (rs761387, rs10305423, rs10305441, rs742762, and rs10305492) and recorded biochemical data during a 5-mg glipizide challenge and a 75-g oral glucose tolerance test (OGTT) following 4 doses of metformin 500 mg over 2 days. MAIN OUTCOMES: We used an additive mixed-effects model to evaluate the association of these variants with glucose, insulin, and incretin levels over multiple timepoints during the OGTT. RESULTS: During the OGTT, the G-risk allele at rs761387 was associated with higher total GLP-1 (2.61 pmol/L; 95% CI, 1.0.72-4.50), active GLP-1 (2.61 pmol/L; 95% CI, 0.04-5.18), and a trend toward higher glucose (3.63; 95% CI, -0.16 to 7.42 mg/dL) per allele but was not associated with insulin. During the glipizide challenge, the G allele was associated with higher insulin levels per allele (2.01 IU/mL; 95% CI, 0.26-3.76). The other variants were not associated with any of the outcomes tested. CONCLUSIONS: GLP1R variation is associated with differences in GLP-1 levels following an OGTT load despite no differences in insulin levels, highlighting altered incretin signaling as a potential mechanism by which GLP1R variation affects T2D risk.

A deeper analysis in thyroid research: A meta-epidemiological study of the American Thyroid Association clinical guidelines.

BACKGROUND: The American Thyroid Association (ATA) uses the GRADE or the American College of Physicians (ACP) system to develop recommendations. Recommendations based on low-quality evidence should spur for the conduction of clinical studies, if feasible. The extent to which recommendations by the ATA based on low-quality of evidence are being actively researched remains unknown. METHODS: Clinical guidelines produced by the ATA using the GRADE or the ACP system to classify evidence were deemed eligible. Reviewers, in duplicate and independently, extracted therapeutic recommendations based on low-quality evidence, whereas recommendations with higher quality of evidence, aimed at diagnosis, or best practice statements were excluded. Eligible recommendations based on low-quality evidence were deconstructed to their components using the PICO format. We then searched on clinicaltrials.gov to identify ongoing research. Trials were deemed eligible if they addressed the PICO question with at least one of the intended outcomes. RESULTS: A total of 543 recommendations were retrieved, of which 305 (56%) were based on low-quality of evidence and only 90 were deemed eligible. Of these, we found that 33 (37%) recommendations were actively being researched in 53 clinical trials. Most of the trials were randomized and funded by non-profit organizations. Many clinical trials studied thyroid nodules and differentiated thyroid cancer (26/53; 49%), whereas few studied were aimed at anaplastic thyroid cancer (2/53; 4%). CONCLUSION: One out of three of gaps in evidence, identified as low quality during the development of ATA guidelines, are currently actively researched. This finding calls for the need to develop a better research infrastructure and funding to support thyroid research.