Multiple comparisons tests (MCTs) are performed several times on the mean of experimental conditions. When the null hypothesis is rejected in a validation, MCTs are performed when certain experimental conditions have a statistically significant mean difference or there is a specific aspect between the group means. A problem occurs if the error rate increases while multiple hypothesis tests are performed simultaneously. Consequently, in an MCT, it is necessary to control the error rate to an appropriate level. In this paper, we discuss how to test multiple hypotheses simultaneously while limiting type I error rate, which is caused by α inflation. To choose the appropriate test, we must maintain the balance between statistical power and type I error rate. If the test is too conservative, a type I error is not likely to occur. However, concurrently, the test may have insufficient power resulted in increased probability of type II error occurrence. Most researchers may hope to find the best way of adjusting the type I error rate to discriminate the real differences between observed data without wasting too much statistical power. It is expected that this paper will help researchers understand the differences between MCTs and apply them appropriately.

Lee DK, et al. Korean J Anesthesiol. 2015 Jun;68(3):220-223. http://dx.doi.org/10.4097/kjae.2015.68.3.220

Background: Prolotherapy, which stimulates the healing of loosened ligaments and tendons, is a cost-effective and safe treatment modality for chronic musculoskeletal pain. Its benefits may be affected by injection protocols, comparative regimens, and evaluation scales. The aim of this study was to determine the effectiveness of dextrose prolotherapy as a long-term treatment for chronic musculoskeletal pain.Methods: Medline, Embase, Cochrane Central, KoreaMed, and KMbase databases were searched for studies published up to March 2019. We included randomized controlled trials which compared the effect of dextrose prolotherapy with that of other therapies such as exercise, saline, platelet-rich plasma, and steroid injection. The primary outcome was pain score change during daily life.Results: Ten studies involving 750 participants were included in the final analysis. Pain scores from 6 months to 1 year after dextrose prolotherapy were significantly reduced compared to saline injection (standardized mean difference [SMD] –0.44; 95% confidence interval [CI] –0.76 to –0.11, P = 0.008) and exercise (SMD –0.42; 95% CI –0.77 to –0.07, P = 0.02). Prolotherapy yielded results similar to platelet-rich plasma or steroid injection, that it showed no significant difference in pain score.Conclusions: Dextrose prolotherapy is more effective in the treatment of chronic pain compared to saline injection or exercise. Its effect was comparable to that of platelet-rich plasma or steroid injection. Adequately powered, homogeneous, and longer-term trials are needed to better elucidate the efficacy of prolotherapy.

Is the primary endpoint clearly defined?

In J, et al. Korean J Anesthesiol. 2017 Jun;70(3):267-276. https://doi.org/10.4097/kjae.2017.70.3.267

Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute and chronic infection in human tissues, including in the lungs of cystic fibrosis (CF) patients, acts as an interkingdom immunomodulatory signal that facilitates pathogen persistence, and host tolerance to infection. Transcriptome results have led to the hypothesis that 2-AA causes further harm to the host by triggering mitochondrial dysfunction in skeletal muscle. As normal skeletal muscle function is essential to survival, and is compromised in many chronic illnesses, including infections and CF-associated muscle wasting, we here determine the global effects of 2-AA on skeletal muscle using high-resolution magic-angle-spinning (HRMAS), proton (¹H) nuclear magnetic resonance (NMR) metabolomics, in vivo ³¹P NMR, whole-genome expression analysis and functional studies. Our results show that 2-AA when injected into mice, induced a biological signature of insulin resistance as determined by ¹H NMR analysis-, and dramatically altered insulin signaling, glucose transport, and mitochondrial function. Genes including Glut4, IRS1, PPAR-γ, PGC1 and Sirt1 were downregulated, whereas uncoupling protein UCP3 was up-regulated, in accordance with mitochondrial dysfunction. Although 2-AA did not alter high-energy phosphates or pH by in vivo ³¹P NMR analysis, it significantly reduced the rate of ATP synthesis. This affect was corroborated by results demonstrating down-regulation of the expression of genes involved in energy production and muscle function, and was further validated by muscle function studies. Together, these results further demonstrate that 2-AA, acts as a mediator of interkingdom modulation, and likely effects insulin resistance associated with a molecular signature of mitochondrial dysfunction in skeletal muscle. Reduced energy production and mitochondrial dysfunctional may further favor infection, and be an important step in the establishment of chronic and persistent infections.