ABSTRACT
Background: The effect of first-line complex decongestive therapy (CDT) for breast cancer-related lymphedema (BCRL) depending on various factors forces patients to seek additional treatment. Therefore, this meta-analysis was conducted to evaluate the effect of different conservative medical interventions as a complement to CDT. This is the first meta-analysis that includes various kinds of conservative treatments as adjunctive therapy to get broader knowledge and improve practical application value, which can provide recommendations to further improve BCRL patients' health status. Methods: RCTs published before 18 December 2023 from PubMed, Embase, Cochrane Library, and Web of Science databases were searched. RCTs that compared the effects of conservative medical intervention were included. A random-effects or fixed-effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool. Results: Sixteen RCTs with 690 participants were included, comparing laser therapy, intermittent pneumatic compression (IPC), extracorporeal shock wave therapy (ESWT), electrotherapy, ultrasound, diet or diet in combination with synbiotic supplement, traditional Chinese medicine (TCM), continuous passive motion (CPM), and negative pressure massage treatment (NMPT). The results revealed that conservative medical intervention as complement to CDT had benefits in improving lymphedema in volume/circumference of the upper extremity [SMD = -0.30, 95% CI = (-0.45, -0.15), P < 0.05, I 2 = 51%], visual analog score (VAS) for pain [SMD = -3.35, 95% CI (-5.37, -1.33), P < 0.05, I 2 = 96%], quality of life [SMD = 0.44, 95% CI (0.19, 0.69), P < 0.05, I 2 = 0], and DASH/QuickDASH [SMD = -0.42, 95% CI (-0.70, -0.14), P < 0.05, I 2 = 10%] compared with the control group. Subgroup analysis revealed that laser therapy and electrotherapy are especially effective (P < 0.05). Conclusion: Combining conservative medical interventions with CDT appears to have a positive effect on certain BCRL symptoms, especially laser therapy and electrotherapy. It showed a better effect on patients under 60 years old, and laser therapy of low to moderate intensity (5-24 mW, 1.5-2 J/cm2) and of moderate- to long-term duration (≥36-72 sessions) showed better effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354824, identifier CRD42022354824.
ABSTRACT
Individuals can vary drastically in their response to the same treatment, and this heterogeneity has driven the push for more personalized medicine. Accurate and interpretable methods to identify subgroups that respond to the treatment differently from the population average are necessary to achieving this goal. The Virtual Twins (VT) method is a highly cited and implemented method for subgroup identification because of its intuitive framework. However, since its initial publication, many researchers still rely heavily on the authors' initial modeling suggestions without examining newer and more powerful alternatives. This leaves much of the potential of the method untapped. We comprehensively evaluate the performance of VT with different combinations of methods in each of its component steps, under a collection of linear and nonlinear problem settings. Our simulations show that the method choice for Step 1 of VT, in which dense models with high predictive performance are fit for the potential outcomes, is highly influential in the overall accuracy of the method, and Superlearner is a promising choice. We illustrate our findings by using VT to identify subgroups with heterogeneous treatment effects in a randomized, double-blind trial of very low nicotine content cigarettes.
Subject(s)
Precision Medicine , Humans , Precision Medicine/methods , Double-Blind MethodABSTRACT
Background: Despite neuroinflammation being an important component of the pathology of Alzheimer's disease (AD), effective therapies to alleviate neuroinflammation are still lacking. Many animal experiments in AD have found that acupuncture may ameliorate cognition by decreasing neuroinflammation and modulating cytokines, but its effects have not been systematically examined. We aimed to assess its efficacy on neuroinflammation in AD and to investigate the potential mechanisms. Materials and methods: The following databases were searched from inception until 24 August 2022: Web of Science, EMBASE, PubMed, the Cochrane Library, and China National Knowledge Infrastructure. Animal studies that reported the efficacy of acupuncture on neuroinflammation in AD were included. The SYRCLE Robt was utilized to evaluate methodological quality. Stata 17 was utilized to conduct a meta-analysis of cytokine levels and the results of the Morris water maze. Results: 23 studies were included, with a total of 417 rats/mice. The overall quality of all included reports was medium. The results indicated that acupuncture significantly reduced the expressions of pro-inflammatory cytokines which included IL-1ß [SMD = -3.50, 95% CI (-4.31, -2.69); I 2 = 78.6%] (P < 0.05), TNF-α [SMD = -3.05, 95% CI (-3.86, -2.24); I 2 = 69.6%] (P < 0.05), IL-6 [SMD = -3.22, 95% CI (-4.62, -1.81); I 2 = 77.6%] and enhanced the expressions of anti-inflammatory cytokines including IL-4 [SMD = 2.77, 95% CI (1.95, 3.59); I 2 = 33.9%] (P < 0.05), IL-10 [SMD = 1.84, 95% CI (1.20, 2.49); I 2 = 41.0%] (P < 0.05) in an animal model of AD. Regarding the Morris water maze, compared to the control group, the acupuncture group showed a shorter escape latency [SMD = -2.23, 95% CI (-2.89, -1.57); I 2 = 79.2%] (P < 0.05), longer duration in platform quadrant [SMD = 2.34, 95% CI (1.44, 3.23); I 2 = 81.7%] (P < 0.05), and increased platform crossing number [SMD = 2.79, 95% CI (2.06, 3.53); I 2 = 71.9%] (P < 0.05). Conclusion: Acupuncture may reduce neuroinflammation in AD by modulating cytokine expression. This modulation significantly improved cognitive function in animal models of AD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354878.