Efficacy and safety of radiofrequency treatment for improving knee pain and function in knee osteoarthritis: a meta-analysis of randomized controlled trials

Background The clinical utility of radiofrequency (RF) in patients with knee osteoarthritis (OA) remains unclear. We conducted a meta-analysis to systematically evaluate the efficacy and safety of RF treatment in patients with knee OA. Methods Searches of the PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data databases were performed through August 30, 2021. The major outcomes from published randomized controlled trials (RCTs) involving patients with knee OA were compared between RF and control groups, including Visual Analogue Scale (VAS) or Numerical Rating Scale (NRS) scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), Global Perceived Effect (GPE) scale, and adverse effects at available follow-up times. Results Fifteen RCTs involving 1009 patients were included in this meta-analysis, and the results demonstrated that RF treatment correlated with improvements in pain relief (VAS/NRS score, all P < 0.001) and knee function (WOMAC, all P < 0.001) at 1–2, 4, 12, and 24 weeks after treatment as well as patients’ degree of satisfaction with treatment effectiveness (GPE scale, 12 weeks, P < 0.001). OKSs did not differ significantly between the two groups. Moreover, treatment with RF did not significantly increase adverse effects. Subgroup analysis of knee pain indicated that the efficacy of RF treatment targeting the genicular nerve was significantly better than intra-articular RF at 12 weeks after treatment (P = 0.03). Conclusions This meta-analysis showed that RF is an efficacious and safe treatment for relieving knee pain and improving knee function in patients with knee OA.

Impact of tourniquet during total knee arthroplasty when tranexamic acid was used: a meta-analysis of randomized controlled trials

Introduction The efficacy of tourniquet use during primary total knee arthroplasty (TKA) is thought to reduce intraoperative blood loss, improve surgical exposure, and optimize cement fixation. Tranexamic acid (TXA) use can decrease postsurgical blood loss and transfusion requirements. This review aimed to appraise the effects of tourniquet use in TKA for patients with tranexamic acid use. Methods A meta-analysis was conducted to identify relevant randomized controlled trials involving TXA plus a tourniquet (TXA-T group) and use of TXA plus no tourniquet (TXA-NT group) in TKA. Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database were searched from 2010 through October 2021. Results We identified 1720 TKAs (1690 patients) assessed in 14 randomized controlled trials. Compared with the TXA-NT group, the TXA-T group resulted in less intra-operative blood loss (P < 0.00001) and decreased duration of surgery (P < 0.00001), however more hidden blood loss (P = 0.0004) and less knee range of motion (P < 0.00001). No significant differences were found between two groups in terms of decrease in hemoglobin (P = 0.84), total blood loss (P = 0.79), transfusion rate (P = 0.18), drainage volume (P = 0.06), Visual Analogue Scale (VAS) at either the day of surgery (P = 0.2), 1 day (P = 0.25), 2 day (P = 0.39), 3 day (P = 0.21), 5 day (P = 0.21), 7 day (P = 0.06) or 1 month after surgery (P = 0.16), Hospital for Special Surgery (HSS) score at either 7 day (P = 0.10), 1 month (P = 0.08), 3 month (P = 0.22) or 6 month after the surgery (P = 0.92), Knee circumference (P = 0.28), length of hospital (P = 0.12), and complications such as intramuscular venous thrombosis (P = 0.81), deep venous thrombosis (P = 0.10), superficial infection (P = 0.45), deep wound infection (P = 0.64), and delayed wound healing (P = 0.65). Conclusion No big differences could be found by using or not tourniquet when use the TXA, though some benefits are related to operation time and less intra-operative blood loss by using tourniquet and TXA, Using the tourniquet was related to more hidden blood loss and less knee range of motion. More adequately powered and better-designed randomized controlled trials (RCTs) studies with long-term follow-up are required to validate this study.

Efficacy and Safety of Transcutaneous Electrical Acupoint Stimulation (TEAS) for Postoperative Pain in Laparoscopy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objectives. This meta-analysis aimed to assess the efficacy and safety of transcutaneous acupoint electrical stimulation (TEAS) for postoperative pain in laparoscopy. The review has been registered on the “INPLASY” website and the registration number is INPLASY202150101. Methods. Relevant randomized controlled trials are selected from seven electronic databases (PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP Information, WanFang Data, and Chinese Biomedical Database) from their inception up to November 30, 2020. Twenty-eight studies were included in this meta-analysis, and the statistical analyses and the exploration of heterogeneity sources were conducted by Stata 15.0 software. Besides, the bias assessment of the included studies was evaluated using the Cochrane risk of bias tool. Results. In total, 28 RCTs covering 2787 participants were included. The meta-analysis suggested that TEAS can effectively relieve pain in the short term after laparoscopy, reduce the postoperative consumption of rescue analgesics, improve the quality of life of patients, and shorten the length of hospitalization. And no serious adverse events are related to TEAS. Therefore, TEAS is relatively safe and efficacy for clinical application. The most used acupoints were Hegu (LI14), Neiguan (PC6), and Zusanli (ST36). Conclusions. TEAS can be recommended as a complementary and alternative therapy for the treatment of postoperative pain after laparoscopy. However, the included RCTs had some methodological limitations. Therefore, larger-size, more rigorous, and higher-quality RCTs are needed in the future to further explore the efficacy and safety of TEAS for postoperative pain after laparoscopy.

High-cited favorable studies for COVID-19 treatments ineffective in large trials

Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results for these interventions. Methods. Scopus (last update December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine/azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and that had received >150 citations. Their conclusions were assessed and correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained. Findings. 40 articles of clinical studies on these index interventions had received >150 citations (7 exceeded 1,000 citations). 20/40 (50%) had favorable conclusions and 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs while those without favorable conclusions were mostly RCTs (3/20 vs 15/20, p=0.0003). Only 1 RCT with favorable conclusions had sample size >160. Citation counts correlated strongly with Altmetric scores, in particular news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical to the highly-cited study. Conclusion. Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.

Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). Methods: A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. Results: The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) −3.04 (95% CI −4.47, −1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD −0.54; 95% CI −1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. Conclusions: Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies’ heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.

An Analytics Approach to Guide Randomized Controlled Trials in Hypertension Management

Blood pressure (BP) is a significant controllable risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. BP comprises two interrelated measurements: systolic and diastolic. CVD risk is minimized at intermediate BP values, a notion known as the J-curve effect. The J-curve effect imposes fundamental trade-offs in simultaneous management of systolic and diastolic BP; however, assessing a comprehensive set of joint systolic/diastolic BP treatment thresholds while explicitly considering the J-curve effect via randomized controlled trials (RCTs) is not feasible because of the time and cost-prohibitive nature of RCTs. In this study, we propose an analytics approach to identify promising joint systolic/diastolic BP threshold levels for antihypertensive treatment. More specifically, using one of the largest longitudinal BP progression data sets, we first build and fit Brownian motion processes to capture simultaneous progression of systolic/diastolic BP at the population level and externally validate our BP progression model on unseen data. We then analytically characterize the hazard ratio, which enables us to compute the optimal treatment decisions. Finally, building upon the optimal joint BP treatment thresholds, we devise a practical and easily implementable approximate policy. We estimate the potential impact of our findings through a simulation study, which indicates that the impact of explicitly considering the J-curve effect and joint systolic/diastolic BP in treatment decisions could be substantial. Specifically, we estimate that between approximately 3,000 and 9,000 premature deaths from cardiovascular disease in the United States could be prevented annually, a finding that could be tested empirically in randomized trials. This paper was accepted by Stefan Scholtes, healthcare management.