Pharmacological Use of Gamma-Aminobutyric Acid Derivatives in Osteoarthritis Pain Management: A Systematic Review

Background Pain is the major complication of osteoarthritis (OA) patients and is a decisive symptom for medical intervention. Gamma-aminobutyric acid (GABA) derivatives are optional painkillers but not widely used in pain management of OA patients. We synthesized the efficacy and safety of GABA derivatives for OA pain management. Methods We searched Medline, Cochrane CENTRAL, Embase, and ClinicalTrals.gov from inception to 13 October 2021 and included randomized controlled trials (RCTs) comparing the efficacy and safety of GABA derivatives with placebo or standard control in OA pain management. Two independent reviewers extracted data and assessed these studies for risk of bias using Cochrane Collaboration’s tool for RCT. Results In total, three eligible RCTs (n=3) meeting the eligibility criteria were included. Among these RCTs, one focused on hand OA pain management, while two RCTs focused on knee OA. In hand OA, pregabalin reduced numerical rating scale (NRS) score and the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score significantly compared with placebo, and caused 55 AEs. In knee OA, pregabalin reduced visual analogue scale (VAS) score and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score significantly with no recorded adverse event (AE). Meanwhile, in knee OA, gabapentin reduced both VAS score and WOMAC pain score compared with acetaminophen and caused 9 AEs. Conclusions GABA derivates are effective and safe in OA pain management. However, future researches with large sample size are needed to further prove the efficacy of GABA derivates in OA pain control. Trial registration: CRD42021240225.

Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial

Objective To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. Methods This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). Results No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. Conclusions ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. Trial registration: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964

A new prediction model for patient satisfaction after total knee arthroplasty and the roles of different scoring systems: a retrospective cohort study

Background Although total knee arthroplasty (TKA) is an efficacious treatment for end-stage osteoarthritis, ~20% of patients are dissatisfied with the results. We determined which factors contribute to patient satisfaction and compared the various scoring systems before and after surgery. Methods In this retrospective cohort study, 545 patients were enrolled and evaluated preoperatively and 1 year postoperatively. Patient demographics, as well as scores for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form (SF)-12, and 1989 Knee Society Clinical Rating System (1989 KSS), were recorded preoperatively and postoperatively. The possible predictors were introduced into a prediction model. Scores for overall satisfaction and the 2011 Knee Society Score (2011 KSS) were also assessed after TKA to identify the accuracy and agreement of the systems. Results There were 134 male patients and 411 female patients, with an overall prevalence of satisfaction of 83.7% 1 year after surgery. A history of surgery (p < 0.001) and the 1989 KSS and SF-12 were of the utmost importance in the prediction model, whereas the WOMAC score had a vital role postoperatively (change in WOMAC pain score, p < 0.001; change in WOMAC physical function score, p < 0.001; postoperative WOMAC pain score, p = 0.004). C-index of model was 0.898 > 0.70 (95% confidence interval (CI): 0.86-0.94). The Hosmer-Lemeshow test showed a p value of 0.586, and the AUC of external cohort was 0.953 (sensitivity=0.87, specificity=0.97). The agreement between the assessment of overall satisfaction and the 2011 KSS satisfaction assessment was general (Kappa=0.437 > 0.4, p < 0.001). Conclusion A history of surgery, the preoperative 1989 KSS, and the preoperative SF-12 influenced patient satisfaction after primary TKA. We recommend the WOMAC (particularly the pain subscale score) to reflect overall patient satisfaction postoperatively.

TO COMPARE THE EFFICACY OF GENICULAR NERVE BLOCK AND INJECTION OF HYLAN G-F 20 VERSUS GENICULAR NERVE BLOCK ONLY FOR IMPROVING PAIN AND FUNCTION OF GRADE-II AND GRADE-III OSTEOARTHRITIS KNEE

Introduction: Osteoarthritis (OA) of knee joint is a degenerative joint disease; heterogeneous and progressive in nature. Clinically presented with stiffness, swelling and pain which leads to a decrease in the quality of life. The presence of chronic knee pain has been found to be a strong predictor of future disability and dependency in older adults. Usually managed conservatively but if conservative treatment fails, Total Knee Replacement (TKR) is traditionally considered. This is associated with multiple perioperative morbidities. On the contrary, many patients are not suitable for surgical procedure and some do not want to go for surgical intervention. As many patients are not surgical candidates due to co-morbidities or unwillingness; other treatment options available are being sought for. The genicular nerve block (GNB) reduces pain and improves patient functions by blocking pain transmission of the sensory nerves. Combining this genicular nerve block with viscosupplementation (Injection Hylan G-F 20) appears to play a role and can be tried in patients suffering in grade II and grade III (radiological grading) osteo arthritis. There is paucity of information so as to compare the efcacy of genicular nerve block and injection of Hylan G-F 20 versus genicular nerve block only. Material And Methods: This Parallel group open label randomized controlled trial was done between July, 2018 to December, 2019 (Eighteen months). Patients with knee pain in grade II and III, OA knee attending the PMR OPD in IPGME&R, Kolkata in the specied tenure was considered for the study. The selected patients were allotted by random table. All the procedures were performed by single person. A total number of 60 patients with knee osteoarthritis of grade II and III, who did not respond with conservative management were included. Combined therapy of intra-articular injection of Hylan G-F 20 and genicular nerve block in Group 1 (Genicular Nerve Block and Injection Hylan G-F 20) and Genicular Nerve Block only in Group 2, performed to 30 patients in each arm. The three branches of the genicular nerve [superior lateral (SL), superior medial (SM), and inferior medial (IM) genicular nerves] were selected. Patients were evaluated initially (0 week) and at the 4th and 12th week followed up after intervention using VAS and WOMAC scale. Ultrasound guided genicular nerve block conducted under strict asepsis after proper dressing and draping with the visualization of genicular nerves (upper medial, upper lateral and lower medial quadrant) by musculoskeletal probe of Ultrasound machine (SAMSUNG/ Model PT60A/Musculoskeletal probe 12MHz). Injection Hylan G-F 20 (6 ml) intra-articular injection was given under strict asepsis. Results: 47% patients in group 1 and 67% patients in group 2 were in between 60-69 years. There is female preponderance in both the groups. WOMAC-pain score for dual intervention at 4th week was statistically signicantly lower compared to WOMAC-pain score obtained at any time of observation and any type of intervention. WOMAC- stiffness score for dual intervention at 4th week was statistically signicantly lower compared to WOMAC- stiffness score obtained at any time of observation. WOMAC SCORE: The changes in each intervention group at 0-week, 4th week and 12th week were statistically signicant. Statistically signicant difference of two groups were lost during 4th and 12th weeks observation. VAS: During 4th and 12th weeks observation, statistically signicantly different VAS score was observed among the two interventions; Genicular nerve block with injection consistently had a lower VAS score. This nding imply that Genicular nerve block alone did reduce the pain; however, reduction was greater in case of Genicular nerve block with Injection Hylan G-F 20 in both 4th and 12th week of observation. Conclusion: Genicular Nerve Block with injection HYLAN GF 20 (Combined Therapy Group) and Genicular Nerve Block alone are effective method of pain reduction in osteoarthritis knee. Combined Therapy doesn't have an added advantage as per WOMAC Score. But Combined therapy has a denite advantage over Genicular Nerve Block alone as per VAS Score.

A New Prediction Model of Patient Satisfaction After Total Knee Arthroplasty and The Roles of Different Score Systems: A retrospective cohort study

BACKGROUNDAlthough total knee arthroplasty (TKA) is efficacious treatment for end-stage osteoarthritis, ~20% patients are dissatisfied with the results. We determined which factors contribute to patient satisfaction and compared the various scoring systems before and after surgery.METHODSIn this retrospective cohort study, 545 patients were enrolled and were evaluated preoperatively and 1 year postoperatively. Patient demographics, as well as scores for Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form (SF)-12, and 1989 Knee Society Clinical Rating System (KSS) were recorded preoperatively and postoperatively. The possible predictors were introduced into a prediction model. Scores for overall satisfaction and 2011 Knee Society Score(KSS) were also assessed after total knee arthroplasty to identify the accuracy and agreement of the systems.RESULTSThere were 134 male patients and 411 female patients, with an overall prevalence of satisfaction of 83.7% 1 year after surgery. A history of surgery(p<0.001) , 1989 KSS and SF-12 were of the utmost importance in the prediction model, whereas the WOMAC score had a vital role postoperatively(change of WOMAC pain score, p<0.001; change of WOMAC physical function score, p<0.001; postoperative WOMAC pain score, p=0.004). The agreement between assessment of overall satisfaction and 2011 KSS satisfaction assessment was general(Kappa=0.437>0.4, p<0.001). CONCLUSIONA history of surgery, preoperative 1989 KSS and preoperative SF-12 influenced patient satisfaction after primary total knee arthroplasty. We recommend WOMAC (particularly the subscale score of pain) to reflect the overall patient satisfaction postoperatively.

Tibial component coverage affects tibial bone resorption and patient-reported outcome measures for patients following total knee arthroplasty

Purpose The aim of this study is to investigate the prognostic value of tibial component coverage (over-hang and under-hang) and the alignment of total knee arthroplasty (TKA) components 1 week after surgery. We select patient-reported outcome measures (PROMS) (the Knee Society score (KSS score) and the Western Ontario and McMaster Universities Osteoarthritis Index-pain score (WOMAC pain score)) and tibial bone resorption (TBR) 2 years after surgery as the end points. Methods The study retrospectively analyzed 109 patients undergoing TKA (fixed-bearing prosthesis with asymmetrical tibial tray) from January 2014 to December 2017 in Huashan Hospital. By using standard long-leg X-rays, anteroposterior (AP) and lateral X-rays of the knee, tibial component coverage (under-hang or over-hang), AP tibial-femoral anatomical angle (AP-TFA), AP femoral angle (AP-FA), AP tibial angle (AP-TA), and lateral tibial angle (L-TA) were measured at 1 week after surgery, while TBR was measured through postoperative 1-week and 2-year AP and lateral radiographs of the knee on three sides (medial side, lateral side on AP radiograph, and anterior side on lateral radiograph). The Pearson correlation analysis, simple linear regression, multiple linear regression, the Student’s t test, and one-way ANOVA together with Tukey’s post hoc test (or Games-Howell post hoc test) were used in the analyses. Results Tibial under-hang was more likely to appear in our patients following TKA (42%, medially, 39%, laterally, and 25%, anteriorly). In multivariate linear regression analysis of TBR, tibial under-hang (negative value) 1 week after surgery was positively correlated with TBR 2 years later on the medial (p = 0.003) and lateral (p = 0.026) side. Tibial over-hang (positive value) 1 week after surgery on the medial side was found negatively related with KSS score (p = 0.004) and positively related with WOMAC pain score (p = 0.036) 2 years later in multivariate linear regression analysis of PROMS. Both scores were better in the anatomically sized group than in the mild over-hang group (or severe over-hang) (p < 0.001). However, no significant relationship was found between the alignment of TKA components at 1 week after surgery and the end points (TBR and PROMS) 2 years later. Conclusion Under-hang of the tibial component on both the medial and lateral sides can increase the risk of TBR 2 years later. Over-hang of tibial component on the medial side decreases the PROMS (KSS score and WOMAC pain score) 2 years later. An appropriate size of tibial component during TKA is extremely important for patient’s prognosis, while the alignment of components might not be as important.

Acupotomy Therapy for Knee Osteoarthritis Pain: Systematic Review and Meta-Analysis

Background and Purpose. Knee osteoarthritis (OA) is a major public health problem, and currently, few effective medical treatments exist. Chinese acupotomy therapy has been widely used for the treatment of knee OA in China. We conducted this systematic review and meta-analysis to evaluate the efficacy of Chinese acupotomy in treating knee OA to inform clinical practice. Methods. We performed a comprehensive search on PubMed, the Cochrane Library, EMBASE, and four Chinese databases for articles published prior to June 2020. We included only randomized controlled trials (RCTs) that used acupotomy therapy as the major intervention in adults with knee OA, were published in either Chinese and English, included more than 20 subjects in each group, and included pain and function in the outcome measures. Knee OA was defined by the American College of Rheumatology or Chinese Orthopedic Association criteria in all studies. We extracted the visual analogue scale (VAS) pain score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the total effectiveness rate, the modified Japanese Orthopedic Association (JOA) activities of daily living score, and Lysholm’s score. We calculated the mean difference (MD) or risk ratio (RR) for all relevant outcomes. Meta-analyses were conducted using random-effects models when appropriate. Results. We identified 1317 potentially relevant studies, thirty-two of which met the eligibility criteria and were conducted in China between 2007 and 2020. A total of 3021 knee OA patients (62.96% female, median age: 57 years, and median disease duration: 33 months) were included. The treatment duration ranged from 1 week to 5 weeks (median: 3 weeks). The typical acupotomy treatment involved releasing soft tissue adhesions and was performed once a week for 1–5 weeks until the pain was relieved. The control group treatments included acupuncture (8 studies), electroacupuncture (10 studies), sodium hyaluronate (8 studies), radiofrequency electrotherapy (1 study), and nonsteroidal anti-inflammatory drugs (NSAIDs, 5 studies). The results from the meta-analysis showed that acupotomy led to superior improvements in the VAS pain score (MD = −1.11; 95% confidence interval (CI), −1.51 to −0.71; p < 0.00001) and WOMAC pain score (MD = −2.32; 95% CI, −2.94 to −1.69; p < 0.00001), a higher total effectiveness rate (RR = 1.15; 95% CI, 1.09–1.21; p < 0.00001), and superior improvements in the JOA score (MD = 6.39; 95% CI, 4.11–9.76; p < 0.00001) and Lysholm’s score (MD = 12.75; 95% CI, 2.61–22.89; p = 0.01) for overall pain and function. No serious adverse events were reported. Conclusion. Chinese acupotomy therapy may relieve pain and improve function in patients with knee OA. Furthermore, rigorously designed and well-controlled RCTs are warranted.

Efficacy of Balneotherapy and Mud Therapy in Patients with Knee Osteoarthritis: A Systematic Literature Review

Objectives To identify literature reporting on thermal mineral water and mud therapy effectiveness on pain, stiffness and knee function in patients with knee osteoarthritis. Design Systematic evidence scan of MEDLINE and PubMed was performed to identify the randomized controlled trial studies published from 2004 to December 2018. Study selection Papers reporting the effect of balneotherapy and mud therapy for treating knee OA, a duration of ≥2 weeks and in which Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used as an outcome measure. Data extraction Not RCT, Studies not in English. Results A quantitative meta-analysis of ten studies (831 patients) was performed. Five clinical studies (407 patients) measured effectiveness of balneotherapy and there was significant difference between the groups in WOMAC pain score, WOMAC stiffness score and WOMAC function score, with the differences in favour of balneotherapy. Six clinical studies (500 patients) measured effectiveness of mud therapy and there was significant difference between the groups in WOMAC pain score, WOMAC stiffness score and WOMAC function score, with the differences in favour of mud therapy. Conclusion This meta-analysis indicates that balneotherapy and mud therapy were clinically effective in relieving pain, stiffness, and improving function, as assessed by WOMAC score.

Preoperative Medial Meniscal Extrusion Is Associated With Patient-Reported Outcomes After Medial Opening Wedge High Tibial Osteotomy

Background: Although the medial compartment continues to sustain some loading after medial opening wedge high tibial osteotomy (MOWHTO) in varus-deformed knees, no studies have examined the relationship between medial meniscal extrusion (MME) and patient-reported outcome measures after MOWHTO. Purpose: To examine whether compartmental baseline MME was associated with patient-reported outcome measures after MOWHTO. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective study was composed of 149 MOWHTOs in 147 patients with clinical and radiological assessments. Patients were grouped according to severity of MME in the medial compartment at the time of surgery. MME was categorized into 4 groups according to MOAKS (MRI [magnetic resonance imaging] Osteoarthritis Knee Score) criteria and relative value of MME. We compared preoperative characteristics, including Kellgren-Lawrence (KL) grading scale, meniscal tear pattern, and postoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores. Associations between extent of MME and WOMAC subscores at postoperative 1 and 2 years were assessed with generalized linear models. Results: Pattern of meniscal tear ( P < .05) and KL grade ( P < .05) were associated with MME. Patients with KL grades 3 and 4 at the time of surgery had significantly greater MME than those with KL grade 2 ( P < .05). When patients were divided into 4 groups according to MOAKS criteria at the time of surgery, there were significant differences in WOMAC pain scores among groups at 1 and 2 years after the operation (all P < .05). The WOMAC function score also differed among groups at postoperative 1 year ( P < .05) but not postoperative 2 years ( P > .05). When patients were divided into 4 groups according to relative MME at the time surgery, the WOMAC pain score differed significantly among groups at postoperative 1 and 2 years (all P < .05). Analysis of WOMAC pain score as the dependent variable in multivariate analyses revealed that severity of absolute and relative MME and KL grade were independent predictors of worse WOMAC pain score at postoperative 1 and 2 years (all P < .05). Conclusion: Greater preoperative MME at the time of surgery was associated with inferior patient-reported outcomes, especially pain, in patients with MOWHTO at 1 and 2 years after surgery.

Effect of laser moxibustion for knee osteoarthritis: a multi-site double-blind randomized controlled trial

Objective To examine the effects of laser moxibustion on pain and function in patients with knee osteoarthritis. Methods A double-blind randomized clinical trial (4-week treatment, 20-week follow-up) was conducted. A total of 392 symptomatic knee osteoarthritis patients with moderate or greater clinically significant knee pain were randomly assigned to laser treatment or sham laser control group (1:1). Twelve sessions of laser moxibustion treatments or sham on the acupuncture points at the affected knee(s) were performed three times a week for 4 weeks. The primary outcome measurement was change in WOMAC pain score from baseline to week 4. Results Among the 392 randomized participants, 364 (92.86%) completed the trial. The median WOMAC pain score significantly decreased at week 4 in the active group than in the sham group (2.1; 95% CI, 1.6 to 2.6; P < .01). At week 24, compared to the sham laser, active laser treatment resulted in significant pain reduction and function improvement (3.0; 95% CI, 2.5 to 3.6; P < 0.01, and 14.8; 95% CI, 11.9 to 17.6; P < .01, respectively). The physical component of the quality of life significantly improved in the active group than in the sham control at week 4 (3.2; 95% CI, 1.3 to 5.0; P = 0.001) up to week 24 (5.1; 95% CI, 3.3 to 7.0; P < .001). No serious adverse effects were reported. Conclusion Laser moxibustion resulted in statistically and clinically significant pain reduction and function improvement following a 4-week treatment in patients with knee osteoarthritis. Keywords: 10.6μm laser moxibustion, knee osteoarthritis, pain, traditional Chinese medicine, phototherapy