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Synopsis of the 2020 US Department of Veterans Affairs/US Department of Defense Clinical Practice Guideline: The Non-Surgical Management of Hip and Knee Osteoarthritis
Abstract
In July 2020, the US Department of Veterans Affairs (VA) and US Department of Defense (DoD) approved a new joint clinical practice guideline for the non-surgical management of hip and knee osteoarthritis. This synopsis highlights some of the recommendations. In February 2019, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the National Academy of Medicine’s tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched (ie, Cochrane Database of Systematic Reviews, EMBASE, MEDLINE PreMEDLINE, PubMed, and the Agency for Healthcare Research and Quality website) and evaluated the literature, created a simple 1-page algorithm, and advanced 19 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. This synopsis summarizes key recommendations in all 6 topics covered in the guideline. These topics are diagnosis, self-management, physical therapy, pharmacotherapy, orthobiologics, and complementary and integrative health.
... Oral duloxetine is a serotonin and norepinephrine reuptake inhibitor that has an indication for chronic musculoskeletal pain in adults and can help decrease pain. 12 Topical agents commonly used for hip pain include capsaicin and topical NSAIDs such as diclofenac. Intra-articular corticosteroid injections can help alleviate infl ammation. ...
... Conservative treatments for hip pain include the use of activities such as aquatic exercises, stretching, weight training, and aerobics, which can be benefi cial. 10,12,16 Dietary counseling and subsequent weight reduction can signifi cantly improve hip pain for individuals with a BMI greater than 25. 10,12 Patients should also have proper footwear and may need referral to a podiatrist. ...
... 10,12,16 Dietary counseling and subsequent weight reduction can signifi cantly improve hip pain for individuals with a BMI greater than 25. 10,12 Patients should also have proper footwear and may need referral to a podiatrist. 9 Activity should be modifi ed to decrease the cause of the pain, and the use of a supportive device such as a cane can help offl oad the hip and reduce the pain. ...
Hip pain is a common and sometimes disabling condition that affects adults in the primary care setting. The NP must understand the assessment, diagnosis, and treatment options for patients with hip pain. Proper care of these patients often involves conservative medical management and coordination with physical therapy.
... In addition, studies have shown that acupuncture is more effective in treating KOA than other physical therapies such as pulsed electrical stimulation, aerobic exercise, and muscle strengthening exercise [18]. However, some guidelines stated that there was insufficient evidence to recommend acupuncture for KOA patients [19,20]. Additionally, some research reports show that although patients report less pain, the improvement in verum acupuncture over sham acupuncture is not clinically significant [21,22]. ...
... Topical non-steroidal anti-inflammatory drugs (NSAIDs) are another method for clinical treatment of KOA. Current management guidelines recommend topical NSAIDs as first-line therapy for KOA, especially in elderly patients [19,23]. Topical NSAIDs are nearly as effective as oral NSAIDs in analgesia, improving physical function, and reducing stiffness, with fewer systemic adverse reactions [24,25]. ...
Background
Acupuncture has been used to relieve chronic pain in patients with knee osteoarthritis (KOA), but the evidence is contradictory. Therefore, we carefully designed a double-dummy randomized controlled trial (RCT) to explore the therapeutic effect of acupuncture for KOA.
Methods/design
A total of 138 eligible participants with KOA who consent to participate will be randomly divided into Groups A, B, and C in a ratio of 1:1:1. Participants in Group A will receive verum acupuncture and placebo gel, while those in Groups B and C will be treated with diclofenac diethylammon gel and sham acupuncture, sham acupuncture and placebo gel, respectively. The patients will receive 4 weeks of treatment, five times a week, including acupuncture treatment once a day for 30 min and gel treatment three times a day. The primary outcome will be the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4. The secondary outcomes will include visual analog scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline, week 4, 8, and 12 after randomization.
Discussion
This double-dummy RCT used diclofenac diethylammon gel as a positive control, and the completion of this trial will provide detailed and accurate evidence of the efficacy and safety of acupuncture for KOA.
Trial registration: China Clinical Trials Registry No.ChiCTR2100043947. Registered on September 24, 2020. https://www.chictr.org.cn/showproj.html?proj=122536.
... In addition, studies have shown that acupuncture is more effective in treating KOA than other physical therapies such as pulsed electrical stimulation, aerobic exercise and muscle strengthening exercise [18] . However, some guidelines stated that there was insu cient evidence to recommend acupuncture for KOA patients [19,20] . Additionally, some research reports show that although patients report less pain, the improvement of verum acupuncture over sham acupuncture is not clinically signi cant [21,22] . ...
... Current management guidelines recommend topical NSAIDs as rst-line therapy for KOA, especially in elderly patients [19,23] . Topical NSAIDs are nearly as effective as oral NSAIDs in analgesia, improving physical function, and reducing stiffness, with fewer systemic adverse reactions [24,25] . ...
Background
Acupuncture has been used to relieve chronic pain in patients with knee osteoarthritis (KOA), but the evidence is contradictory. Therefore, we carefully designed a double-dummy randomized controlled trial (RCT) to explore the therapeutic effect of acupuncture for KOA.
Methods/design:
Total of 138 eligible participants with KOA who consent to participate will be randomly divided into groups A, B and C in a ratio of 1:1:1. Participants in group A will receive verum acupuncture and placebo gel, while those in groups B and C will be treated with Diclofenac Diethylammon gel and sham acupuncture, sham acupuncture and placebo gel respectively. The patients will receive 4 weeks of treatment, 5 times a week, including acupuncture treatment once a day for 30 minutes and gel treatment three times a day. The primary outcome will be the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4th. The secondary outcomes will include Visual Analog Scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline, week 4th, 8th and 12th after randomization.
Discussion
This double-dummy RCT used Diclofenac Diethylammon gel as a positive control, and the completion of this trial will provide detailed and accurate evidence of the efficacy and safety of acupuncture for KOA.
Trial registration:
China Clinical Trials Registry No.ChiCTR2100043947. Registered on September 24, 2020.https://www.chictr.org.cn/showproj.html?proj=122536
... At present, the prevalence rate for adults aged 65 years in the United States is 33.6%. 15 Risk factors for OA include advanced age, female sex, obesity, genetic factors, race, and heavy physical work or activity. 15 Its pathogenesis is complex, involving mechanical overload, an increase of inflammatory mediators, metabolic changes, cell senescence, and so on. ...
... 15 Risk factors for OA include advanced age, female sex, obesity, genetic factors, race, and heavy physical work or activity. 15 Its pathogenesis is complex, involving mechanical overload, an increase of inflammatory mediators, metabolic changes, cell senescence, and so on. 24 Among these, with the aggravation of knee joint degeneration, the meniscus, cartilage, anterior and posterior cruciate ligament (PCL), and other tissues in the joint may be gradually destroyed. ...
Background
Mechanoreceptors in the posterior cruciate ligament (PCL) can produce proprioception, which is an important reason why patients choose cruciate-retaining total knee arthroplasty (TKA). The number of mechanoreceptors in the PCL of patients with knee osteoarthritis (OA) is unknown.
Purpose
To provide a theoretical basis for estimating the number of mechanoreceptors in the PCL by evaluating the relationship between this number and patient age or OA severity.
Study Design
Cross-sectional study; Level of evidence, 3.
Methods
An overall 28 PCLs from patients with knee OA were collected at the time of TKA and grouped according to patient age (group A, 60-69 years [n = 8]; group B, 70-79 years [n = 12]; group C, ≥80 years [n = 8]) and OA based on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (group I, ≤80 [n = 8]; group II, 81-120 [n = 10]; group III, >120 [n = 10]). Hematoxylin and eosin and S-100 immunohistochemical staining were performed on the slices near the tibial attachment of the PCL, and the number of mechanoreceptors in each slice was counted. Multifactor analysis of variance was used to evaluate the relationship between the number of mechanoreceptors and patient age or WOMAC score.
Results
The number of mechanoreceptors (mean ± SD) in groups A, B, and C was 24.00 ± 15.19, 30.92 ± 11.41, and 23.38 ± 11.39, respectively, with no significant between-group differences. The number of mechanoreceptors in groups I, II, and III was 43.50 ± 4.99, 25.00 ± 5.27, and 15.20 ± 5.61, with significant differences between groups I and II, groups I and III, and groups II and III ( P < .001 for all).
Conclusion
In patients with knee OA, age had no significant effect on mechanoreceptor count, but the number of mechanoreceptors in the PCL decreased significantly with higher (worse) WOMAC score. These findings suggest that in patients of any age with high WOMAC scores, there may be little value as it relates to knee proprioception in performing a PCL-retaining TKA.
... The main focus of treatment is to relieve pain, restore function, and slow down disease progression [6,7]. There are six key recommendations comprising diagnosis, self-management, physiotherapy, pharmacotherapy, orthobiology, and complementary and integrative health care available in the latest guide published in the USA in 2020 for the non-surgical treatment of knee osteoarthritis (Table 1) [8]. Most commonly, pharmacological treatments have been adopted. ...
... The European Research Journal Volume 8 Issue 5 September 2022 addition, the dissatisfaction with traditional treatments due to medical, psychological, social, and economic costs leads patients and physicians to seek alternative methods [8,9]. Traditional medicine is defined as the sum of knowledge, skills, and practices based on the theories, beliefs, and experiences of different cultures in the prevention, diagnosis, and treatment of physical and mental diseases an in the protection and improvement of health [9]. ...
Objectives: This study aims to determine the traditional and complementary medicine (TCM) use in patients with knee osteoarthritis, by whom these methods are recommended, which methods provide the patients with the best outcome, and to contribute to the awareness of physicians about TCM methods. Methods: One hundred four patients over the age of 40 who were diagnosed with knee osteoarthritis and had complaints for at least 6 months were included in the study. The TCM applications in the previous treatments of the patients, and whether they used additional medications or not, and finally, the TCM method they benefited from the most, and who recommended and applied these methods were questioned and recorded. Results: In our study, we found that the most commonly used treatments were phytotherapy products and supportive drugs, in line with the literature. We did not find the use of hypnosis, hirudotherapy, reflexology, homeopathy, osteopathy, chiropractic, maggot applications, apitherapy, or music therapy methods. TCM methods of patients, we determined that they learned from their families and close circles rather than the doctors they applied to. Conclusions: Patients diagnosed with knee osteoarthritis commonly use TCM methods, phytotherapy being in the first place.
... The current treatment strategy for KOA includes improving function, reducing disability, and alleviating pain, thereby enhancing the quality of life. While these approaches may slowing down the progression of structural and functional changes associated with KOA, they cannot completely cure KOA [5][6][7]. Platelet-rich plasma (PRP) therapy, which has regenerative and reparative effects on tissues, offers new hope for the treatment of KOA. ...
Objective
To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections.
Methods
One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients’ conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up.
Results
Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups.
Conclusions
The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.
... MT may have a positive effect on reducing pain [9,10] and is reportedly used by approximately 15.4 million people in the USA for treatment of KOA, for example [11]. In some countries, MT is considered a first-line treatment option [12], whereas in others, it is recommended to be used as part of a broader treatment program that includes exercise; alternatively, MT is not recommended because of a lack of evidence [13]. Despite widespread use of MT, few studies have reported the efficacy of MT alone for treatment of KOA, with poor methodological quality [14]. ...
Background
Manual therapy (MT) is frequently used in combination with management of osteoarthritis of the knee, but there is no consensus on the exact efficacy of this treatment strategy. The purpose of this systematic review and meta-analysis was to evaluate the pain relief and safety of MT for treatment of knee osteoarthritis (KOA).
Methods
Randomized controlled trials evaluating MT in patients with KOA in major English and Chinese journals were searched in the following databases: Wanfang, China Science and Technology Journal Database (VIP database), China National Knowledge Infrastructure (CNKI), PubMed, Embase, Web of Science, and the Cochrane Library databases through June 2023. The methodological quality and quality of evidence of the included studies were assessed using Cochrane’s risk-of-bias 2 (ROB 2) tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Stata version 15.0 software. After use of Galbraith plots to exclude studies that could lead to heterogeneity, random effects models were used to analyze the remaining data and test the consistency of the findings. We used meta-regression to assess the effect of treatment period, patient age, and sex ratio on outcomes. Funnel plots and Egger’s test were used to evaluate publication bias. Sensitivity analyses were used to determine the reliability of the results.
Results
A total of 25 studies, with 2376 participants, were included in this review. The overall methodological quality of the included studies was limited. Our findings suggest that MT has a positive impact on pain relief outcomes in KOA patients. The meta-analysis showed that MT was superior to usual care (SMD = 2.04, 95% CI 0.94, 3.14, I² = 96.3%; low evidence quality) and exercise (SMD = 1.56, 95% CI 0.41, 2.71, I² = 96.3%; low evidence quality) for reducing pain. In terms of improvement in visual analogue scale (VAS) scores, MT treatment beyond 4 weeks (SMD = 1.56, 95% CI 0.41, 2.71, I² = 96.3%) may be superior to treatments less than or equal to 4 weeks (SMD = 1.24, 95% CI 0.56, 1.95, I² = 94.7%). No serious adverse events associated with MT were reported.
Conclusions
MT may be effective at reducing pain in patients with KOA and may be more effective after a 4-week treatment period. Compared with usual care and exercise therapy, MT may be superior at reducing KOA pain in the short term (9 weeks), but its long-term efficacy requires careful consideration of evidence-based outcomes. MT appears to be safe for KOA patients, though clinicians should inform patients of the potential risk of MT-related adverse events.
... Exercise-based physical therapy (PT) is a key component of guideline concordant knee OA management [13][14][15][16]. However, PT is underutilized for knee OA [17,18], resulting in missed opportunities to improve outcomes for the many patients with this health condition [19][20][21][22][23][24]. ...
Background
Knee osteoarthritis (OA) is a leading cause of chronic pain and disability and one of the most common conditions treated in outpatient physical therapy (PT). Because of the high and growing prevalence of knee OA, there is a need for efficient approaches for delivering exercise-based PT to patients with knee OA. A prior randomized controlled trial (RCT) showed that a 6-session Group Physical Therapy Program for Knee OA (Group PT) yields equivalent or greater improvements in pain and functional outcomes compared with traditional individual PT, while requiring fewer clinician hours per patient to deliver. This manuscript describes the protocol for a hybrid type III effectiveness-implementation trial comparing two implementation packages to support delivery of Group PT.
Methods
In this 12-month embedded trial, a minimum of 16 Veterans Affairs Medical Centers (VAMCs) will be randomized to receive one of two implementation support packages for their Group PT programs: a standard, low-touch support based on Replicating Effective Programs (REP) versus enhanced REP (enREP), which adds tailored, high-touch support if sites do not meet Group PT adoption and sustainment benchmarks at 6 and 9 months following launch. Implementation outcomes, including penetration (primary), adoption, and fidelity, will be assessed at 6 and 12 months (primary assessment time point). Additional analyses will include patient-level effectiveness outcomes (pain, function, satisfaction) and staffing and labor costs. A robust qualitative evaluation of site implementation context and experience, as well as site-led adaptations to the Group PT program, will be conducted.
Discussion
To our knowledge, this study is the first to evaluate the impact of tailored, high-touch implementation support on implementation outcomes when compared to standardized, low-touch support for delivering a PT-based intervention. The Group PT program has strong potential to become a standard offering for PT, improving function and pain-related outcomes for patients with knee OA. Results will provide information regarding the effectiveness and value of this implementation approach and a deeper understanding of how healthcare systems can support wide-scale adoption of Group PT.
Trial registration
This study was registered on March 7, 2022 at ClinicalTrials.gov (identifier NCT05282927 ).
... Many clinical practice guidelines are available to manage osteoarthritis (OA) affecting the hips and knees, and fewer so for hand OA. [1][2][3][4][5][6][7][8][9] Unfortunately, there are some inconsistencies across these guidelines, which can confuse clinicians and researchers. To help clarify and provide more insight into optimal evidence-based OA management approaches, several publications this year critically evaluated and compared the different clinical practice guidelines. ...
Objective:
We systematically reviewed the literature to identify comparative studies of core treatments (exercise, education, or weight management), adjunct treatments (e.g. electrotherapeutical modalities, bracing), or multimodal treatments (core plus other treatments), for treating osteoarthritis (OA) complaints, published between 1 March 2022 and 1 March 2023.
Design:
We searched three electronic databases for peer-reviewed comparative studies evaluating core treatments, adjunct treatments, or multimodal treatments for OA affecting any joint, in comparison to other OA treatments. Two authors independently screened records. Methodological quality was assessed using the PEDro scale. A narrative synthesis focusing on pain and function outcomes was performed in studies with a mean sample size of at least 46 participants per treatment arm.
Results:
33 publications (28 studies), 82% with PEDro ratings of good or excellent, were eligible for narrative synthesis: 23 studies evaluated knee OA; one knee OA or chronic low back pain; two knee or hip OA; one hip OA only; and one thumb OA. No studies identified a dose, duration or type of exercise that resulted in better pain or function outcomes. Core treatments generally showed modest benefits compared to no or minimal intervention controls.
Conclusions:
Rehabilitation research continues to be focused on the knee. Most studies are not adequately powered to assess pain efficacy. Further work is needed to better account for contextual effects, identify treatment responder characteristics, understand treatment mechanisms, and implement guideline care.
... The effect of proprioceptive training on pain intensity was not maintained over time in our study or in previous studies that performed similar conservative interventions of orthotic intervention, exercise, or ADL re-education [41][42][43]. Based on other research, proprioceptive work may help to recover the osteoarticular balance and coordination and improve the performance of daily activities and consequently decrease pain intensity [44][45][46]. ...
A randomized controlled trial of forty-five females over 18 years of age with diagnosis of thumb basal osteoarthritis in their dominant hand and with a minimum pain rating of 4/10 on the Visual Analogue Scale (VAS) during activities of daily living (ADLs) were recruited from March to June 2021. The group receiving proprioception training was compared to routine conservative physiotherapy treatment. The main purpose of this clinical trial is to test the effect of proprioception training on pain intensity in subjects with thumb osteoarthritis. Primary outcome was joint position sense (JPS) for the assessment of CMC proprioception and secondary outcomes were Visual Analogue Scale (VAS) and Canadian Occupational Performance Measure (COPM) for the assessment of patient satisfaction and the Quick-DASH which assessed upper limb function. A block randomization was carried out for the control group (n = 22) and experimental group (n = 23). Participants and evaluator were blinded to the group assignment. Proprioception training produced a statistically significant reduction in pain post intervention, but this reduction was small (d = 0.1) at the 3-month follow-up. JPS accuracy demonstrated statistically significant differences between the groups (p = 0.001) post-intervention and at the 3-month follow-up (p < 0.003). Statistically significant differences between means were found in both the Quick-Dash and COPM post intervention (both, p < 0.001), as well as at the 3-month follow-up (both, p < 0.001). There was a significant time factor for the reduction of pain intensity over time but effect sizes between groups was small at the 3-month follow-up period. Proprioceptive training improves thumb JPS accuracy; however, it does not contribute to a reduction in pain intensity in the long term. The inclusion of a proprioceptive program may be beneficial for improving individuals with thumb CMC OA sensorimotor performance. The study was registered at ClinicalTrials.gov NCT04738201. No funding was provided for this study.
... Further, the cause of OA is still unclear. It is not caused by a single factor but a result of the combination of multiple factors, among which old age and overweight are the main pathogenic factors (Krishnamurthy et al., 2021). The work capacity of OA patients is greatly impaired, which affects their quality of life and causes an economic burden on individuals and society (Losina et al., 2015). ...
Osteoarthritis (OA) is a progressive chronic inflammation that leads to cartilage degeneration. OA Patients are commonly given pharmacological treatment, but the available treatments are not sufficiently effective. The development of sustained-release drug delivery systems (DDSs) for OA may be an attractive strategy to prevent rapid drug clearance and improve the half-life of a drug at the joint cavity. Such delivery systems will improve the therapeutic effects of anti-inflammatory effects in the joint cavity. Whereas, for disease-modifying OA drugs (DMOADs) which target chondrocytes or act on mesenchymal stem cells (MSCs), the cartilage-permeable DDSs are required to maximize their efficacy. This review provides an overview of joint structure in healthy and pathological conditions, introduces the advances of the sustained-release DDSs and the permeable DDSs, and discusses the rational design of the permeable DDSs for OA treatment. We hope that the ideas generated in this review will promote the development of effective OA drugs in the future.
... [7,8] The current treatments for KOA include drug therapy, physical therapy, exercise, intraarticular injection therapy, cognitive behavioral therapy, cell therapy, and even surgery. [9,10] Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line drugs for KOA and can effectively relieve pain. However, for elderly and frail patients with osteoarthritis, long-term use of oral NSAIDs can affect the gastric mucosa and cause adverse reactions such as gastric ulcers and gastric bleeding. ...
Background:
Knee osteoarthritis (KOA) is a chronic degenerative disease involving cartilage and surrounding tissues. It causes a huge burden to social and medical resources and seriously affects people's living and working ability. In recent years, people have become increasingly interested in the application of Chinese medicine monomers to treat KOA. Among them, icariin plays an important role in the clinical treatment of KOA. Therefore, to evaluate the effectiveness and safety of icariin in the treatment of KOA, we conducted this study to provide a new basis for the clinical treatment of KOA.
Methods:
We propose a systematic search of the PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and China Biomedical databases for all randomized controlled trials examining the use of icariin in the treatment of KOA patients up to October 20, 2021. The screening and data extraction processes will be performed independently by 2 researchers. We will use the Cochrane risk bias assessment tool to evaluate the quality of the studies that met the inclusion criteria. The data will be statistically analyzed using RevMan5.3 software.
Result:
This study will provide high-quality evidence for the effectiveness and safety of icariin in the treatment of KOA.
Conclusion:
The purpose of this study was to explore the efficacy of icariin in the treatment of KOA and to provide clinicians and patients with new treatment strategies.
Inplasy registration number:
INPLASY2021110015.
Introduction
Knee osteoarthritis (KOA) is still a challenging degenerative joint disease with high morbidity and disease burden. Early-stage KOA, the focus of this study, could present a Window of Opportunity to arrest the disease process and reduce the disease burden. Yijinjing exercise is an important part of physical and psychological therapies in Traditional Chinese Exercise and may be an effective treatment. However, there is no clinical efficacy assessment of Yijinjing exercise for patients with early-stage KOA. Therefore, we designed a randomised controlled trial to evaluate the effectiveness of Yijinjing exercise on patients with early-stage KOA.
Methods and analysis
This is a parallel-design, two-arm, analyst assessor-blinded, randomised controlled trial. In total, 60 patients with early-stage KOA will be recruited and randomly assigned to the Yijinjing exercise group (n=30) and health education group (n=30) at a ratio of 1:1, receiving 12 weeks of Yijinjing exercise or health education accordingly. The primary outcome will be measured with the Western Ontario and McMaster Universities Osteoarthritis Index, and the secondary outcomes will include the Visual Analogue Scale, Short-Form 36 Item Health Survey Questionnaire, Beck Depression Inventory, Perceived Stress Scale, Berg Balance Scale, and Gait Analysis for a comprehensive assessment. Outcome measures are collected at baseline, at 12 week ending intervention and at the 12 week, 24 week and 48 week ending follow-up. The primay time point will be 12 weeks postintervention. Adverse events will be recorded for safety assessment.
Ethics and dissemination
This study has been approved by the ethical application of the Shanghai Municipal Hospital of Traditional Chinese Medicine Ethics Committee (2021SHL-KY-78).
Trial registration number
ChiCTR2200065178
Background :
Clinical practice guidelines (CPGs) are essential in healthcare, but their quality varies. This study aims to analyze 18 high-quality CPGs for knee osteoarthritis (KOA), identify areas for improvement, and establish common recommendations from contemporary CPGs for effective KOA management.
Methods:
We systematically searched guideline websites and databases until June 30, 2023, for KOA-related guidelines. Two independent reviewers assessed these using AGREE II and RIGHT checklists. The intra-class correlation coefficient (ICC) evaluated reviewer agreement, and recommendations and evidence levels were summarized.
Results:
We analyzed 18 Clinical Practice Guidelines (CPGs) from 1,411 records. Most were from China and the USA, published from 2016 to 2022, with 44.44% updates. Methodological quality was reliable, with 14 CPGs "recommended," but three had low "editorial independence" scores. Reporting quality ranged from 41.43–95.71%, with 66.66% scoring ≥ 80%. Recommendations included conservative measures, Tai Chi, Yoga, cane use, and various complementary and alternative medicines. Topical NSAIDs, oral NSAIDs, and intra-articular glucocorticoids were favored. Foreign guidelines stressed shared decision-making and patient preferences in KOA management.
Conclusions:
Over half of KOA CPGs are of good quality. However, there's substantial methodological variation and reporting quality gaps. Future efforts should enhance both. Our research supports a core set of interventions, including education, exercise, weight management, and personalized NSAID use, for evidence-based KOA practice and guideline development
Osteoarthritis (OA) is the most common form of arthritis globally and a major cause of pain, physical disability, and loss of economic productivity, with currently no causal treatment available. This review article focuses on current research on OA biomarkers and the potential for using biomarkers in future clinical practice and clinical trials of investigational drugs. We discuss how biomarkers, specifically soluble ones, have a long path to go before reaching clinical standards of care. We also discuss how biomarkers can help in phenotyping and subtyping to achieve enhanced stratification and move toward better-designed clinical trials. We also describe how biomarkers can be used for molecular endotyping and for determining the clinical outcomes of investigational cell-based therapies. Biomarkers have the potential to be developed as surrogate end points in clinical trials and help private-public consortia and the biotechnology and pharmaceutical industries develop more effective and targeted personalized treatments and enhance clinical care for patients with OA.
Background:
Most primary care providers do not routinely discuss nutrition and diet with their patients, largely due to lack of time, inadequate resources, and perceived complexity of the topic. This article describes development and implementation of a brief protocol for systematically assessing and discussing diet during routine primary care visits to increase the frequency of these conversations and improve patient health outcomes.
Methods:
The authors developed a protocol for assessing both nutrition and stage of change as well as a guide for engaging in patient-led conversations about nutrition. The protocol was modeled after Screening, Brief Intervention, and Referral to Treatment and informed by the Dietary Guidelines for Americans, the Transtheoretical Model of Behavior Change, and principles of motivational interviewing. It was implemented over three months at a rural health clinic staffed by one NP.
Results:
The protocol and conversation guide were easy to use with minimal training and seamlessly incorporated into clinic workflow. The likelihood of making diet changes increased significantly following the diet conversation, with persons who initially scored lower in readiness to change ultimately reporting significantly greater increases.
Conclusion:
A protocol for assessing diet and engaging patients in a stage of change-appropriate diet conversation can be efficiently integrated into a single primary care visit and increase patients' intent to change their diet. Further investigation is needed to evaluate the protocol more completely and in multiple clinics.
Clinical question
Is acupuncture effective in treating knee osteoarthritis (KOA)?
Current practice
Although increasingly used in the clinical setting, acupuncture is not mentioned or weakly recommended in guidelines for the treatment of KOA.
Recommendations
We suggest acupuncture rather than no treatment in adult KOA (weak recommendation, moderate certainty evidence), and acupuncture combined with nonsteroidal anti‐inflammatory drugs (NSAIDs) rather than acupuncture alone when KOA symptoms are severe (weak recommendation, moderate certainty evidence), with duration of acupuncture for 4–8 weeks depending on KOA severity and treatment response (weak recommendation, moderate certainty evidence), and discussing with patients in shared decision‐making.
How this guideline was created
This rapid recommendation was developed following the Making GRADE the Irresistible Choice (MAGIC) methodological framework. First, the clinical specialist identified the topic of recommendation and demand for evidence. Then the independent evidence synthesis group performed a systematic review to summarize available evidence and evaluate the evidence using the GRADE approach. Finally, the clinical specialist group produced recommendations for practice through a consensus procedure.
The evidence
The linked systematic review and meta‐analysis included 9422 KOA patients, 61.1% of whom were women. The median mean age was 61.8 years. Compared with no treatment, acupuncture had beneficial effect on KOA in improving the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (moderate certainty evidence), and WOMAC pain (very low certainty evidence), WOMAC stiffness (low certainty evidence), and WOMAC function (low certainty evidence) subscale scores. Compared with usual care, acupuncture improved WOMAC stiffness subscale score (moderate certainty evidence). Subgroup analyses showed different effects in the improvement of WOMAC total scores by different durations of acupuncture and whether acupuncture combined with NSAIDs, but no difference between manual acupuncture and electroacupuncture was found.
Understanding the recommendations
Compared with no treatment, acupuncture is suggested to reduce pain, stiffness, and disfunction in KOA patients, ultimately improving the patient's health status. Acupuncture can be used as an alternative therapy when usual care is ineffective or there are adverse reactions so that patients can no longer continue the treatment. Manual acupuncture or electroacupuncture is suggested for 4–8 weeks to improve the health status of KOA. The patient's values and preferences should be considered when selecting acupuncture for KOA treatment.
Objective
The benefits of traditional Chinese non-pharmacological therapies in the treatment of Knee osteoarthritis (KOA) are receiving increasing attention. Therefore, this study aims to systematically analyze the global research on the treatment of KOA by Chinese traditional non-pharmacological therapies using bibliometric analysis and present the results with a knowledge map form.
Methods
Literature related to traditional Chinese non-pharmacological therapies used in the treatment of KOA from 2012 to 2022 was searched from the Web of Science core database and PubMed database. CiteSpace, SCImago Graphica and VOSviewer were used to extract nations, institutions, journals, authors, references, keywords, as well as the most widely used acupoints, therapies and evaluation indexes.
Results
A total of 375 literature have been included. 32 countries around the world have participated in the research. China, the United States, and Europe were at the center of the global cooperation network. The most prolific institutions and authors were from China represented by Cun-zhi Liu and Jian-feng Tu of Beijing University of Chinese Medicine, the institution with the highest cited frequency was University of York, and “Osteoarthritis Cartilage” was the most frequently cited journal. The most frequently cited literature was “OARSI guidelines for the non-surgical management of knee, hip, and poly articular osteoarthritis.” 22 kinds of Chinese non-pharmacological therapies were used to treat KOA, among which acupuncture was the most commonly used one, and ST36 (Zusanli) and WOMAC were the most commonly selected acupoint and evaluation index.
Conclusion
In the past decade, the value of Chinese non-pharmacological therapies in the treatment of KOA has received widespread attention. It was a common concern of global researchers to relieve the pain of KOA patients and restore the quality of life. Under the background that acupuncture accounts for a relatively high proportion, the next step may consider how to make the balanced development of a variety of Chinese non-pharmacological therapies. In addition, the problem of how to eliminate the placebo effect maybe the direction of future research.
Objective:
To summarize changes in recommendations for injection treatments for knee osteoarthritis (OA) in current clinical practice guidelines (CPGs) and to assess whether these changes have affected public interest according to Google data and content in YouTube videos.
Design:
A literature search to identify CPGs revised since 2019 that provide recommendations regarding the five intra-articular injection treatments for knee OA (corticosteroid [CS], hyaluronic acid [HA], stem cell [SC], platelet-rich plasma [PRP], and botulinum toxin [BT]) was conducted to assess perspective changes for each treatment. Data from Google Trends were examined to identify changes in search volume from 2004 to 2021 using a join-point regression model. Relevant YouTube videos were divided into those uploaded before and after changes in CPGs and compared according to degrees of recommendation for each treatment to identify the effect of changes in CPGs on video production.
Results:
All eight identified CPGs released after 2019 recommended HA and CS use. Most CPGs were the first to state a neutral or opposing stance concerning the use of SC, PRP, or BT. Interestingly, relative searches on Google for SC, PRP, and BT has increased greater than those for CS and HA. YouTube videos produced after CPGs changed continue to recommend SC, PRP, and BT as much as those produced before CPGs were revised.
Conclusions:
Although knee OA CPGs have changed, public interest and healthcare information providers on YouTube have not reacted to this shift. Improved methods to propagate updates to CPGs warrant consideration.
Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease. It weakens the motor function of patients and imposes a significant economic burden on society. The current medications commonly used in clinical practice do not meet the need for the treatment of OA. Recombinant protein drugs (RPDs) can treat OA by inhibiting inflammatory pathways, regulating catabolism/anabolism, and promoting cartilage repair, thereby showing promise as disease-modifying OA drugs (DMOADs). However, the rapid clearance and short half-life of them in the articular cavity limit their clinical translation. Therefore, the reliable drug delivery systems for extending drug treatment are necessary for the further development. This review introduces RPDs with therapeutic potential for OA, and summarizes their research progress on related drug delivery systems, and make proper discussion on the certain keys for optimal development of this area.
Medical research involving US active duty, reservist, and veteran populations can and should improve. Because the US healthcare system is accountable to active duty personnel, reservists, and veterans (ADRV), the US healthcare system must partner to improve healthcare and medical research. Aiming to summarize current issues and opportunities for ADRV research infrastructure alongside healthcare, an exploratory literature review was conducted. Additionally, a broad analysis of search utilizing Cochrane, Google Scholar, and PubMed from the years 2001 to 2021 was undertaken. There are opportunities to refine biomedical, social-behavioral, health service research (HSR), and other research portfolios involving ADRV. There are urgent and serious opportunities to improve the rigor and quality of research. Additionally, there is a clear need for coordinated implementation and translation of research. In this attention to research involving ADRV, the US government, public health, non-profit organizations, private industry, and individuals are birds of a feather. Advancing efforts for research improvement should be handled together.
Intra-articular viscoelastic supplements are commonly administered by musculoskeletal radiologists for the treatment of symptomatic osteoarthritis (OA). This article provides an overview of the putative mechanism of action of the agents, a brief review of the evidence base underlying the practice, a commentary on some of the major society guidelines regarding the treatment, and a description of the adverse events that are associated with intra-articular hyaluronic acid administration.
This article discusses the pathophysiology, assessment techniques, and management of hip pain in adults and the role of nurses in caring for patients with hip pain.
Background:
Intra-articular injections containing a corticosteroid are used frequently, and periprosthetic joint infection is a serious complication after total joint arthroplasty. There is debate regarding whether intra-articular corticosteroid injections before arthroplasty increase periprosthetic joint infection after surgery.
Questions/purposes:
(1) Does a previous intra-articular corticosteroid injection increase the odds of infection after subsequent hip or knee arthroplasty? (2) Does this risk vary based on how soon before the arthroplasty (such as less than 3 months before surgery) the injection is administered?
Methods:
Using the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to July 2021, we searched for comparative studies in English on patients who received intra-articular corticosteroid injections before arthroplasty and that tracked the frequency of infection after arthroplasty. We extracted data on the risk of infection after subsequent joint arthroplasty. The keywords included "corticosteroid," "steroid," "arthroplasty," "knee replacement," and "hip replacement." Eleven retrospective, comparative studies from four countries were included, of which 10 reported the specific diagnosis criteria and one did not. These articles included data on 173,465 arthroplasties in the hip or knee, as well as of 73,049 injections and 100,416 control patients. The methodologic quality of the included studies was evaluated according to the Newcastle-Ottawa Quality Assessment Scale; the articles' scores ranged from 6 to 7 (the score itself spans 0 to 9, with higher scores representing better study quality). We found no evidence of publication bias based on the Egger test, and tests of heterogeneity generally found heterogeneity, so a random-effects model was used of our meta-analyses. A meta-analysis was performed with Review Manager 5.3 software and Stata version 12.0 software.
Results:
Overall, there were no differences in the odds of periprosthetic joint infection between the injection group and the control group among patients who received any kind of injection (odds ratio 1.22 [95% CI 0.95 to 1.58]; p = 0.12). However, in a subgroup analysis, there was a higher OR for postoperative PJI in patients with an intra-articular corticosteroid injection in the knee or hip within 3 months (OR 1.39 [95% CI 1.04 to 1.87]; p = 0.03). There were no differences in the infection risk in patients who had injections between 3 and 6 months before arthroplasty (OR 1.19 [95% CI 0.95 to 1.48]; p = 0.13) or between 6 and 12 months before arthroplasty.
Conclusion:
The current evidence suggests ipsilateral intra-articular corticosteroid injections within 3 months before arthroplasty were associated with an increased risk of periprosthetic joint infection during subsequent joint arthroplasty. We recommend against performing total joint arthroplasty on a patient who has received an intra-articular corticosteroid injection within 3 months. Further high-quality studies on this topic from registries, national databases, or insurance company data are still required to confirm and extend our findings.
Level of evidence:
Level III, therapeutic study.
Purpose:
The purpose of this meta-analysis was to compare platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with knee osteoarthritis (KOA).
Methods:
Randomized controlled trials (RCTs) comparing the use of PRP and HA in KOA patients were retrieved from each database from the establishment date to April 2018. Outcome measurements were the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), International Knee Documentation Committee, and Lequesne Index scores and adverse events. The pooled data were evaluated with Review Manager 5.3.5.
Results:
Fifteen RCTs (N = 1,314) were included in our meta-analysis. The present meta-analysis indicated that PRP injections reduced pain more effectively than HA injections in patients with KOA at six and 12 months of follow-up, as evaluated by the WOMAC pain score; the VAS pain score showed a significant difference at 12 months. Moreover, better functional improvement was observed in the PRP group, as demonstrated by the WOMAC function score at three, six, and 12 months. Additionally, PRP injections did not display different adverse event rates compared with HA injections.
Conclusion:
In terms of long-term pain relief and functional improvement, PRP injections might be more effective than HA injections as a treatment for KOA. The optimal dosage, the timing interval and frequency of injections, and the ideal treatment for different stages of KOA remain areas of concern for future investigations.
Objective
Human adipose-derived mesenchymal progenitor cells (haMPCs) are stem cells with multiple differentiation potential and immunomodulatory function. Re-Join® comprises in vitro expanded haMPCs from adipose tissue of patients combined with cell suspension solution. This study was undertaken to evaluate the efficacy and safety of Re-Join® in patients with symptomatic knee osteoarthritis (OA).
Methods
Patients with Kellgren–Lawrence grade 1–3 knee OA were recruited from two centers and randomized to receive intra-articular injection of Re-Join® or HA. Pain and function were assessed by using WOMAC score, VAS, and SF-36. Magnetic resonance imaging (MRI) analysis was performed to measure cartilage repair. Adverse events (AEs) were collected.
Results
Fifty-three patients were randomized. Significant improvements in WOMAC, VAS, and SF-36 scores were observed in both groups at months 6 and 12 compared with baseline. Compared with the HA group, significantly more patients achieved 50% improvement of WOMAC and a trend of more patients achieved a 70% improvement rate in Re-Join® group after 12 months. Meanwhile, there was notably more increase in articular cartilage volume of both knees in the Re-Join® group than in the HA group after 12 months as measured by MRI. AEs were comparable between two groups. Most AEs were mild and moderate except one SAE of right knee joint infection in the HA group.
Conclusions
Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months.
Trial registration
ClinicalTrials.gov Identifier: NCT02162693. Registered 13 June 2014.
Electronic supplementary material
The online version of this article (10.1186/s13287-019-1248-3) contains supplementary material, which is available to authorized users.
Objective
Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.
Methods
A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once).
Results
Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09–1.46; I² = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03–1.38; I² = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08–1.80; I² = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01–2.10; I² = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80–1.83; I² = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22–2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21–2.29; 0%).
Conclusions
In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.
Objective
We aimed to assess the safety of opioids in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.
Methods
A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once).
Results
Database searches identified 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42–7.89); ER opioids (RR 4.22, 95% CI 3.44–5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87–18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22–5.18); ER opioids (RR 4.03, 95% CI 3.37–4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74–7.43; ER opioids: RR 7.87, 95% CI 5.20–11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90–4.02; ER opioids: RR 2.76, 95% CI 2.19–3.47) was found with all opioid formulations versus placebo.
Conclusions
Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.
Objective
Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta‐analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.
Methods
We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration–approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs).
Results
We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD –0.43 [95% CI –0.48, –0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.
Conclusion
NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.
Mesenchymal stem cells (MSCs) have been the focus of an emerging treatment for osteoarthritis. However, few studies reported about outcomes of an intra-articular injection of autologous adipose-derived mesenchymal stem cells (AD-MSCs). This study aimed to assess the efficacy and safety of a single intra-articular injection of AD-MSCs for patients with knee osteoarthritis. It was a prospective double-blinded, randomized controlled, phase IIb clinical trial. AD-MSCs were administered for 12 patients (MSC group), and the group was compared with 12 knees with injection of normal saline (control group) up to 6 months. All procedures were performed in the outpatient clinic. Primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score. Secondary outcome measure included various clinical and radiologic examination, and safety after injection. Change of cartilage defect after injection was evaluated using magnetic resonance imaging (MRI). Single injection of AD-MSCs led to a significant improvement of the WOMAC score at 6 months. In the control group, there was no significant change in the WOMAC score at 6 months. No serious adverse events were observed in both groups during the follow-up period. In MRI, there was no significant change of cartilage defect at 6 months in MSC group whereas the defect in the control group was increased. An intra-articular injection of autologous AD-MSCs provided satisfactory functional improvement and pain relief for patients with knee osteoarthritis in the outpatient setting, without causing adverse events at 6 months' follow-up. Larger sample size and long-term follow-up are required. Stem Cells Translational Medicine 2019.
Aim: To evaluate the efficacy of autologous adipose-derived mesenchymal stem cell (ADMSC) therapy on pain, function and disease modification in knee osteoarthritis. Methods: 30 participants with symptomatic knee osteoarthritis were randomized into three groups. Two treatment groups received intra-articular ADMSC therapy consisting of either a single injection (100 × 10 ⁶ ADMSCs) or two injections (100 × 10 ⁶ ADMSCs at baseline and 6 months). The third group served as control and continued conservative management. Results: No serious adverse events were observed. Both treatment groups receiving ADMSCs showed clinically significant pain and functional improvement at completion of follow-up at 12 months. Radiological analysis using the Magnetic Resonance Imaging Osteoarthritis Knee Score indicated modification of disease progression. Conclusion: Autologous ADMSC therapy appears to be a safe and effective therapy for knee osteoarthritis and may have the potential to prevent disease progression.
Trial registration number: ACTRN12614000814673
Introduction
Mesenchymal stem cells (MSCs) have gained popularity for articular cartilage repair. However, efficacy of intra-articular MSCs in osteoarthritis remains unclear. In the setting of a meta-analysis of randomized controlled trials (RCTs), we aimed to investigate the efficacy of intra-articular MSCs on clinical outcomes and cartilage repair in patients with knee osteoarthritis.
Materials and methods
PubMed, EMBASE, Cochrane Library, CINAHL, and Scopus were searched from inception to March 31, 2017. This study included RCTs using cell population containing MSCs for treatment of knee osteoarthritis. The quality was assessed by Cochrane Collaboration`s risk of bias tool. For meta-analysis, data on clinical outcomes measured by visual analog scale (VAS), Lysholm score, WOMAC and data on cartilage repair measured by MOCART and WORMS were extracted. In studies with several cell concentrations, outcomes of recommended concentration were used mainly to ensure robustness.
Results
A total of five RCTs (220 patients) were included. Two studies were deemed to have low risk of bias. In pooled analysis, there was significant difference in VAS score (mean difference [MD], − 9.2; 95% CI: − 17.21, − 1.20) and Lysholm score (MD, 8.70; 95% CI 0.06, 17.34), but not WOMAC (MD, − 7.44; 95% CI − 20.38, 5.50). In cumulative functional analysis using Lysholm score and WOMAC in recommended concentration, there was a significant improvement (standard mean difference [SMD], 0.53; 95% CI 0.13, 0.94) after treatment. In cartilage repair assessed by MRI, there was no significant difference (SMD, 0.53; 95% CI− 0.28, 1.34).
Conclusions
This meta-analysis demonstrated that intra-articular MSCs have a limited evidence in pain relief and functional improvement in knee osteoarthritis. While MSCs may result in favorable clinical outcomes with a recommended concentration, use of concomitant treatment should be considered. In addition, current evidence does not support the use of intra-articular MSCs for improving cartilage repair in knee osteoarthritis.
Level of evidence
Systematic review of Level-II studies.
Background Knee pain is one of the common complaints patients present with in any community based health camps and Osteoarthritis of knee is a usual diagnosis. Injecting a long acting steroid is a common practice to alleviate the symptoms of osteoarthritic knee. Objective To evaluate the clinical outcome of injecting Triamcinolone acetenoid in osteoarthritis of knee in a community set up over a randomized double-blind placebo control trial. Method A prospective, randomized, double blind, placebo control trial was carried out in community after obtaining the ethical clearance from the IRC. Patients with clinically diagnosed osteoarthritis of knee were injected either Triamcinolone or Placebo after recording the baseline scores of the knee by Knee injury and Osteoarthritis Outcome Score (KOOS) - Physical Function Short form (KOOS-PS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS). The same tools were used at two, six and at twelve weeks post injection to evaluate the functional outcome and pain. Result One hundred and seventeen patients were available for analysis among which, 55(48.7%) patients received Triamcinolone and 58(51.3%) received placebo. The baseline status of knees of two groups was comparable at the start of study. There was significant pain relief in the group receiving Triamcinolone at two and six week but not in twelve weeks. Group receiving placebo had pain relief only for first two weeks. Functional outcome was significantly improved compared to baseline in both the groups until six weeks however, in the triamcinolone group, it was significant until twelve weeks. No major complications were noted. Conclusion Intra-articular injection of Triamcinolone acetenoid is effective in symptoms control and improving functional outcome in clinically diagnosed osteoarthritis of knees in community set up during health camps.
Purpose:
To prospectively compare the efficacy of intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA) with a sham control group (normal saline solution [NS]) for knee osteoarthritis in a randomized, dose-controlled, placebo-controlled, double-blind, triple-parallel clinical trial.
Methods:
A total of 87 osteoarthritic knees (53 patients) were randomly assigned to 1 of 3 groups receiving 3 weekly injections of either leukocyte-poor PRP (31 knees), HA (29 knees), or NS (27 knees). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and International Knee Documentation Committee (IKDC) subjective score were collected at baseline and at 1, 2, 6, and 12 months after treatment. Data were analyzed using generalized estimating equations.
Results:
All 3 groups showed statistically significant improvements in both outcome measures at 1 month; however, only the PRP group sustained the significant improvement in both the WOMAC score (63.71 ± 20.67, increased by 21%) and IKDC score (49.93 ± 17.74, increased by 40%) at 12 months. For the intergroup comparison, except for the first month, there was a statistically significant difference between the PRP and NS groups in both scores throughout the study duration (regression coefficients of 8.72 [P = .0015], 7.94 [P = .0155], and 11.92 [P = .0014] at 2, 6, and 12 months, respectively, for WOMAC score, and 9.1 [P = .0001], 10.28 [P = .0002], and 13.97 [P < .0001], respectively, for IKDC score). There was no significant difference in both functional outcomes between the HA and NS groups at any time point. Only the PRP group reached the minimal clinically important difference in the WOMAC score at every evaluation (15%, 21%, 18%, and 21% at 1, 2, 6, and 12 months, respectively) and the minimal clinically important difference in the IKDC score at 6 months (improvement of 11.6).
Conclusions:
Intra-articular injections of leukocyte-poor PRP can provide clinically significant functional improvement for at least 1 year in patients with mild to moderate osteoarthritis of the knee.
Level of evidence:
Level I, randomized controlled single-center trial.
Background
The intra-articular implantation of mesenchymal stromal cells (MSCs) as a treatment for knee osteoarthritis (OA) is an emerging new therapy. In this study, patients with knee OA received intra-articular implantations of autologous bone marrow–derived MSCs. We sought to assess the safety and efficacy of this implantation.
Materials and Methods
This was a phase 1/2 single-center, triple-blind, randomized controlled trial (RCT) with a placebo control. The subjects consisted of patients with knee OA randomly assigned to either an intra-articular implantation of MSCs (40 × 10⁶ cells) or 5 mL normal saline (placebo). Patients were followed up for 6 months after the implantations. The pain level and function improvements for patient-reported outcomes were assessed based on a visual analog scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and its subscales, walking distance, painless walking distance, standing time and knee flexion compared with the placebo group at 3 and 6 months following the implantations.
Results
Overall, 43 patients (Kellgren-Lawrence grades 2, 3 and 4) were assigned to either the MSCs (n = 19) or placebo (n = 24) group. Patients who received MSCs experienced significantly greater improvements in WOMAC total score, WOMAC pain and physical function subscales and painless walking distance compared with patients who received placebo. There were no major adverse events attributed to the MSC therapy.
Conclusion
This randomized, triple-blind, placebo-controlled RCT demonstrated the safety and efficacy of a single intra-articular implantation of 40 × 10⁶ autologous MSCs in patients with knee OA. Intra-articular implantation of MSCs provided significant and clinically relevant pain relief over 6 months versus placebo and could be considered a promising novel treatment for knee OA. We propose that further investigations should be conducted over an extended assessment period and with a larger cohort.
Background:
Blended physiotherapy, in which physiotherapy sessions and an online application are integrated, might support patients in taking an active role in the management of their chronic condition and may reduce disease related costs. The aim of this study was to evaluate the cost-effectiveness of a blended physiotherapy intervention (e-Exercise) compared to usual physiotherapy in patients with osteoarthritis of hip and/or knee, from the societal as well as the healthcare perspective.
Methods:
This economic evaluation was conducted alongside a 12-month cluster randomized controlled trial, in which 108 patients received e-Exercise, consisting of physiotherapy sessions and a web-application, and 99 patients received usual physiotherapy. Clinical outcome measures were quality-adjusted life years (QALYs) according to the EuroQol (EQ-5D-3 L), physical functioning (HOOS/KOOS) and physical activity (Actigraph Accelerometer). Costs were measured using self-reported questionnaires. Missing data were multiply imputed and bootstrapping was used to estimate statistical uncertainty.
Results:
Intervention costs and medication costs were significantly lower in e-Exercise compared to usual physiotherapy. Total societal costs and total healthcare costs did not significantly differ between groups. No significant differences in effectiveness were found between groups. For physical functioning and physical activity, the maximum probability of e-Exercise being cost-effective compared to usual physiotherapy was moderate (< 0.82) from both perspectives. For QALYs, the probability of e-Exercise being cost-effective compared to usual physiotherapy was 0.68/0.84 at a willingness to pay of 10,000 Euro and 0.70/0.80 at a willingness to pay of 80,000 Euro per gained QALY, from respectively the societal and the healthcare perspective.
Conclusions:
E-Exercise itself was significantly cheaper compared to usual physiotherapy in patients with hip and/or knee osteoarthritis, but not cost-effective from the societal- as well as healthcare perspective. The decision between both interventions can be based on the preferences of the patient and the physiotherapist.
Trial registration:
NTR4224 (25 October 2013).
Objective
Pain management is a cornerstone of osteoarthritis (OA) management. The aim of this review is to obtain current, literature-based estimates of the effect of common pharmacologic treatments on pain reduction in OA.
Methods
A MEDLINE search (2006–2016) was conducted for randomized controlled trials studying acetaminophen, oral NSAIDs, topical NSAIDs, COX-2 inhibitors, and opioids in the treatment of OA pain. Drug effect on pain was estimated using relative change in pain, and expressed as percentage change. An overall effect for each drug category was obtained as a weighted average of study-specific effects, with weights based on each study’s sample size.
Results
Twenty-nine studies were included. The effect on pain was estimated in a total of 43 treatment arms (acetaminophen n = 6, oral NSAIDs n = 9, topical NSAIDs n = 8, COX-2 inhibitors n = 9, and opioids n = 11). Relative (%) changes in pain were found to be as follows: acetaminophen = 32.5, oral NSAIDs = 34.3, topical NSAIDs = 40.9, COX-2 inhibitors = 36.9, and opioids = 35.4.
Conclusion
The effects of 5 major drug categories in the treatment of OA pain were reviewed with data extracted from 29 studies published from 2006 to 2016. Acetaminophen was found to have an RC value close to that of oral NSAIDs. The effects of oral NSAIDs, COX-2 inhibitors, and opioids in controlling pain were similar to what has been demonstrated in previous literature. Topical NSAIDs were found to have a greater RC than oral NSAIDs.
Background:
Knee osteoarthritis (OA) is a disease with a high prevalence in the adult population. Nonsteroidal anti-inflammatory drugs (NSAID) or intra-articular injections [hyaluronic acid (HA) or platelet-rich plasma (PRP)] can provide clinical benefit. Magnetic resonance imaging (MRI) has proven to be useful for the evaluation of cartilage volume and thickness in knee osteoarthritis. The purpose of this study was to evaluate the benefit provided by PRP injection in comparison with hyaluronic acid and NSAID in knee OA patients and to compare the radiographic evolution at the 52-week follow-up.
Methods:
One hundred and six patients were enrolled and randomized according to the Spanish Rheumatology Society knee osteoarthritis diagnosis criteria. Ninety-eight patients completed the study (33 received NSAID treatment, 32 a single hyaluronic acid injection and 33 a single PRP injection). Patients were prospectively evaluated at baseline, 26 and 52 weeks using the Western Ontario McMaster Universities osteoarthritis index (WOMAC) and the visual analogue scale (VAS), and at baseline and 52 weeks with X-ray and MRI.
Results:
A 20% decrease in WOMAC pain and increase in physical function was found in 30 and 24%, respectively, of those patients who received PRP treatment, at the 52-week follow-up. WOMAC pain and VAS improved in the hyaluronic acid and NSAID groups. However, better results were obtained in the PRP group compared to hyaluronic acid and NSAIDs (P < 0.05). No differences in Kellgren-Lawrence or cartilage thickness progression were found.
Conclusions:
Leukocyte-poor platelet-rich plasma (LP-PRP) injections are better in terms of clinical improvement with respect to HA injections or oral NSAID treatment in knee osteoarthritis patients at the 52-week follow-up. Moreover, a single LP-PRP injection is effective. However, LP-PRP has no influence on cartilage progression.
Level of evidence:
Level II.
Background:
Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs.
Methods:
In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit.
Results:
The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: -3.12 versus -2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments.
Conclusions:
FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point).
Level of evidence:
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Objective:
Many clinical trials of viscosupplementation have been conducted, although only the Gel-200 (primary) trial included a different patient population. A subgroup analysis of a multicenter, randomized controlled trial comparing the efficacy of single intra-articular injections of Gel-200 with phosphate buffered saline (PBS) was performed to demonstrate its benefit as treatment of osteoarthritis of the knee in a population similar to those of other reported trials of viscosupplementation.
Design:
The subgroup population was defined as patients in the intention-to-treat (ITT) population who met the specified criteria. Changes from baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores following treatment with Gel-200 or PBS were derived from a longitudinal model and treatment differences compared between groups at weeks 12 and 26, and over 26 weeks.
Results:
The subgroup included 311 subjects (152 Gel-200; 159 PBS). Mean improvements from baseline in WOMAC pain subscores in the Gel-200 over PBS groups were statistically significant at week 12 (P = 0.031) and week 26 (P = 0.019). Treatment group differences in WOMAC stiffness and total scores were statistically significant at week 26 (P = 0.023 and P = 0.036, respectively).
Conclusions:
The efficacy of Gel-200 following a single injection for knee osteoarthritis was demonstrated in WOMAC pain, stiffness, and total scores as well as clinically important improvements in pain at 26 weeks in this subset of patients with comparable characteristics to populations evaluated in other viscosupplementation treatment trials.
Background:
To evaluate the efficacy and safety of intra-articular methylprednisolone for reducing pain in patients with knee osteoarthritis.
Methods:
We conduct electronic searches of Medline (1966-2017.11), PubMed (1966-2017.11), Embase (1980-2017.11), ScienceDirect (1985-2017.11), and the Cochrane Library (1900-2017.11) for randomized clinical trials comparing the use of methylprednisolone to treat knee osteoarthritis. The primary outcomes are Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores and WOMAC function scores. Each outcome was combined and calculated using the statistical software STATA 12.0. Fixed/random effect model was adopted based on the heterogeneity tested by I statistic.
Results:
A total of 739 patients were analyzed across 4 randomized controlled trials (RCTs). The present meta-analysis revealed that there were significant differences between groups regarding the WOMAC pain scores at 4 weeks (WMD = -1.384, 95% CI: -1.975 to -0.793, P = .000), 12 weeks (WMD = -1.587, 95% CI: -2.489 to -0.685, P = .001), and 24 weeks (WMD = -1.563, 95% CI: -2.245 to -0.881, P = .000). Significant differences were identified in terms of physical function at 4 weeks (WMD = -7.925, 95% CI: -13.359 to -2.491, P = .004), 12 weeks (WMD = -7.314, 95% CI: -13.308 to -1.320, P = .117), and 24 weeks (WMD = -6.484, 95% CI: -11.256 to -1.711, P = .008).
Conclusion:
Intra-articular methylprednisolone injection was associated with an improved pain relief and physical function in patients with knee osteoarthritis. Additionally, no severe adverse effects were observed. Due to the limited quality of the evidence currently available, higher quality RCTs were required.
Objective:
To compare the effectiveness of physical therapy (PT, evidence-based approach) and internet-based exercise training (IBET), each versus a wait list (WL) control, among individuals with knee osteoarthritis (OA).
Design:
Randomized controlled trial of 350 participants with symptomatic knee OA, allocated to standard PT, IBET and WL control in a 2:2:1 ratio, respectively. The PT group received up to 8 individual visits within 4 months. The IBET program provided tailored exercises, video demonstrations, and guidance on progression. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, range 0 [no problems]-96 [extreme problems]), assessed at baseline, 4 months (primary time point) and 12 months. General linear mixed effects modeling compared changes in WOMAC among study groups, with superiority hypotheses testing differences between each intervention group and WL and non-inferiority hypotheses comparing IBET with PT.
Results:
At 4-months, improvements in WOMAC score did not differ significantly for either the IBET or PT group compared with WL (IBET: -2.70, 95% Confidence Interval (CI) = -6.24, 0.85, p=0.14; PT: -3.36, 95% (CI) = -6.84, 0.12, p=0.06). Similarly, at 12-months mean differences compared to WL were not statistically significant for either group (IBET: -2.63, 95%CI = -6.37, 1.11, p=0.17; PT: -1.59, 95% CI = -5.26, 2.08, p=0.39). IBET was non-inferior to PT at both time points.
Conclusions:
Improvements in WOMAC score following IBET and PT did not differ significantly from the WL group. Additional research is needed to examine strategies for maximizing benefits of exercise-based interventions for patients with knee OA.
Trial registration:
NCT02312713.
Abstract Background Intra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens. Methods We conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline. Results Thirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2–4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = −0.76; −0.98 to −0.53, 95% CI, P
Purpose:
To analyze the early outcomes of viscosupplementation in patients with severe knee osteoarthritis.
Method:
A randomized, double-blind clinical trial of 143 knees divided into three groups: Group 1 - intra-articular injection of triamcinolone; Group 2 - hylan GF20; and Group 3 - triamcinolone + hylan GF20. Outcomes were evaluated using Lysholm and KSS scores before treatment and after one, three and six months.
Results:
Within-group comparisons revealed improvements in Lysholm scores in all groups in the one month evaluation relative to pre-treatment levels (p < 0.01). This improvement was maintained in the third month after treatment (p > 0.05). Scores at six months were significantly lower than those observed in the previous follow-up assessments (p < 0.05), but still higher than pre-treatment levels (p < 0.05). KSS scores also improved after one month relative to pre-treatment levels (p < 0.01). This improvement was still present at three and six months after treatment in the corticosteroid group (p > 0.05). Patients treated with hylan GF20 showed lower scores in the last evaluation relative to month one (p < 0.05). No significant differences were observed between the treatment groups (p > 0.05).
Conclusions:
Viscosupplementation increased functional scores in patients with severe osteoarthritis of the knee, especially within three months of injection. However, it was not superior to the use of triamcinolone.
Background: Osteoarthritis (OA) is the most common chronic progressive joint disease that takes place when the cartilage or a low friction surface between joints breaks down leading to pain, stiffness and swelling. The aim of this study was to determine the comparative efficacy and safety of intraarticular corticosteroid (Depomedrol 80mg) and intra articular hyaluronic acid (HA) in knee osteoarthritis. A randomized single blind comparative trial was carried out in a physical medicine and rehabilitation outpatient department. Method: 150 patients with knee osteoarthritis, who were followed for 6 months, were randomized to receive intra articular injection of either Hyaluronic acid or corticosteroid. With the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the visual analog pain scale, an independent, blinded evaluator assessed the patients two times. Assessment included recording of: visual analog scores (VAS) for pain; WOMAC scoring, duration of stiffness; range of movement; joint effusion; local heat; synovial thickening; joint-line and periarticular tenderness. Results: The mean age of the patients in the Hyaluronic acid group was 71.4 ± 1.4 years and corticosteroid group was 69.5±1.7 years. Both the groups treated with Hyaluronic acid and corticosteroid demonstrated improvements from baseline WOMAC scores (a median decrease from 52 to 38 points and from 55 to 40 points, respectively; p < 0.01 for both). The scores on the visual analog scale improved for patients receiving Hyaluronic acid (median, 66 to 50 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 72 to 60 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes. Conclusions: No differences were detected between patients treated with intra-articular injections of Hyaluronic acid and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all outcome scales. Such significant gender-related differences warrant further investigation. © 2017, Indian Journal of Public Health Research and Development. All rights reserved.
Objective: The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe prevalence of adverse effects in both groups.
Materials and methods: A prospective randomized controlled clinical trial was carried out. The analysis of pain and changes in osteoarthritis symptoms after a single intra-articular bone marrow-derived mononuclear cell injection into the knee joint in the Kellgren–Lawrence stage II–III osteoarthritis during the 12-month period were performed. The results were compared with the control group treated routinely by hyaluronic acid injections therapy. A therapy group of patients (n = 28) received single bone marrow-derived mononuclear cell intra-articular injections. A control group of patients (n = 28) was treated with a total of three sodium hyaluronate intra-articular injections each one performed a week apart. The clinical results were obtained using the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before and 3, 6, and 12 months after injection.
Results: A statistically significant improvement was observed in the mononuclear cell group over the starting point in all scores. At the endpoint at month 12, the KOOS score improved significantly (P
Objective: This study aims at evaluating the clinical effects of Platelet Rich Plasma (PRP) and Hyaluronic Acid (HA) as individual treatments for mild to moderate Osteoarthritis (OA) and it also examines the potential synergistic effects of PRP in combination with HA. Research continues to emerge examining the potential therapeutic efficacy of HA and PRP as autologous injectable treatments for joint arthritis. However, there is a paucity of research investigating the effects of combining HA and PRP on pain and functional status in patients with OA.
Design: In this multi-center, randomized, controlled, double blind, prospective trial, 105 patients with mild to moderate knee osteoarthritis, who met the study criteria, were randomly allocated to one of three interventions: HA (n=36), PRP (n=36), or HA+PRP (n=33). Each patient received 3 intra-articular knee injections of their assigned substance, with 2 week intervals between each injection. Clinical outcomes were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale (VAS) questionnaire at baseline and after 1,3,6 and 12 months.
Results: The study showed that the PRP group have significant reduction in VAS scores at 1 (p= 0.003), 3 (p= 0.0001), 6 (p= 0.0001) and 12 (p= 0.000) months when compared to HA. In addition, the PRP group illustrated greater improvement in WOMAC physical activity scale at 12 months (p= 0.008) when compared to the HA group. Combining HA and PRP resulted in a significant decreases in pain (p=0.0001) and functional limitation (p=0.0001) when compared to HA alone at 1 year post treatment; and significantly increased physical function at 1 (p=0.0004) and 3 (p=.011) months when compared to PRP alone.
Conclusion: The findings of the study support the use of autologous PRP as an effective treatment of mild to moderate knee osteoarthritis. It also shows that the combination of HA and PRP resulted to better outcomes than HA alone up to 1 year and PRP alone up to 3 months. Furthermore, the results suggest that combination of PRP and HA could potentially provide better functional outcomes in the first 30 days after treatment with both PRP and HA alone.
Background:
Use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) to treat chronic musculoskeletal conditions has become widely accepted because they can provide pain relief without associated systemic adverse events. This review is an update of 'Topical NSAIDs for chronic musculoskeletal pain in adults', originally published in Issue 9, 2012.
Objectives:
To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs for chronic musculoskeletal pain in adults.
Search methods:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and our own in-house database; the date of the last search was February 2016. We also searched the references lists of included studies and reviews, and sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' web sites.
Selection criteria:
We included randomised, double-blind, active or inert carrier (placebo) controlled trials in which treatments were administered to adults with chronic musculoskeletal pain of moderate or severe intensity. Studies had to meet stringent quality criteria and there had to be at least 10 participants in each treatment arm, with application of treatment at least once daily.
Data collection and analysis:
Two review authors independently assessed studies for inclusion and extracted data. We used numbers of participants achieving each outcome to calculate risk ratio and numbers needed to treat (NNT) or harm (NNH) compared to carrier or other active treatment. We were particularly interested to compare different formulations (gel, cream, plaster) of individual NSAIDs. The primary outcome was 'clinical success', defined as at least a 50% reduction in pain, or an equivalent measure such as a 'very good' or 'excellent' global assessment of treatment, or 'none' or 'slight' pain on rest or movement, measured on a categorical scale.
Main results:
We identified five new studies for this update, which now has information from 10,631 participants in 39 studies, a 38% increase in participants from the earlier review; 33 studies compared a topical NSAID with carrier. All studies examined topical NSAIDs for treatment of osteoarthritis, and for pooled analyses studies were generally of moderate or high methodological quality, although we considered some at risk of bias from short duration and small size.In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier for reducing pain; about 60% of participants had much reduced pain. With topical diclofenac, the NNT for clinical success in six trials (2343 participants) was 9.8 (95% confidence interval (CI) 7.1 to 16) (moderate quality evidence). With topical ketoprofen, the NNT for clinical success in four trials (2573 participants) was 6.9 (5.4 to 9.3) (moderate quality evidence). There was too little information for analysis of other individual topical NSAIDs compared with carrier. Few trials compared a topical NSAID to an oral NSAID, but overall they showed similar efficacy (low quality evidence). These efficacy results were almost completely derived from people with knee osteoarthritis.There was an increase in local adverse events (mostly mild skin reactions) with topical diclofenac compared with carrier or oral NSAIDs, but no increase with topical ketoprofen (moderate quality evidence). Reporting of systemic adverse events (such as gastrointestinal upsets) was poor, but where reported there was no difference between topical NSAID and carrier (very low quality evidence). Serious adverse events were infrequent and not different between topical NSAID and carrier (very low quality evidence).Clinical success with carrier occurred commonly - in around half the participants in studies lasting 6 to 12 weeks. Both direct and indirect comparison of clinical success with oral placebo indicates that response rates with carrier (topical placebo) are about twice those seen with oral placebo.A substantial amount of data from completed, unpublished studies was unavailable (up to 6000 participants). To the best of our knowledge, much of this probably relates to formulations that have never been marketed.
Authors' conclusions:
Topical diclofenac and topical ketoprofen can provide good levels of pain relief beyond carrier in osteoarthritis for a minority of people, but there is no evidence for other chronic painful conditions. There is emerging evidence that at least some of the substantial placebo effects seen in longer duration studies derive from effects imparted by the NSAID carrier itself, and that NSAIDs add to that.
Background:
Efficient approaches are needed for delivering non-pharmacological interventions for knee osteoarthritis (OA).
Objective:
This trial compared group-based vs. individual physical therapy (PT) interventions for knee OA.
Design & methods:
320 patients with knee OA at the VA Medical Center in Durham, NC (mean age = 60 years, 88% male; 58% non-white) were randomized to either the group intervention (GPT; six one-hour sessions, typically eight participants / group) or the individual intervention (IPT; two one-hour sessions). Both programs included instruction in home exercise, joint protection techniques and individual physical therapist evaluation. The primary outcome was the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC; range 0-96, higher scores indicate worse symptoms), measured at baseline, 12 weeks and 24 weeks. The secondary outcome was the Short Performance Physical Battery (SPPB; range 0-12, higher scores indicate better performance), measured at baseline and 12 weeks. Linear mixed models assessed the difference in WOMAC scores between arms.
Results:
At 12-weeks, WOMAC scores were 2.7 points lower in GPT vs. IPT [95% confidence interval (CI) = -5.9, 0.5; p=0.10], indicating no between-group difference. At 24-weeks, WOMAC scores were 1.3 points lower in GPT vs. IPT [95% CI =-4.6, 2.0; p=0.44], indicating no significant between-group difference. At 12-weeks, SPPB scores were 0.1 points lower in the GPT arm vs, IPT [95% CI = -0.5, 0.2, p=0.53], indicating no difference between groups.
Limitations:
This study was conducted in one VA Medical Center. Outcome assessors were blinded, but participants and physical therapists were not.
Conclusions:
GPT was not more effective than IPT for primary or secondary study outcomes. Either GPT or IPT may be reasonable delivery models for health care systems to consider.
Background:
Both physical therapy and intraarticular injections of glucocorticoids have been shown to confer clinical benefit with respect to osteoarthritis of the knee. Whether the short-term and long-term effectiveness for relieving pain and improving physical function differ between these two therapies is uncertain.
Methods:
We conducted a randomized trial to compare physical therapy with glucocorticoid injection in the primary care setting in the U.S. Military Health System. Patients with osteoarthritis in one or both knees were randomly assigned in a 1:1 ratio to receive a glucocorticoid injection or to undergo physical therapy. The primary outcome was the total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 1 year (scores range from 0 to 240, with higher scores indicating worse pain, function, and stiffness). The secondary outcomes were the time needed to complete the Alternate Step Test, the time needed to complete the Timed Up and Go test, and the score on the Global Rating of Change scale, all assessed at 1 year.
Results:
We enrolled 156 patients with a mean age of 56 years; 78 patients were assigned to each group. Baseline characteristics, including severity of pain and level of disability, were similar in the two groups. The mean (±SD) baseline WOMAC scores were 108.8±47.1 in the glucocorticoid injection group and 107.1±42.4 in the physical therapy group. At 1 year, the mean scores were 55.8±53.8 and 37.0±30.7, respectively (mean between-group difference, 18.8 points; 95% confidence interval, 5.0 to 32.6), a finding favoring physical therapy. Changes in secondary outcomes were in the same direction as those of the primary outcome. One patient fainted while receiving a glucocorticoid injection.
Conclusions:
Patients with osteoarthritis of the knee who underwent physical therapy had less pain and functional disability at 1 year than patients who received an intraarticular glucocorticoid injection. (ClinicalTrials.gov number, NCT01427153.).
Background:
Tramadol is often prescribed to treat pain and is associated physical disability in osteoarthritis (OA). Due to the pharmacologic mechanism of tramadol, it may lead to fewer associated adverse effects (i.e. gastrointestinal bleeding or renal problems) compared to non-steroidal anti-inflammatory drugs (NSAIDs). This is an update of a Cochrane Review originally published in 2006.
Objectives:
To determine the benefits and harms of oral tramadol or tramadol combined with acetaminophen or NSAIDs in people with osteoarthritis.
Search methods:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases, as well as the US National Institutes of Health and World Health Organization trial registries up to February 2018. We searched the LILACS database up to August 2015.
Selection criteria:
We included randomized controlled trials (RCTs) that evaluated the effect of tramadol, or tramadol in combination with acetaminophen (paracetamol) or NSAIDs versus placebo or any comparator in people with osteoarthritis.
Data collection and analysis:
We used standard methodologic procedures expected by Cochrane.
Main results:
We included 22 RCTs (11 more than the previous review) of which 21 RCTs were included in meta-analyses for 3871 participants randomized to tramadol alone or tramadol in combination with another analgesic and 2625 participants randomized to placebo or active control. Seventeen studies evaluated tramadol alone and five evaluated tramadol plus acetaminophen. Thirteen studies used placebo controls and eleven studies used active controls (two trials had both placebo and active arms). The dose of tramadol ranged from 37.5 mg to 400 mg daily; all doses were pooled. Most trials were multicenter with a mean duration of two months. Participants were predominantly women with hip or knee osteoarthritis, with a mean age of 63 years and moderate to severe pain. There was a high risk of selection bias as only four trials reported both adequate sequence generation and allocation concealment. There was a low risk for performance bias as most studies blinded participants. There was a high risk of attrition bias as 10/22 trials showed incomplete outcome data. Most of the trials were funded by the pharmaceutical industry.Moderate quality evidence (downgraded due to risk of bias) indicated that tramadol alone and in combination with acetaminophen had no important benefit on pain reduction compared to placebo control (tramadol alone: 4% absolute improvement, 95% confidence interval (CI) 3% to 5%; 8 studies, 3972 participants; tramadol in combination with acetaminophen: 4% absolute improvement, 95% CI 2% to 6%; 2 studies, 614 participants).Fifteen out of 100 people in the tramadol group improved by 20% (which corresponded to a clinically important difference in pain) compared to 10/100 in the placebo group (5% absolute improvement). Twelve out of 100 people improved by 20% in the tramadol in combination with acetaminophen group compared to 7/100 in the placebo group (5% absolute improvement).Moderate quality evidence (downgraded due to risk of bias) indicated that tramadol alone and in combination with acetaminophen led to no important benefit in physical function compared to placebo (tramadol alone: 4% absolute improvement, 95% CI 2% to 6%; 5 studies, 2550 participants; tramadol in combination with acetaminophen: 4% absolute improvement, 95% CI 2% to 7%; 2 studies, 614 participants).Twenty-one out of 100 people in the tramadol group improved by 20% (which corresponded to a clinically important difference in physical function) compared to 16/100 in the placebo group (5% absolute improvement). Fifteen out of 100 people improved by 20% in the tramadol in combination with acetaminophen group compared to 10/100 in the placebo group (5% absolute improvement).Moderate quality evidence (downgraded due to risk of bias) indicated that, compared to placebo, there was a greater risk of developing adverse events with tramadol alone (risk ratio (RR) 1.34, 95% CI 1.24 to 1.46; 4 studies, 2039 participants) and tramadol in combination with acetaminophen compared to placebo (RR 1.91, 95% CI 1.32 to 2.76; 1 study, 308 participants). This corresponded to a 17% increase (95% CI 12% to 23%) with tramadol alone and 22% increase (95% CI 8% to 41%) with tramadol in combination with acetaminophen.The three most frequent adverse events were nausea, dizziness and tiredness. Moderate quality evidence (downgraded due to risk of bias) indicated that there was a greater risk of withdrawing from the study because of adverse events with tramadol alone compared to placebo (RR 2.64, 95% CI 2.17 to 3.20; 9 studies, 4533 participants), which corresponded to a 12% increase (95% CI 9% to 16%).Low quality evidence (downgraded due to risk of bias and inconsistency) indicated that there was a greater risk of withdrawing from the study because of adverse events with tramadol in combination with acetaminophen compared to placebo (RR 2.78, 95% CI 1.50 to 5.16; 2 studies, 614 participants), which corresponded to a 8% absolute improvement (95% CI 2% to 19%).Low quality evidence (downgraded due to risk of bias and imprecision) indicated that there was a greater risk of developing serious adverse events with tramadol alone compared to placebo (110/2459 participants with tramadol compared to 22/1153 participants with placebo; RR 1.78, 95% CI 1.11 to 2.84; 7 studies, 3612 participants), which corresponded to a 1% increase (95% CI 0% to 4%). There were no serious adverse events reported in one small study (15 participants) of tramadol with acetaminophen compared to placebo.
Authors' conclusions:
Moderate quality evidence indicates that compared to placebo, tramadol alone or in combination with acetaminophen probably has no important benefit on mean pain or function in people with osteoarthritis, although slightly more people in the tramadol group report an important improvement (defined as 20% or more). Moderate quality evidence shows that adverse events probably cause substantially more participants to stop taking tramadol. The increase in serious adverse events with tramadol is less certain, due to the small number of events.
Background
Knee osteoarthritis (OA) is one of the most common joint diseases, and pharmacotherapy is necessary to control its symptoms.
Aim
To evaluate efficacy and tolerability of duloxetine in patients with knee OA.
Methods
PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched to identify randomized controlled trials (RCTs) comparing duloxetine with placebo for knee OA. Data including pain, stiffness, physical function, and adverse events were extracted for meta‐analysis. The protocol was prospectively registered in PROSPERO (CRD42018097110).
Results
Data from six RCTs including 2059 participants were pooled. Duloxetine achieved significant reductions in primary outcomes including Brief Pain Inventory 24‐h average pain score [weighted mean difference (WMD) = −0.74, 95% confidence interval (CI) = −0.92 to −0.57], weekly mean of the 24‐h average pain score (WMD = −0.76, 95% CI =−0.96 to −0.56), WOMAC stiffness score (WMD = −0.47, 95% CI = −0.60 to −0.34), and WOMAC physical function score (WMD = −4.44, 95% CI = −5.24 to −3.64). Furthermore, duloxetine demonstrated a higher number of treatment‐emergent adverse events [risk ratio (RR) = 1.31, 95% CI = 1.20 to 1.44] and discontinuations (RR = 2.26, 95% CI = 1.63 to 3.12); however, no difference in serious adverse events (RR = 0.92, 95% CI = 0.40 to 2.11) was observed.
Conclusion
Duloxetine is effective in the management of chronic pain and loss of physical function in knee OA with acceptable adverse events despite having no advantage in treating joint stiffness. Future trials should focus on determining the optimal treatment regimen.
This article is protected by copyright. All rights reserved.
Background:
Paracetamol (acetaminophen) is vastly recommended as the first-line analgesic for osteoarthritis of the hip or knee. However, there has been controversy about this recommendation given recent studies have revealed small effects of paracetamol when compared with placebo. Nonetheless, past studies have not systematically reviewed and appraised the literature to investigate the effects of this drug on specific osteoarthritis sites, that is, hip or knee, or on the dose used.
Objectives:
To assess the benefits and harms of paracetamol compared with placebo in the treatment of osteoarthritis of the hip or knee.
Search methods:
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, AMED, CINAHL, Web of Science, LILACS, and International Pharmaceutical Abstracts to 3 October 2017, and ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) portal on 20 October 2017.
Selection criteria:
We included randomised controlled trials comparing paracetamol with placebo in adults with osteoarthritis of the hip or knee. Major outcomes were pain, function, quality of life, adverse events and withdrawals due to adverse events, serious adverse events, and abnormal liver function tests.
Data collection and analysis:
Two review authors used standard Cochrane methods to collect data, and assess risk of bias and quality of the evidence. For pooling purposes, we converted pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index function) scores to a common 0 (no pain or disability) to 100 (worst possible pain or disability) scale.
Main results:
We identified 10 randomised placebo-controlled trials involving 3541 participants with hip or knee osteoarthritis. The paracetamol dose varied from 1.95 g/day to 4 g/day, and the majority of trials followed participants for three months only. Most trials did not clearly report randomisation and concealment methods and were at unclear risk of selection bias. Trials were at low risk of performance, detection, and reporting bias.At 3 weeks' to 3 months' follow-up, there was high-quality evidence that paracetamol provided no clinically important improvements in pain and physical function. Mean reduction in pain was 23 points (0 to 100 scale, lower scores indicated less pain) with placebo and 3.23 points better (5.43 better to 1.02 better) with paracetamol, an absolute reduction of 3% (1% better to 5% better, minimal clinical important difference 9%) and relative reduction of 5% (2% better to 8% better) (seven trials, 2355 participants). Physical function improved by 12 points on a 0 to 100 scale (lower scores indicated better function) with placebo and was 2.9 points better (0.95 better to 4.89 better) with paracetamol, an absolute improvement of 3% (1% better to 5% better, minimal clinical important difference 10%) and relative improvement of 5% (2% better to 9% better) (7 trials, 2354 participants).High-quality evidence from eight trials indicated that the incidence of adverse events was similar between groups: 515/1586 (325 per 1000) in the placebo group versus 537/1666 (328 per 1000, range 299 to 360) in the paracetamol group (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.92 to 1.11). There was less certainty (moderate-quality evidence) around the risk of serious adverse events, withdrawals due to adverse events, and the rate of abnormal liver function tests, due to wide CIs or small event rates, indicating imprecision. Seventeen of 1480 (11 per 1000) people treated with placebo and 28/1729 (16 per 1000, range 8 to 29) people treated with paracetamol experienced serious adverse events (RR 1.36, 95% CI 0.73 to 2.53; 6 trials). The incidence of withdrawals due to adverse events was 65/1000 participants in with placebo and 77/1000 (range 59 to 100) participants with paracetamol (RR 1.19, 95% CI 0.91 to 1.55; 7 trials). Abnormal liver function occurred in 18/1000 participants treated with placebo and 70/1000 participants treated with paracetamol (RR 3.79, 95% CI 1.94 to 7.39), but the clinical importance of this effect was uncertain. None of the trials reported quality of life.Subgroup analyses indicated that the effects of paracetamol on pain and function did not differ according to the dose of paracetamol (3.0 g/day or less versus 3.9 g/day or greater).
Authors' conclusions:
Based on high-quality evidence this review confirms that paracetamol provides only minimal improvements in pain and function for people with hip or knee osteoarthritis, with no increased risk of adverse events overall. Subgroup analysis indicates that the effects on pain and function do not differ according to the dose of paracetamol. Due to the small number of events, we are less certain if paracetamol use increases the risk of serious adverse events, withdrawals due to adverse events, and rate of abnormal liver function tests.Current clinical guidelines consistently recommend paracetamol as the first-line analgesic medication for hip or knee osteoarthritis, given its low absolute frequency of substantive harm. However, our results call for reconsideration of these recommendations.
Background::
Platelet-rich plasma (PRP) injections have been proposed as a new conservative option for knee degeneration to provide symptomatic relief and delay surgical intervention. Although the current literature provides some evidence on the benefits of this technique compared with viscosupplementation, no studies have been performed to compare their long-term effects.
Purpose::
To compare the long-term clinical outcomes provided by intra-articular injections of either PRP or hyaluronic acid (HA) to treat knee degenerative disease.
Study design::
Randomized controlled trial; Level of evidence, 1.
Methods::
Patients with a history of chronic symptomatic knee degenerative changes and osteoarthritis (Kellgren-Lawrence grade 0-3) were enrolled: 192 patients were randomized to undergo 3 blinded weekly intra-articular injections of either PRP or HA. Patients were prospectively evaluated before the injection and then at 2, 6, 12, and 24 months and a mean of 64.3 months (SD, 7.8 months) of follow-up. Evaluation was based on International Knee Documentation Committee (IKDC) subjective (main outcome), EuroQol visual analog scale, and Tegner scores; 167 patients reached the final evaluation.
Results::
Both treatments were effective in improving knee functional status and symptoms over time: Mean ± SD IKDC subjective score improved significantly for both PRP and HA groups ( P < .0005) and remained stable over time up to 24 months (from 53.3 ± 14.3 to 67.3 ± 18.1 and from 50.3 ± 13.2 to 62.1 ± 20.8 for PRP and HA groups, respectively). At final evaluation, a significant IKDC reduction was observed in both treatment groups, with the PRP group still presenting significantly higher values compared with baseline: PRP 60.5 ± 19.0 ( P < .001 vs baseline), HA 55.7 ± 18.8 (not significant vs baseline). A comparative analysis showed no significant intergroup difference in any of the clinical scores at any follow-up point. The median duration of patient subjective perception of symptomatic relief was 9 months for HA and 12 months for PRP (not significant). The only significant difference was observed in the rate of reintervention at 24 months, which was significantly lower in the PRP group (22.6% vs 37.1%, P = .036).
Conclusion::
Both treatments were effective in improving knee functional status and symptoms over time. PRP did not provide an overall superior clinical improvement compared with HA in terms of either symptomatic-functional improvement at different follow-up points or effect duration.
Registration::
NCT01670578 (ClinicalTrials.gov identifier).
Knee osteoarthritis is the most common degenerative disease of the joints caused by articular cartilage injury, degradation of the joint edge and subchondral bone hyperplasia. Various treatments are used to alleviate the symptoms of patients with knee osteoarthritis, including analgesics and intra-articular injections. Platelet-rich plasma (PRP) is an autologous and multifunctional platelet concentrate of the blood, which stimulates the cartilage healing process and improves the damage caused by articular disease. Hyaluronic acid (HA) is an effective treatment for patients with knee osteoarthritis. In the current study, the effectiveness of PRP and HA combination therapy administered via intra-articular injections for patients with knee osteoarthritis was analyzed. A total of 360 patients with knee osteoarthritis were randomized into four different treatment groups as follows: Double-blind treatment with PRP (2-14 ml); double-blind treatment with HA (0.1-0.3 mg); combination therapy of PRP and HA; and placebo groups. Following treatment, all patients were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Common Toxicity Criteria. The most common treatment-emergent adverse events were hypertension and proteinuria. The current study demonstrated that PRP and HA treatment significantly improved arthralgia, and PRP treatment was determined to be significantly more effective than HA treatment using the WOMAC pain score (P<0.05). PRP and HA combination treatment significantly improved arthralgia, reduced humoral and cellular immune responses and promoted angiogenesis, which improved the patients' histological parameters compared with PRP or HA treatment alone. These results suggested that PRP and HA combination treatment may be a potential treatment option for patients with knee osteoarthritis in the future.
Background:
This study aims to compare the efficacy of intra-articular injection of hyaluronic acid (HA) and platelet-rich plasma (PRP) for treating hip osteoarthritis (OA).
Methods:
We performed systematic searches in PubMed, EmBase, ScienceDirect Web of science and the Cochrane Library for relevant literature published in or before February 2018. Only randomized controlled trials (RCTs) were included. The risk of bias assessment was performed using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). We used STATA 14.0 (College Station, TX, USA) to analyze the data.
Results:
A total of 287 records were identified by the initial database search. Finally, 4 RCTs were included in our study. The present meta-analysis indicated that PRP was associated with a significant reduction of VAS score at 2 months compared with HA. However, it did not show significantly better outcomes at 6 and 12 months. There was no significant difference regarding the WOMAC and HHS at a 12-month follow up. No increased risk of adverse effects were observed.
Conclusion:
Intra-articular injection of PRP was associated with a significant reduction of VAS at 2 months. Both of them showed comparable results in terms of functional recovery. Further studies were still necessary.
The aim of this study was to test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1) retrovirally transduced to overexpress transforming growth factor-β1. A total of 163 Kellgren-Lawrence grade 3 patients with knee osteoarthritis were randomly assigned to receive intra-articular TG-C or placebo. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks. Secondary efficacy measures included IKDC and VAS at 26 and 39 weeks; pain, stiffness, and physical function by the Western Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms, daily activities, function in sports and recreation, and quality of life by the Knee Injury and Osteoarthritis Outcome Score (KOOS), X-ray, magnetic resonance imaging, and soluble urine and blood biomarkers. TG-C was associated with statistically significant improvement over placebo in the total IKDC score and individual categories, and in the VAS score at 26, 39, and 52 weeks. WOMAC and KOOS scores also improved with TG-C over placebo. Patients treated with TG-C showed trends directed toward thicker cartilage and slower growing rates of subchondral bone surface area in the medial tibia, lateral tibia, lateral patella, and lateral patella femoral regions, although these were not statistically significant (p > 0.05). Serum C-terminal telopeptide of type I collagen (CTX-I) and urine CTX-II levels were lower over 1 year in TG-C than placebo-treated patients, with CTX-I level reaching statistical significance. These tendencies supported TG-C as holding great potential as a disease-modifying osteoarthritis drug. The most frequent adverse events in the TG-C group were peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection site pain (5%). TG-C was associated with statistically significant improvements in function and pain in patients with knee osteoarthritis. The unexpected adverse events were not observed.
Objective:
To test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1), retrovirally transduced to overexpress TGF-β1.
Design:
We randomly assigned 163 with knee osteoarthritis to receive intra-articular TG-C or placebo in Kellgren-Lawrence grade 3 patients for clinical trial. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks. Secondary efficacy measures included IKDC and VAS at 26 and 39 weeks; pain, stiffness, and physical functions by the Western Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms, daily activities, functions in sports and recreation, and quality of life by the Knee Injury and Osteoarthritis Outcome Score (KOOS), X ray, MRI, and soluble urine and blood biomarkers.
Results:
TG-C was associated with statistically significant improvement over placebo in the total IKDC score and individual categories, and in the VAS score at 26, 39, and 52 weeks. WOMAC and KOOS scores also improved with TG-C over placebo. Patients treated with TG-C showed trends directed towards thicker cartilage and slower growing rates of subchondral bone surface area in the medial tibia, lateral tibia, lateral patella, and lateral patella femoral regions, although not statistically significant (P > 0.05). Serum CTX-I and urine CTX II levels showed lower over 1 year in TG-C than placebo treated patients with CTX-I level reaching statistical significance. These tendencies supported TG-C as holding a great potential for disease-modifying osteoarthritis drug. The most frequent adverse events in the TG-C group were peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%).
Conclusions:
TG-C was associated with statistically significant improvements in functions and pain in patients with knee osteoarthritis. The unexpected adverse events were not observed.
Trial registration:
clinicaltrials.gov NCT02072070 and CRiS: KCT0001112.
Objectives: To explore the relative efficacy of oral pharmacologic interventions in the treatment of knee OA.
Methods: A systematic literature review was conducted using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases to identify trials conducted in patients with knee OA with a minimum 6 weeks of follow-up. The standardized mean differences of the change from baseline to week 6 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain between the treatment groups were estimated using Bayesian random-effects network meta-analyses. Subgroup analyses of baseline pain status (high, pain score ≥ 60 mm; low, pain score < 60 mm) were performed.
Results: Of 4,067 manuscripts, 44 were included in the evidence synthesis. Etoricoxib had the highest ranking for improving WOMAC pain (probability of being top ranked, P (best)=0.43) followed by naproxen (P (best)=0.12), acetaminophen (P (best)=0.04), and celecoxib (P (best)=0.02). The top 3 ranked interventions were etoricoxib, celecoxib, and aceclofenac in the higher pain group, and tramadol, celecoxib, and diclofenac in the lower pain group.
Conclusions: In the overall analysis, etoricoxib, celecoxib, and aceclofenac had the highest rankings for improving WOMAC pain. The ability to improve knee OA symptoms may differ depending on baseline pain and radiologic features.
Background:
Osteoarthritis (OA) is a debilitating disease resulting in substantial pain and functional limitations. A novel blood derivative has been developed to concentrate both growth factors and antagonists of inflammatory cytokines, with promising preliminary findings in terms of safety profile and clinical improvement.
Purpose:
To investigate if one intra-articular injection of autologous protein solution (APS) can reduce pain and improve function in patients affected by knee OA in a multicenter, randomized, double-blind, saline-controlled study.
Study design:
Randomized controlled trial; Level of evidence, 2.
Methods:
Forty-six patients with unilateral knee OA (Kellgren-Lawrence 2 or 3) were randomized into the APS group (n = 31), which received a single ultrasound-guided injection of APS, and the saline (control) group (n = 15), which received a single saline injection. Patient-reported outcomes and adverse events were collected at 2 weeks and at 1, 3, 6, and 12 months through visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee injury and Osteoarthritis Outcome Score (KOOS), Short Form-36 (SF-36), Clinical Global Impression of Severity/Change (CGI-S/C), Patient Global Impression of Severity/Change (PGI-S/C), and Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder rate. Imaging evaluation was also performed with radiograph and magnetic resonance imaging (MRI) before and after treatment (12 months and 3 and 12 months, respectively).
Results:
The safety profile was positive, with no significant differences in frequency and severity of adverse events between groups. The improvement from baseline to 2 weeks and to 1, 3, and 6 months was similar between treatments. At 12 months, improvement in WOMAC pain score was 65% in the APS group and 41% in the saline group ( P = .02). There were no significant differences in VAS pain improvement between groups. At 12 months, APS group showed improved SF-36 Bodily Pain subscale ( P = .0085) and Role Emotional Health subscale ( P = .0410), as well as CGI-C values ( P = .01) compared with saline control. Significant differences between groups were detected in change from baseline to 12 months in bone marrow lesion size as assessed on MRI and osteophytes in the central zone of the lateral femoral condyle, both in favor of the APS group ( P = .041 and P = .032, respectively). There were no significant differences between APS and control groups in other measured secondary endpoints.
Conclusion:
This study provides evidence to support the safety and clinical improvement at 1-year follow-up of a single intra-articular injection of APS in patients affected by knee OA. Treatment with APS or a saline injection provided significant pain relief over the course of the study with differences becoming apparent at between 6 and 12 months after treatment.
Trial registration:
NCT02138890.
Objective:
To assess the efficacy of viscosupplementation (HA) in hip osteoarthritis (OA) pain, disability and adverse events.
Data sources:
Pubmed, EMBASE, Cochrane Library, ClinicalTrials.gov database and specific journals up to March 2017.
Study selection:
Randomized controlled trials comparing HA with any other intra-articular injection.
Data extraction:
Performed according to Cochrane/GRADE criteria. Two authors extracted data, assessed risk of bias and quality of evidence. Random-effects meta-analysis was conducted. Protocol registered on PROSPERO under CRD42015017312 DATA SYNTHESIS: Eight RCTs were retrieved (n=807): four comparing HA to placebo (PBO); three with platelet-rich plasma (PRP), three with methylprednisolone (MPA), and one mepivacaine (MPV). Some RCTs had three arms. There is VERY LOW evidence that HA is not superior to PBO in pain at 3 months (SMD=-0.06 [95% CI -0.38; 0.25], p=0.69), and HIGH evidence that is not superior in adverse events (RR=1.21 [95%CI 0.79; 1.86], p=0.38). There is LOW evidence that HA is not superior to PRP for pain at 1 month. There is VERY LOW evidence that HA is not superior to PRP for pain at 6 and 12 months (mean difference in VAS in cm= -0.05 [95%CI -0.81, 0.71]; 1.0 [95%CI -1.5, 3.50]; 0.81 [95%CI -1.11, 2.73], respectively). There is HIGH evidence that HA is no different from MPA for pain at 1 month (SMD=0.02 [95% CI -0.18; 0.22], p=0.85). There is LOW evidence HA is no different from MPA for OMERACT-OARSI responders index at 1 month (RR=0.44 [95%CI 0.10; 1.95], p=0.28; There is HIGH evidence HA is no different from MPA for adverse events (RR=1.21 [95%CI 0.79; 1.87], p=0.38).
Conclusions:
We do not recommend viscosupplementation for hip OA. Compared to placebo, data shows scarce evidence of its efficacy up to 3 months, and suggests no difference at 6 months. However, future RCTs could present HA as an alternative to MPA for short-term symptom relief.
Objective:
Aim of this trial was to compare efficacy of activated platelet-rich plasma against hyaluronic acid as intra-articular injections to people with osteoarthritis of the knee.
Design:
Phase-2 randomized controlled trial, with blind patients and outcome assessors.
Setting:
Outpatient rehabilitation service; years 2011-2013.
Subjects:
Patients with knee osteoarthritis grades 2-3 at magnetic resonance imaging (MRI) were included after consent and randomized. Target sample size was 25 patients per group.
Interventions:
Patients received three activated platelet-rich plasma (intervention group) or hyaluronic acid (controls) intra-articular injections at 4-week intervals.
Main measures:
Main outcome measure was proportion of patients with >1 grade improvement at six months from last injection, as assessed by a radiologist blind to study group. Patients were evaluated over time clinically and with functional scales (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm, Tegner, American Knee Society Score (AKSS), Lequesne, visual analogue scale (VAS) for pain).
Results:
Overall, 30 patients were randomized to intervention and 28 to control group. For primary outcome, 28 patients (29 knees) in the intervention and 22 (25 knees) in the control group were available. Patients with at least 1 grade improvement at repeat MRI were 14 (48.3%) in the intervention and 2 (8%) in the control group ( P < 0.003). Improvement in symptoms and functional scales was consistently higher in the intervention group. No side-effects were observed in either group.
Conclusion:
Activated platelet-rich plasma reduces articular damage as evident at MRI, as soon as six months after treatment; it reduces pain and improves patient's function and overall quality of life.
Background
Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis pain in a network meta-analysis.
Methods
For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose–response relation, we used preparation-specific covariates assuming linearity on log relative dose.
Findings
We identified 8973 manuscripts from our search, of which 76 randomised trials with a total of 58 451 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] −0·37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES −0·57, 95% credibility interval [CrI] −0·69 to −0·45) and etoricoxib 60 mg/day (ES −0·58, −0·74 to −0·43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for naproxen (p=0·034). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis.
Interpretation
On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients.
Funding
Swiss National Science Foundation (grant number 405340-104762) and Arco Foundation, Switzerland.
Objective
To systematically review and synthesize the effect of soft braces on pain, and self-reported and performance-based physical function in patients with knee osteoarthritis.
Data sources
The following electronic databases were searched from inception to April 20, 2016: The Cochrane Central Registry for Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, SportDiscuss, Web of Science and PEDro.
Study selection
Randomized controlled trials (RCT) and non-randomized controlled trials (non-RCTs), such as controlled clinical trials, crossover studies and case-control studies were included. Two reviewers independently screened articles and determined inclusion through predefined criteria.
Data extraction
Data related to participant demographics, study design, and methods, interventions, and outcomes, including numerical means and SDs, were extracted by one reviewer. Methodological quality assessment was independently performed by two reviewers.
Data synthesis
11 studies were identified, including six randomized controlled trials (RCTs) and five non-RCTs. The methodological quality of included RCTs was low. There was a moderate improvement in pain (SMD 0.52, 95% CI 0.14 to 0.89; P=0.007; 284 participants) in favor of wearing a brace compared to not wearing a brace for the immediate, within-group comparison. There was a moderate improvement in pain (SMD 0.61, 95% CI 0.33 to 0.89; P<0.001; 206 participants) and small to moderate improvement in self-reported physical function (SMD 0.39, 95% CI 0.11 to 0.67; P=0.006; 206 participants) in favor of patients receiving soft brace versus standard care for the prolonged effect, between-group comparison.
Conclusion
Currently available evidence indicates that soft braces have moderate effects on pain and small to moderate effects on self-reported physical function in knee osteoarthritis. These findings highlight the importance of soft braces as a technique to improve pain and physical function in both, short and long-term. Further, high quality studies are warranted to improve confidence in the findings.
Objective:
A meta analysis to compare efficacy and safety of intraarticular hyaluronic acid (HA) and intraarticular corticosteroids (CS) in patients with knee osteoarthritis.
Method:
Potential studies were searched from the electronic databases included PubMed,Embase,web of science and the Cochrane Library up to August 2016.High quality randomized controlled trials(RCTs) were selected based on inclusion criteria.RevMan 5.3 were used for the meta-analysis.
Results:
12 RCTs containing 1794 patients meet the inclusion criteria.Visual analog scale(VAS) score in CS group decrease more than HA group up to 1 month (p=0.03) and it shows equal efficacy at 3 months (p=0.29);HA is more effective than CS at 6 months (p=0.006).To Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) score,there is no significant difference for two groups at 3 months (p=0.29);HA shows greater relative effect than CS at 6 months (p=0.005).No significant difference is found on proportion of rescue medication use after initiation of treatment (p=0.58)and proportion of withdrawal for knee pain (p=0.54).HA and CS exhibit equal efficacy on improvement of active range of knee flexion at 3 months (p=0.73) and 6 months (p=0.43).More topical adverse effects occurred in intraarticular HA group when compared with intraarticular CS group.
Conclusion:
Intraarticular CS is more effective on pain relief than intraarticular HA in short term (up to 1 month),while HA is more effective in long term (up to 6 months).Two therapies benefit similarly for knee function improvement.Both two methods are relatively safe,but intraarticular HA causes more topical adverse effects compared with intraarticular CS.
Objective
To investigate whether simultaneous telephone coaching improves the clinical effectiveness of a physiotherapist-prescribed home-based physical activity program for knee osteoarthritis (OA). MethodsA total of 168 inactive adults ages 50 years with knee pain on a numeric rating scale 4 (NRS; range 0-10) and knee OA were recruited from the community and randomly assigned to a physiotherapy (PT) and coaching group (n=84) or PT-only (n=84) group. All participants received five 30-minute consultations with a physiotherapist over 6 months for education, home exercise, and physical activity advice. PT+coaching participants also received 6-12 telephone coaching sessions by clinicians trained in behavioral-change support for exercise and physical activity. Primary outcomes were pain (NRS) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC; score range 0-68]) at 6 months. Secondary outcomes were these same measures at 12 and 18 months, as well as physical activity, exercise adherence, other pain and function measures, and quality of life. Analyses were intent-to-treat with multiple imputation for missing data. ResultsA total of 142 (85%), 136 (81%), and 128 (76%) participants completed 6-, 12-, and 18-month measurements, respectively. The change in NRS pain (mean difference 0.4 unit [95% confidence interval (95% CI) -0.4, 1.3]) and in WOMAC function (1.8 [95% CI -1.9, 5.5]) did not differ between groups at 6 months, with both groups showing clinically relevant improvements. Some secondary outcomes related to physical activity and exercise behavior favored PT+coaching at 6 months but generally not at 12 or 18 months. There were no between-group differences in most other outcomes. Conclusion
The addition of simultaneous telephone coaching did not augment the pain and function benefits of a physiotherapist-prescribed home-based physical activity program.
This study was conducted to investigate the safety and efficacy of 3 intraarticular injections of the low-molecular-weight fraction of 5% human serum albumin (LMWF-5A) administered every 2 weeks for knee pain as a result of osteoarthritis. This single-center, randomized, vehicle-controlled, double-blind, phase II study was designed to ensure the safety of multiple intra-articular injections of LMWF-5A and to explore its efficacy in reducing pain as a result of knee osteoarthritis. Patients were randomized 1:1 to receive 3 biweekly intra-articular knee injections of either 4 mL LMWF-5A or vehicle control (saline), administered at weeks 0 (baseline), 2, and 4. Safety was examined as the incidence and severity of adverse events. Efficacy was assessed by the mean (SD) change between treatment groups in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 20. A total of 40 patients were randomized and received treatment. No drug-related serious adverse events and no deaths were reported. Adverse events were similar in patients who received saline (18, 90%) and LMWF-5A (19, 95%). Those treated with LMWF-5A had a significant decrease in pain at 20 weeks compared with the saline group (-1.41 [SD, 0.81] vs -0.85 [SD, 0.64], P=.02), corresponding to improvement in pain at week 20 of 64% with LMWF-5A compared with 40% with saline. This preliminary clinical trial showed that repeated intra-articular injections of LMWF-5A are safe when administered at 2-week intervals and are effective in providing relief of the pain of osteoarthritis of the knee at 20 weeks. [Orthopedics. 201x; xx(x):exx-exx.].
Background:
Male athletes participating in certain elite sporting activities may be at an increased risk for development of hip osteoarthritis (OA) later in life. However, the strength of the association of participation in sporting activities with the increased risk of hip OA has not been well summarized.
Purpose:
To investigate the association of certain high-impact sporting activities with the risk of development of hip OA in elite athletes by conducting a systematic review of the available literature.
Study design:
Systematic review; Level of evidence, 3.
Methods:
PubMed, Cochrane, and EMBASE databases were searched to identify all potential studies. Eleven studies met the inclusion criteria, which included participation in elite-level sporting activities, greater than 50% male athletes in the study population, diagnosis of hip OA by radiograph, hospital admission or total hip arthroplasty (THA), and greater than 80% follow-up. Exclusion criteria were recreational sporting activities, primarily female cohorts as there was a dearth of available literature on the topic, and self-reported symptoms without radiographic confirmation of diagnosis. Most studies were with European athletes, where elite-level was defined as involvement in national- or professional-level competition.
Results:
Participation across elite-level impact sports was associated with increased risk of development of hip OA when compared with matched controls (odds ratio, 1.8-8.7). Twelve of 15 studies reviewed demonstrated an odds ratio of 1.8 or greater of developing hip OA in elite-level athletes. Handball was associated with the highest rate of OA of any sport, nearly 5 times that of matched controls. Soccer players demonstrated between 2 and 9 times increased risk of hip OA as defined by radiography or THA. Hockey players demonstrated 2 to 3 times increased risk of hip OA (THA or hospital admission). Five studies investigating the association of competitive long-distance running with hip OA demonstrated inconsistent results.
Conclusion:
Currently available literature suggests that male athletes participating in elite impact sports (soccer, handball, track and field, or hockey) are at an increased risk of developing hip OA, while those participating in high-level long-distance running do not have a clearly elevated risk. Further research is warranted to elucidate the pathomechanics of development of hip OA in these patients.
Objective:
International guidelines recommend intra-articular steroid injections (IASI) in the management of hip osteoarthritis (OA), though these recommendations are extrapolated primarily from studies of knee OA. The aim of this systematic review was to assess the efficacy of IASI on pain in hip OA.
Methods:
MEDLINE, EMBASE, AMED, CINAHL Plus, Web of Science and the Cochrane Central Register of Controlled Trials were searched to May 2015. RCTs assessing the efficacy of hip IASI on pain were included. Pre-specified data was extracted using a standardised form. Quality was assessed using the Jadad score.
Results:
Five trials met the inclusion criteria. All had a small number of participants (≤101). All studies reported some reduction in pain at 3-4 weeks post-injection compared to control. Based on data from individual trials the treatment effect size was large at 1 week post-injection but declined thereafter. A significant (moderate effect size) reduction in pain was reported in 2 trials up to 8 weeks following IASI. Pooled results of 2 trials (N=90) showed an increased likelihood of meeting the OMERACT-OARSI response criteria at 8 weeks post-IASI, odds ratio 7.8 (95% CI 2.7-22.8). The number needed to treat to achieve one OMERACT-OARSI responder at 8 weeks post-injection was 2.4 (95% CI 1.7-4.2). Hip IASI appear to be generally well tolerated.
Conclusions:
Hip IASI may be efficacious in short term pain reduction in those with hip OA though the quality of the evidence was relatively poor. Further large, methodologically rigorous trials are required to verify whether intra-articular corticosteroids are beneficial and for how long.
Objectives
Chronic osteoarthritis of knee is very commonly encountered in clinical practice. Pain relief and restoration of physical function are the targets of therapy. This study aims to compare the efficacy and safety of tapentadol with etoricoxib in the management of osteoarthritis of knee.
Methods
This is a randomised, open labelled, controlled study in which patients received either tablet tapentadol (100 mg twice daily) or etoricoxib (30 mg twice daily) for 12 weeks. Follow-up was done after 2nd, 4th, 8th and 12th weeks of initiation of treatment and also after 2 weeks of treatment completion. Assessment of improvement in pain perception on Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) sub-score for stiffness and physical function were performed.
Results
108 patients receiving tapentadol and 110 patients receiving etoricoixb were analysed on Intention to Treat basis. Steady improvement was seen in VAS and WOMAC scores in both the groups, though there was no significant difference between the groups. Clinical Global Impression measured by physician showed significant difference between groups with greater number of patients experiencing at least satisfactory response at the end of the study in the tapentadol group (p = 0.036). The total number of adverse events was less with tapentadol than etoricoxib.
Conclusions
Tapentadol is as effective as etoricoxib in the management of mild to moderate grades of chronic osteoarthritis of knee with lower incidences of adverse effects.
Aim:
To explore the effects of exercise (water-based or land-based) and/or manual therapies on pain in adults with clinically and/or radiographically diagnosed hip osteoarthritis (OA).
Methods:
A systematic review and meta-analysis was performed, with patient reported pain assessed using a visual analogue scale (VAS) or the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Data were grouped by follow-up time (0-3 months=short term; 4-12 months=medium term and; >12 months=long term), and standardised mean differences (SMD) with 95% CIs were used to establish intervention effect sizes. Study quality was assessed using modified PEDro scores.
Results:
19 trials were included. Four studies showed short-term benefits favouring water-based exercise over minimal control using the WOMAC pain subscale (SMD -0.53, 95% CI -0.96 to -0.10). Six studies supported a short-term benefit of land-based exercise compared to minimal control on VAS assessed pain (SMD -0.49, 95% CI -0.70 to -0.29). There were no medium (SMD -0.23, 95% CI -0.48 to 0.03) or long (SMD -0.22, 95% CI -0.51 to 0.06) term benefits of exercise therapy, or benefit of combining exercise therapy with manual therapy (SMD -0.38, 95% CI -0.88 to 0.13) when compared to minimal control.
Conclusions:
Best available evidence indicates that exercise therapy (whether land-based or water-based) is more effective than minimal control in managing pain associated with hip OA in the short term. Larger high-quality RCTs are needed to establish the effectiveness of exercise and manual therapies in the medium and long term.