Effectiveness of Maitland and Mulligan mobilization methods for adults with knee osteoarthritis: A systematic review and meta-analysis

INTRODUCTION

Osteoarthritis (OA) is the most common type of arthritis, with 1 in 3 people over age 65 affected and a higher prevalence in women[1,2]. The knees are among the most commonly affected joints in OA[3,4]. Knee osteoarthritis (KOA) is characterized as pain, joint stiffness, functional impairment and even disability, contributing to a heavy burden on healthcare service[5,6]. Considering the severe socioeconomic burden, nonpharmacological, pharmacological and surgical approaches were applied[7]. Physical therapy has been known to play a vital role in pain relief and restoration of mobility and function in KOA patients[8]. Manual therapy is a widely used physical treatment for KOA[9]. Several studies have reported positive effects of manual physical therapy on KOA[9-11]. The American College of Rheumatology recommends the combination of manual therapy with exercise for KOA patients under the supervision of a physiotherapist[12]. Besides, for the patients with deficits in range of motion (ROM), manual therapy plays a role to restore or maximize ROM improvement before surgeries[13].

Maitland and Mulligan mobilization are two types of manual therapy used in OA treatment[14]. Mulligan mobilization allows the patients to perform the offending movements in a functional position, hence, leading to a rewarding outcome[15].Maitland mobilization aims to reestablish the spinning, gliding and rolling motions of the two joints[14]. In clinical practice, movement quality can be increasedimproving joint stability of weak muscles by applying Maitland mobilization combined with psychological effects (self-confidence and motivating factors) and corrected mechanical loading. Maitland and Mulligan mobilization therapies have been used to treat multiple diseases, such as primary adhesive capsulitis of the shoulder[16], hip osteoarthritis[17] and knee osteoarthritis[18]. As reported by previous studies, Maitland or Mulligan mobilizations were used by 99.8% of physical therapists to treat cervicogenic dizziness[19].

Recently, some reviews have found that the manual therapies might be effective and safe in ameliorating osteoarthritis symptoms[16,18,20]. A meta-analysis by Qinguang Xu[18] demonstrated that manual therapy effectively and safely alleviated pain,reduced stiffness and restored physical function in KOA patients, and thus it could be considered as a complementary and alternative option. In the studies on primary adhesive capsulitis of the shoulder, Noten[16] identified the efficacy of mobilization techniques. Although Maitland mobilization was recommended in these studies[16,20], there still was no systematic review and meta-analysis to compare the efficacy of different mobilization techniques, such as MaitlandMulligan mobilization. Therefore, this study used an evidence-based method to determine the efficacy of Maitland and Mulligan mobilization methods in adults with KOA.

MATERIALS AND METHODS

This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA)[21] and the Cochrane Collaboration Handbook[22]. The protocol of this systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews(PROSPERO: CRD42020182532) on April 28, 2020.

质量标准的制定应考虑日常检验的经济适用性，不能一味地求全、求新。目前，有些标准过于复杂，应研究方法简化标准，如一测多评、一标多测方法。标准起草完成后，应征求企业意见，既要注重保证药品安全性与检测方法的专属性和灵敏度相结合，还要注意环保，尽量不使用毒性较大的试剂，并进行耐用性考察，提高标准的经济和实用性、避繁就简、绿色检验。

Information sources

Two reviewers performed literature search individually in the following electronic databases: PubMed, The Cochrane Library, Web of Science, Embase and Google Scholar, from the time of inception to September 20, 2020. We also reviewed the reference lists of relevant reviews and meta-analyses[23,24].

紫玉兰的分布信息主要来源于标本数据库的搜索、相关文献记载。通过查询中国数字植物标本馆(http://www.cvh.org.cn/)、中国自然标本馆(http://www.cfh.ac.cn/)和全球生物多样性信息网(http://www.gbif.org/)，分别获得501条、2487条、134条信息。结合文献资料记载，排除错误鉴定、人工引种及信息模糊不清的标本，最终获得紫玉兰39个自然分布点，其地理位置信息落实到乡镇行政单位。利用Google Earth卫星图拾取39个分布点的经纬度。

由于温度变量没有明确的界限,因此其分类可以通过模糊集理论的软划分来实现。根据温度变量的相似度或亲疏性质,模糊聚类分析通过模糊相似关系来实现温度变量的分类。为了使处理过程简单直观,一般将相似关系转化为模糊矩阵,然后进行模糊聚类分析。

电位传感技术是利用离子选择性电极的电位随溶液中被测离子含量不同而变化的传感技术。这种传感技术，因选择性识别能力强、测量参数单一、易于小型甚至芯片化和应用范围广等优点，成为最具有发展潜力的一种生物和化学传感技术[1]。但是，由于传统的离子选择性电极因受电极的选择性和灵敏度的限制，以及通常电极需要内充液而不易微型化，所以传统的电位传感技术在过去的一段时间发展缓慢。

国家能源局《特殊和稀缺煤类开发利用管理暂行规定》中明确要求特殊和稀缺煤类全部洗选，经洗选加工的优质特殊和稀缺煤类优先用于冶金、化工、材料等行业，限制直接燃烧。“十二五”期间要求单位国内生产总值CO2排放降低17%，COD、SO2排放分别减少8%。对于选煤厂来说，节能减排意味着减少浪费，节约成本，更有利于煤炭行业的健康、持续发展。

Search strategy

July 9, 2021

Eligibility criteria

Trials were considered eligible if the following items were met: (1) Adult patients with KOA at any stage according to Kellgren and Lawrence grading system; (2) Containing data about Maitland joint mobilization or mobilization with movement technique with or without other interventions; (3) Reporting pain, range of motion, functional performance/ability or other relevant outcomes; and (4) Controlled clinical trials.

Since our aim was to explore the different efficacy of these two techniques in ROM,pain and functional performance in KOA, some experiments containing the combination of joint mobilization (Maitland or Mulligan) with other common treatments were also included, as long as they mainly focused on assessing the effect of these two types of joint mobilization methods.

Study selection

Two independent reviewers (Li LL, Hu XJ) removed duplication, screened titles,abstracts and full texts and agreed on the final eligibility. Negotiation was required when there was disagreement[25]. We recorded the reasons for exclusion of full texts.

Data collection process and data items

Two independent reviewers (Li LL, Di YH) extracted the data from included articles using a pre-designed form, including the following parameters: Author’s name,publication year, sample size, study design, type/frequency/duration of the intervention and outcome assessment. Any disagreements were discussed and resolved by the two authors.

Risk of bias in individual studies

The quality of the included articles was assessed by two reviewers individually using PEDro scale. The results given by the two reviewers were compared and any disagreements were resolved by all three authors. The PEDro scale is based on the Delphi list and reported to be reliable for randomized controlled trials (RCTs) of physical therapy in systematic reviews. The PEDro scale consists of 11 items,including: (1) Specified eligibility criteria of studies; (2) Random allocation of studies;(3) Concealed allocation; (4) Similarity between groups at baseline; (5) Blinding of all subjects; (6) Blinding of all therapists; (7) blinding of all assessors; (8) Less than 15%dropouts; (9) Intention-to-treat analysis; (10) statistical comparisons between groups;and (11) Point measures and variability data. PEDro score was calculated by assessing the items 2-11. Each item was scored as either 1 or 0 according to whether the item was met or not, respectively. The total score of the scale is 10. Articles were classified into three distinct categories, including high (7-10), moderate (4-6) and low (0-3) quality.

Statistical analysis

All data were analyzed by using Cochrane Collaboration software (Review Manager Version 5.2 for Windows). Only continuous variables (range of motion, pain, function scale) were identified, therefore, the difference in means between the intervention groups with 95% confidence intervals (CI) was used as the main summary measures to determine the effect size of the results[26]. The final value and the standard deviation of the results were recorded as well as the number of patients in each treatment group at the last time of the follow-up. To evaluate the heterogeneity of the included studies,the chi² statistical test andstatistic were performed. The extent of heterogeneity was measured by theIstatistical test and presented as the total percentage of variation between the studies. Thevalue was considered low ifwas 0%-25%, moderate ifwas 25%-50% and high ifwas 50%-90%. A random effect model was employed if the heterogeneity was relatively high. Conversely, in case of low heterogeneity, a fixed effect model was used to analyze the data with inverse variance weighting[27].Sensitivity analysis was conducted to identify the potential sources of high heterogeneity[28]. The statistical significance was assessed by using the Z index of overall effects[27]. Funnel plots was used to assess potential publication biases. If the included trials were < 10, we did not test for publication bias[29].

RESULTS

A total of 341 articles were screened from five electronic databases. After removing 333 articles, of which 125 were duplicates, 206 articles were screened out through title and abstract review, 10 articles were still for further consideration. After excluding two studies, eight trials involving 471 subjects were included in the present systematic review and meta-analysis (the reasons for their exclusion were given in Figure 1).

Characteristics of included studies

The characteristics regarding the study population, intervention, follow-up period and main results of the studies are presented in Table 1.

翌日上午取回采样纸，用工业显微镜把附着药液的1.2mm2试纸放大160倍，读入计算机中，利用图像处理技术统计上面的雾滴的粒数和当量粒径；再利用Excel软件统计和计算平均粒径的大小及粒数[3]。由于雾滴在采样纸上的痕迹大致为圆形，应校正为球体直径，按下列公式计算，即

Risk of bias

For ROM, Mulligan mobilization might have the same efficacy as Maitland mobilization. Mulligan and Maitland mobilization, as two kinds of manual therapies,have been found to improve the mechanical loading, joint stability and strength of weak muscles through mechanical, self-confidence and motivating factors. In a cohort study, KOA patients received a manual physical therapy program focusing on passive extension mobilization of the knee, and the restoration effects in Mulligan mobilization group was not better than that in the exercise group[38]. In another study, ROM in Mulligan mobilization was improved in the long term[33]. According to the studies by Stathopoulos[17], Mulligan mobilization could only ameliorate joint dysfunctions of the upper and lower extremities and facilitated the immediate recovery of full and pain-free ROM. However, no studies have focused on the treatment period and the site of arthritis. In our study, we focused on the ROM of knees and included studies with various treatment periods. Besides, the high heterogeneity might decrease the reliabilities of the results. Further study and follow-ups will be needed to validate the conclusion.

Pain

Seven studies[14,15,30-34] with continuous data on pain degree were included in the meta-analysis, with a total of 354 participants. Five studies[14,15,30,31,33] reported the severity of pain using visual analogue scale, while the other two studies[32,34]adopted another Numeric Pain Rating Scale. The Numeric Pain Rating Scale is a segmented numeric version of the visual analogue scale, and both scales use a horizontal bar or line to rate the degree of pain. Thus, these two scales could be considered as the same. According to the forest plot (Figure 2), the pooled standardized mean difference (SMD) was 0.60 (SMD = 0.60; 95%CI: 0.17 to 1.03;=0.007).

ROM

Data were collected from five studies[14,30,31,33,35] with continuous data containing a total population of 204 participants. According to the forest plot (Figure 3), random effect model showed that there was no difference in the effect of the two mobilization methods on improving ROM (SMD = 9.63; 95%CI: -1.23 to 20.48;= 0.08).

Western Ontario and McMaster Universities (WOMAC) function score

Six studies, with 297 participants, reported WOMAC function score[14,15,31-33,35],and one study[14] reported WOMAC function and pain score. According to the forestplot (Figure 4), Mulligan dynamic joint mobilization was more effective in improving the WOMAC function score of patients with knee arthritis. (SMD = 7.41; 95%CI: 2.36 to 12.47;= 0.004).

Publication bias

The analysis of the funnel plot for publication bias suggested the absence of bias because of plot symmetry (Figure 5).

DISCUSSION

Summary of evidence

In this systematic review and meta-analysis of eight randomized controlled trials including 471 KOA patients, Mulligan mobilization was found to be a promising alternative option for KOA treatment. Particularly, the Mulligan mobilization has been recommended to be applied in alleviating pain and improving WOMAC function score. Because of the poor methodological quality of included studies, more studies are needed to assess the effect of manual therapies on pain, WOMAC function score and ROM.

Unsolicited article; Externally peer reviewed.

All the articles included were assessed with the PEDro Scale (Table 2). The total score of methodological quality varied from 5 to 10 out of 11. The score of most studies exceeded the cut-off point 6, but only two studies scored 9. Many studies missed points on blinding of patients[14,15,30-32], therapists[14,15,30-34] and assessors[14,15,30,32]. In addition, there was often a lack of the concealment of allocation. These are shortcomings for RCTs.

Overall, KOA is regarded as a complex disorder with multiple risk factors, such as generalized constitutional factors (age, female sex,)[39] and local adverse mechanical factors (trauma, malalignment,.)[40]. Confined to the current evidence,we did not limit sex, age, body weight or even history, which may influence the representativeness and application of conclusions. In addition, it was found that the heterogeneity of most included RCTs was high. Thus, the positive effects of the Mulligan mobilization should be interpreted with caution. Finally, because manual therapies require hands-on treatments, it is not possible to perform the study in a blinded way, resulting in the poor score on the PEDro Scale. In the future clinical trials, attention should be paid to all the points above in study design.

Strengths and limitations

Our research has several strengths. First, as far as we are aware, this is the first systematic review and meta-analysis aiming to determine the efficacy of MaitlandMulligan mobilization with movement in KOA patients. Secondly, this meta-analysis included as many relevant outcomes as possible and was completed according to the accepted guideline[41]. Thus, the results were relatively comprehensive.

However, similar to other meta-analyses, there were also limitations[42]. Firstly,since not all the grey literature could be searched, some studies might have been missed[43]. This may be negligible with comprehensive and reliable research strategy.Secondly, the sample size in this review might not be enough, which could affect the quality of evidence. Thirdly, due to less than 10 included studies, interpretation of publication bias assessment should be done with caution[29]. Finally, we did not report the cost due to the lack of data. Thus, more RCTs should be conducted,including novel interventions, and more data on adverse effects (AEs) safety will be of necessity.

变压器油化验中，由于对应变压器油的应用中存在着很多的影响因素，通过对变压器油的物理性能检测分析，能够衡量出变压器油应用是否存在着缺陷性。一般情况下，变压器油在应用过程中，其初始油颜色为淡黄色，随着变压器应用的时间逐渐增长，其对应的油体颜色也会出现新的变化，按照变压器油应用的时间变化其油体颜色会逐渐加深，这是由于变压器应用中，其对应的油体出现了老化现象，并且生成了二氧化碳和杂质，造成了整体的变压器油应用质量下降，影响最终的变压器油应用效果。因此，在进行变压器油的化验过程中，对应的化验人员及时地按照变压器油化验的物理性能变化将其物理性能上的影响处理好，降低变压器油应用的故障。

CONCLUSION

Mulligan joint mobilization is a promising intervention with the potential to improve the pain and joint function for patients with KOA. Based on real-world and other epidemiological settings, more data and surveillance will be necessary to identify the efficacy. Also, further studies are necessary to explore the cost of KOA in other ethnicities.

Our meta-analysis revealed that Mulligan mobilization will be a promising alternative option for KOA treatment. Unfortunately, because of the poor methodological quality of included studies, more data and surveillance will be necessary to identify the efficacy. Also, further studies are needed to explore the cost of KOA in other ethnicities.

The Mulligan mobilization has been recommended to be applied in alleviating pain and improving Western Ontario and McMaster Universities function score.

课程创新以创造性实践活动为落脚点，而创造性实践活动的成效一方面有赖于创造性思维水平，另一方面取决于创造性实践能力。因此，应用型本科院校实施课程创新，不仅要关注师生创造性思维的训练，而且要重视师生创新实践能力的培养。由于能力形成、发展于活动之中，故应用型本科院校一方面要鼓励和支持教师从事创新实践活动，另一方面要组织学生开展创新实践活动。

We would like to thank all authors of the included primary studies.