### *2.2. Selection of Studies and Inclusion Criteria*

All those studies that met the search phrase were considered, and only those that met the following inclusion criteria were selected: (a) Country: interventions developed in countries belonging to Latin America; (b) Sample: people over 60 years of age; (c) Language: English, Spanish and Portuguese; (d) Methodological Design: Randomized controlled clinical trial. No reviews, editorial documents, protocols, or thesis were included. The articles selected by title and abstract had to meet the conditions indicated in Table 1.

### **Table 1.** Inclusion criteria of the studies.

### *2.3. Data Extraction*

Duplicate articles were removed from the databases using Mendeley. Articles that met the inclusion criteria were selected, and when decisions could not be made considering only the title and abstract of the article, the full text was retrieved (Figure 1). A standardized questionnaire was used and applied by the authors to extract the data from the included articles, to synthesize the evidence. The information extracted included: (a) general characteristics of the studies and of the participants (author, year, initial and final sample, adherence, reasons for withdrawal, age range, sex, health condition, recruitment and place of intervention, (b) main characteristics of the interventions based on physical activity and exercise (duration of the intervention, number of sessions per week, time of the session, responsible professional, type of intervention and components of physical fitness addressed and the time allocated to each one of them); (c) main variables evaluated (physical health, mental health and cognitive abilities); (d) main assessment instruments used (physical health, mental health and cognitive abilities).

**Figure 1.** Literature search Flow chart. \* Whole search strings for all databases are presented in the supplementary material (Table S2).

### *2.4. Risk of Bias Assessment Tool and Consensus on Exercise Reporting Template (CERT) Assessment Form*

The Cochrane "Cochrane Manual of Systematic Reviews of Interventions" tool [38] was used to assess the methodological validity of the studies included in this review, evaluating the risk of bias in each of the items proposed by this manual, detailed as follows: (a) Selection bias, (b) Performance bias, (c) Detection bias, (d) Attrition bias and (e) Reporting bias. Only the item: "Other biases" was not considered. The results of this analysis are presented in Figure 2. In addition, the Consensus on Exercise Reporting Template (CERT) assessment form was added to know the proportion of articles that met the CERT items [39] (Table S3).

### *2.5. Strategy for Data Synthesis*

A synthesis of the main findings of the included studies is provided, related to the interventions developed based on PE for OAs in Latin America. The main information is presented in summary tables. In addition, in the discussion, the most relevant methodological and applicability aspects are analyzed and some suggestions are given for future research, in order to standardize the application of this methodology.

## **3. Results**

### *3.1. Literature Search*

Figure 1 shows the flow chart of systematic reviews proposed by the PRISMA statement. 4.642 potential studies on PA and exercise in OAs in Latin America were identified. After the exclusion of the duplicates in the databases, the screening and eligibility criteria were applied. Finally, for data synthesis, 101 articles were included [40–140] (Figure 1).

### *3.2. General Characteristics of the Studies*

A total of 101 articles were included, of these, 91 were from Brazil, five from Chile, two Colombia, two Mexico and one from Ecuador. The number of participants at the beginning of the studies was 5013 and 4334 at the end (79% women and 21% men), presenting a compliance with the interventions of 86%. Only 35% of the studies had 100% adherence. Three quarters of the studies suffered losses in their sample, the main reasons for withdrawal being categorized as follows: attendance, does not meet the criteria of the study and personal reasons, the latter being the one that was repeated the most (78%). Furthermore, in 15% of the cases the reason for withdrawal was not specified. Regarding the age range, 97% of the studies included participants between 60 and 70 years, 83% between 71 and 80 years, and only 16% included participants older than 80 years. The health condition with the highest prevalence was cardiometabolic diseases. Just over half (58%) of the OAs resided in the community and 44% of the studies detailed information regarding the place of intervention; of these studies, 61% of the interventions occurred at university facilities (Table 2).

[100] Vargas M. (2019) Ecuador 50/50 100 1 30 70 1 1

**Table 2.** Characteristics of the articles.

*Int. J. Environ. Res. Public Health* **2021**, *18*, 2812

criterion of the study. Recruitment: COM, Community; HC, Health center; INST, Institutionalized. Place of intervention: HC, Health center; SC, Sports center; UC, University center.

#### *3.3. Assessment of Risk of Bias and CERT Compliance Level*

The risk of bias of the studies was assessed using the Cochrane 'Cochrane Handbook for Systematic Reviews of experimental study interventions' tool. The risk of bias was included for each of the items proposed by the manual, excluding the item "other biases". It was observed that the distribution of biases classified as unclear risk or high risk was similar between the items selection bias, detection bias and attrition bias (40–60% of the studies). However, it was observed that 95% of the studies had unclear risk and high risk of performance bias, and 100% of the studies had low risk of reporting bias (Figure 2).

Nine out of nineteen items compliant (rated "yes" on the CERT items) in at least 75% of the articles (C1 = 90%, C3 = 100%, C4 = 100%, C5 = 93%, C7b = 100%, C10 = 100%, C13 = 100%, C14a = 100%, C16a = 93%). The items categories with the highest level of compliance were those included in the materials (one item, C1 = 90%) and dosage (one item, C13 = 90%) categories. In contrast, the items categories with the lowest level of compliance were those related to the delivery (ten items, C6 = 5%, C7a = 50%, C8 = 21%, C9 = 0% and C11 = 41%) and location (one item, C12 = 40%) categories (Table S3).

### *3.4. Main Characteristics of the Interventions*

95% of the articles had interventions with a duration of 2 to 6 months, 2% less than 2 months and 3% more than 9 months. 95% had a session frequency of 2 or 3 times a week. The sessions had a duration that varied between 30 and 60 min in 93.8% of the articles, taking into account that 20.8% of the studies did not specify this information. In 51% of the studies the sessions were led by physical activity qualified professionals, such as physical education teachers or personal trainers, while 14% of the studies presented interventions led by a health professional, most of whom were a physiotherapist. 35% of the studies did not specify this information. Regarding the training modality, 89% of the studies included interventions based on therapeutic PE, 11% of the studies included interventions based on non-traditional physical disciplines such as Tai Chi, Pilates and dance, 7% included interventions based in exercise with digital support, known as Exergames, 5% included interventions based on exercise complemented with other interventions such as vibration and auriculotherapy and 2% included interventions based on water training, known as hydrogymnastics. Regarding the components of physical fitness addressed during the interventions, 77% of the studies included muscular strength, 47% cardiorespiratory fitness, 27% balance, 14% coordination, 12% flexibility, 7% gait and 5% proprioception. Furthermore, 48% of the studies included a warm-up stage and 34% of the studies included a cool-down stage (Table 3).

Additionally, the characteristics of multicomponent exercise were analyzed according to the components of physical fitness. Muscle strength was commonly exercised with 1 to 3 sets (61%), 8–15 repetitions (71%), and one-minute rest (18%).The intensity of the exercise was controlled with scales of perception of effort (30%) and multifunctional machines were used to train (65%). In relation to cardiorespiratory fitness, this was developed mainly on a treadmill (39%), for 20 min or more (61%). The intensity of the exercise was controlled through the heart rate (52%). With regard to flexibility, this was exercised through static stretching (25%) and was controlled through the time performed (42%), With regard to gait, coordination, and proprioception, these components of fitness were trained primarily through circuits (56%, 50% and 40, respectively).

### *3.5. Outcome Variables Analyzed*

Outcome variables were grouped and described in three broad categories: (a) physical health, (b) mental health and quality of life and (c) cognitive skills.

(a) Physical health: This category was considered in 100% of the studies and was divided into 10 outcome variables. Of these, the most evaluated was muscle strength (74 of the studies). The following most frequent were: nutritional status and diet, functionality, balance, gait and vital signs, blood tests and others (blood pressure, pain, dyspnea, heart rate variability and blood tests). The least evaluated was coordination (7 studies) (Figure 3a).

**Figure 3.** Variables of (**a**) physical health, (**b**) mental health and quality of life and (**c**) cognitive skills. The data are presented in absolute frequency. BBPE: Barriers and Benefits Perceived for the Execution of the Exercise.

interventions complemented with other interventions. Components and time of each intervention: WS: warm-up stage; CS: cool down stage; AER, Aerobic; STR, Strength; FL, Flexibility;

GAI: Gait; COO, Coordination; BAL, Balance; PRO, Proprioception.

### *3.6. Assessment Instruments Used*

The evaluations were grouped and described in three broad categories: (a) physical health, (b) mental health and quality of life, and (c) cognitive skills.

#### *3.7. Effects by Sex and Type of Intervention*

Regarding the effects of physical exercise interventions according to sex, in the physical health category, more than 50% of the articles with female-only samples presented significant effects in six of nine outcomes. More than 50% of the articles with male-only samples presented significant effects in four of seven outcomes, and more than 50% of the articles with mixed samples (both sexes) presented significant effects in three of nine outcome variables. In the mental health category, more than 50% of the articles with femaleonly samples presented significant effects in two of five outcomes. Articles with male-only samples did not include mental health outcome variables. More than 50% of the articles with mixed samples (both sexes) presented significant effects in four of six outcomes. Regarding the cognitive skills category, more than 50% of the articles with female-only samples presented significant effects in four of 10 outcomes. 100% of the articles with male-only samples presented significant effects in eight of eight outcome variables. More than 50% of the articles with mixed samples (both sexes) presented significant effects in five of 10 outcomes (Figure 5).

Regarding the effects according to the type of intervention, in the physical health category, more than 50% of the therapeutic physical exercise-based interventions presented significant effects in seven of nine outcomes. More than 50% of the hydrogymnasticsbased interventions had significant effects in three of six outcomes. More than 50% of the non-traditional physical disciplines-based interventions had significant effects in two of nine outcomes. More than 50% of the digitally supported exercise-based interventions had significant effects in one of nine outcomes. More than 50% of the exercise-based interventions complemented with other interventions had significant effects in two of five outcomes. Regarding the mental health category, more than 50% of therapeutic physical exercise-based interventions presented significant effects in six of nine outcomes. There was no hydrogymnastics-based intervention that evaluated mental health outcomes. More than 50% of the non-traditional physical disciplines-based interventions had significant effects in one of three outcomes. More than 50% of the digitally supported exercise-based interventions had significant effects in one of three outcomes and 100% of the exercise-based interventions complemented with other interventions had significant effects on fear of falling. Regarding the category of cognitive skills, more than 50% of the therapeutic physical exercise-based interventions presented significant effects in 11 of 12 outcomes. There was

no hydrogymnastics-based intervention that evaluated cognitive skills outcomes. More than 50% of the non-traditional physical disciplines-based interventions had significant effects in one of nine outcomes. 100% of the exercise-based interventions complemented with other interventions had significant effects in two of three outcomes (Figure 5).

**Figure 4.** Instruments for measuring (**a**) Physical Health variables. Strength: MR, Maximum repetition; DYN, Dynamometer. Flexibility: CHSR, Chair sit and reach; BS, Back Scratch. cardiorespiratory fitness: ERG. Ergospirometry; TM, Treadmill. Walk test: 6'WT, 6-min walk test; 10 mWT, 10-m walk test. Balance: O-Lss, One-legged stand test; BBS, Berg Balance Scale. Chair test: SST, Sit to Stand Test. Step Test: 2'ST, 2 min Step Test, SCT, Stair Climb Test Risk of falling: TUG, Time up and go; 8FG, 8-fit and go. Functionality: KI, Katz index; TEMPA, Test d'Evaluation des Membres Supérieurs de Personnes Âgées. Body composition: ANT. ME., Anthropometric measures; US, Ultrasound. (**b**) Mental health and quality of life variables. Sleep quality: PSQI, Pittsburgh Sleep Quality Index; ESS, Epworth sleepiness scale. Suspected depression: YGDS, Yesavage Geriatric Depression Scale; GDS, Geriatric Depression Scale. Quality of life: WHOQOL, The World Health Organization Quality of Life; HRQOL, Health Related Quality of Life. Others: FES-I, Falls Efficacy Scale International; EBBE, Exercise Benefits Barriers Scale. (**c**) Cognitive skills variables. Cognitive skills: MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment. Suspected dementia: WHODAS 2.0, World Health Organization Disability Assessment Schedule; CDR, Clinical Dementia Rating. The data are presented in absolute frequency.

**Figure 5.** Effects by sex and by type of intervention on the outcomes of physical health and quality of life, mental health and cognitive skills. The percentage of articles that present significant effects on each health outcome measures is shown. 0–25% red, 26–50% orange, 51–75% yellow, 76–100% green and white: no studies. Physical health Coor: Coordination, Fle: Flexibility, Aer: cardiorespiratory fitness, VBT: Vital signs, blood tests and others, Gai: Gait; Bal: Balance, Fun: Functionality, NS&D: Nutritional status and diet, MuS: Muscular strength. Mental health and quality of life: Beh: Behavior, Anx: Anxiety, EWB: Emotional well-being, SoF: Social functions, AfR: Affective response, BBPE: Barriers and Benefits Perceived for the Execution of the Exercise, FoF: Fear of falling, Dep: Depression, QoL: Quality of life. Cognitive skills Not S: Not specific, CogF: Cognitive flexibility, Plan: Planning, InhC: Inhibitory control, Orie: Orientation, Perc: Perception, ViO: Visuospatial orientation, ProS: Processing speed, Mem: Memory, Att: Attention, ExeF: Execution Function, Lang: Language.

## **4. Discussion**

The main results of this systematic review focused on five large areas: general characteristics, risk of bias and level of compliance with the CERT of the articles, characteristics of the interventions, outcome measures, and instruments used for their analysis. Its importance and possible implications are discussed below.

### *4.1. General Characteristics of the Articles Reviewed*

Regarding the geographic location, the interventions occurred in only five Latin American countries, most of them in Brazil. This could be associated with the fact that Brazil is the country with the largest population in Latin America, and the sixth in the world [141], being also one of the Latin American countries that invests the most in developing and publishing research in the area of biological and medical sciences [142,143]. Regarding the characteristics of OA, female participants predominated (79%), which is striking considering that South American population surveys position women as more physically inactive than men [144]. Adherence was higher than 80% in 75% of the studies, which suggests a high degree of commitment to this type of intervention and contrasts with the evidence that indicates that the practice of AP decreases over the years [145]. In addition, OAs were mainly recruited from the community and most of the interventions were carried out in university facilities, suggesting that OA living in the community are willing to participate in PE-related activities. This could motivate researchers to develop interventions that include more OAs as study subjects in future research. Although the evidence is clear that the benefits of PA and PE are independent of age and health status [11], it is interesting that only 16% of the studies included people over 80 years of age, which could be associated with the higher prevalence of comorbidities at that age [146]. This would generate a higher risk of unwanted side effects related to exercise, although if the training program is prescribed properly, the risk of side effects should be like those that occur in OAs below 80 years [9,10]. Regarding the health condition of the OAs, the comorbidities with the highest prevalence were neurodegenerative and cardiometabolic diseases, which is related to the increase in NCDs worldwide [13].

#### *4.2. Evaluation of the Methodological Quality of the Studies and CERT Compliance*

From the results found, it stands out that 95% of the studies presented unclear risk and high risk in performance bias. This point is relevant as it is related to the blinding of the study participants and staff, and although the Cochrane manual states that simply blinding does not ensure successful blinding, it also states that the lack of blinding in this item could produce a bias by affecting the results of the participants [39]. In any case, the predominant classification in this item was unclear risk, which is associated with a lack of information on this bias by the authors, rather than a possible bias in the results. On the contrary, 100% of the studies presented a low-risk classification in the reporting bias item. This could be due to the fact that all the studies had an experimental and randomized methodological design (RCT), which corresponds to the best level of evidence in quantitative studies. Only nine out of nineteen items compliant in at least 75% of the RTC analyzed. Furthermore, the items categories with the highest level of compliance were those included in the materials and dosage categories. Conversely, the item categories with the lowest level of compliance were those related to the delivery and location categories. Similar results on the level of compliance had already been observed in another systematic review. This could be because the CERT was developed in 2016 with the goal of making exercise-based clinical trials transparent and replicable and have not yet been sufficiently assimilated by researchers [147].

### *4.3. Main Characteristics of the Interventions*

Most of the interventions had a duration of 2 to 6 months, with a frequency of 2 to 3 times a week and a duration of 30 to 60 min per session, and were directed by qualified professionals, characteristics that are related to the WHO recommendations [19,20]

and to the GPAR [21–35]. 89% of the interventions were based on traditional PE, while 11% of the studies included interventions based on non-traditional disciplines such as Tai Chi and Pilates, disciplines that in recent years have increased their adherence and level of evidence [44,81,111,125,148] being even included by some countries in their GPAR [21,27,29,32,33]. 7% of the studies included exercise-based interventions with digital support, known as Exergames [74,78,117,120,126] a modality not so well known today, which has been shown to be effective in improving balance and mobility function in OA [149,150]. On the other hand, some authors suggest that more research is lacking regarding this type of interventions and the effects they propose [151]. 2% of the studies included interventions based on hydro gymnastics [125,127], and although few studies have covered this type of exercise, it has shown positive effects on the physical functioning of OAs [152]. Finally, 5% included exercise interventions supplemented with other interventions such as vibration and auriculotherapy [48,57,82,140]. Regarding the vibration modality, benefits have been shown in physical performance [153] and in balance and gait of OAs [154], in addition to being an effective intervention to reduce the risk of falls [155]. However, some authors suggest that more evidence is needed to know which is the most effective vibration modality [156]. This indicates that although interventions based on traditional exercise predominate (mainly resistance training [157] and aerobic training [158]), whose effects have been widely supported, non-traditional interventions have been developed during the last decade that have shown to be as effective as traditional exercise interventions [48,57,82,140]. Regarding the components of the interventions, 77% considered the muscle strength component as the main training variable and 47% the aerobic exercise, the latter being the first recommendation by the WHO and the GPAR. This may be due to the fact that muscle strength training, associated with an improvement in muscle quality in OAs, is more closely related to improvements in functionality, decreased risk of falls, and health-related improvements in quality of life [159,160], variables in which aerobic training has a minor effect [160]. At the same time, the small number of studies that consider the training of balance, coordination and proprioception components within their interventions is striking, given that alteration of these components increases the risk of falls. This variable that is of great interest to OAs, because falls are associated with a decrease in functionality, a higher level of dependency and a higher risk of mortality [12–16]. Lastly, the flexibility component was considered only in 7% of the studies, a variable that is not specifically found within the WHO recommendations, and is only found in some of the GPAR. This contrasts with the fact that flexibility exercises have been shown to improve aspects of physical health and mental well-being in OAs [36,161].

A fifth of the studies included in this review developed combined PE interventions, modalities known as concurrent training and multicomponent training, which had positive effects on the variables studied. In particular, the multicomponent training modality, which has important scientific support in terms of its effectiveness [162,163], is being strongly recommended in the European continent for the development of PA in OA [164]. In addition, it could be that in the near future, the recommendations proposed by the WHO will undergo modifications, proposing multicomponent training as a more effective alternative than training each component of physical fitness in isolation in OA.

#### *4.4. Outcome Variables Studied in the Articles and Instruments Used in Evaluations*

The aging process is not only associated with deterioration in physical skills, but also with disorders of mental health and cognitive skills [165]. Along these lines, although the interventions were based on PE that considered physical health variables in 100% of the studies, 28% of the studies also considered the effects of these interventions on mental health variables and 11% on cognitive skills. Even though the percentage is low, this is related to understanding how exercise is a therapeutic agent with multiple benefits in the health of OA [17].

Sixty-three instruments were used to evaluate the physical health variables, 18 to evaluate the mental health variables, and 22 to evaluate the cognitive skills variables. This highlights the great diversity of instruments used to identify the effects of PE in OA, and although there are some instruments that are used more frequently, this highlights the lack of consensus that exists for the evaluation of the different variables.

#### *4.5. Effects by Sex and by Type of Intervention*

Regarding the effects of interventions by sex, positive effects were observed in a greater number of physical health outcome measures in male-only samples, in a greater number of mental health outcome measures in mixed samples, and in a greater number of cognitive function outcome measures in single samples of men. Older women are known to have lower levels of PA and fitness than older men [144]. Considering this baseline condition, a PE-based intervention could show greater benefits for women in the different physical health outcomes [166], Furthermore, it has been observed that mixed sample generates greater collaboration, motivation and challenge for OA of both genders [167].

In relation to the effects according to different types of exercise, positive effects were observed in a greater number of physical health, mental health and cognitive function outcome measures in therapeutic PE-based interventions. This could be related to the fact that this type of intervention is usually implemented as an intervention for OA with altered physical health status. In addition, this type of intervention is more structured, individualized and with specific objectives for each participant, allowing greater control of exercise dose such as intensity, frequency, length and training progression. Furthermore, therapeutic PE-based interventions commonly included in the same session a greater number of components of physical condition [45,100,103,131], than those interventions based on non-traditional disciplines. Hydro-gymnastics and with digital support, which although have shown positive effects in some interventions, some authors agree that evidence to support their effects is lacking [151,156]. In particular, therapeutic PE-based interventions seem to improve muscle strength in a greater number of RTC. This finding could be associated with the fact that other types of exercise such as hydro-gymnasticsbased interventions and digitally supported exercise-based interventions consider very light workloads and are more focused on other fitness qualities, such as aerobic endurance, balance and coordination [151].

Additionally, the component of physical fitness with the most positive effects was balance, regardless of sex and type of intervention. The interventions were mainly with a duration of 3 months, a frequency of 3 times a week, with 30–60 min sessions. OAs often have problems with balance [168]. Thus, PE-based interventions could promote improvements in these components of physical fitness [169,170].

Particularly, quality of life improved regardless of the type of exercise trained, which reinforces the positive effect of PE on health-related quality of life of the elderly [171,172]. In cognitive skills, therapeutic PE-based interventions, presenting effectiveness greater than 60% of the articles in 11 of the 12 analyzed outcomes. It should be noted that few studies analyzed mental health and cognitive skills outcomes, most of which were therapeutic PE-based interventions. This finding suggests a lack of evidence on mental health and cognitive skills outcomes that should be explored in future research.

## *4.6. Limitations*

Although articles from other countries such as Chile, Mexico, Ecuador and Colombia were considered, most of the included studies were developed in Brazil, which does not allow a complete overview in relation to PE interventions for OAs in all of Latin America. This in turn could be considered a challenge for researchers in the rest of the Latin American countries in terms of developing similar research in their respective countries. On the other hand, we restricted the search the last 5 years to find the latest and updated available evidence. We are aware that there may be high-quality evidence in previous years that was not included. Another limitation of this review was the quality of the RTCs included. Thus, a high percentage of RCTs had unclear risk of bias in selection bias, performance bias, detection bias, and attrition bias. In addition, 52.6% of the CERT items showed a low percentage of articles that complied with describing and detailing the CERT categories. Furthermore, this scoping review lacked meta-analysis due to the studies' heterogeneity, so there is only a qualitative analysis of the phenomenon studied.

#### *4.7. How Does this Literature Review Contribute to the Existing One?*

This systematic review provides a broad and updated view of the characteristics of the PA and PE interventions that are being developed in Latin America, thus allowing the generation of a profile, outcome variables, and evaluation instruments used. On the other hand, this review allowed to identify that, although there are certain similarities between the recommendations proposed by the WHO and the GPAR of the different Latin American countries, there are also differences, for example, in the type of exercise, its frequency and its duration. Therefore, this review could serve to determine the more and less frequent characteristics of the interventions used by Latin American researchers.

This review also provides updated information derived from RTC on the characteristics of PE based-interventions, as well as the most frequently used outcome measures and instruments that should serve to help exercise professionals prescribe exercise for older adults.

Additionally, it allowed the understanding of new PE modalities that are being implemented and their characteristics, being able to encourage the development of future studies that are based on non-traditional PE interventions, in little-explored age groups and health conditions.

## **5. Conclusions**

A total of 101 articles were included (90% focused on Brazil), with a total sample of 5013 OA (79% women). 97% of the studies included participants between 60–70 years of age. The studies had an average adherence of 86%. The main cause of withdrawal was personal reasons (78% of cases). The studies were mainly carried out with OAs who lived in the community with the diagnosis of some disease, with cardiometabolic diseases being the most prevalent. A large percentage of studies had an unclear risk of bias in the items: selection, performance, detection and attrition. Furthermore, a heterogeneous level of compliance was observed in the CERT items. The interventions were mainly based on therapeutic PE, lasted between 2–6 months, with a frequency of 2–3 times a week, with a duration of sessions between 30–60 min and were led by professionals of PA sciences. For the most part, there was no warm-up stage before exercise and cool-down stage after exercise. As well as the components of physical fitness that were exercised the most were muscle strength and cardiorespiratory fitness.

This systematic review provides a broad and updated view of the characteristics of PE-based interventions that are being developed for OAs in Latin America. The findings will be useful for prescribing future PE programs for OAs, being able to encourage the development of future studies in this area of knowledge.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/1660-4 601/18/6/2812/s1, Table S1: PRISMA Checklist, Table S2: Search strings for all databases in the systematic review, Table S3: Proportions of "Yes" per CERT item for 101 included trials

**Author Contributions:** Conceptualization, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; methodology, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; validation, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; formal analysis, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; investigation, E.V.-A., R.I.S.-V., S.M.- M., R.Z.-L. and I.C.; data curation, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; writing—original draft preparation, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; writing—review and editing, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; supervision, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C.; project administration, E.V.-A., R.I.S.-V., S.M.-M., R.Z.-L. and I.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable. **Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The systematic review protocol was registered in the PROSPERO repository with the code: CRD42020208833. This information was already provided in the methodology section of the systematic review.

**Conflicts of Interest:** The authors declare no conflict of interest.

## **References**

**\***

### *Review* **Isokinetic Trunk Strength in Acute Low Back Pain Patients Compared to Healthy Subjects: A Systematic Review**

**Waleska Reyes-Ferrada 1,2, Luis Chirosa-Rios 1, Angela Rodriguez-Perea 1, Daniel Jerez-Mayorga 3,\* and Ignacio Chirosa-Rios 1**

	- Correspondence<EMAIL_ADDRESS>Tel.: +56-9-77697643

**Abstract:** Background: The purpose of this systematic review was to: (I) determine the quality of evidence from studies assessing trunk isokinetic strength in subjects with acute low back pain (ALBP) compared to healthy subjects and (II) establish reference values of isokinetic trunk strength in subjects with ALBP. Methodology: Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statements were followed using keywords associated with trunk, strength and low back pain. Four databases were used: PubMed, Web of Science, Scopus and SPORTDiscus. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Results: A total of 1604 articles were retrieved, four included in this review. All were evaluated as high risk of bias (Rob). Due to the high Rob and the diversity of protocols, instruments and variables used, it was not possible to determine reference values for subjects with ALBP, we can only establish a range of flexion peak torque (PT) between 175.1 and 89.7 Nm at 60◦/s and between 185 and 81.5 Nm at 120◦/s, and for extension PT between 240.0 and 91.5 Nm at 60◦/s and between 217.5 and 69.2 Nm at 120◦/s in subjects with ALBP. Conclusions: Due to the low quality of the evidence and the diversity of protocols used when measuring trunk isokinetic strength, it is necessary to carry out new high-quality research to establish reference values of trunk strength in subjects with ALBP.

**Keywords:** dynamometer; core muscles; trunk strength testing; reference data; peak torque

## **1. Introduction**

Low back pain (LBP) is among the three leading causes of years lived with disability [1], only in 2017 577 million people suffered from LBP [2]. LBP refers to pain, muscle tension or stiffness below the costal border and over the lower gluteal fold, with or without sciatia. It can be classified according to its duration in acute low back pain (ALBP), less than six weeks, or chronic low back pain (CLBP) when the pain persists for more than three months [3]. It is estimated that 80% of the population will suffer from LBP at least once in their lives [4,5], but these symptoms should disappear within six weeks. Although a significant number of patients will have recurrences or persistent pain and disability [6,7], even in the follow-up to one year, some patients will still show mild to moderate levels of pain and disability [8]. Da Silva et al. [9] reports a pain episode recurrence in 70% of the patients within 12 months after recovery from the first ALBP episode, of which 40% will suffer a moderate functional limitation or will need to use the health system, suggesting that the good prognosis of ALBP has been overestimated.

Regarding the cause of the LBP, it is not often possible to determine an anatomical source of pain (e.g., epidural abscess, compression fracture, spondyloarthropathy, malignancy or cauda equina syndrome) [10]. Most of the times, in 90% of cases, no specific cause is identified for which it is denominated non-specific LBP (NSLBP) [10]. However, multiple

**Citation:** Reyes-Ferrada, W.; Chirosa-Rios, L.; Rodriguez-Perea, A.; Jerez-Mayorga, D.; Chirosa-Rios, I. Isokinetic Trunk Strength in Acute Low Back Pain Patients Compared to Healthy Subjects: A Systematic Review. *Int. J. Environ. Res. Public Health* **2021**, *18*, 2576. https:// doi.org/10.3390/ijerph18052576

Academic Editor: Alberto Soriano-Maldonado

Received: 20 January 2021 Accepted: 1 March 2021 Published: 4 March 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

factors have been associated with the occurrence of NSLBP, among them the alteration of the neuromuscular response of the trunk [11,12], the deconditioning (or decrease in the function) of the lumbar musculature [13,14], the reduction in the muscular mass of the trunk [15], and the reduction in the muscular strength of the trunk [13,16,17].

The spine needs to be mechanically stable at all times to avoid injuries that can eventually lead to pain [18]. Maintaining this stability is role of the active neuromuscular system [19], and thus the trunk strength plays an important role in different aspects related to health and sport [20–23]. The trunk is the center of the kinematic chains, transferring forces and acting as a bridge between the upper and lower extremities [24]. Arms and legs can be compared with their contralateral to define deficits or imbalances but, unlike the extremities, the trunk does not have this possibility, which makes it difficult to find parameters of normality or reference. Trunk strength has been related to injury prevention [25,26], which is why it plays an important role in the functional evaluation of people or athletes [27,28].

To evaluate trunk strength, several methods have been developed. The gold standard is the isokinetic dynamometry, which consists of measuring muscle strength capacity under linear or rotational movements at constant velocities [29]. This method allows a quick quantification of several muscle function parameters at different positions and angular velocities, and its use has been recommended for clinical and research purposes [30].

Prospective studies have shown that trunk strength imbalance [17] and decreased trunk muscle strength could be considered risk factors for developing NSLBP, specifically isometric and isokinetic strength of trunk flexors and lumbar extensors muscles [16]. To the best of our knowledge, there are no reference values in the development of the first episode of ALBP; instead, the evidence shows that, when comparing healthy subjects with CLBP patients, the lumbar extensor peak torque is lower, but the flexor peak torque does not decrease in the same way, so the ratio flexors/extensors (F/E) do not decrease [31]. These data are important since the parameters of isokinetic strength could be used for the early detection of people at risk for developing NSLBP. However, these reference data correspond to subjects with CLBP, and were obtained from reviews in which no assessment of the quality of the evidence was carried out. This could limit our confidence in the reported data [31,32]. Furthermore, in CLBP, the evidence shows that pain and disability do have physical causes and have multifactorial etiology [33], with psychological factors [34], central sensitization [35] and kinesiophobia [36] playing a role in this type of patient. De Souza et al. [37] demonstrated that the peak torque of lumbar extensors in women with CLBP who have fear or negative beliefs related to the activity could be modified merely by using kinesiotape. This suggests that probably the strength values obtained in this type of patient may be influenced by other processes related to chronic pain and may not be an appropriate measurement on their own.

This allows us to question whether we estimate the ability to exert maximum trunk strength in subjects with chronic pain. Establishing whether an alteration in trunk muscle strength is present in those subjects who suffer from ALBP compared to healthy subjects is paramount in order to be able to develop training programs for preventing ALBP in the general population, and to manage this type of patient, avoiding its progression to CLBP. It is necessary to have data on the trunk's isokinetic strength in patients with ALBP that will allow determination of which people are at risk for developing ALBP and thus prevent its appearance in healthy people. Moreover, this is necessary to manage it and avoid its progression to CLBP. Thus, the objective of this systematic review was (I) to determine the quality of evidence from studies assessing trunk isokinetic strength in subjects with ALBP compared to healthy subjects and (II) establish reference values of isokinetic trunk strength in subjects with ALBP.

### **2. Materials and Methods**

The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines (PRISMA) were used [38] (Supplementary Table S1). The protocol of this review was registered in PROSPERO (CRD42020193458).

### *2.1. Study Search*

Two authors (WR-F and DJ-M) conducted the search. The databases used were PubMed, Web of Science, Scopus and SPORTDiscus. The search was carried out from their inception to October 2020, the following keywords were included: "isokinetic", "muscle strength", "dynamometer", "CORE", "abdominal muscles", "abdominal wall", "torso", "trunk", "low back pain", "low back ache" y "lumbago". Search strategies are presented in Supplementary Table S2.

### *2.2. Eligibility Criteria*

Articles that met the following criteria were included in this review. For aim (I): adult participants (age ≥18 years old), measures of isokinetic trunk flexors and extensors strength comparing a group of individuals with ALBP with a healthy control group, fulltext available, and articles in English. For aim (II), the criteria for aim (I) were applied, but all the studies assessing isokinetic trunk flexors and extensors strength in individuals with ALBP, regardless of having a healthy control group or not, were included. Studies that only included either healthy people or subjects with chronic low-back pain were excluded.

### *2.3. Study Selection*

Articles that were found eligible for inclusion in this review were entered into the Rayyan QCRI application, an app that assists in the article selection process, optimizing the screening time and allowing collaborative tasks (available for free at http://rayyan.qcri.org (accessed on 19 June 2020)) [39]. Duplicate references were removed, and two independent researchers (WR-F and DJ-M) reviewed titles and abstracts to identify articles met the eligibility criteria. The selected articles were then read in full, and the reference list was checked for relevant articles that could be included.

#### *2.4. Assessment of the Risk of Bias and Quality of Evidence*

Each article included in this systematic review was independently assessed for methodological quality and risk of bias by two researchers (WR-F and DJ-M). To the best of our knowledge, there is no scale for methodological evaluation adequate for the purpose of this review; therefore, we used the checklist proposed by Castro et al. [40], which combines some items from QUADAS [41] and a checklist to evaluate the methodological quality of both randomized and non-randomized studies of health care interventions [42]. This scale has 15 items divided into three sections (study sample, test procedures and data analysis, and results presentation). Each item was scored as "yes," "no," "unclear," or "not applied". A study was considered high risk of bias (low quality) when it received five or more "no" or "unclear" scores; in contrast, a study was considered low risk of bias (high quality) when it received less than five "no" or "unclear" scores. This cut-off score was determined on the basis of previous reviews that determined that 30% of negative results discriminate between studies of low or high methodological quality [43]. In case of disagreement among researchers, the consensus approach was used; for the case in which consensus could not be reached, a third researcher was consulted (LC-R).

### *2.5. Data Extraction and Analysis*

The data extraction was performed by each researcher independently; the information extracted was related to the identification of the article (authors, year of publication, design and objective), the characteristics of the participants (total sample, gender, age, weight and height) and the isokinetic evaluation protocol (movement, position, range of

movement, angular velocity, repetitions and contraction mode), in addition to results and main conclusions.

## **3. Results**

### *3.1. Article Selection*

No systematic reviews with a similar objective as the present study were found. From the initial search, a total of 1603 articles were retrieved (Figure 1), of which 610 were eliminated because they were duplicates. One additional article was identified from other sources. All the articles that assessed isokinetic trunk strength in individuals with ALBP presented a control group. Therefore, the number of articles included for aim (I) and aim (II) were the same. After evaluating titles and abstracts, 977 articles were excluded because they did not meet the inclusion criteria, leaving 17 articles for full-text analysis.

**Figure 1.** Flow chart for the systematic review.

Of the 17 articles, two could not be retrieved because when contacting the authors, they did not have a digital copy to share due to the age of the publication (1982 and 1994). Of the remaining 15, after reading the full text, 11 articles were eliminated because they did not include the evaluation of subjects with ALBP. Thus, four articles were selected, and their reference lists were checked, and there were no new articles found.

### *3.2. Characteristics of the Studies*

Table 1 presents the main characteristics of the included studies. One study [44] divided patients according to the duration of symptoms as acute and chronic, two [45,46] did so in acute, subacute and chronic, and only one [47] considered only subjects with acute pain. The number of participants with ALBP ranged from 21 to 46 subjects; Gabr et al. [46] do not indicate the exact number of ALBP subjects enrolled in their study. Age was not specified in the ALBP group in three of four studies, with only Hupli et al. [47] reporting an average age of 40.1 ± 8.9 years for men and 43.5 ± 9.2 for women. The physical activity profile was reported in only one study [47], but it does not specify which tool is measured.

**Table 1.** Characteristics of individual studies.

135

Regarding the isokinetic dynamometer used, Suzuki et al. [44] used Cybex II, Akebi et al. [45] did not specify it, Hupli et al. [47] compared two dynamometers: Ariel 5000 (Ariel dynamics Inc., Trabuco Canyon, CA, USA) and Lido Multi-Joint II (loredan Biomedical, Inc., West Sacramento, CA, USA), while Gabr et al. [46] used biodex system 4 pro. Regarding the position in which the trunk strength was measured, three studies were performed in the standing position with knees in semi-flexion [45–47] and one study [44] used the supine position. In relation to the range of movement used, there was no concordance among the studies. One study used natural movement [47], another one 30◦ of flexion–extension [44], another one [45] a range of 0◦–60◦ and another one the movement of maximum flexion and extension [46]. Three studies measured at velocities of 60◦/s and 120◦/s [45–47], while Suzuki et al. [44] used 30◦/s.

The strength variables calculated were: (I) average peak torque (Nm), (II) trunk flexion (J), (III) trunk extension (J), (IV) abdominal strength (J), (V) average power, (VI) flexion– extension ratio (%) (flexion strength/extensor strength), (VII) fatigue (%) calculated as: (initial muscle strength–final muscle strength/initial muscle strength) x 100, and (VIII) Coefficient of Torque Variation (%).

### *3.3. Methodological Quality and Risk of Bias*

In this review, 57 items (95%) were evaluated in the agreement between the two reviewers, the remaining three were decided by agreement (Table 2).

**Table 2.** Methodological quality of the studies included.

Items considered for rating: 1. Was the study population adequately described (i.e., sex, age, body mass, body height, kind of physical activity/lifestyle (sedentary, athlete, level of physical activity))?; 2. Was the description of selection criteria presented?; 3. Was there justification of appropriate sample size (through calculation or guidelines)?; 4. Were warm-ups and a familiarization protocol performed?; 5. Were type of muscle action (i.e., concentric and eccentric), sequence of action (i.e., concentric–concentric, concentric–eccentric, eccentric– eccentric), and velocity of movement described?; 6. Was the order of tests (velocities and trunk) randomized or counterbalanced?; 7. Was the lower limb dominance considered?; 8. Was the standardization of positions, movements and stabilization performed and properly described?; 9. Did participants receive the same encouragement during the test?; 10. Was gravity correction considered?; 11. Were the outcome measures clearly described?; 12. Were data extracted from the isokinetic load range?; 13. Were measures of reliability (e.g., Intraclass correlation coefficients (ICC), Standard error of the mean (SEM)) presented?; 14. Were results clearly described?; 15. Were appropriate inferential statistics presented?. N: no; Y: yes; UC: unclear; NA: not applied; RoB: risk of bias.

## 3.3.1. Sample

Regarding the sample, three studies [44,46,47] describe the sample properly (item 1), however, only Gabr et al. [46] specified the inclusion criteria (item 2), none of the included articles explained how the sample size was calculated (item 3).

## 3.3.2. Procedure

In relation to the trunk isokinetic evaluation procedure, two studies [45,47] report a familiarization process prior to measurement (item 4), none of them properly report the type or sequence of contraction only reporting the angular velocity used (item 5), only one study [47] reports a randomized order in the evaluations (item 6), and none of the four inform of the dominance of the extremities (item 7) which was evaluated as "not applied" because it is the trunk. All four studies [44–47] correctly describe the assessment position, the movements, and the form of stabilization used (item 8). None of the studies specify whether or not the same encouragement was given to each participant during the assessment (item 9). Considering the data analysis, only Hupli et al. [47] report that the

Lido dynamometer software compensates for gravity, while Ariel does not (item 10); it is not clear if the other three studies performed gravity correction. Regarding the dependent variable, two studies clearly describe how the data extraction was performed [46,47], while, in the other two studies [44,45], it is not clear how data such as fatigue or the coefficient of variation were determined. None of the studies clarify whether the data were extracted from the isokinetic load range (item 12), and none report reliability measures, such as the intra-class correlation coefficient or standard error measurement (item 13).

### 3.3.3. Presentation of Results

Regarding the presentation of results, three studies [44,46,47] adequately presented the results (item 14) and two [45,46] properly presented the inferential statistics (item 15). In summary, the four studies showed a high risk of bias [44–47].

### *3.4. Trunk Strength Parameters*

Only two studies [46,47] measured peak torque in a similar way (Table 3).

#### 3.4.1. Average Peak Torque in Flexion and Extension

Two studies [46,47] determined the average peak torque in flexion and extension in healthy subjects and those with ALBP, measuring in standing, concentric mode, at velocities of 60◦/s and 120◦/s. Hupli et al. [47] compared men and women with ALBP and healthy subjects using two dynamometers, finding small, non-statistically significant differences between groups. Gabr et al, [46] when comparing men with ALBP and healthy controls, found significant differences in the peak torque of flexors (*p* = 0.004) and extensors (*p* = 0.003) at 60◦/s and flexors (*p* < 0.001) and extensors (*p* < 0.001) at 120◦/s, with an inverse F/E ratio at speeds of 120◦/s in the ALBP group (Table 3).

### 3.4.2. Coefficient of Variation

Akebi et al. [45] evaluated the relationship of the variability of the torque curves (CV) between subjects with ALBP and healthy controls finding CV values lower than the evaluation at 60◦/s compared to 120◦/s and, in addition, in both men and women the CV was lower in the control subjects compared to ALBP (Table 3).

### 3.4.3. Average Power

Gabr et al. [46] found significant differences between average power in flexion (*p* = 0.004) and extension (*p* = 0.014) at 60◦/s and between average power in flexion (*p* = 0.001) and extension (*p* = 0.045) at 120◦/s between men with ALBP and a control group (Table 3).

### *3.5. Adverse Outcome from Trunk Isokinetic Assessment*

From all the articles reviewed, none report adverse effects during trunk strength measurement using an isokinetic dynamometer in patients with ALBP. Suzuki et al. [44] and Gabr et al. [46] report that the assessment was performed without any complaints, Akebi et al. [45] do not report any undesirable effects during the assessment, and only Hupli et al. [47] reports a pain measured with visual analogue scale (VAS) (0–100) of 26.3 using the Ariel dynamometer and 15.2 with the Lido dynamometer in subjects with ALBP.

**Table 3.** Isokinetic trunk strength in acute low back pain patients (ALBP) and healthy adults for trunk extension and flexion.

> SD: standard deviation; s: seconds.

## **4. Discussion**

The present systematic review was designed to (I) determine the quality of evidence from studies assessing trunk isokinetic strength in subjects with ALBP compared to healthy subjects and (II) establish reference values of isokinetic trunk strength in subjects with ALBP. The main findings of this study were (I) the articles included in this review present a high risk of bias; therefore, this indicates low quality of evidence, and (II) it was not possible to determine reference values, neither was it possible to determine whether trunk strength can distinguish between patients with ALBP and healthy subjects. However, based on data provided in the articles reviewed, we can report a range of peak flexion torque

between 175. 1 Nm and 89.7 Nm at 60◦/s and between 185 Nm and 81.5 Nm at 120◦/s, and for peak torque in extension between 240.0 Nm and 91.5 Nm at 60◦/s and between 217.5 Nm and 69.2 Nm at 120◦/s in subjects with ALBP.

In addition to considering research with a low risk of bias, we should also consider studies with similar evaluation protocols to suggest reference values. Estrázulas et al. [48] after reviewing the literature, recommend reliable protocols for the evaluation of trunk flexors and extensors, carried out in a sitting position at velocities of 30◦/s and 60◦/s with a range of 30◦ (10◦ of flexion and 20◦ of extension) and/or in a standing position at velocities of 60◦/s and 90◦/s with a range between 90◦ and 95◦ of flexion and 15◦ of extension, both protocols in concentric mode with the axis in the anterior superior iliac spine. In the four studies reviewed, none included evaluation in sitting position; three of them [45–47] used the standing position but in a different range to the suggested and with velocities of 60◦/s and 120◦/s, which are commonly used in the measurement of trunk strength [48].

Concerning the variable analyzed, we know that the peak torque is widely used as a reference, allowing a direct comparison between studies. It has been previously used by Mueller et al. [31,49] to analyze subjects with low back pain, to determine deficits and to assess the effectiveness of training or therapy. In this review, two of the four included studies used peak torque in their analysis; however, Hupli et al. [47] found differences between the dynamometers used and therefore conclude and recommend that these data should not be compared among themselves. Analyzing this same variable, Gabr et al. [46] found that, unlike patients with CLBP, patients with ALBP have a significant reduction in the strength of trunk flexors and extensors, with an inverse F/E ratio at 120◦/s, that is, greater than one, which indicates that the extensor muscles were mostly affected by the weakness. Mueller et al. [31] had previously reported the same, but with data from CLBP subjects, where a greater decrease in extensors' strength was observed than in flexors, so the F/E ratio was higher than in healthy subjects. It is important to note that only the 60◦/s flexor values obtained by Gabr et al. [46] are similar to those described by Mueller et al. [31] for the CLBP group, and those of 60◦/s flexors in healthy subjects by Hupli et al. [47] with the control group by Mueller et al. [31]. On the other hand, Suzuki et al. [44] report differences in the strength of flexors and trunk extensors between ALBP and asymptomatic subjects, however, this variable was measured in Joules, which does not allow comparison, and also only indicates the existence of statistical differences, but does not report the *p*-value.

It is important to consider that none of the studies included in this review performed an isometric strength assessment of trunk flexors and extensors in subjects with ALBP using an isokinetic dynamometer. Among the studies reviewed, only Suzuki et al [44] evaluated isometric strength; however, they considered as a single group patients with acute and chronic pain (who had an average of eleven years of pain); so, unfortunately, it was not possible to distinguish isometric strength values in subjects with ALBP. Isometric evaluation is reliable in subjects with CLBP [50], and lower values of trunk strength have been observed in athletes and non-athletes with CLBP compared to healthy individuals. Cho et al. [16] propose that the risk for LBP and its severity would be associated with isokinetic weakness and the isometric weakness of trunk flexors and extensors.

From this, it is necessary to consider the importance of measuring these parameters in patients with ALBP, which could be used as an indicator of functionality or prognosis in these subjects, since isokinetic dynamometry has been widely used to evaluate the trunk strength but in patients with CLBP [50–53]; however, few studies have evaluated patients with ALBP.

Based on this systematic review, we cannot recommend reference values for the strength of trunk flexors and extensors in subjects with ALBP due to the high risk of bias of the articles included and the diversity of protocols, instruments and variables used in each article. Although three [44–46] of the four studies reviewed report differences in some strength parameters between individuals with ALBP and healthy subjects, these data are not confident given the limited quality of the evidence. Thus, it was also not possible to

determine whether strength levels can help us distinguish between patients with ALBP and healthy subjects. On the other hand, we did not identify any studies that compared eccentric strength among these people. The eccentric contraction occurs when the external force is greater than the muscle strength, therefore, it plays an important role in the activities of daily life and sports, in the deceleration of the body during movements [54], so it would be interesting to investigate different types of contraction and eccentric/concentric ratio in subjects with ALBP compared to healthy subjects to understand the muscle dynamics of the trunk in different contexts or activities.

We can consider this review's strength as having considered research with no prior date limit until 2020. However, that presents us with an associated difficulty since the studies we include have a range of 36 years of difference, time in which the standards of scientific publication have changed, and new guidelines have been developed [55,56], which could explain the high risk of bias found in this review.

In this context, it is necessary to conduct rigorous longitudinal studies, based on current methodological guidelines, that allow us to detect people at risk for developing ALBP and that consider the multiple aspects involved in LBP, both physical and psychological. For this reason, we can suggest the formation of working groups to determine consensus on the best way to approach the evaluation of this type of patient. For the reasons mentioned earlier, we consider it necessary to carry out new studies of high methodological quality that allow us to clarify if there are levels of strength associated with ALBP and to be able to prevent its appearance. In addition, given the questions regarding the evaluation of unnatural movements or those that do not necessarily represent the physiology or velocity of the movement performed on the isokinetic dynamometer [57], it is necessary to develop new technologies [28,58] that allow the evaluation of trunk strength related to a functional or athletic context that mimics the functional demands of the athlete or patient.

## **5. Conclusions**

The findings of this systematic review indicate that the quality of studies assessing isokinetic trunk strength in subjects with ALBP compared to healthy controls was weak. Moreover, the available data did not allow presentation of reference values in patients with ALBP. Future research of high methodological quality is needed to establish reference values of trunk isokinetic strength in subjects with ALBP and to determine the ability of trunk strength to discriminate ALBP patients from healthy individuals.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/1660-460 1/18/5/2576/s1, Table S1: PRISMA 2009 check list, Table S2: Search strategy for each database and number of articles found.

**Author Contributions:** Conceptualization, W.R.-F. and D.J.-M.; methodology, W.R.-F. and D.J.-M.; formal analysis, W.R.-F., D.J.-M., A.R.-P., L.C.-R.; writing—original draft preparation W.R.-F. and D.J.-M.; writing—review and editing, W.R.-F., D.J.-M., A.R.-P., L.C.-R., I.C.-R.; visualization, W.R.-F., D.J.-M., A.R.-P., L.C.-R., I.C.-R.; supervision, W.R.-F., L.C.-R. and D.J.-M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study has been partially supported by FEDER/ Ministry of Science, Innovation and Universities-State Research Agency (Dossier number: RTI2018-099723-B-I00).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Acknowledgments:** This paper will be part of Waleska Reyes-Ferrada's Doctoral Thesis performed in the Biomedicine Doctorate Program of the University of Granada, Spain.

**Conflicts of Interest:** The authors declare no conflict of interest.

## **References**

## *Systematic Review*

### **The Effects of Martial Arts on Cancer-Related Fatigue and Quality of Life in Cancer Patients: An Up-to-Date Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials**

**Daniel Sur 1,2,\*, Shanthi Sabarimurugan 3 and Shailesh Advani 4**

**Citation:** Sur, D.; Sabarimurugan, S.; Advani, S. The Effects of Martial Arts on Cancer-Related Fatigue and Quality of Life in Cancer Patients: An Up-to-Date Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. *Int. J. Environ. Res. Public Health* **2021**, *18*, 6116. https://doi.org/10.3390/ ijerph18116116

Academic Editor: Alberto Soriano-Maldonado

Received: 19 March 2021 Accepted: 2 June 2021 Published: 6 June 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

**Abstract:** Background: To evaluate and synthesize the existing evidence of the effects of practicing martial arts by cancer patients and cancer survivors in relation to overall quality of life (QoL) and cancer-related fatigue (CRF). Methods: Randomized controlled trials (RCTs) from 1 January 2000 to 5 November 2020 investigating the impact of martial arts were compared with any control intervention for overall QoL and CRF among cancer patients and survivors. Publication quality and risk of bias were assessed using the Cochrane handbook of systematic reviews. Results: According to the electronic search, 17 RCTs were retrieved including 1103 cancer patients. Martial arts significantly improved social function, compared to that in the control group (SMD = −0.88, 95% CI: −1.36, −0.39; *p* = 0.0004). Moreover, martial arts significantly improved functioning, compared to the control group (SMD = 0.68, 95% CI: 0.39–0.96; *p* < 0.00001). Martial arts significantly reduced CRF, compared to that in the control group (SMD = −0.51, 95% CI: −0.80, −0.22; *p* = 0.0005, I2 > 95%). Conclusions: The results of our systematic review and meta-analysis reveal that the effects of practicing martial arts on CRF and QoL in cancer patients and survivors are inconclusive. Some potential effects were seen for social function and CRF, although the results were inconsistent across different measurement methods. There is a need for larger and more homogeneous clinical trials encompassing different cancer types and specific martial arts disciplines to make more extensive and definitive cancer- and symptom-specific recommendations.

**Keywords:** cancer; QOL; fatigue; martial arts; clinical trial; meta-analysis

## **1. Introduction**

In 2020, 19.3 million new cancer cases were diagnosed globally, where breast, lung, and prostate were the most frequent type of malignancies [1]. Cancer is the second cause of mortality worldwide after ischemic heart disease, with 8.97 million deaths, and it is predicted to become the leading cause of death by 2060 with approximately 18.63 million deaths [2]. Improvements in diagnostics and treatments have increased the survival rate of the most prevalent cancers in developed countries [3]. As of January 2019, there were an estimated 16.9 million cancer survivors in the United States. The number of cancer survivors is projected to increase to 22.2 million by 2030 [4]. Furthermore, the burden of cancer incidence and survivors continues to increase in low- and middle-income countries as well [5].

The physical, emotional, and financial impacts of cancer diagnosis and its management, along with the side effects of treatments, normally have long-term consequences

on the patient's overall quality of life (QoL) that can interfere in their activities of daily living [6,7]. The World Health Organization (WHO) defines QoL as an individual's perception of their position in life in the context of the culture, as well as the value systems in which they live and in relation to their goals, expectations, standards, and concerns [8]. Cancer-specific QoL encompasses all stages of the disease [9].

Cancer standard treatment (surgery, radiation, chemotherapy, hormone therapy, targeted therapy, and immunotherapy) can cause a series of side effects, including nausea, vomiting, diarrhea, constipation, fatigue, depression, and weight loss, which affects physical and psychological functioning, as well as overall QoL [10–12]. Fatigue remains one of the most important components of QoL that can vary in intensity and impact based on the stage of disease, treatment received, and patients' functional status [13]. Cancerrelated fatigue (CRF) seems to be due mainly to alterations promoted by cancer in patient homeostasis, such as proinflammatory cytokine upregulations, hydroxytryptophan dysregulation, hypothalamic–pituitary–adrenal axis dysfunction, circadian rhythm disturbances, and increased vagal tone. It is also shown that CRF can vary based on the cancer type [14]. The CRF is defined as a distressing, persistent, and subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning [15]. Moreover, it can lead to a decrease in the participation of activities of daily living and impairment of the patient mood; moreover, it is an important predictor of reduced overall QoL [16,17]. The CRF has been estimated to affect between 25% and 99% of cancer patients and depends on several factors, including patient population, type of treatment received, and assessment method, which can persist for five or more years after cancer diagnosis [18].

Several interventions, such as exercise, heat, cryotherapy, or manual therapy, can be followed to ameliorate some of the above-mentioned side effects and improve QoL [19]. Different exercise programs offer benefits and are safe in cancer patients during and after cancer treatment [20], improving health and functional outcomes in these patients [21]. National guidelines recommend the prescription of exercise to cancer patients; however, it should be tailored to their needs and capabilities [22]. This physical activity has to be done 3–5 times/week and for at least 20 min to be effective and should involve aerobic, resistance exercises, or a combination of both [23].

Martial arts present several benefits to those who practice them. The benefits include physical and psychological aspects, including lessening negative emotional reactions, enhancing balance, and improving cardiovascular and musculoskeletal fitness [24]. Although there is limited evidence of studies with limited number of participants assessing the effects of practicing martial arts in cancer patients [25–27], there is a need to clarify their effects on CRF and QoL. This systematic review and meta-analysis aimed to comprehensively review the use of martial arts among cancer survivors and its impact on QoL and CRF. Furthermore, it was attempted to determine the benefits of these types of programs, identify the strengths and gaps in the evidence, and suggest directions to overcome the highlighted limitations.

### **2. Materials and Methods**

Cochrane's handbook of systematic reviews of interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were utilized in this study to develop and perform this systematic review and meta-analysis [28].

### *2.1. Literature Search*

Online databases, including PubMed (Medline), Cochrane Web, Web of Science, and Scopus, were searched from 1 January 2000 to 5 November 2020 using the keywords: (Martial Arts OR Hap Ki Do OR Judo OR Karate OR Jujitsu OR Tae Kwon Do OR Aikido OR Wushu OR Kung Fu OR Gong Fu OR Gongfu) AND (Cancer\* OR Neoplasm\* OR Tumor\* OR Malignancy\*). Furthermore, the search was continued for PubMed (Medline), which was then formatted to perform the search in other databases.

### *2.2. Eligibility Criteria*

Following the PICO principles (patient, intervention, control, and outcomes) [29], the inclusion criteria were: (a) randomized controlled trials (RCTs) that investigated cancer patients with the primary intervention of martial arts and compared with any comparator for QoL and fatigue; (b) original articles in peer reviewed journals; and (c) eligible studies in English. Non-randomized or any other trials rather than RCTs, non-English RCTs, trials that did not assess the QoL or CRF, non-human studies, studies with no full text, single arm studies, and reviews and secondary works were excluded from this study.

### *2.3. Screening of Results*

Initially, two authors (D.S. and S.S.) screened all titles and abstracts using the inclusion criteria. Subsequently, they coded the abstracts as "yes" for inclusion in full text-review and "no" for excluding the abstract. If both authors coded an abstract as "yes", they were considered for full text review. If both were coded as no, they were excluded. For abstracts where there were discrepancies, the decision was made through either mutual discussion or with the help of a third reviewer (S.A). In the next stage, a full text review of all articles was performed against the inclusion criteria. Following that, the full text was read carefully for eligibility criteria.

### *2.4. Data Extraction*

The extracted data were divided into three categories. The first one was baseline characteristics, including author name, country, sample size, age, gender, marital status, and cancer treatment (surgery, chemotherapy, and radiation, as well as author name). The second contained the key characteristics of the included studies, such as country, cancer type, the timing of intervention, duration of the intervention (sessions, frequency, and period), and outcomes. The last one was outcome measures, including: (I) quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [30], Functional Assessment of Cancer Therapy—General (FACT-G) [31], and The Short-Form 36 (SF-36) [32]; and (II) fatigue by The Brief Fatigue Inventory (BFI) [33], Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F) [34], and the Multidimensional Fatigue Symptom Inventory—Short Form (MFSI-SF) [35,36].

### *2.5. Quality Assessment*

The quality of this meta-analysis was judged based on the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guideline [37]. GRADE is a transparent and reproducible system that allows the researcher to grade the quality and certainty of the evidence. Based on the quality of the evidence, the level of confidence was assessed that an estimate of the effect could be correct. Following that, two researchers (D.S. and S.S.) evaluated each study. An overall quality score was assigned to each study, ranging from high, moderate, low, to very low grade of evidence. These grades mean the grade certainty/quality of the evidence of the studies. If there was any uncertainty between the two independent researchers, a third researcher (S.A.) evaluated the evidence to obtain the conclusion. The risk of bias of the included studies was also evaluated using the Cochrane's risk of bias tool [38]. This tool was used to evaluate the RCTs regarding randomization tools; concealment of allocation; blinding of assessors, participants, and personnel; and selective reporting, attrition, and other biases. No paper evaluated was excluded from the results because of low quality or high risk of bias.

### *2.6. Statistical Analysis*

The data were analyzed as a standardized mean difference (SMD) and 95% confidence interval (CI) under a random-effects model using the inverse-variance method in the Review Manager Software (version 5.3, The Nordic Cochrane Centre, Copenhagen, Denmark) package. The heterogeneity was considered when I-square test (I2) and Chi-Square P were more and less than 50% and 0.1, respectively [38–40].

## **3. Results**

### *3.1. Search Results and Summary of Included Studies*

Our electronic search retrieved 801 records, 744 of which underwent title and abstract screening after removal of duplicates. Out of these, 38 records progressed for full-text screening, and 21 of them were excluded from the study. Finally, 17 RCTs were included for further analysis [41–57]. Figure 1 illustrates the study selection process. These studies included a total of 1103 cancer patients who were divided into control groups (*n* = 546) and treatment groups with martial arts (*n* = 557). The mean age of the included cancer patients was 58 ± 3.1 years. The baseline characteristics and summary of the included studies are shown in Tables 1 and 2.

### *3.2. Description of Intervention*

Most of the studies analyzed martial arts, such as Tai Chi and Qigong, in one of the comparator arms. They compared the effect of martial arts with standard care, control, psychosocial support, strength training, and even dance. Tai Chi is a traditional Chinese martial art used for defense as well as for its health benefits [58]. Tai Chi and its derivates (Tai Chi Chih, Tai Chi Chuan, Tai Chi Qi Qong, and Tai Chi Easy) are efficient complementary approaches used in improving wellbeing and fatigue [59]. Qigong is considered a form of Chinese martial arts with benefits in immune regulation, balancing the "qi", and strengthening muscles and tendons [60]. These traditional martial arts forms involved meditation, breathing techniques, coordinating the movements, and relaxation exercises [61]. Another martial art used in the clinical trials was Kyoshu Jitsu. This martial art focuses on pressure points for self-defense as well as its benefits for healing [53]. The majority of the studies analyzed for this meta-analysis focused on breast cancer. Only a small number of studies considered other tumor types, such as lymphoma, ovary, colon, lung, prostate, and nasopharyngeal cancer (Tables 1 and 2).

**Figure 1.** PRISMA flow diagram.

**Table 1.** Baseline characteristics of the included studies.

Values reflect number or mean (standard deviation); 1 median (range); 2 standard error of the mean.

Cancer Quality of Life Questionnaire; 5 FACT-G, Functional Assessment of Cancer Therapy—General; 6 SF-36, the Short-Form 36; 7 BFI, the Brief Fatigue Inventory; 8 FACIT-F, Functional

Assessment of Chronic Illness Therapy—Fatigue; 9 MFSI-SF, the Multidimensional Fatigue Symptom Inventory—Short Form.

**Table 2.** Summary of the included studies.

## *3.3. Outcomes*

In total, three studies [43,50,53] assessed QoL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). A pooled analysis compared the impact of martial arts vs. no intervention among cancer patients and showed no significant improvement in global health, (SMD = 1.30, 95% CI:−1.18, 3.78; *p* = 0.30, I2 > 95%), physical function (SMD = 0.84, 95% CI: −1.42–3.10; *p* = 0.47, I2 > 95%), role function (SMD = 1.03, 95% CI: −1.01–3.08]; *p* = 0.32, I2 > 95%), emotional function (SMD = 1.37, 95% CI: −1.12–3.85; *p* = 0.28, I2 > 95%), cognitive function (SMD = 1.37, 95% CI: −0.82–3.55]; *p* = 0.22, I2 > 95%), and social function (SMD = 1.17, 95% CI: −0.99–3.34; *p* = 0.29, I2 > 95%) (Figure 2). It should be noted that the heterogeneity was solved after excluding the study by Chuang (2017) [43] (*p* > 0.1), and the results remained non-significant (Figure A1).

**Figure 2.** Analysis of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30).

### *3.4. Functional Assessment of Cancer Therapy-General*

In total, five studies [42,46,51,54,55] reported the effect of martial arts on QoL by FACT-G. Pooled data show non-significant improvement between the groups in terms of the Functional Assessment of Cancer Therapy—General (SMD = 0.34, 95% CI: −0.02– 0.70]; *p* = 0.06) (Figure 3). The analysis was heterogeneous (*p* = 0.04, I2 = 61%), and the heterogeneity was solved when removing the study by Oh (2009) [51] (*p* = 0.70, I2 = 0%). The results remained non-significant (SMD = 0.16, 95% CI: −0.11–0.43; *p* = 0.25) (Figure A2).

### *3.5. The Short-Form 36 (SF-36)*

The Short-Form 36 (SF-36) was reported in three studies [41,45,52]. The combined SMD between martial art and control groups showed non-significant results regarding physical function (SMD = 0.16, 95% CI: −0.18–0.50; *p* = 0.36), mental health (SMD = 0.05, 95% CI: −0.27–0.36; *p* = 0.77), and social function (SMD = 0.07, 95% CI: −1.87–2.01; *p* = 0.94). It is worth noting that the results of physical function and mental health were homogeneous (*p* = 0.33, I2 = 10% and *p* = 0.95, I2 = 0%, respectively) (Figure 4). However, the social function was heterogeneous (*p* < 0.00001, I2 = 97%), and the heterogeneity was solved by excluding the study by Larkey (2016) [45] (*p* = 0.47, I2 = 0%). The results after sensitivity analysis show that martial arts significantly reduced social function compared to the control group (SMD = −0.88, 95% CI: −1.36, −0.39]; *p* = 0.0004) (Figure A3).

### *3.6. The Brief Fatigue Inventory*

Pooled data of three studies [42,43,47] report that the BFI showed no significant reduction of fatigue between the two groups (SMD = −1.04, 95% CI: −2.96–0.87; *p* = 0.29). According to the results, the analysis was heterogeneous (*p* < 0.00001, I2 = 98%) (Figure 5). Furthermore, the heterogeneity was solved after removing the study by Chuang (2017) [43] (*p* = 0.24, I2 = 26%), and the results remained non-significant (SMD = 0.01, 95% CI: −0.39–0.41; *p* = 0.96) (Figure A4).

### *3.7. Functional Assessment of Chronic Illness Therapy-Fatigue*

Totally, three studies [48,49,51] reported the use of Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F). The results show martial arts significantly improved fatigue, compared to the control group (SMD = 0.68, 95% CI: 0.39–0.96; *p* < 0.00001). According to the results, the data are homogeneous (*p* = 0.73, I2 = 0%) (Figure 6).

### *3.8. The Multidimensional Fatigue Symptom Inventory-Short Form*

The multidimensional Fatigue Symptom Inventory—Short Form was used in three studies [44,56,57]. The results reveal that the SMD between martial art and control groups was non-significant (SMD = −0.31, 95% CI: −0.71–0.10; *p* = 0.14), and the data are heterogeneous (*p* = 0.06, I2 = 64%) (Figure 7). Furthermore, the heterogeneity was solved after excluding the study by Irwin (2017) [44] (*p* = 0.92, I2 = 0%), and the results show that

martial arts significantly reduced fatigue, compared to the control group (SMD = −0.51, 95% CI: −0.80, −0.22]; *p* = 0.0005) (Figure A5).

### **Figure 4.** Analysis of the Short-Form 36.

**Figure 6.** Analysis of Functional Assessment of Chronic Illness Therapy—Fatigue.

**Figure 7.** Analysis of the multidimensional fatigue symptom inventory-short form.

### *3.9. Quality Assessment of the Included Studies*

An overall moderate risk of bias was found in selection, reporting, and other bias. Furthermore, performance, detection, and attribution biases were judged as having a high risk of bias. Detailed risk of bias summary and graph are shown in Figures 8 and 9.

**Figure 8.** Risk of bias summary.

**Figure 9.** Risk of bias graph.

## **4. Discussion**

Cancer patients are encouraged to participate in an exercise program during and following treatment [15]; however, there are still gaps related to regimes and forms of exercise appropriate for each individual. Improvement of QoL in cancer patients and management of their CRF have gained importance in recent years to enhance the general wellbeing of cancer patients and ameliorate the side effects of cancer therapies [62]. Multiple studies have covered the role of physical activity and exercise studying their effects on QoL and CRF of cancer patients during and after standard cancer treatment [63]. In this regard, martial arts have gained popularity in western countries as a new form of physical activity. In addition, martial arts combine musculoskeletal conditioning and training in cognitive skills, together with breathing exercises, which are typically delivered in group training sessions that also provide social support for cancer patients [24]. The results of the benefits of martial arts on QoL and CRF have been reported in several studies with a limited number of participants covering limited martial arts disciplines and cancer types [41–57].

This is the first systematic review and meta-analysis grouping martial arts and their effects on QoL and CRF as a primary intervention in cancer patients during and after treatment, regardless of the cancer type and treatment received. The data extracted from different studies of cancer patients practicing martial arts show a significant improvement of social function measured through SF-36 and a significant reduction of CRF measured using FACIT-F and MFSI-SF. The effects reported on social function by Campo et al. [41] and Sprod et al. [52] were positive but modest in their studied population. Social function is an important dimension for cancer patients since the disease and its treatment can affect diverse aspects, such as marital relationships, parental responsibilities, work environment, and social activities [64]. Regarding the significant reduction of CRF using the FACIT-F assessment scale, Oh et al. found a significant difference in their study of breast cancer survivors practicing Tai Chi Chuan for 60 min, 3 times per week, for 12 weeks [51]. Mustian et al. found a non-significant positive effect on fatigue measured by the same tool in breast cancer survivors practicing Tai Chi, possibly due to the small number of participants in their studies [48,49]. Considering the CRF measured through the MFSI-SF scale, Zhou et al. found a significant reduction of CRF in nasopharyngeal patients undergoing radiotherapy after practicing Tai chi for 60 min, 5 times per week, for 8 months [57]. In line with these results, another study found that lung cancer patients who followed a Tai Chi program of 60 min every other day for 12 weeks and underwent chemotherapy had a significant reduction of CRF, compared to those who were in a low-impact exercise program. This reduction was observed after 6 and 12 weeks of the program initiation [56]. Other outcomes analyzed in this meta-analysis did not reach a significant difference, even after heterogeneity was solved.

In the articles analyzed by our team, most of the patients in the trials were breast cancer patients who finished their treatment and started a program for physical activity or are undergoing chemotherapy or radiotherapy. The trials analyzed had small batches of patients enrolled and the population was too heterogeneous for us to be able to conclude about the optimal load and specifics of exercises. Furthermore, most of the martial arts sessions presented ranged from a period of 3 weeks to 24 weeks of practice, with a normal session being 40–60 min. The schedule of the sessions was from 2 weekly classes to 12 weekly classes depending on the type of martial arts. Taking into account the results of the analyzed trials, we consider that practicing martial arts is safe and recommended for patients undergoing treatment as well as for cancer survivors at the completion of their oncological therapy

Other meta-analyses have reviewed the effects of martial arts in QoL and/or CRF [64,65]. Tao et al. in a study analyzed the effects of acupuncture, Tuina, Tai Chi, Qigong, and traditional Chinese music therapy on symptom management and QoL in cancer patients. According to the results, Tai Chi and Qigong had no effect on QoL or CRF in breast cancer survivors [65]. Wayne et al. also analyzed the effects of Tai Chi and Qigong in cancer survivors, finding a significant improvement in CRF, sleep difficulty, depression, and overall QoL, as well as a non-significant trend in pain control [66].

Albeit all the evidence points to the benefits of physical activity in cancer patients, these changes to increase their physical activity seem harder to implement by cancer patients [67]. Martial arts have been demonstrated in several studies to be a feasible option for cancer patients [41,53]. Moreover, they may reduce some of the negative effects of cancer and improve physical as well as psychological health [68]. This study may help healthcare professionals involved in cancer management and patients decide to choose an activity to improve QoL and reduce CRF. Martial arts offer a wide variety of disciplines with different levels of intensity that would allow cancer patients the possibility of deciding the activity that fits better with their needs.

Different guidelines covering CRF, such as NCCN (National Comprehensive Cancer Network) guidelines, focused on CRF [15], and the guidelines from the Oncology Nursing Society "Putting Evidence into Practice" [69] proposed exercise and physical activity as a first-line intervention for CRF. Other interventions, in addition to erythropoiesisstimulating agents and low-dose dexamethasone, do not offer effectiveness reducing CRF in patients with cancer [69]. The beneficial effects of martial arts in QoL of cancer patients can be due to the relaxation response and the immunomodulatory [50,70] and hormonal effects [71].  The same study showed an impact on physical and mental health, improving limb-muscular function and promoted sleep [72].

There is some evidence showing that CRF and QoL are not improved only by physical exercises [73,74], supporting the concept that a more holistic approach should be considered in order to benefit these outcomes in cancer patients. Adverse effects due to martial arts practice did not exist in several studies [42,49,51].

Meta-analyses allow overcoming several limitations. First, pooling the data from different studies allows correcting the statistical limitation of the small sample data of some of the analyzed studies. Another strength is that meta-analyses allow detecting the heterogeneity existing in different studies that used martial arts as a primary intervention in cancer patients. It also helps settle the effect from conflicting results coming from different studies.

Regarding the limitations of this study, one can refer to the analysis of only studies that were published in English. This fact excludes the articles written in other languages that could represent the evidence better and make more general conclusions. Second, the diversity of the outcomes measured in the studies analyzed in this meta-analysis made the task of comparison arduous. Future studies should report outcomes in a more homogeneous way in order to be able to pool all available data. Another limitation is that the majority of the studies analyzed were performed on breast cancer survivors, limiting

the conclusions drawn in this study to this group of patients. Accordingly, future studies involving the investigation of the effects on QoL and CRF of martial arts in cancer patients should cover other cancer types. In that way, it would be possible to stratify the results by cancer types and other variables, such as age or other interesting conditions, including gender or grade of disability, which could help tailor the interventions to the patients' needs. In addition, the control groups analyzed were very heterogeneous, and this could be a source of heterogeneity of this study. Another limitation comes from the fact that the analyzed studies covered broad inclusion criteria related to how fatigue was evaluated in those patients enrolled. Finally, some limitations are due to the sample size of the studies and the fact that the patients in some cases were not homogenously under cancer treatment, limitations that are intrinsic to the scarce available data in this regard.

Future studies should address the limitations existing in previous trials. Sample size was an issue in several trials, not providing enough statistical power to draw significant observations. Furthermore, martial arts should be studied in more cancer types, and patients should be stratified in order to be able to extract cancer- and population-specific conclusions. Moreover, trials should try to overcome a common issue where neither the participants nor the instructors or investigators were blinded to the condition against drug trial recommendations. Another limitation was related to the selection bias found in several of the analyzed studies. Longer intervention periods should be followed in order to see if the interventions have effects on cancer survivors.

## **5. Conclusions**

The results of this systematic review and meta-analysis reveal that the effects of practicing martial arts on CRF and QoL in cancer patients and survivors are inconclusive. Although some potential effects were seen for social function and CRF, the results are inconsistent across different measurement methods. Therefore, larger and more homogeneous clinical trials encompassing different cancer types and specific martial arts disciplines are needed before definitive cancer- and symptom-specific recommendations can be made.

**Author Contributions:** Formal analysis, S.S.; Investigation, D.S., S.S. and S.A.; Resources, S.A.; Data curation, D.S., S.S. and S.A.; writing—original draft preparation, D.S.; and writing—review and editing, D.S., S.S. and S.A. All authors have read and agreed to the published version of the manuscript.

**Funding:** There is no financial support for this study.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data that support the findings of this study are available on request from the corresponding author.

**Acknowledgments:** The authors would like to thank all people who participated in this study and Antoni Torres for professional medical writing and editing services.

**Conflicts of Interest:** The authors have no conflict of interests regarding the publication of this study.

## **Appendix A**

**Figure A1.** Results of EORTC QLQ-C30 after sensitivity analysis.

**Figure A2.** Results of FACT-G change after sensitivity analysis.

**Figure A3.** Results of SF-36 after sensitivity analysis.

**Figure A5.** Results of MFSI-SF after sensitivity analysis.

## **References**

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