Physiotherapeutic and non-conventional approaches in patients with chronic low-back pain: a level I Bayesian network meta-analysis

Chronic low back pain (cLBP) is a major cause of disability and healthcare expenditure worldwide. Its prevalence is increasing globally from somatic and psychosocial factors. While non-pharmacological management, and in particular physiotherapy, has been recommended as a first-line treatment for cLBP, it is not clear what type of physiotherapeutic approach is the most effective in terms of pain reduction and function improvement. This analysis is rendered more difficult by the vast number of available therapies and a lack of a widely accepted classification that can effectively highlight the differences in the outcomes of different management options. This study was conducted according to the PRISMA guidelines. In January 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All the randomised controlled trials (RCTs) which compared the efficacy of physiotherapy programs in patients with cLBP were accessed. Studies reporting on non-specific or mechanical cLPB were included. Data concerning the Visual Analogic Scale (VAS) or numeric rating scale (NRS), Roland Morris Disability Questionnaire (RMQ) and Oswestry Disability Index (ODI). Data from 12,773 patients were collected. The mean symptom duration was 61.2 ± 51.0 months and the mean follow-up was 4.3 ± 5.9 months. The mean age was 44.5 ± 9.4 years. The mean BMI was 25.8 ± 2.9 kg/m2. The Adapted Physical Exercise group evidenced the lowest pain score, followed by Multidisciplinary and Adapted Training Exercise/Complementary Medicine. The Adapted Physical Exercise group evidenced the lowest RMQ score followed by Therapeutic Exercises and Multidisciplinary. The Multidisciplinary group evidenced the lowest ODI score, followed by Adapted Physical Exercise and Physical Agent modalities. Within the considered physiotherapeutic and non-conventional approaches to manage nonspecific and/or mechanic cLBP, adapted physical exercise, physical agent modalities, and a multidisciplinary approach might represent the most effective strategy to reduce pain and disability.


Search strategy
This study was conducted according to the 2015 PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions 35 .The following algorithm was established: • P (Problem): cLBP; • I (Intervention): Physiotherapy; • C (Comparison): different modalities of physiotherapy; • O (Outcomes): pain and disability.
In January 2024, the following databases were accessed: PubMed, Web of Science, and Embase.No time constraint was set for the search.The search was restricted to only RCTs.The medical subject headings (MeSH) used in PubMed are shown in the appendix.No additional filters were used in the database search.

Selection and data collection
Two authors (A.K., L.S.) performed the database search.Disagreements were settled by a third author (N.M.) with long experience on systematic reviews.All the resulting titles were screened by hand and, if suitable, the abstract was accessed.If the abstract matched the topic, the full text was accessed.If the full text was not accessible or available, the article was not considered for inclusion.A cross reference of the bibliography of the full text was also conducted to identify additional studies.All pdf of full texts were saved in a dedicated folder shared between the authors in a private cloud.Duplicates were deleted.Study selection and collection lasted three months and the search was updated at each revision phase (last update January, 28 2024).

Data categorisation
Categorization was carried out by three authors (M.N., B.M., F.C.) assessing therapeutic interventions reported in the articles identified.Two independent authors involved in Physical and Rehabilitation Medicine (PRM) used their expertise and referred to recent guidelines and/or systematic reviews regarding the topic of cLBP re-educational techniques to divide treatment protocols into 11 categories: Therapeutic Exercise (TE), Adapted Physical Exercise (APE), Adaptive Training Exercise/Complementary Medicine (CM), Manual Therapy (MT), Physical Agent modalities (PA), Education, Cognitive Re-education (CR), Multidisciplinarity, Kinesiotaping (KT), Sham Therapy (ST), No Intervention.It is important to highlight that most of these categories (TE, APE, MT, PA, Education, CR, Multidisciplinarity, KT and ST) were considered as physiotherapeutic approaches performed by a physiotherapist.Physiotherapy "is services provided by physiotherapists to individuals and populations to

Assessment of the risk of bias and quality of the recommendations
The risk of bias was evaluated in accordance with the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions 44 .Two reviewers (A.K. and L.S.) evaluated the risk of bias in the extracted studies independently.Disagreements were solved by a third senior author (N.M.).RCTs were evaluated using the risk of bias of the software Review Manager 5.3 (The Nordic Cochrane Collaboration, Copenhagen).The following endpoints were evaluated: selection, detection, performance, attrition, reporting, and other biases.

Synthesis methods
The statistical analyses were performed by the main author (F.M.) following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions 45 .Cohen's Kappa (K) was used to quantify the inter-rater agreement among authors for full-text selection.The IBM SPSS version 25 was used.Cohen's K was interpreted according to Altman's definition 46 : K <0.2: poor, 0.2< K <0.4: fair, 0.41< K <0.60: moderate, 0.61< K <0.80: good, and K >0.81 excellent.For descriptive statistics, IBM SPSS version 25 was used.The mean and standard deviation were used.To assess baseline comparability, data distribution was analysed using the Shapiro-Wilk test.Analysis of variance (ANOVA) and the Kruskal-Wallis test were used for parametric and non-parametric data, with P values > 0.1 considered satisfactory.The network meta-analyses were performed using STATA SoftwareMP (version 14; StataCorporation, College Station, Texas, USA).The network meta-analyses were performed through the STATA routine for Bayesian hierarchical random-effects model analysis using the inverse variance method.The standardized mean difference (STD) was used for continuous data.The overall inconsistency was evaluated through the equation for global linearity via the Wald test.If P Wald > 0.1, the null hypothesis could not be rejected, and the consistency assumption is accepted at the overall level of each treatment.Both confidence (CI) and percentile (PrI) intervals were set at 95% in each interval plot.Edge plots were performed to display direct and indirect comparisons and respective statistical weights.Interval plots were performed to

Risk of bias assessment
The analysis of the risk of bias showed a low risk of selection bias because all included studies were RCTs.The allocation of patients to each treatment group was performed with a high degree of quality in most studies, resulting in a low to moderate risk of allocation bias.Moderate risk was present for the risk of detection and

Discussion
Within the considered physiotherapeutic and non-conventional approaches to manage nonspecific and/or mechanic cLBP, adapted physical exercise, physical agent modalities, and a multidisciplinary approach seemt to represent the most effective strategy in reducing pain and disability.
One of the main difficulties in comparing different types of physiotherapeutic management in cLBP is the lack of a comprehensive and widely accepted classification of the various available therapies.The present work is based on a novel, expert-based classification of the different types of physiotherapeutic and non-conventional approaches available for the management of cLBP.While different classifications have been proposed over time, none has been able to successfully highlight the different effectiveness of each kind of management in terms of disability and pain levels 30,31 .As opposed to the previously published works, the presented classification was able not only to include all the treatments available in the current literature but also to differentiate between the efficacy of different types of management.Hopefully, this classification will simplify comparisons between different types of regimens.
APE showed to be one of the most efficient physiotherapeutic strategy, and it is also one of the most investigated commonly management option in the literature.The results of the present work contrast with those of a recent network meta-analysis (NMA) that compared different types of exercise and physiotherapeutic management in the setting of cLBP 196 .While there is agreement that PE and MT are less effective than active therapy options, Owen et al. 196  www.nature.com/scientificreports/ to aggregate data from different studies and achieve a higher numerosity for the analysed category.In turn, this might have led to stronger evidence supporting APE in the present work.In support of the role of APE in the setting of cLBP, a recent NMA by Fernandez-Rodriguez et al. 28 showed that the most effective treatment protocol included, among others, at least one session of Pilates or strength exercise per week.Similar results were also obtained by Hayden et al. 197 , who compared APE schemes to other exercise and treatment types, and concluded that Pilates and McKenzie regimens promoted functional restoration and reduced pain intensity.
Recently, APE has gained popularity for the management of cLBP, and its use has been supported by a number of publications [198][199][200][201][202][203] .In addition to its efficacy, APE presents further advantages such as the possibility of individualizing the therapeutic regimen according to the specific needs and interests of the patients 204,205 .These characteristics can increase compliance with the management 197 and, consequently, its efficacy.Furthermore, APE protocols have been applied safely in elderly and fragile cLBP patients, a particularly relevant group considering population aging 205 .In this setting, APE seems to be able not only to improve pain and function but also to reduce the fear of falling and increase balance 205 .Interestingly, while improving symptoms and function, APE does not seem to increase trunk muscle size 55 .This finding might be related to the short duration of the study (eight weeks) 55 , but might also indicate that the efficacy of APE does not only rely on muscule size.This, in turn, might explain why APE was more effective than other forms of exercise.Possible intervening mechanisms might be the focus of APE on functional improvement or balance, or the encouraging effects of APE on psychosocial outcomes 206 and improvement of kinesiophobia 207,208 : further studies will be required to understand more clearly why this type of management is particularly effective in patients with cLBP.
This important finding can be explained considering that active physiotherapy involves the active participation of the patient in performing therapeutic exercises or activities that promote mobility, strength, and functional improvement 17 .It encourages patients to actively participate in their rehabilitation, fostering self-management and independence 17 .This translates into a greater awareness of patients of their means, in adapting their body to the surrounding environment.Patient do not feel that they have a disability that limits the activities of daily living, but, thanks to the Adapted Physical Exercise, subjects develop the means to differently tackle the required tasks.www.nature.com/scientificreports/ The application of physical agents also proved to be an effective strategy for the management of cLBP.Passive physiotherapy refers to interventions where the patient receives treatment without actively engaging in physical movements, as happens during the application of the physical agents.It relies on external therapeutic interventions facilitated by the physiotherapist on the affected muscles, which often appear hypercontracted in case of pain.Passive stretch reduces stiffness (viscoelastic stress relaxation) and decreases stretch-induced pain 16 .This could represent the first step to consequently work on the functional use of these muscles, as it happens in APE.In other terms, passive treatment can help with immediate pain relief, but active treatment keeps the patient functional in the long term.
Lastly, considering the weight of psychosocial factors in the setting of cLBP 209 , it is not surprising that multimodal therapy was effective under the outcomes of interest considered.Furthermore, the available evidence supports the hypothesis that multimodal management exerts a positive influence in return to work 210 and reduction of work absenteeism 211 .Heitz et al. 212 identified several modifiable and non-modifiable risk factors for the development of persistent cLBP in patients with subacute and cLBP, 56 of them somatic and 61 of them psychosocial.These figures show clearly that focussing solely on the somatic aspects leaves out a vast number of psychological factors involved in the development of cLBP.These data and the evidence presented in the present work thus support the inclusion of psychologic management in the therapy of nonspecific cLBP.While similar positive findings around the employment of multimodal management in cLBP have been reported by different studies [213][214][215][216][217] , future research should focus on what type of psychological therapy is best used in what type of setting 215 .This work does not come without limitations.The main one is represented by the heterogeneity in the inclusion criteria and therapeutic schemes in the available literature.Future studies should focus on adopting a uniform classification of different therapeutic options to allow easier comparability, and larger cohorts with subanalysis of patients in different age ranges or with different symptom durations will be helpful to analyze whether

Figure 1 .
Figure 1.PRISMA flow chart of the literature search.

Figure 3 .
Figure 3. From left to right: edge, interval, and funnel plot of the comparison pain.

Figure 4 .
Figure 4. From left to right: edge, interval, and funnel plot of the comparison RMQ.

Figure 5 .
Figure 5. From left to right: edge, interval, and funnel plot of the comparison ODI.

This allowed Figure 2. Cochrane risk of bias tool. Author, year Journal Class of treatment Type of movement Type of Treatment Patients (n) Follow-up (months) Mean age Women (%)
reported no-to-low evidence for the efficacy of Pilates and McKenzie regimens for the management of cLBP.Both therapeutic options fall in the same APE category in the present work.

Table 1 .
Generalities and patient baseline of the included studies.