physical therapy research articles

• Open access
• Published: 21 May 2024

Efficacy of interventions and techniques on adherence to physiotherapy in adults: an overview of systematic reviews and panoramic meta-analysis

• Clemens Ley   ORCID: orcid.org/0000-0003-1700-3905 1 &
• Peter Putz   ORCID: orcid.org/0000-0003-2314-3293 2  

Systematic Reviews volume  13 , Article number:  137 ( 2024 ) Cite this article

3 Altmetric

Metrics details

Adherence to physiotherapeutic treatment and recommendations is crucial to achieving planned goals and desired health outcomes. This overview of systematic reviews synthesises the wide range of additional interventions and behaviour change techniques used in physiotherapy, exercise therapy and physical therapy to promote adherence and summarises the evidence of their efficacy.

Seven databases (PEDro, PubMed, Cochrane Library, Web of Science, Scopus, PsycINFO and CINAHL) were systematically searched with terms related to physiotherapy, motivation, behaviour change, adherence and efficacy (last searched on January 31, 2023). Only systematic reviews of randomised control trials with adults were included. The screening process and quality assessment with AMSTAR-2 were conducted independently by the two authors. The extracted data was synthesised narratively. In addition, four meta-analyses were pooled in a panoramic meta-analysis.

Of 187 reviews identified in the search, 19 were included, comprising 205 unique trials. Four meta-analyses on the effects of booster sessions, behaviour change techniques, goal setting and motivational interventions showed a significantly small overall effect (SMD 0.24, 95% CI 0.13, 0.34) and no statistical heterogeneity ( I 2  = 0%) in the panoramic meta-analysis. Narrative synthesis revealed substantial clinical and methodological diversity. In total, the certainty of evidence is low regarding the efficacy of the investigated interventions and techniques on adherence, due to various methodological flaws. Most of the RCTs that were included in the reviews analysed cognitive and behavioural interventions in patients with musculoskeletal diseases, indicating moderate evidence for the efficacy of some techniques, particularly, booster sessions, supervision and graded exercise. The reviews provided less evidence for the efficacy of educational and psychosocial interventions and partly inconsistent findings. Most of the available evidence refers to short to medium-term efficacy. The combination of a higher number of behaviour change techniques was more efficacious.

Conclusions

The overview of reviews synthesised various potentially efficacious techniques that may be combined for a holistic and patient-centred approach and may support tailoring complex interventions to the patient’s needs and dispositions. It also identifies various research gaps and calls for a more holistic approach to define and measure adherence in physiotherapy.

Systematic review registration

PROSPERO CRD42021267355.

Peer Review reports

Adherence to physiotherapeutic1 treatment and recommendations is crucial to achieving the planned goals and desired effects [ 1 , 2 ]. This is because the desired effects are usually only achieved in the long term if the recommended treatment and home-based exercises are carried out regularly. However, non-adherence in physiotherapy can be as high as 70%, particularly in unsupervised home exercise programmes [ 1 , 3 ] and may differ among medical conditions [ 4 ]. The World Health Organization defines adherence to therapy as ‘the extent to which a person’s behaviour—taking medication, following a diet and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider’ [ 5 ]. Long-term adherence often requires lifestyle changes, which can be supported by behaviour change techniques (BCTs). BCTs are considered the ‘active, replicable and measurable component of any intervention designed to modify behaviour’ ([ 6 ],cf. [ 7 ]). BCTs are defined and operationalised in the behaviour change taxonomy [ 8 ], based on theoretical underpinnings and a Delphi study. Theoretical models to explain (non-)adherence and (a) motivation as well as techniques to promote behaviour change have been extensively studied in health and exercise psychology [ 9 , 10 , 11 ]. Rhodes and Fiala [ 12 ] argue that despite several strong psychological theories that have been developed to explain behaviour, few provide guidance for the design and development of interventions. Furthermore, theories may not be equally applicable to all behavioural domains, therapeutic regimes and settings. For example, the factors determining adherence to (passive) medication use differ from those influencing adherence to (active) physical therapies and exercise behaviour (cf. [ 5 ]). This review specifically addresses the domain of physiotherapy and therapeutic exercise.

Existing reviews of predictive studies identified factors influencing adherence positively or negatively, showing the predominately conflicting and low evidence of a wide range of predictive factors for adherence [ 1 , 2 , 13 ]. Moderate to strong evidence was shown for some factors, referring to previous (adherence) behaviour and treatment experiences, physical activity level, social support and psychosocial conditions, number of exercises and motivational dispositions. Such predictive studies have identified the possible targets for intervention but do not provide evidence on the efficacy of interventions. In contrast, randomised control trials (RCTs) are recognized as the preferred study design for investigating the efficacy of interventions. Thus, this overview of reviews Footnote 1 aimed at providing a synthesis of reviews that examined RCTs, allowing for the discussion of the efficacy of different interventions and BCTs on adherence-related outcomes.

There are numerous reviews on adherence to physiotherapy and (home-based) exercise, and on BCTs to increase physical activity levels, therapeutic exercise or self-organised exercise [ 1 , 2 , 3 , 14 , 15 , 16 , 17 , 18 ]. Yet, no systematic overview of reviews has been identified that specifically synthesised the efficacy of interventions and techniques to enhance adherence to physiotherapy.

Objectives and research questions

Therefore, the aim of this overview of reviews was to synthesise the evidence on the efficacy of interventions and techniques on adherence in physiotherapy, to explore heterogeneity regarding the theoretical underpinnings, types of interventions used, and the adherence-related measures and outcomes reported, and finally to identify research gaps. Thus, the primary research question is the following: How efficacious are interventions and techniques in increasing adherence to physiotherapy? Secondary research questions are as follows: What types of intervention and behaviour change techniques were investigated? Which theoretical underpinning was reported? How was adherence defined and related outcomes measured?

This overview of reviews is guided by the research questions and aligns with the common purposes of overviews [ 19 , 20 ] and the three functions for overviews proposed by Ballard and Montgomery [ 21 ], i.e. to explore heterogeneity, to summarize the evidence and to identify gaps. This overview approach is appropriate for addressing the research questions specified above by exploring different types of interventions and behaviour change techniques and by synthesising the evidence from systematic reviews of RCTs on their efficacy. The review protocol was registered ahead of the screening process in PROSPERO (reg.nr. CRD42021267355). The only deviations from the registration were that we excluded reviews of only cohort studies, due to the already broad heterogeneity of intervention and outcome measures, and that we additionally performed a panoramic meta-analysis.

Information sources, search strategy and eligibility criteria

The search in seven databases, PEDro, PubMed, Cochrane Library, Web of Science, Scopus, PsycInfo and CINAHL (Cumulative Index to Nursing and Allied Health Literature), was last updated on January 31, 2023. The search strategy was structured according to the PICOS (Population, Intervention, Comparison, Outcome and Study Type) scheme. The search terms related to physiotherapy and motivation or behaviour change and adherence and effectiveness/efficacy (details on the searches are listed in Additional file 1 ). A filter was applied limiting the search to (systematic) reviews. No publication date restrictions were applied.

Table 1 outlines the study inclusion and exclusion criteria. Only studies published in peer-reviewed journals were included. The review addressed adult patients, with any illness, disease or injury, and thus excluded studies on healthy populations. Reviews in the field of physiotherapy, physical therapy or the therapeutic use of exercise or physical activity were included if they investigated adherence as a primary outcome. Studies measuring adherence as a secondary outcome were excluded as they do analyse interventions that were not primarily designed to promote adherence and thus are outside the scope of this overview. Reviews that analysed only studies on digital apps or tools (e.g. virtual reality, gamification, exergames or tele-rehabilitation) were excluded from this overview, as they were outside of the scope of this overview. Only systematic reviews that appraised RCTs were included. Reviews appraising RCTs and other study designs were included if RCT results could be extracted separately. Systematic reviews are in our understanding literature reviews of primary studies with a comprehensive description of objectives, materials and methods; considering the risk of bias and confidence in the findings; and reporting according to the PRISMA statement [ 22 , 23 , 24 ]. Adherence is defined as the extent to which a person’s behaviour corresponds with treatment goals, plans or recommendations [ 5 ]. Related terms used in the literature are compliance, maintenance, attendance, participation and behaviour change or lifestyle modification and were thus included in the search strategy.

Screening and selection process

Author CL conducted the search in the seven different databases and removed duplicates, using the Zotero bibliography management tool. Following this, authors CL and PP both independently screened the titles and abstracts of the resulting sources (see Fig.  1 Flow diagram). After removing the excluded studies, PP and CL independently screened the remaining full texts in an unblinded standardised manner. Reasons for exclusion were noted in a screening spreadsheet. Any discrepancy was discussed, verified and resolved by consensus.

Data collection process and data items

Data extraction was done by CL after agreeing with PP on the criteria. A spreadsheet was created with the following data extraction components: (i) objectives and main topic of the review; (ii) study design(s) and number of studies included and excluded; (iii) search strategies (incl. PICO); (iv) population including diagnosis, sample sizes and age; (v) intervention and comparison, theoretical foundations and models used for designing the intervention; (vi) time frames, including follow-up; (vii) adherence-related outcome and outcome measures; (viii) key findings; (ix) analysis of primary studies (meta-analytical, other statistical or narrative analysis); and (x) tools used for the quality assessment, risk of bias and evidence grading. Primary outcomes on adherence included, adherence rates or categories, engagement, attendance and participation, and accomplished physical activity levels. PP verified the data extraction results. The data was extracted as reported in the systematic reviews, then reformatted and displayed in the tables and used for the narrative synthesis.

Assessment of risk of bias across reviews

Systematic reviews of RCTs are ranked highest in the evidence level [ 25 ], but are subjected to risk of bias (RoB). In an overview of reviews of systematic reviews, there are further risks of bias, in addition to those deriving from the primary studies and those deriving from the review of those studies. Particularly, the overlap of reviews regarding the included individual studies may bias the findings. According to the purpose of this overview, i.e. to synthesise the wide range of interventions and behaviour change techniques used to promote adherence and to summarise the evidence of their efficacy, the overlap of reviews regarding intervention or population was not an exclusion criterion. For considering the overlap of primary studies among the reviews, CL extracted the primary RCTs from the included reviews, identified the unique trials and compared the frequency of their use across the reviews (see results overlap of review and Additional file 2 ). Furthermore, where two or more reviews provided findings on the same technique (e.g. on the efficacy of behavioural graded activities), the overlap of primary studies was assessed specifically for that finding. If the evidence came from the same study, this was taken into account and marked accordingly in Table  5 to avoid double counting and overestimation of evidence.

Assessment of risk of bias within the reviews

CL and PP independently assessed the quality and risk of bias of the systematic reviews included, using the AMSTAR-2 tool [ 26 ]. Any discrepancy was discussed and resolved by consensus. AMSTAR (A MeaSurement Tool to Assess systematic Reviews) was developed to evaluate systematic reviews of randomised trials. The AMSTAR-2 revision enables a more detailed assessment of systematic reviews which may also include non-randomised studies of healthcare interventions. The applied AMSTAR-2 checklist consists of 16 items, whereof seven are classified as critical, and the appraisal results in an overall confidence rating distinguishing between critically low, low, moderate or high [ 26 ]. In addition, the overall confidence in the review was stipulated by the number of positive assessments in relation to the applicable domains (depending if meta-analysis was performed or not) and considering whether an item represents a critical domain or not [ 26 ].

Synthesis methods

Panoramic meta-analysis.

Among the included reviews, there were four meta-analyses [ 7 , 16 , 27 , 28 ], which were pooled as a panoramic meta-analysis based on the reported effect sizes and standard errors using IBM SPSS Version 29 (IBM Corp., Armonk, NY, USA). All four meta-analyses used the standardized mean difference as effect size. Standard errors were calculated from the reported 95% CI as \(\frac{\mathrm{upper bound }-\mathrm{ lower bound}}{3.92}\) . Inverse variance was used to weight the meta-analyses, statistical heterogeneity was assessed by I -squared and a fixed-effects model was selected based on the absence of statistical heterogeneity of true effects. Eisele et al. [ 7 ] included 15 primary trials that examined the effect of BCTs on physical activity adherence. They pooled results for medium-term (3–6 months) and long-term (7–12 months) interventions, from which we selected the medium-term model that best matched the eligibility criteria of the other included meta-analyses. Levack et al. [ 27 ] included nine primary trials that examined the effect of goal-setting strategies on engagement in rehabilitation. Among models with other outcomes, we selected this model because it best matched the aim of this overview, and it was most consistent with the outcomes of the other included meta-analyses. McGrane et al. [ 28 ] included six primary trials, representing 378 subjects that examined the effects of motivational interventions on physiotherapy session attendance. They reported another model with perceived self-efficacy as an outcome, but we selected the attendance model because it best matched the aim of this overview, and it was most consistent with the outcomes of the other included meta-analyses. Nicolson et al. [ 16 ] included two primary trials that examined the effect of booster sessions on self-rated adherence. Results were summarized by a forest plot and publication bias was assessed graphically by a funnel plot, although the small number of individual meta-analyses included limits its interpretability. Alpha was set at 0.05.

Narrative synthesis

The narrative synthesis was performed by CL in constant dialogue with and verification of PP. Guided by the research questions, the narrative synthesis of the extracted data was manifold. First, we explored the heterogeneity of interventions, measures and adherence-related outcomes across and within the reviews using the data extraction table. Definitions and measures of adherence were compared among the reviews and discussed. Second, analysis of the descriptions of the interventions and their respective components/techniques, their theoretical underpinning and their objectives was used to classify the interventions according to different types of intervention, namely the informational/educational, the cognitive/behavioural/motivational and the relational/psychosocial intervention. Consequently, for each type of intervention, the results on the efficacy were narratively synthesised. In addition, reported differences in efficacy among medical conditions, theoretical underpinnings and physiotherapeutic settings were summarised based on the data extraction table. Third, the results on the efficacy of the interventions and BCTs were further summarised in a table and then restructured according to the evidence level as reported in the systematic reviews and the confidence in the reviews as analysed by the AMSTAR-2. Therefore, the levels of evidence were extracted as reported in the reviews, which are based on different evidence appraisal schemes: GRADE (high, moderate, low, very low certainty of evidence), Cochrane Collaboration Back Review Group Evidence Levels (strong, moderate, conflicting, limited, no evidence) and self-developed tools. Afterwards, they were compared for the respective intervention/technique across the relevant reviews, considering the confidence in the review and the comprehensiveness of the review as well. The levels of evidence are presented in the table with the categories high, moderate, low and very low. The efficacy supported by the evidence is also based on the results reported in the reviews. In case of overlapping reviews or discrepancies between the reviews, the primary studies were consulted. The category yes refers to results of merely positive effects, and inconsistent refers to findings of positive and no effects of the intervention (techniques) analysed. The category no indicates that the intervention was not efficacious. No negative effects (i.e. favouring the control condition) were reported for the intervention (techniques) shown.

The reporting of findings followed the PRIOR reporting guideline for overviews of reviews of healthcare interventions [ 29 ].

Study selection results

Of the 187 records screened, 19 were included (see Fig.  1 ). Main reasons for exclusion were not a systematic review of RCTs ( n  = 79), adherence not the primary outcome ( n  = 60), and lack of physiotherapy relevance ( n  = 39) (see Fig.  1 ).

Flow diagram, based on PRISMA [ 24 ] and PRIOR [ 29 ] guidelines. Legend: *Multiple reasons for exclusion were possible

Characteristics and diversity of included reviews

The selection strategy resulted in a broad heterogeneity of included reviews. The 19 included reviews differed in their eligibility criteria of the primary studies as well, resulting in substantial clinical diversity, i.e. the inclusion of heterogenous conditions, intervention types and settings (see Table  2 ) and methodological diversity, i.e. the variability in study design, outcome measurements and risk of bias (see Tables 3 , 4 and 5 ). Musculoskeletal diseases [ 6 , 7 , 17 , 30 , 31 , 32 ] and pain [ 13 , 16 , 33 , 34 , 35 ] were the most investigated medical conditions. Those reviews that did not limit their search to a specific disease [ 12 , 27 , 28 , 36 , 37 , 38 , 39 , 40 ] yielded predominantly studies on musculoskeletal diseases. All reviews included adults only (18 and older). One focused on elderly (65 and older) people [ 40 ] and one on older (45 and older) adults [ 16 ]. Fourteen of the 19 reviews analysed RCTs only [ 6 , 7 , 16 , 17 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 39 , 40 ]; one also included besides RCT cohort studies [ 13 ] and three [ 12 , 37 , 38 ] also included any other quantitative study design (see Table  3 ). Four reviews performed a meta-analysis [ 7 , 16 , 27 , 28 ], and two studies were Cochrane Reviews [ 27 , 35 ]. Four reviews [ 6 , 7 , 17 , 40 ] analysed the use of BCTs and rated the interventions according to a BCT taxonomy [ 8 ].

Results of the individual reviews

The 19 reviews contained a total of 205 unique RCTs. Table 3 shows the main results of each review.

Results of quality assessment and confidence in the reviews

The critical appraisal with the AMSTAR-2 tool (see Table  4 ) showed that four reviews were rated with moderate to high quality [ 7 , 16 , 27 , 35 ], whereas all others resulted in a critically low to low overall confidence in the review. Frequent shortcomings were not explaining the reasons for the inclusion of primary study designs, and an insufficient discussion of the heterogeneity observed. Furthermore, as many reviews did not explicitly mention a pre-established, published or registered protocol or study plan, it is uncertain whether the research followed a pre-specified protocol and whether there were changes and/or deviations from it, and, if so, whether decisions during the review process may have biased the results [ 26 ].

Risk of bias and evidence assessment within reviews

The reviews used various approaches to appraise the evidence, particularly the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system [ 13 , 16 , 26 , 27 ], the evidence levels by the Oxford Centre for Evidence-Based Medicine [ 28 ] or the system by Cochrane Collaboration Back Review Group [published by 25,30] [ 31 , 32 , 33 , 34 ]. Three reviews modified existing or developed their own tool or checklist [ 12 , 35 , 36 ]. For the assessment of the risk of bias and/or quality of the individual studies, the reviews used the following tools: PEDro Scale [ 7 , 13 , 26 , 32 , 37 ], Cochrane Collaboration Back Review Group Quality Assessment Tool [ 31 , 34 ], Cochrane Risk of Bias criteria [ 6 , 16 , 17 , 27 , 33 , 37 , 38 , 39 ], the Delphi List [ 40 ] or modified or developed own tools [ 12 , 35 , 36 ].

A recurring concern regarding potential performance bias was the lack of therapist blinding, which is almost impossible to implement in this research field [ 7 ]. Attrition bias, due to low sample size or drop-outs, and measurement bias, due to the mere use of subjective measures, were also highlighted in the reviews. Another concern was the availability and selection of adequate control groups. Control groups, such as usual practice, unspecific exercise group or alternative intervention commonly include varying numbers of BCTs which must be considered when assessing and comparing contents of interventions [ 7 ]. The comparability of the intervention and control group regarding adherence-related outcomes is further hindered by poor descriptions of the intervention, uncertainty about treatment fidelity and implementation processes, varying competences and proficiency of the therapist, and the diverse translation of theoretical models and use of intervention techniques [ 7 , 34 , 39 ]. Rhodes and Fiala [ 12 ] pointed out that procedures of RCTs, such as several pre-screenings and measurement batteries, may lead to a potential self-selecting of only the most motivated individuals. This may limit the ability to compare intervention to the control group, as both groups are (already) highly motivated, and to detect changes, due to the already high motivation and disposition to adhere. This may explain in part, that the reviews reported many studies that failed to provide evidence for intervention efficacy on adherence. In addition, the restricted timeline (limited duration for observation and follow-up) of the studies may confound/skew the results, as drop-out may occur shortly after the end of the study and long-term adherence is not measured [ 12 ].

Overlap of reviews

The 19 reviews included from 3 to 42 individual RCTs. In sum, the reviews included 261 RCTs (multiple publications on the same trial were counted as one; thus, the number of trials was counted), whereby 34 trials were included in various reviews (see Additional file 2 , Overlap of reviews), resulting in 205 unique RCTs. Of these 34 trials included in multiple reviews, 25 were included in two different reviews. The following trials were included more than twice: Basler et al. 2007 (8x), Friedrich et al. 1998 (7x), Schoo et al. 2005 (4x), Vong et al. 2011 (4x), Asenlof et al. 2005 (3x), Bassett and Petrie 1999 (3x), Brosseau et al. 2012 (3x), Bennell et al. 2017 (3x), Gohner and Schlicht 2006 (3x) and Duncan and Pozehl 2002, 2003 (3x).

In total, the overlap of primary trials in the reviews is considered low; except among reviews [ 27 , 39 ] and among reviews [ 12 , 16 , 28 , 30 ]. Two reviews [ 27 ] and [ 39 ] were conducted by the same authors, within the same field, i.e. goal planning and setting, however with a different approach and research question. Reviews [ 12 , 16 , 28 , 30 ] have a considerable amount of overlap. Still, each of these reviews included unique RCTs, not analysed in any of the other reviews, and they do focus on different research questions, foci and analyses. Therefore, we did not exclude an entire review due to an overlap of studies.

Synthesis of results

The synthesis focused on answering the research questions. We began by presenting the narrative synthesis findings on how adherence was measured, what types of intervention and BCTs were investigated, and which theoretical underpinnings were reported. Afterwards, we synthesised the evidence on the efficacy of the interventions and BCTs, both meta-analytically and narratively.

Measures of adherence and related outcomes

The reviews included studies with a heterogeneous use, breadth and measures of adherence. Mostly, they refer to adherence as the extent to which a person’s behaviour corresponds with treatment goals, plans or recommendations ([ 30 ],cf. [ 5 ]). McLean and colleagues [ 30 ] expressed that within physiotherapy, the concept of adherence is multi-dimensional and could refer to attending appointments, following advice or undertaking prescribed exercises. The terms adherence and compliance were sometimes used interchangeably, referring to the degree of treatment attendance or accomplishment of physical activity levels, participation and recommendations, irrespective of how the treatment goals and plans were established. Yet, for definition purposes, the distinction between agreed and prescribed goals and plans was occasionally used in the reviews to distinguish adherence from compliance .

For analytical purposes, adherence was frequently dichotomised, establishing a cutoff point or percentage used to distinguish adherence from non-adherence. One was considered adherent, for example, if he/she achieved more than 70% or 80% of the targeted, recommended or prescribed sessions. Few studies graded the degree of adherence according to multi-categorical cut-off points (e.g. very low, low, moderate and high adherence). Only in one review [ 13 ], one study was named that distinguished a certain fluctuation in the adherence pattern, i.e. Dalager et al. [ 41 ] included besides the minutes exercised in a week the regularity of participation, distinguishing regular from irregular participation. Self-reported diaries, exercise logs and attendance lists were the most commonly used data recording instruments [ 33 , 35 , 37 ]. Adherence to home-based programmes was mainly measured with self-reported diaries, which are problematic as the only source, due to poor completion rates, and the possibility of inaccurate recall and self-presentation bias [ 18 , 33 ]. Digital devices (e.g. accelerometers or pedometers) may be used additionally to measure adherence; however, their use may also be problematic, as they require certain adherence to a systematic use of the device and the mere use of the device also may increase adherence [ 18 , 33 ]. One study reported the use of the Sport Injury Rehabilitation Adherence Scale (SIRAS) [ 42 ], which measures the patients’ degree and manner of participation in a session and compliance with the therapist’s instructions and plan. Thus, it does not measure adherence over a certain period of time nor adherence to recommendations or home-based exercise, but it can be used to assess the intensity of rehabilitation exercises, the frequency with which they follow the practitioner’s instructions and advice, and their receptivity to changes in the rehabilitation programme during that day’s appointment [ 42 ].

Interventions used to promote adherence

The reviews included a wide range of different interventions, which we grouped into three different intervention types:

Information provision and patient education were investigated in seven reviews [ 12 , 13 , 30 , 31 , 33 , 34 , 36 ], including (i) video- and audio-assisted patient education, (ii) phone calls, (iii) use of supporting materials and spoken or graphically presented information or (iv) other didactical interventions. Patient education has been defined as ‘any combination of learning experiences designed to facilitate voluntary adoption of behaviour conducive to health’ [ 43 ]. Niedermann et al. [ 31 ] distinguished between ‘purely’ educational programs based on knowledge transfer and psychoeducational programs. In the latter, motivational techniques and shared knowledge-building processes are added to the educational programme, which is done similarly in health coaching [ 34 ], and thus also relate to the cognitive, behavioural and relational/psychosocial interventions.

Cognitive and behavioural motivational interventions were relating frequently to cognitive-behavioural and social-cognitive theories, and applied (i) behavioural graded exercise; (ii) booster sessions, refresher or follow-up in situ by the therapist or via phone call; (iii) behavioural counselling (focusing on readiness to change); (iv) psychoeducational counselling; (v) supervision; (vi) (unspecified) motivational intervention; (vii) positive reinforcement; (viii) action and coping planning; and (ix) goal setting [ 7 , 12 , 13 , 16 , 27 , 28 , 30 , 32 , 33 , 34 , 39 ].

Relational and psychosocial interventions were less investigated overall. Related aspects included (i) social support; (ii) patient-centeredness, in particular patient-led goal setting, motivational interviewing and the therapeutic or working alliance; and (iii) emotional components [ 6 , 13 , 17 , 33 ].

The included reviews focused either on one particular or several types of intervention. Particularly, four reviews [ 6 , 7 , 17 , 40 ], which used a BCT taxonomy to analyse the interventions of the primary studies, described BCTs relating to all three intervention types. While this distinction of different types of interventions is useful to showcase the range of diverse interventions and techniques, they do have a great overlap and include a mix of different BCTs. For example, the way of facilitation of information, supervision or goal setting was approached differently according to the relational approach, i.e. being more instructive, directive or more collaborative, participatory, patient-led ([ 31 ],cf. [ 34 ]).

Theoretical underpinning of interventions

No review focused on only one theoretical foundation or excluded studies based on any theoretical model or not underpinning the intervention. In total, the reviews included studies with diverse theoretical models and varying degrees of theoretical underpinning. References to the cognitive behavioural theory (CBT) and to the social-cognitive theory were frequent in the individual studies. Furthermore, the self-determination theory, the transtheoretical model, the health belief model, the social learning theory and the socioemotional selectivity theory were used in some individual studies (cf. [ 11 ]). The heterogeneity in the theoretical underpinning of the interventions is reinforced by the given overlap of the theories and models (cf. [ 11 ],[ 28 ]) and various BCTs are key components of several theories [ 17 ]. Furthermore, theories were not used enough to explicitly inform and underpin interventions and they were translated into practise in different ways; thus, interventions based on the same theory may differ substantially [ 17 ].

The BCT Taxonomy v1 [ 8 ], which relates to various theoretical models, was used in four reviews [ 6 , 7 , 17 , 40 ] to identify BCTs in interventions in a standardized manner. The Behaviour Change Wheel [ 44 ], which is linked to the BCT Taxonomy v1, was referred to in one review [ 40 ] pointing to its usefulness for designing a behaviour change intervention. The number of BCTs used appears to be relevant, as interventions using a higher number (≥ 8) of BCTs achieved a significant effect (pooled SMD = 0.29, 95% CI 0.19–0.40, p  < 0.001), whereas interventions using a lower number (< 8) of BCTs did not (pooled SMD = 0.08, 95% CI -0.11 to 0.27, p  = 0.41).

Overall efficacy and heterogeneity according to the panoramic meta-analysis

Although there was statistical heterogeneity ( I 2 from 41 to 63%) between the primary studies included in each meta-analysis [ 7 , 16 , 27 , 28 ], there was no heterogeneity between the pooled effects of these four meta-analyses ( I 2 0%). This means that all variability in the effect size estimates (SMD from 0.20 to 0.39) was attributable to sampling error, but there was no variability in the true effects. Although the interventions were selected based on different eligibility criteria (BCTs, goal-setting strategies, motivational interventions and booster sessions), they appear to be very similar in terms of the effects they trigger. There was no overlap between the primary trials included in the meta-analyses. The pooled SMD was 0.24 (95% CI 0.13, 0.34) (Fig.  2 ). Effect size estimates were somewhat larger in those meta-analyses with less weight in the model (i.e. due to a larger standard error). However, no obvious publication bias could be detected in the funnel plot (Fig.  3 ). Sensitivity analyses in the meta-analysis in Eisele et al. [ 7 ], considering only studies with PEDro scores of 6 or more, revealed slightly lower effect sizes but still statistically significant effect sizes regarding medium-term effects (SMD PEDro>=6 0.16, 95% CI 0.04–0.28, p  < 0.01 versus SMD all 0.20, 95% CI 0.08–0.33, p  < 0.01) and higher numbers of BCTs (SMD PEDro>=6  = 0.26, 95% CI 0.16–0.37, p  < 0.001 versus SMD all  = 0.29, 95% CI 0.19–0.40, p  < 0.001), indicating that low-quality studies may tend to overestimate the efficacy ([ 7 ],cf. [ 31 ]).

Forest plot of panoramic meta-analysis: interventions aiming at improving adherence, adherence-related outcomes

Legend: Eisele 2019. Intervention: Interventions aiming at improving physical activity levels or adherence, containing at least one BCT. Comparison: Usual care, minimal intervention, placebo or no intervention. Outcome: Any measure of physical activity level or adherence to any kind of physical activity. Levack 2015. Intervention: Goal setting (with or without strategies to enhance goal pursuit). Comparison: No goal setting. Outcome: Engagement in rehabilitation. McGrane 2015. Intervention: Motivational interventions as part of a package, psychological strategies, theory-based instructional manuals, Internet-based behavioural programmes and relapse prevention, and re-inforcement strategies. Comparison: Any comparison (not specified). Outcome: Attendance at physiotherapy sessions/exercise classes. Nicolson 2017. Intervention: Booster sessions to increase adherence to therapeutic exercise. Comparison: Contextually equivalent control treatments. Outcome: Self-rated adherence

Funnel plot of publication bias

Efficacy of informational and educational interventions

The results of five—partly overlapping—reviews [ 12 , 30 , 31 , 34 , 36 ] showed, with a very low evidence base, that interventions that primarily aimed at information provision and knowledge transfer to the patient had limited efficacy on adherence-related outcomes. There was conflicting evidence and inconsistent efficacy of video-assisted patient education [ 36 ] and individualised exercise videos [ 12 , 30 ] in modifying behaviour or adherence. However, the authors identified the format in which the educational information is presented and the complexity of the addressed behaviour as crucial factors [ 36 ]. Videos that provide only spoken or graphically presented health information are inappropriate tools for changing patient behaviour. However, videos with a narrative format appear to be a powerful education tool [ 36 ]. Low evidence based on one study [ 12 , 30 ] indicates that additional written information seems superior to verbal instructions alone (mean difference between groups 39.3%, p  < 0.001). With a high overlap of studies, two reviews [ 30 , 31 ] showed that there is limited evidence for long-term effects of patient education targeting knowledge acquisition. While the informative and instructive educational approach is an essential part of patient education, patient education often involves more than the transfer of knowledge [ 30 , 31 , 34 ]. Niedermann et al. [ 31 ] compared educational and psychoeducational interventions and provided arguments in favour of psychoeducational approaches that enrich patient education with motivational strategies and techniques (cf. [ 34 ]).

Efficacy of cognitive and behavioural motivational interventions

Several (though partly overlapping) reviews [ 12 , 16 , 28 , 30 , 33 , 37 ] examined studies on additional motivational interventions that were based on social-cognitive or cognitive-behavioural theories. McGrane et al. [ 28 ] concluded heterogeneity of motivational interventions, outcomes and measurements as potential causes for conflicting evidence regarding effects on exercise attendance and PT adherence, as they found no significant difference ( p  = 0.07) in exercise attendance between additional motivational intervention groups and their controls (pooled SMD 0.33, 95% CI -0.03 to 0.68, I 2 62%), but a significant ( p  < 0.01) medium-sized effect of additional motivational interventions on self-efficacy beliefs (pooled SMD 0.71, 95% CI 0.55 to 0.87, I 2 41%). The heterogeneity hindered in this meta-analysis the statistical analysis of subgroups to determine and compare the efficacy of different components and approaches to motivational interventions [ 28 ]. Another meta-analysis [ 16 ] found moderate-quality evidence that booster sessions with a physiotherapist helped people with hip/knee osteoarthritis to better adhere to therapeutic exercise (pooled SMD 0.39, 95% CI 0.05 to 0.72, p  = 0.02, I 2 35%). Moderate evidence for the efficacy of supervision (2 studies, n  = 193) favouring adherence was shown [ 13 , 33 , 35 ].

In four reviews [ 16 , 32 , 33 , 35 ], four unique high-quality trials supported the use of motivational strategies and behavioural graded exercise to improve adherence to exercise (effect sizes 0.26–1.23)[ 16 ]. Behavioural graded exercise includes a preset gradual increase of the physical activity through facility-based interventions followed by booster sessions [ 45 ] and uses principles of operant conditioning and self-regulation [ 16 ].

While cognitive behavioural programmes seem superior to exercise alone for short-term adherence and clinical attendance [ 30 ], behavioural counselling focusing on readiness to change, action and coping plans and/or audio/video exercise cues seem not to improve adherence significantly [ 16 ]. Holden [ 34 ] concludes inconsistent evidence for health coaching based on the transtheoretical model of change, with one RCT showing some efficacy on exercise compliance (SMD = 1.3). However, the frequently referred to study of Göhner and Schlicht [ 46 ], who analysed a cognitive-behavioural intervention with a strong emphasis on action and coping planning [ 12 ], showed no difference between experimental and control groups in the first 11 weeks, but a significant difference 5 months later on behaviour (SMD = 0.83) as well as differences over all time-points on self-efficacy (interaction effect of time by group, F (3, 43) 10.36, p  < 0.001, n  = 47) favouring the intervention [ 46 ]. Motivational interventions, including positive reinforcement, increased (i) adherence to home exercise in one RCT [ 33 ], (ii) reported frequency of exercise in two RCTs [ 35 ] and (iii) self-efficacy beliefs in two RCTs, in the short-term (SMD = 1.23) and in the long-term (SMD = 0.44) ([ 16 ],cf. [ 30 ]). Self-efficacy beliefs relate to the trust in one’s capacities/competencies to cope with daily demands [ 47 ] and are associated (moderate evidence) with adherence [ 13 , 48 ].

Levack et al. [ 27 ] conclude some evidence that goal planning/setting improves engagement in rehabilitation (motivation, involvement and adherence) over the duration of the programme (9 studies, 369 participants, SMD 0.30, 95% CI -0.07 to 0.66). Furthermore, they show a low-quality evidence for effects on patient self-efficacy from more structured goal setting compared to usual care with or without goal setting (2 studies, 134 participants; SMD 0.37, 95% CI 0.02 to 0.71) and from goal setting compared to no goal setting (3 studies; 108 participants; SMD 1.07, 95% CI 0.64 to 1.49). The review did not detect differences in efficacy between the approach taken to goal planning. However and similar to patient education [ 34 ], the review authors argue that the lack of clarity about the effects and the low evidence is due to the heterogeneity of the implementation of goal planning, lack of detailed descriptions of the goal-setting process in the intervention groups but also in the control groups, and methodological flaws ([ 27 , 39 ],cf. [ 13 ]).

The BCTs from the cluster goals and planning showed various positive effects, although not fully consistently [ 6 , 7 , 40 ]. Eisele et al. [ 7 ] identified goal setting (behaviour) , problem-solving , goal setting (outcome) , action planning and reviewing behaviour goal(s) as often used in non-effective interventions but also in effective ones. A trial that showed negative effects included problem-solving and goal setting (outcome) as well. Room et al. [ 40 ] found one study on older people and Thacker et al. [ 6 ] two home-exercise-related studies that used BCTs from the goals and planning cluster (i.e. problem-solving and action planning), but none of the studies found differences in favour of the intervention. Willett et al. [ 17 ] adjusted the BCTv1 taxonomy to differentiate patient-led and therapist-led goal setting and showed that patient-led goal setting (behaviour) achieved among the highest efficacy ratios across time points.

Efficacy of relational and psychosocial interventions

The BCT Social Support (unspecified) refers to ‘advise on, arrange or provide social support (e.g. from friends, relatives, colleagues, ’buddies’ or staff) or non-contingent praise or reward for the performance of the behaviour . It includes encouragement and counselling, but only when it is directed at the behaviour’ [8, Supplementary Material]. Eisele et al. [ 7 ] identified this BCT in 19 interventions and 10 control conditions. They found this BCT in three trials supporting efficacy and in seven trials supporting inefficacy. In contrast, Thacker et al. [ 6 ] found this BCT in all effective interventions but not in the non-effective ones. Willet et al. [ 17 ] concluded from their review that this BCT has among the highest efficacy ratios across time points to promote adherence to physical activity.

Social support may come along with monitoring and feedback, which can be graphically or narratively presented by the therapist. Willett et al. [ 17 ] recommend that self-monitoring (e.g. activity diaries), feedback on behaviour as well as social support should be used—beyond monitoring purposes—for explicit intervention purposes (e.g. to foster self-efficacy beliefs). Feedback on behaviour alone does not seem to be efficacious [ 6 ], but feedback can be efficacious for instance in combination with social support or goal setting and planning [ 17 , 40 ].

Patient-centred approaches were also included in the relational/psychosocial intervention type. Motivational interviewing, which is a collaborative, patient-centred communication style to promote behaviour change [ 49 ], was used in three studies, indicating positive effects on exercise compliance, physical activity and exercise at home in two trials, whereas no effect in a pilot study [ 28 ]. There is low evidence from three RCTs for positive effects of the therapist-patient alliance on global assessments; however, the efficacy on adherence-related outcomes is unclear [ 36 ]. The terms working or therapeutic alliance refer to the social connection or bond between therapist and patient/client, including reciprocal positive feelings, (assertive) communication, empathy, and mutual respect as well as collaboration, shared decision-making, agreement on the treatment goals and tasks [ 36 , 50 ]. The therapeutic alliance is a patient-centred approach as well. Patient-led goal setting was more often a component within efficacious interventions than therapist-led goal setting [ 17 ].

None of the included reviews focused specifically on affective interventions. However, some interventions relate to affective components, for example patient-led goal setting or motivational interviewing may cover emotional needs [ 27 ]; health coaching, therapeutic alliance or social support may include emotional support [ 13 , 34 , 35 , 38 ]; monitoring may consider emotional consequences [ 6 ]; or messaging and information provision may include emotional components [ 36 ]. Room et al. [ 40 ] included one RCT [ 51 ], comparing emotionally meaningful messages against factual informational messages, but with no significant differences between the groups.

Efficacy according to the theoretical underpinning

McGrane et al. [ 28 ] provide a narrative analysis of the efficacy of interventions according to the different theoretical underpinnings. In their review, the cognitive-behavioural theory (CBT) was the most popular theory (4 primary studies) and showed to be efficacious in improving self-efficacy and activity limitations, but not consistently regarding attendance and attrition [ 28 ]. The social-cognitive theory was used in three studies, showing improvements in self-efficacy, action and coping planning, and attendance, but conflicting results for exercising in the short and long term. One intervention [ 52 ] based on self-determination theory showed to be efficacious to improve adherence to physical activity. In contrast to McGrane et al. [ 28 ], the reviews [ 12 , 30 , 35 ] point to moderate to conflicting evidence for no or inconsistent efficacy of CBT-based approaches to physiotherapy programmes (see Efficacy of cognitive and behavioural motivational interventions ). Jordan [ 35 ] concluded that the addition of transtheoretical model-based counselling to physiotherapy is no more effective than physiotherapy and a sham intervention (GRADE: High (high quality); Silver). Notably, the interventions may not be representative of the theory described due to diverse translations of the theory into practice and the overlap of the same BCTs among the theories.

Various theories (e.g. the transtheoretical model or the Health Action Process Approach [ 53 ]) and studies [ 54 ] distinguish the action or adoption phase from the maintenance phase at 6 months. Interestingly, Willet et al. [ 17 ] found in total higher short (< 3 months) and long-term (12 months and more) than medium-term (around 6 months) efficacy ratios, pointing to the risk of drop-out when changing from the (short-term) adoption phase to the (long-term) maintenance phase [ 17 ]. Eisele et al. [ 7 ] divided in their meta-analysis the short-term (< 3 months), medium-term (3–6 months) and long-term (7–12 months post-intervention) differently, showing a small medium-term overall effect (pooled SMD 0.20, 95% CI 0.08–0.33, p  < 0.01), but no significant long-term effect of interventions comprising BCTs in enhancing physical activity adherence (pooled SMD 0.13, 95% CI 0.02–0.28, p  = 0.09).

Efficacy according to the different types of exercise, physiotherapeutic settings and medical condition

In their Cochrane review, Jordan et al. [ 35 ] compared the evidence for the efficacy of different types of exercises and physiotherapy settings. Graded exercise is beneficial for adherence (moderate evidence). The exercise type does not appear to play an important role (moderate evidence). Whether water-based exercise favours adherence is unclear (low evidence and inconsistent results). Furthermore, the supervision of exercising (moderate evidence) is beneficial for adherence, but also self-management programmes improve exercise frequency compared to waiting list or no-intervention control groups (moderate evidence). Exercising individually seems to improve attendance at exercise classes more than exercising in a group (moderate evidence), as individual sessions could be scheduled at more convenient times and missed sessions could be rescheduled, whereas group sessions were scheduled at relatively inflexible times, and missed sessions could not be rescheduled [ 35 ]. However, adding group exercise to a home exercise programme can increase overall physical activity levels (moderate evidence) [ 35 ]. While the results of home- versus clinic-based interventions were conflicting and confounded by the intervention approaches, a combination of home- and clinic-based approaches may be promising [ 12 ] and aligns with the moderate-quality evidence that self-management programmes, refresher or booster sessions with a physiotherapist assist people to better adhere to therapeutic exercise [ 16 ].

No study was identified in the reviews that compared other settings, such as private- and public-funded physiotherapy or primary care and rehabilitation settings regarding adherence outcomes. No review and no study comparing the same educational, motivational, or BCT-based intervention across different conditions were identified.

This overview of systematic reviews addresses adherence in the physiotherapy and therapeutic exercise domain, aiming to summarise the evidence on the efficacy of interventions, to explore heterogeneity and to identify research gaps. The overview of reviews provided an adequate approach to generate answers to the research questions. Nineteen reviews, covering 205 unique trials, were included and narratively synthesised. In addition, four meta-analyses were pooled in a panoramic meta-analysis. The findings provide an overview of the diverse interventions and techniques aiming to enhance adherence, ranging from informational/educational to cognitive/behavioural/motivational and to relational/psychosocial intervention types. Furthermore, it synthesised their efficacy in physiotherapy for adults.

Confidence in the reviews was rated moderate or high in four reviews [ 7 , 16 , 27 , 35 ], but low or very low in the others (Table  3 ). The individual reviews considered the evidence levels as mostly low or very low (Table  4 ; see Risk of bias and evidence assessment ). Table 5 summarizes the evidence on the efficacy of each intervention and technique according to (a) whether the evidence supports efficacy, (b) the evidence level based on the report in the systematic reviews and (c) the confidence in the reviews as assessed with AMSTAR-2. It must be noted that the components of the intervention which caused the efficacy were not always clear. Some interventions lacked detailed definitions and descriptions of the specific BCTs included [ 33 ]. A single technique or mechanism of action was not always identifiable; moreover, various techniques seem to influence each other in such a way that they achieved efficacy only jointly [ 17 , 40 ].

No clear conclusion can be drawn on the efficacy of informational/educational interventions. Five reviews [ 12 , 30 , 31 , 34 , 36 ] showed low evidence for the efficacy of interventions on knowledge acquisition and low evidence for limited short-term efficacy on adherence. Providing knowledge alone seems not enough and should be complemented with supportive material (very low evidence) and combined with other interventions (low evidence). Patient education should also include social-cognitive or cognitive-behavioural approaches, psychoeducational interventions and collaborative processes as it is included in the therapeutic alliance approach [ 31 , 34 , 36 ]. Patient education with a more constructive educational approach builds upon the knowledge of the patient, supporting him/her in exploring and co-constructing knowledge which is very relevant in physiotherapy as research has shown [ 55 , 56 ].

The reviews on additional motivational, cognitive and behavioural interventions showed findings ranging from non-efficacy of behavioural counselling based on readiness to change (with low to moderate evidence) to moderate efficacy for booster sessions and behavioural graded physical activity (with moderate evidence) (see Table  5 ). Overall, a small overall effect size (SMD 0.24) for motivational interventions is indicative of the findings of the panoramic meta-analysis. The four pooled meta-analyses [ 7 , 16 , 27 , 28 ] included studies analysing interventions with a considerable amount of content overlap (e.g. goal-setting and booster sessions are BCTs and often part of motivational interventions), and no statistical heterogeneity of the true effect was found. Nevertheless, the diversity of interventions and techniques included constrain the explanatory power for potential components responsible for the efficacy of adherence. The sensitivity analyses in the meta-analysis of Eisele et al. [ 7 ] indicate that low-quality studies tend to overestimate the efficacy (cf. [ 31 ]). While some evidence exists on short- and medium-term effects of motivational programmes on adherence, no clear evidence for long-term effects can be concluded [ 7 , 30 ]. Furthermore, there is moderate and low evidence that additional motivational interventions and goal planning/setting improve adherence to self-efficacy beliefs [ 27 , 28 , 39 ]. Since self-efficacy beliefs play an important role in motivation and adherence [ 13 , 48 ], the results are relevant for physiotherapists to promote motivation and adherence. Experiencing that one can reach the set goals and manage daily challenges, complemented with feedback and reinforcement from the therapist (or important others), may increase self-efficacy beliefs and human agency [ 48 , 57 , 58 , 59 ].

A closer look at how and in which manner goals and actions are planned and reviewed seems crucial. The patient-led approach was only reported in 5 of the 26 interventions that incorporated the BCT goal setting (behaviour) , although it is associated with greater engagement and achievement than goals which are set by the therapist [ 17 ]. Goal setting and action planning should be informed by the patient’s motives, interests and values in order to promote intrinsic motivation, self-determination and subsequently better adherence ([ 17 ],cf. [ 27 , 28 , 60 , 61 ]). The reviews on the BCTs displayed various positive effects relating to the BCT cluster goals and planning ; however, they point out that the BCT goal setting is not used alone but in connection with several other BCTs. Feedback on outcomes of behaviour , behavioural contract and non-specific reward as well as patient led-goal setting , self-monitoring of behaviour and social support (unspecified) was included in efficacious interventions [ 17 ]. Social support seems to have an important influence on adherence [ 6 , 7 , 17 , 40 ], for example through regular phone-calls or home visits, encouraging messaging, supervision or community-based group programs (cf. [ 1 , 2 , 3 ],[ 37 , 62 ]). Social support also relates to the promotion of self-efficacy beliefs, if it endorses confidence in own abilities and competences [ 6 ].

Some BCTs seem inherent to standard practices of physiotherapy [ 6 ] even though physiotherapists seem to use rather a small number of BCTs [ 15 ]. Control groups also contained BCTs [ 6 , 7 ]; in particular instruction on how to perform a behaviour , generalisation of the target behaviour and social support (unspecified) were frequently coded [ 6 ]. Thus, it seems difficult to identify those BCTs that are (most) efficacious in promoting adherence ([ 7 ],cf. [ 50 ]). Unsurprisingly, the reviews revealed conflicting results and a high risk of bias in the individual studies. However, combining a greater number of BCTs (≥ 8) can be highly recommended, as this achieved a larger effect than interventions using fewer BCTs [ 7 ]. It is fairly unlikely that any single BCT changes adherence [ 6 , 7 , 17 , 40 ]. In that regard, Ariie et al. [ 63 ] argue that not only the amount of BCTs but also the quality, appropriateness and feasibility of the use of the BCTs is crucial.

Meaningful combinations of several BCTs are required. However, the combinations of BCTs may also differ among conditions, personal factors and therapeutic interventions ([ 7 ],cf. [ 63 , 64 ], [ 64 , 65 , 66 ]), and over the time. Two reviews consistently point to the same crucial time point (i.e. after 6 months) when BCT efficacy seems to drop, and more attention is required to maintain adherence [ 7 , 17 ]. Action planning , feedback on behaviour and behavioural practice/rehearsal seem efficacious particularly on short-term. Patient led-goal setting , self-monitoring of behaviour and social support (unspecified) are among those BCTs that seem more efficacious at long-term [ 17 ]. These findings are also in line with findings in non-clinical adults [ 54 ] and with motivational theories (e.g. the Health Action Process Approach [ 53 ]).

Limitations

Conducting an overview of reviews is per se associated with methodological limitations. A limitation is that reviews were analysed and not the original RCTs, which adds further risks of bias domains such as selection, analysis and reporting bias. A specific potential source of bias in overviews of reviews is the overlap of primary studies among the included reviews. The small overlap, caused by a few reviews with similar thematic scope, was controlled for in the data analysis. The substantial non-overlap of primary studies across the reviews reflects the clinical and methodological diversity of the included reviews and showcases the efforts to address (a) motivation and (non-)adherence as complex phenomena and from various perspectives.

Another methodological limitation originates from the search strategies. Considering different health-care systems and delimitations of the physiotherapy profession among countries, divergences among the definitions of terms and the use of diverse approaches to physical therapy, physiotherapy or the therapeutic use of exercise and physical activity, made a clear delimitation in the search strategy and inclusion/exclusion criteria difficult. Therefore, we may have missed out some relevant reviews by reducing our search to the two terms physiotherapy and physical therapy. Equally, we may also have included some aspects that were not primarily investigated for physiotherapists or physical therapists. Including only studies with adults, the findings may not be applicable to promote adherence among children.

While we did not exclude reviews from another language, the search was conducted only in English, which may omit important reviews in other languages. All included reviews (and as far as reported, also the original RCTs) were conducted in economically developed countries; however, social-cultural and context-specific factors influence participation and adherence [ 67 , 68 , 69 , 70 , 71 ]. Furthermore, we are aware that our own cultural background and experiences may have influenced the analysis and synthesis of the results and that conclusions drawn in this overview of reviews may not be suitable for every setting around the world. Therefore, we encourage the readers to critically assess the applicability of the findings to their specific context.

Another gap in coverage of this overview is that interventions that were analysed in RCTs but not included in any systematic review are not considered in this overview. Thus, there may be new or alternative intervention approaches that resulted efficacious but were not covered by this overview. Furthermore, reviews that focused only on the use of digital apps or tools, e.g. virtual reality, gamification, exergames or tele-rehabilitation, were excluded from this overview. Several reviews in this field include adherence-related outcomes, showing potential efficacy as well as limitations of the use of digital tools [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ].

Research gaps, recommendations and measuring adherence

This overview of reviews highlighted some gaps in the existing knowledge. First, there is a lack of clear evidence on the efficacy of the interventions. The use of BCTs in the intervention as well as in the control groups may be a reason for inconsistent findings and conflicting evidence. Furthermore, the clinical and methodological heterogeneity constrains drawing clear conclusions on the efficacy. Second (and related to the previous), interventions are insufficiently described regarding their theoretical underpinning and active ingredients/techniques and thus limit the comparison of interventions. Theoretical underpinnings were used partly and translated into practise differently. Difficulties concerning the derivation or deduction of concrete, practical techniques or strategies from the theories were reported. A broader use of the BCT taxonomies would make interventions more comparable. Recently, the BCT Ontology was published, which claims to provide a standard terminology and a comprehensive classification system for the content of behaviour change interventions, suitable for describing interventions [ 84 ]. Third, there is a need for studies on holistic approaches, complex interventions based on integrative theories and the combination of multiple BCTs. While many theories are based on cognitive and behavioural approaches, affective and psychosocial factors are hardly investigated, overlooked and probably underestimated. Rhodes and Fiala [ 12 ] call for studying the influences of affective attitudes on adherence (e.g. enjoyment and pleasing behaviour) which may oppose the more cognitive, instrumental attitudes (e.g. the utility of behaviour). Jordan et al. [ 35 ] refer to a meta-analysis in another therapeutic regime [ 85 ] to explicit the potential efficacy of affective interventions (e.g. appealing to feelings, emotions or social relationships and social supports) in combination with educational and behavioural interventions on patient adherence [ 35 ]. Fourth, more research in patient-led approaches to goal setting and action planning and the relationship of patient-centeredness to adherence is promising [ 60 , 61 , 86 , 87 ].

Fifth, the reviews reported many studies that failed to provide evidence for intervention efficacy on adherence, particularly on long-term adherence. There is a need for prolonged observation to investigate long-term effects on adherence. Probably, intervention or follow-up interventions (e.g. booster sessions) must also be prolonged or repeated to avoid drop out to medium-term follow-ups (around 6 months) and to maintain participation. Sixth, studies should pay more attention to the actual efficacy of adherent behaviour on the desired therapeutic outcomes.

Seventh, another research gap lies in the analysis of the potential variation of the intervention efficacy across medical conditions, physiotherapeutic settings, personal characteristics (e.g. age, gender, sociocultural background) and dispositions (e.g. motives, affective attitudes, previous behaviour) and diverse context-related factors. Huynh et al. [ 79 ] showed for the case of multiple sclerosis that the efficacy of BCTs is not investigated in all disease stages or throughout the disease course; participants with mild-to-moderate level disability were more frequently included in the studies (cf. [ 18 ]). Ariie et al. [ 73 ] stated that the response to BCTs may be different according to the condition (cf. [ 76 ]). On the one hand, studies analysing the use of the same intervention or same combination of BCTs in different intervention groups (according to the categories mentioned above) could be beneficial for comparison purposes. On the other hand, studies should analyse how to find the ‘right’ (ideally, the ‘most efficacious’) adherence promotion intervention for the patient or target group. Qualitative studies may explore adequate combinations of BCTs and contribute to the understanding of complex intervention processes. The findings showcased that different interventions and BCTs may contribute to adherence and that the BCT Taxonomy defines a wide range of techniques, providing the physiotherapists with an overview of which techniques are useable and thus may inspire and support them to develop additional interventions and to enrich their current physiotherapeutic practise. The physiotherapist may use this knowledge to tailor interventions in a patient-centred manner to promote adherence, and to adapt to the condition, characteristics, dispositions and context-related factors of the patient. Hence, experimental studies could compare the efficacy of tailored to not-tailored interventions.

Finally, the outcome adherence should be better defined and holistically assessed. The definition of adherence (as the extent to which a person’s behaviour corresponds with treatment goals or plans) and calculation of adherence rates (by reported exercise or attended sessions divided by the recommended or prescribed exercise or sessions) are simplifying a complex phenomenon. The average or the percentages of attended or completed sessions do not picture interruptions, regularity or periods of more and less adherence. Attendance regularity can change over the time and different participation and fluctuation patterns can be identified [ 88 , 89 ]. For example, an adherence rate of 50% can imply (a) that a person attended regularly every second session throughout the period of observation or (b) that a person attended all sessions of the first half of the observation period and then stopped attending. The underlying reasons and motivational factors may be quite different in these two cases. Besides assessing participation and fluctuation patterns, the three dimensions of the SIRAS scale [ 42 ], i.e. frequency, intensity and reciprocity, could be considered for a holistic account of adherence. The findings of this overview emphasized the importance of a patient-led goal setting and planning, which includes a shared decision-making process and the mutual agreement to adhere to the jointly established plan (cf. WHO definition of adherence, [ 5 ]). The measurement of adherence should be able to distinguish a patient-led approach from a therapist-led approach (cf. [ 17 ]) and to appraise the extent of a shared decision-making process. In conclusion, a holistic approach to measure adherence in physiotherapy may include measures of the frequency of attendance/exercising (e.g. attended sessions out of the prescribed/recommended sessions), the regularity of participation and fluctuation (e.g. timeline with pauses and interruptions, visualizing more and less adherent periods), the intensity of attendance/exercising (e.g. the number or the increment of exercises and repetitions performed in comparison to the plan), reciprocity and fidelity to the agreed goals and plan (e.g. therapist’s and patient’s subjective appraisal of the degree of accomplishment of the agreed plan) and persistence/perseverance over the time (e.g. measuring volition via questionnaires or rating persistence in participation in spite of the experienced challenges and barriers).

We conclude that moderate certainty of evidence supports that (i) additional motivational interventions and behaviour change programmes can increase adherence and patients’ self-efficacy beliefs and (ii) interventions applying BCTs increase adherence, particularly when using a greater number of BCTs and combining various BCTs, and particularly on short to medium term. The BCTs’ patient-led goal setting , self-monitoring of behaviour and social support seem promising to promote maintenance; (iii) graded activities, booster sessions with a physiotherapist and supervision foster adherence.

There is low certainty of evidence that (i) goal setting and planning improves adherence to treatment regimens, particularly if a patient-centred approach is taken; (ii) motivational interventions including various techniques, such as positive reinforcement, social support, monitoring or feedback, can foster adherence; (iii) social support seems to play an important role in promoting adherence; however, evidence is low as this BCT is frequently found in the control group; and (iv) information provision and transfer of knowledge to the patient may improve adherence-related outcomes when combined with motivational techniques, as in psychoeducational programmes. Additional written information is superior to verbal instructions alone; (v) a combination of home-based exercise programmes with clinical supervision, refresher or booster sessions, or/and self-management programmes seems promising to increase adherence.

Regarding the implications for future research, a holistic approach to measure adherence in physiotherapy and the investigation of clearly defined interventions combining multiple BCTs is recommended.

Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information files.

Overview of reviews, umbrella review and reviews of reviews are considered as synonyms in this article (cf. [ 19 ]).

Abbreviations

Behaviour change technique

Cognitive behavioural/cognitive behavioural theory

Control/comparator group

Grades of Recommendation, Assessment, Development and Evaluation

Intervention/experimental group

Physical activity

Preferred Reporting Items for Overviews of Reviews

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

Physiotherapy

Randomised controlled trial

Standardised mean difference

Systematic review

Essery R, Geraghty AW, Kirby S, Yardley L. Predictors of adherence to home-based physical therapies: a systematic review. Disabil Rehabil. 2017;39:519–34.

Article   PubMed   Google Scholar  

Jack K, McLean SM, Moffett JK, Gardiner E. Barriers to treatment adherence in physiotherapy outpatient clinics: a systematic review. Man Ther. 2010;15:220–8.

Article   PubMed   PubMed Central   Google Scholar  

Peek K, Sanson-Fisher R, Mackenzie L, Carey M. Interventions to aid patient adherence to physiotherapist prescribed self-management strategies: a systematic review. Physiotherapy. 2016;102:127–35.

Bullard T, Ji M, An R, Trinh L, Mackenzie M, Mullen SP. A systematic review and meta-analysis of adherence to physical activity interventions among three chronic conditions: cancer, cardiovascular disease, and diabetes. BMC Public Health. 2019;19:636.

World Health Organization. Adherence to long-term therapies: evidence for action. World Health Organization; 2003. Available from: https://apps.who.int/iris/handle/10665/42682

Thacker J, Bosello F, Ridehalgh C. Do behaviour change techniques increase adherence to home exercises in those with upper extremity musculoskeletal disorders? A systematic review. Musculoskeletal care. 2020;19(3):340-62.

Eisele A, Schagg D, Kramer L, Bengel J, Gohner W. Behaviour change techniques applied in interventions to enhance physical activity adherence in patients with chronic musculoskeletal conditions: a systematic review and meta-analysis. Patient Educ Couns. 2019;102:25–36.

Michie S, Richardson M, Johnston M, Abraham C, Francis J, Hardeman W, et al. The behavior change technique taxonomy (v1) of 93 hierarchically clustered techniques: building an international consensus for the reporting of behavior change interventions. Ann Behav Med. 2013;46:81–95.

Davis R, Campbell R, Hildon Z, Hobbs L, Michie S. Theories of behaviour and behaviour change across the social and behavioural sciences: a scoping review. Health Psychol Rev. 2015;9:323–44.

Michie S, Johnston M. Theories and techniques of behaviour change: developing a cumulative science of behaviour change. Health Psychol Rev. 2012;6:1–6.

Article   Google Scholar  

Rhodes RE, McEwan D, Rebar AL. Theories of physical activity behaviour change: a history and synthesis of approaches. Psychol Sport Exerc. 2019;42:100–9.

Rhodes RE, Fiala B. Building motivation and sustainability into the prescription and recommendations for physical activity and exercise therapy: the evidence. Physiother Theory Pract. 2009;25:424–41.

Areerak K, Waongenngarm P, Janwantanakul P. Factors associated with exercise adherence to prevent or treat neck and low back pain: a systematic review. Musculoskeletal Science and Practice. 2021;52.

Husebø AML, Dyrstad SM, Søreide JA, Bru E. Predicting exercise adherence in cancer patients and survivors: a systematic review and meta-analysis of motivational and behavioural factors. J Clin Nurs. 2013;22:4–21.

Kunstler BE, Cook JL, Freene N, Finch CF, Kemp JL, O’Halloran PD, et al. Physiotherapists use a small number of behaviour change techniques when promoting physical activity: a systematic review comparing experimental and observational studies. J Sci Med Sport. 2018;21:609–15.

Nicolson PJA, Bennell KL, Dobson FL, Van Ginckel A, Holden MA, Hinman RS. Interventions to increase adherence to therapeutic exercise in older adults with low back pain and/or hip/knee osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2017;51:791–9.

Willett M, Duda J, Fenton S, Gautrey C, Greig C, Rushton A. Effectiveness of behaviour change techniques in physiotherapy interventions to promote physical activity adherence in lower limb osteoarthritis patients: a systematic review. Regnaux J-P, editor. PLoS ONE. 2019;14:e0219482.

Kim Y, Mehta T, Lai B, Motl RW. Immediate and sustained effects of interventions for changing physical activity in people with multiple sclerosis: meta-analysis of randomized controlled trials. Arch Phys Med Rehabil. 2020;101:1414–36.

Pollock M, Fernandes R, Becker L, Pieper D, Hartling L. Chapter V: overviews of reviews. In: Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions version 63 (updated February 2022). Cochrane; 2022 [cited 2022 May 19]. Available from: https://training.cochrane.org/handbook/current/chapter-v

Aromataris E, Fernandez R, Godfrey C, Holly C, Khalil H, Tungpunkom P. Chapter 10: umbrella reviews. In: Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. JBI; 2020 [cited 2021 Apr 19]. Available from: https://jbi-global-wiki.refined.site/space/MANUAL/4687363/Chapter+10%3A+Umbrella+reviews

Ballard M, Montgomery P. Risk of bias in overviews of reviews: a scoping review of methodological guidance and four-item checklist. Res Synth Methods. 2017;8:92–108.

Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD’s guidance for carrying out or commissioning reviews. York, UK: NHSCentre for Reviews and Dissemination, University of York; 2001 [cited 2023 Feb 20]. Available from: http://www.york.ac.uk/inst/crd/crdreports.htm

Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane; 2022 [cited 2022 May 19]. Available from: www.training.cochrane.org/handbook

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71.

Furlan AD, Malmivaara A, Chou R, Maher CG, Deyo RA, Schoene M, et al. 2015 Updated Method Guideline for Systematic Reviews in the Cochrane Back and Neck Group. Spine (Phila Pa 1976). 2015;40:1660–73.

Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008.

Levack WMM, Weatherall M, Hay-Smith EJC, Dean SG, Mcpherson K, Siegert RJ. Goal setting and strategies to enhance goal pursuit for adults with acquired disability participating in rehabilitation. Cochrane Database of Systematic Reviews. 2015;2015.

McGrane N, Galvin R, Cusack T, Stokes E. Addition of motivational interventions to exercise and traditional Physiotherapy: a review and meta-analysis. Physiotherapy. 2015;101:1–12.

Article   CAS   PubMed   Google Scholar  

Gates M, Gates A, Pieper D, Fernandes RM, Tricco AC, Moher D, et al. Reporting guideline for overviews of reviews of healthcare interventions: development of the PRIOR statement. BMJ. 2022;378: e070849.

McLean SM, Burton M, Bradley L, Littlewood C. Interventions for enhancing adherence with physiotherapy: a systematic review. Man Ther. 2010;15:514–21.

Niedermann K, Fransen J, Knols R, Uebelhart D. Gap between short- and long-term effects of patient education in rheumatoid arthritis patients: a systematic review. Arthritis Care Res. 2004;51:388–98.

Cinthuja P, Krishnamoorthy N, Shivapatham G. Effective interventions to improve long-term physiotherapy exercise adherence among patients with lower limb osteoarthritis. A systematic review BMC Musculoskelet Disord. 2022;23:147.

Beinart NA, Goodchild CE, Weinman JA, Ayis S, Godfrey EL. Individual and intervention-related factors associated with adherence to home exercise in chronic low back pain: a systematic review. The Spine Journal. 2013;13:1940–50.

Holden J, Davidson M, O’Halloran PD. Health coaching for low back pain: a systematic review of the literature. Int J Clin Pract. 2014;68:950–62.

Jordan JL, Holden MA, Mason EE, Foster NE. Interventions to improve adherence to exercise for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2010;CD005956.

Abu Abed M, Himmel W, Vormfelde S, Koschack J. Video-assisted patient education to modify behavior: a systematic review. Patient Educ Couns. 2014;97:16–22.

Bachmann C, Oesch P, Bachmann S. Recommendations for improving adherence to home-based exercise: a systematic review. Phys Med Rehab Kuror. 2018;28:20–31.

Hall AM, Ferreira PH, Maher CG, Latimer J, Ferreira ML. The influence of the therapist-patient relationship on treatment outcome in physical rehabilitation: a systematic review. Phys Ther. 2010;90:1099–110.

Levack WMM, Taylor K, Siegert RJ, Dean SG, McPherson KM, Weatherall M. Is goal planning in rehabilitation effective? A systematic review Clin Rehabil. 2006;20:739–55.

Room J, Hannink E, Dawes H, Barker K. What interventions are used to improve exercise adherence in older people and what behavioural techniques are they based on? A systematic review BMJ Open. 2017;7: e019221.

Dalager T, Bredahl TGV, Pedersen MT, Boyle E, Andersen LL, Sjøgaard G. Does training frequency and supervision affect compliance, performance and muscular health? A cluster randomized controlled trial. Man Ther. 2015;20:657–65.

Kolt GS, Brewer BW, Pizzari T, Schoo AMM, Garrett N. The Sport Injury Rehabilitation Adherence Scale: a reliable scale for use in clinical physiotherapy. Physiotherapy. 2007;93:17–22.

Green LW. Determining the impact and effectiveness of health education as it relates to federal policy. Health Educ Monogr. 1978;6:28–66.

Google Scholar  

Michie S, van Stralen MM, West R. The behaviour change wheel: a new method for characterising and designing behaviour change interventions. Implement Sci. 2011;6:42.

Pisters MF, Veenhof C, de Bakker DH, Schellevis FG, Dekker J. Behavioural graded activity results in better exercise adherence and more physical activity than usual care in people with osteoarthritis: a cluster-randomised trial. J Physiother. 2010;56:41–7.

Göhner W, Schlicht W. Preventing chronic back pain: evaluation of a theory-based cognitive-behavioural training programme for patients with subacute back pain. Patient Educ Couns. 2006;64:87–95.

Bandura A. Toward a psychology of human agency: pathways and reflections. Perspect Psychol Sci. 2018;13:130–6.

Ashford S, Edmunds J, French DP. What is the best way to change self-efficacy to promote lifestyle and recreational physical activity? A systematic review with meta-analysis. Br J Health Psychol. 2010;15:265–88.

Frost H, Campbell P, Maxwell M, O’Carroll RE, Dombrowski SU, Williams B, et al. Effectiveness of motivational interviewing on adult behaviour change in health and social care settings: a systematic review of reviews. PLoS ONE. 2018;13: e0204890.

Michie S, West R, Sheals K, Godinho CA. Evaluating the effectiveness of behavior change techniques in health-related behavior: a scoping review of methods used. Translational Behavioral Medicine. 2018;8:212–24.

Gallagher KM. Helping older adults sustain their physical therapy gains: a theory-based intervention to promote adherence to home exercise following rehabilitation. Journal of Geriatric Physical Therapy. 2016;39:20–9.

Silva MN, Vieira PN, Coutinho SR, Minderico CS, Matos MG, Sardinha LB, et al. Using self-determination theory to promote physical activity and weight control: a randomized controlled trial in women. J Behav Med. 2010;33:110–22.

Schwarzer R, Lippke S, Luszczynska A. Mechanisms of health behavior change in persons with chronic illness or disability: the Health Action Process Approach (HAPA). Rehabil Psychol. 2011;56:161–70.

Murray JM, Brennan SF, French DP, Patterson CC, Kee F, Hunter RF. Effectiveness of physical activity interventions in achieving behaviour change maintenance in young and middle aged adults: a systematic review and meta-analysis. Soc Sci Med. 2017;192:125–33.

Areskoug Josefsson K, Andersson A-C. The co-constructive processes in physiotherapy. Lee A, editor. Cogent Medicine. 2017;4:1290308.

Qasem M. Constructivist learning theory in physiotherapy education: a critical evaluation of research. Journal of Novel Physiotherapies. 2015;5.

Brinkman C, Baez SE, Genoese F, Hoch JM. Use of goal setting to enhance self-efficacy after sports-related injury: a critically appraised topic. J Sport Rehabil. 2019;29:498–502.

Fillipas S, Oldmeadow LB, Bailey MJ, Cherry CL. A six-month, supervised, aerobic and resistance exercise program improves self-efficacy in people with human immunodeficiency virus: a randomised controlled trial. Australian Journal of Physiotherapy. 2006;52:185–90.

Ley C, Karus F, Wiesbauer L, Rato Barrio M, Spaaij R. Health, integration and agency: sport participation experiences of asylum seekers. J Refug Stud. 2021;34:4140–60.

Melin J, Nordin Å, Feldthusen C, Danielsson L. Goal-setting in physiotherapy: exploring a person-centered perspective. Physiother Theory Pract. 2021;37:863–80.

Wijma AJ, Bletterman AN, Clark JR, Vervoort SC, Beetsma A, Keizer D, et al. Patient-centeredness in physiotherapy: what does it entail? A systematic review of qualitative studies. Physiother Theory Pract. 2017;33:825–40.

Meade LB, Bearne LM, Sweeney LH, Alageel SH, Godfrey EL. Behaviour change techniques associated with adherence to prescribed exercise in patients with persistent musculoskeletal pain: systematic review. Br J Health Psychol. 2019;24:10–30.

Ariie T, Takasaki H, Okoba R, Chiba H, Handa Y, Miki T, et al. The effectiveness of exercise with behavior change techniques in people with knee osteoarthritis: a systematic review with meta-analysis. PM R. 2022;

Demmelmaier I, Iversen MD. How are behavioral theories used in interventions to promote physical activity in rheumatoid arthritis? A systematic review. Arthritis Care Res. 2018;70:185–96.

Larkin L, Gallagher S, Cramp F, Brand C, Fraser A, Kennedy N. Behaviour change interventions to promote physical activity in rheumatoid arthritis: a systematic review. Rheumatol Int. 2015;35:1631–40.

Rausch Osthoff A-K, Juhl CB, Knittle K, Dagfinrud H, Hurkmans E, Braun J, et al. Effects of exercise and physical activity promotion: meta-analysis informing the 2018 EULAR recommendations for physical activity in people with rheumatoid arthritis, spondyloarthritis and hip/knee osteoarthritis. RMD Open. 2018;4: e000713.

Armstrong TL, Swartzman LC. 3 - cross-cultural differences in illness models and expectations for the health care provider-client/patient interaction. In: Shané S. Kazarian, David R. Evans, editors. Handbook of Cultural Health Psychology. San Diego: Academic Press; 2001 [cited 2013 Aug 20]. p. 63–84. Available from: http://www.sciencedirect.com/science/article/pii/B9780124027718500052

Brady B, Veljanova I, Chipchase L. Culturally informed practice and physiotherapy. J Physiother. 2016;62:121–3.

Jimenez DE, Burrows K, Aschbrenner K, Barre LK, Pratt SI, Alegria M, et al. Health behavior change benefits: perspectives of Latinos with serious mental illness. Transcult Psychiatry. 2016;53:313–29.

Jorgensen P. Concepts of body and health in physiotherapy: the meaning of the social/cultural aspects of life. Physiother Theory Pract. 2000;16:105–15.

Teng B, Rosbergen ICM, Gomersall S, Hatton A, Brauer SG. Physiotherapists’ experiences and views of older peoples’ exercise adherence with respect to falls prevention in Singapore: a qualitative study. Disabil Rehabil. 2022;44:5530–8.

Alfieri FM, da Silva DC, de Oliveira NC, Battistella LR. Gamification in musculoskeletal rehabilitation. Curr Rev Musculoskelet Med. 2022;15:629–36.

Cox NS, Dal Corso S, Hansen H, McDonald CF, Hill CJ, Zanaboni P, et al. Telerehabilitation for chronic respiratory disease. Cochrane Database Syst Rev. 2021;1:CD013040.

Cruz-Cobo C, Bernal-Jiménez MÁ, Vázquez-García R, Santi-Cano MJ. Effectiveness of mHealth interventions in the control of lifestyle and cardiovascular risk factors in patients after a coronary event: systematic review and meta-analysis. JMIR Mhealth Uhealth. 2022;10: e39593.

Darabseh MZ, Aburub A, Davies S. The effects of virtual reality physiotherapy interventions on cardiopulmonary function and breathing control in cystic fibrosis: a systematic review. Games Health J. 2023;12:13–24.

Fernandes CS, Magalhães B, Gomes JA, Santos C. Exergames to improve rehabilitation for shoulder injury: Systematic Review and GRADE Evidence Synthesis. REHABIL NURS. 2022;47:147–59.

García-Bravo S, Cuesta-Gómez A, Campuzano-Ruiz R, López-Navas MJ, Domínguez-Paniagua J, Araújo-Narváez A, et al. Virtual reality and video games in cardiac rehabilitation programs. A systematic review Disabil Rehabil. 2021;43:448–57.

Hawley-Hague H, Lasrado R, Martinez E, Stanmore E, Tyson S. A scoping review of the feasibility, acceptability, and effects of physiotherapy delivered remotely. Disability and Rehabilitation. 2022;

Melillo A, Chirico A, De Pietro G, Gallo L, Caggianese G, Barone D, et al. Virtual reality rehabilitation systems for cancer survivors: a narrative review of the literature. Cancers. 2022;14.

Moulaei K, Sheikhtaheri A, Nezhad MS, Haghdoost A, Gheysari M, Bahaadinbeigy K. Telerehabilitation for upper limb disabilities: a scoping review on functions, outcomes, and evaluation methods. Arch Public Health. 2022;80:196.

Patsaki I, Dimitriadi N, Despoti A, Tzoumi D, Leventakis N, Roussou G, et al. The effectiveness of immersive virtual reality in physical recovery of stroke patients: a systematic review. Frontiers in Systems Neuroscience. 2022;16.

Skov Schacksen C, Henneberg NC, Muthulingam JA, Morimoto Y, Sawa R, Saitoh M, et al. Effects of telerehabilitation interventions on heart failure management (2015–2020): scoping review. JMIR Rehabil Assist Technol. 2021;8: e29714.

Thompson D, Rattu S, Tower J, Egerton T, Francis J, Merolli M. Mobile app use to support therapeutic exercise for musculoskeletal pain conditions may help improve pain intensity and self-reported physical function: a systematic review. J Physiother. 2023;69:23–34.

Marques MM, Wright AJ, Corker E, Johnston M, West R, Hastings J, et al. The behaviour change technique ontology: transforming the behaviour change technique taxonomy v1. Wellcome Open Res. 2023;8:308.

Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998;36:1138–61.

Hansen LS, Præstegaard J, Lehn-Christiansen S. Patient-centeredness in physiotherapy–a literature mapping review. Physiotherapy theory and practice. 2022;38(12):1843-56.

Robinson JH, Callister LC, Berry JA, Dearing KA. Patient-centered care and adherence: definitions and applications to improve outcomes. J Am Acad Nurse Pract. 2008;20:600–7.

Seelig H, Fuchs R. Physical exercise participation: a continuous or categorical phenomenon? Psychol Sport Exerc. 2011;12:115–23.

Shang B, Duan Y, Huang WY, Brehm W. Fluctuation – a common but neglected pattern of physical activity behaviour: an exploratory review of studies in recent 20 years. European Journal of Sport Science. 2018;18(2):266-78.

Download references

Acknowledgements

Not applicable

No funding was received.

Author information

Authors and affiliations.

Department Health Sciences, Physiotherapy, FH Campus Wien University of Applied Sciences, Favoritenstrasse 226, 1100, Vienna, Austria

Clemens Ley

Department Health Sciences, Competence Center INDICATION, FH Campus Wien, University of Applied Sciences, Favoritenstrasse 226, 1100, Vienna, Austria

You can also search for this author in PubMed   Google Scholar

Contributions

CL and PP conceived and designed the review. CL did the database search and data extraction. CL and PP did screening and quality assessment. CL did the narrative synthesis and drafted the manuscript. PP conducted the panoramic meta-analysis and critically revised and substantially contributed throughout the writing of the manuscript. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Clemens Ley .

Ethics declarations

Ethics approval and consent to participate, consent for publication, competing interests.

The authors declare that they have no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1:.

Search details

Additional file 2:

Rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Ley, C., Putz, P. Efficacy of interventions and techniques on adherence to physiotherapy in adults: an overview of systematic reviews and panoramic meta-analysis. Syst Rev 13 , 137 (2024). https://doi.org/10.1186/s13643-024-02538-9

Download citation

Received : 29 November 2023

Accepted : 17 April 2024

Published : 21 May 2024

DOI : https://doi.org/10.1186/s13643-024-02538-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Umbrella review
• Physical therapy
• Rehabilitation
• Behaviour change techniques
• Effectiveness

Systematic Reviews

ISSN: 2046-4053

• Submission enquiries: Access here and click Contact Us
• General enquiries: [email protected]

• Introduction
• Conclusions
• Article Information

PNE indicates pain neuroscience education.

The KOOS 4 primary outcome includes the subscales pain, symptoms, function of daily living, and knee-related quality of life; scores range from 0 to 100, with higher scores indicating better outcomes. Data points are means; error bars represent 95% CI. PNE indicates pain neuroscience education.

The KOOS 4 primary outcome includes the subscales pain, symptoms, function of daily living, and knee-related quality of life; scores range from 0 to 100, with higher scores indicating better outcomes. Positive scores indicate improvements in KOOS 4 , and negative scores indicate a decline in KOOS 4 . PNE indicates pain neuroscience education.

Trial Protocol and Statistical Analysis Plan

eAppendix 1. CONSORT Checklist for Randomized Trials

eAppendix 2. TIDieR Checklist for Information to Include When Describing an Intervention

eAppendix 3. CERT Checklist for What to Include When Reporting Exercise Programs

eMethods 1. Pain Neuroscience Education Session 1

eMethods 2. Pain Neuroscience Education Session 2

eTable 1. Patient Baseline Characteristics for Those Attending the 12-Month Follow-up Assessment and Those who Did Not Attend

eTable 2. Intention-to-Treat Analysis for Risk Ratios for Usage of Pain Medication From Baseline to 12 Months

eTable 3. Per-Protocol Analysis for the Primary and Secondary Outcomes for Change From Baseline to 12 Months

eTable 4. Per-Protocol Analysis for the Changes in Usage of Pain Medication From Baseline to 12 Months

Data Sharing Statement

See More About

Sign up for emails based on your interests, select your interests.

Customize your JAMA Network experience by selecting one or more topics from the list below.

• Academic Medicine
• Acid Base, Electrolytes, Fluids
• Allergy and Clinical Immunology
• American Indian or Alaska Natives
• Anesthesiology
• Anticoagulation
• Art and Images in Psychiatry
• Artificial Intelligence
• Assisted Reproduction
• Bleeding and Transfusion
• Caring for the Critically Ill Patient
• Challenges in Clinical Electrocardiography
• Climate and Health
• Climate Change
• Clinical Challenge
• Clinical Decision Support
• Clinical Implications of Basic Neuroscience
• Clinical Pharmacy and Pharmacology
• Complementary and Alternative Medicine
• Consensus Statements
• Coronavirus (COVID-19)
• Critical Care Medicine
• Cultural Competency
• Dental Medicine
• Dermatology
• Diabetes and Endocrinology
• Diagnostic Test Interpretation
• Drug Development
• Electronic Health Records
• Emergency Medicine
• End of Life, Hospice, Palliative Care
• Environmental Health
• Equity, Diversity, and Inclusion
• Facial Plastic Surgery
• Gastroenterology and Hepatology
• Genetics and Genomics
• Genomics and Precision Health
• Global Health
• Guide to Statistics and Methods
• Hair Disorders
• Health Care Delivery Models
• Health Care Economics, Insurance, Payment
• Health Care Quality
• Health Care Reform
• Health Care Safety
• Health Care Workforce
• Health Disparities
• Health Inequities
• Health Policy
• Health Systems Science
• History of Medicine
• Hypertension
• Images in Neurology
• Implementation Science
• Infectious Diseases
• Innovations in Health Care Delivery
• JAMA Infographic
• Law and Medicine
• Leading Change
• Less is More
• LGBTQIA Medicine
• Lifestyle Behaviors
• Medical Coding
• Medical Devices and Equipment
• Medical Education
• Medical Education and Training
• Medical Journals and Publishing
• Mobile Health and Telemedicine
• Narrative Medicine
• Neuroscience and Psychiatry
• Notable Notes
• Nutrition, Obesity, Exercise
• Obstetrics and Gynecology
• Occupational Health
• Ophthalmology
• Orthopedics
• Otolaryngology
• Pain Medicine
• Palliative Care
• Pathology and Laboratory Medicine
• Patient Care
• Patient Information
• Performance Improvement
• Performance Measures
• Perioperative Care and Consultation
• Pharmacoeconomics
• Pharmacoepidemiology
• Pharmacogenetics
• Pharmacy and Clinical Pharmacology
• Physical Medicine and Rehabilitation
• Physical Therapy
• Physician Leadership
• Population Health
• Primary Care
• Professional Well-being
• Professionalism
• Psychiatry and Behavioral Health
• Public Health
• Pulmonary Medicine
• Regulatory Agencies
• Reproductive Health
• Research, Methods, Statistics
• Resuscitation
• Rheumatology
• Risk Management
• Scientific Discovery and the Future of Medicine
• Shared Decision Making and Communication
• Sleep Medicine
• Sports Medicine
• Stem Cell Transplantation
• Substance Use and Addiction Medicine
• Surgical Innovation
• Surgical Pearls
• Teachable Moment
• Technology and Finance
• The Art of JAMA
• The Arts and Medicine
• The Rational Clinical Examination
• Tobacco and e-Cigarettes
• Translational Medicine
• Trauma and Injury
• Treatment Adherence
• Ultrasonography
• Users' Guide to the Medical Literature
• Vaccination
• Venous Thromboembolism
• Veterans Health
• Women's Health
• Workflow and Process
• Wound Care, Infection, Healing

Get the latest research based on your areas of interest.

Others also liked.

• Download PDF
• X Facebook More LinkedIn

Larsen JB , Skou ST , Laursen M , Bruun NH , Arendt-Nielsen L , Madeleine P. Exercise and Pain Neuroscience Education for Patients With Chronic Pain After Total Knee Arthroplasty : A Randomized Clinical Trial . JAMA Netw Open. 2024;7(5):e2412179. doi:10.1001/jamanetworkopen.2024.12179

Manage citations:

© 2024

• Permissions

Exercise and Pain Neuroscience Education for Patients With Chronic Pain After Total Knee Arthroplasty : A Randomized Clinical Trial

• 1 Musculoskeletal Health and Implementation, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• 2 Research Unit for Musculoskeletal Function and Physiotherapy, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
• 3 The Research and Implementation Unit PROgrez, Department of Physiotherapy and Occupational Therapy, Næstved-Slagelse-Ringsted Hospitals, Region Zealand, Denmark
• 4 Orthopedic Surgery Research Unit, Aalborg University Hospital, Aalborg, Denmark
• 5 Research Data and Biostatistics, Aalborg University Hospital, Aalborg, Denmark
• 6 Translational Pain Biomarkers, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
• 7 ExerciseTech, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark

Question   What is the effect of neuromuscular exercise and pain neuroscience education compared with pain neuroscience education alone on pain and function in patients with chronic pain for more than 1 year after total knee arthroplasty?

Findings   In this randomized clinical trial of 69 patients, neuromuscular exercise and pain neuroscience education did not provide superior pain and function outcomes compared with pain neuroscience education alone, although approximately one-third of all patients experienced clinically important improvements.

Meaning   Findings from this study suggest that neuromuscular exercise and pain neuroscience education do not provide superior pain and function outcomes compared with pain neuroscience education alone, but clinically important improvements in pain and function can be elicited in patients with chronic pain after total knee arthroplasty.

Importance   Up to 20% of patients develop chronic pain after total knee arthroplasty (TKA), yet there is a scarcity of effective interventions for this population.

Objective   To evaluate whether neuromuscular exercise and pain neuroscience education were superior to pain neuroscience education alone for patients with chronic pain after TKA.

Design, Setting, and Participants   A superiority randomized clinical trial was conducted at 3 outpatient clinics at Aalborg University Hospital in Denmark. Participants with moderate-to-severe average daily pain intensity and no signs of prosthesis failure at least 1 year after primary TKA were included. Participant recruitment was initiated on April 12, 2019, and completed on October 31, 2022. The 12-month follow-up was completed on March 21, 2023.

Interventions   The study included 24 sessions of supervised neuromuscular exercise (2 sessions per week for 12 weeks) and 2 total sessions of pain neuroscience education (6 weeks between each session) or the same pain neuroscience education sessions alone. The interventions were delivered in groups of 2 to 4 participants.

Main Outcomes and Measures   The primary outcome was change from baseline to 12 months using the mean score of the Knee Injury and Osteoarthritis Outcome Score, covering the 4 subscales pain, symptoms, activity of daily living, and knee-related quality of life (KOOS 4 ; scores range from 0 to 100, with higher scores indicating better outcomes). The outcome assessors and statistician were blinded. All randomized participants were included in the intention-to-treat analysis.

Results   Among the 69 participants (median age, 67.2 years [IQR, 61.2-71.9 years]; 40 female [58%]) included in the study, 36 were randomly assigned to the neuromuscular exercise and pain neuroscience education group, and 33 to the pain neuroscience education–alone group. The intention-to-treat analysis showed no between-group difference in change from baseline to 12 months for the KOOS 4 (7.46 [95% CI, 3.04-11.89] vs 8.65 [95% CI, 4.67-12.63] points; mean difference, −1.33 [95% CI, −7.59 to 4.92]; P  = .68). Among the 46 participants who participated in the 12-month assessment in the 2 groups, 16 (34.8%) experienced a clinically important improvement (a difference of ≥10 points on the KOOS 4 ) with no between-group difference. No serious adverse events were observed.

Conclusions and Relevance   In this randomized clinical trial, the results demonstrated that neuromuscular exercises and pain neuroscience education were not superior to pain neuroscience education alone in participants with chronic pain after TKA. Approximately one-third of the participants, regardless of intervention, experienced clinically important improvements. Future studies should investigate which patient characteristics indicate a favorable response to exercises and/or pain neuroscience education.

Trial Registration   ClinicalTrials.gov Identifier: NCT03886259

End-stage knee osteoarthritis is commonly treated with total knee arthroplasty (TKA). 1 In 2018, more than 715 000 TKAs were performed in the US, 2 and the number is expected to rise to 1.9 million annually by 2030. 3 Most patients undergoing TKA surgery will experience a positive outcome in terms of pain relief and improved functional performance, but 15% to 20% of patients will develop chronic pain after TKA. 4 , 5 Chronic pain after TKA is defined as pain present for at least 3 to 6 months following surgery. 6

Patients have described the chronic pain after TKA as extreme, constant, and requiring maximal effort to endure. 7 Furthermore, activities of daily living (eg, walking and stair climbing) are impaired in patients with chronic pain after TKA when compared with patients with knee osteoarthritis prior to surgery. 8

Chronic pain after TKA is considered multifactorial and can be influenced by physiological factors, such as central pain mechanisms, and psychosocial factors. 6 , 8 There is a scarcity of high-quality evidence and guidelines on effective treatments of chronic pain after TKA. 6 , 9 The lack of evidence-based treatment guidelines leads to inadequate access to optimal treatment and the risk of patients feeling abandoned by the health care system. 10

Studies have evaluated the inclusion of early postoperative exercises to avoid patients developing chronic pain after TKA but have not found this approach effective. 11 , 12 However, a combination of exercise and education treatment modalities could induce beneficial treatment effects in patients with chronic pain after TKA, 13 but to our knowledge, this has never been investigated.

Therefore, we conducted a superiority randomized clinical trial with the purpose of investigating whether a 12-week treatment consisting of neuromuscular exercise and pain neuroscience education (PNE) would prove superior in terms of improving pain and function compared with receiving PNE alone. It was hypothesized that the participants randomized to neuromuscular exercise and PNE would improve significantly more from baseline to 12 months compared with participants randomized to PNE alone.

The study was designed as a parallel-group superiority randomized clinical trial, entitled the NEPNEP (Neuromuscular Exercises and Pain Neuroscience Education for Chronic Pain) trial. An open access study protocol was published to ensure research quality and transparency. 14 The trial followed the Consolidated Standards of Reporting Trials ( CONSORT ) reporting guideline for randomized clinical trials. 15 The patient flow diagram is provided as Figure 1 , and the trial protocol is provided in Supplement 1 . The CONSORT, Template for Intervention Description and Replication (TIDieR), and Consensus on Exercise Reporting Template (CERT) checklists are provided in eAppendices 1-3, respectively, in Supplement 2 . The trial was approved by the North Denmark Region Committee on Health Research Ethics. All participants signed informed consent before inclusion in the trial.

Participants were recruited from Aalborg University Hospital (Aalborg, Denmark), which included 3 hospital sites in Farsoe, Thisted, and Aalborg. The hospital research database was used to identify participants who underwent TKA at least 1 year before recruitment. Eligible participants were contacted by mail and telephone and invited to participate in the study. Participants willing to enroll and meeting the eligibility criteria of primary TKA due to knee osteoarthritis 12 months or longer after their surgery and, in the index knee, chronic pain for longer than 6 months and an average daily pain score of 4 or more (moderate to severe pain) on a numeric rating scale (ranging from 0 to 10, in which 0 is no pain, and 10 is maximum pain) over the last week were included. The major exclusion criteria were chronic pain due to loosening of an implant or a prosthesis failure requiring revision surgery or primary pain area other than the index knee (eg, low back pain or upper extremity pain). A full list of eligibility criteria can be found in the study protocol ( Supplement 1 ). 14 Participants received the interventions at 1 of the 3 outpatient clinics at Aalborg University Hospital (Farsoe, Thisted, and Aalborg) dependent on their geographical preferences and on which day and time for exercise and PNE suited them best. Recruitment was initiated on April 12, 2019, and completed on October 31, 2022. The 12-month follow-up was completed on March 21, 2023.

Two patients with chronic pain after TKA assisted in designing the trial from a patient perspective. The patients gave feedback concerning study procedures, interventions, and outcome measures and how to describe and explain the study in layperson’s terms to possible participants.

The participants were randomized in a 1:1 ratio and allocated to 1 of 2 intervention arms, neuromuscular exercises and PNE or PNE alone. Randomization with treatment group concealment was done by the project manager (J.B.L.) by using computer-generated random numbers in permuted blocks of 4 to 8 participants. Outcome assessment was performed by trained outcome assessors (not involved in the study), who were masked toward treatment allocation. The statistician (N.H.B.) conducting the analysis was masked toward group allocation.

The neuromuscular exercises and PNE group received a 12-week neuromuscular exercise program 16 and PNE. The neuromuscular exercise program has previously been found feasible for patients following TKA surgery. 17 One-hour group-based sessions consisting of 2 to 4 participants were held twice a week (24 sessions in total). Sessions were supervised by trained physiotherapists and included individualization of the exercise difficulty considering each participant’s physical ability and pain intensity. Full details of the neuromuscular exercise program can be found in the study protocol ( Supplement 1 ). 14

The PNE consisted of two 1-hour group-based educational sessions. The first session was held before the first exercise session for the neuromuscular exercise and PNE group, and the second session took place 6 weeks later. A physiotherapist trained in PNE (J.B.L.) delivered the sessions to both groups. Both intervention groups received the same content in the PNE sessions. The overall aim of PNE was to change maladaptive pain cognitions, enabling the participants to reconceptualize their pain 18 and thereby engage in self-management of their symptoms. Following both PNE sessions, a short information leaflet, summarizing the PNE topics, was given to the participants. Content for the PNE sessions can be found in eMethods 1 and 2 in Supplement 2 . Assessments of outcomes were conducted at baseline and at 3, 6, and 12 months.

The primary outcome was prespecified and reported in the study protocol 14 and the statistical analysis plan. 19 The primary outcome was the between-group change from baseline to 12 months for the Knee Injury and Osteoarthritis Outcome Score (KOOS), using the mean score of the 4 subscales: pain, symptoms, activities of daily living, and knee-related quality of life (KOOS 4 ). The subscales, which include a fifth dimension—sport and recreation—are scored on a 5-point Likert scale; the total is converted into a range of 0 (worst) to 100 (best). 20 , 21 A prespecified minimum clinically important difference of 10 points was used to indicate whether a clinically relevant between-group improvement from baseline to the 12-month follow-up had occurred. 22 The KOOS questionnaire has shown validity, reliability, and responsiveness as a patient-reported outcome measure following TKA. 23

Six prespecified secondary outcomes were evaluated as between-group changes using the mean difference from baseline to a 12-month follow-up. 19 All 5 KOOS subscales, including the sport and recreation subscale, were reported individually to support the clinical interpretation of the primary outcome. 22 The overall change in a participant’s knee condition was measured using the global perceived effect scale by their answer to the question: “How are your knee problems now compared with before you entered this study?” The global perceived effect scale was administered on a 7-point Likert scale ranging from 1 (improved, an important improvement) to 7 (worse, an important worsening). The global perceived effect scale has shown excellent reliability. 24 Three physical performance tests were included. 25 The time to complete the 40-m fast-paced walk test and the stair-climb test, a test of ascending and descending 9 steps on a staircase, was recorded. For the 30-second chair-stand test, the maximum number of chair-rise repetitions within 30 seconds was registered. 25 The physical performance tests have been found reliable. 26 , 27 Use of pain medication was evaluated by asking participants whether they had used pain medication over last week (yes or no). Adverse events occurring during the trial period were registered as either serious or nonserious events by participant self-report and/or by the physiotherapists supervising the neuromuscular exercises. Serious adverse events were defined according to the definitions from the US Food and Drug Administration, and nonserious adverse events comprised all other events. 28 Other treatments initiated because of the index knee received during the trial period were registered by self-reporting from the participants.

A statistical analysis plan was published and available before the 12-month follow-up, and any analyses were initiated. 19 The analyses were conducted as predefined in the statistical analysis plan. To avoid the risk of misleading interpretation, the results from the intention-to-treat analysis were presented to the author group in a blinded version (coded as group A and group B). In writing, the authors agreed on 2 separate interpretations of the results, 29 and documentation for the interpretations was registered online. 30 After finalizing the interpretations, the randomization code was broken, and the appropriate interpretation was chosen.

For this superiority randomized clinical trial, a sample-size calculation was conducted to estimate the sample size required to detect a between-group minimum clinically important difference in change of 10 points from baseline to the 12-month follow-up for the KOOS 4 (with an SD of 15). 17 , 22 The calculation revealed that 49 participants were required in both groups to achieve a study power of 90% from baseline to the 12-month follow-up for the between-group comparison, using a 2-sided significance level of .05. To account for a possible loss to follow-up of 20%, a total of 60 participants in each group were planned to be enrolled. However, the trial was impacted by the COVID-19 pandemic, making recruitment particularly difficult and causing a higher dropout rate than anticipated. Therefore, we were not able to recruit the preplanned number of participants and decided to stop recruitment after recruiting for 42 months.

The main analysis consisted of the between-group differences in mean change from baseline to the 12-month follow-up. Analysis of all outcomes was performed according to the intention-to-treat principle. Furthermore, a prespecified per-protocol analysis was conducted, including participants who participated in at least 18 of 24 (75%) neuromuscular exercise sessions and participated in both PNE sessions (valid for both groups).

Data were checked for normal distribution by reviewing data frequency in histograms and tests for normality (Shapiro-Wilk). Based on the observations, median and IQR were recorded. For the primary and secondary outcomes (except use of pain medication), repeated measures mixed-effects models were applied, with participants as the random effect and time for visit (baseline and 3, 6, and 12 months) and treatment arm (neuromuscular exercises and PNE or PNE alone) as fixed effects, with adjustment for baseline imbalance. Interaction between follow-up and treatment arm was also included in the models. Two models are reported: model 1, adjusted for participant, follow-up, treatment arm, and interaction between follow-up and treatment arm; model 2 further included adjustment for age, sex, and body mass index. The between-group comparison for use of pain medication within the last week was dichotomized as yes or no, and relative risks were analyzed using a Poisson regression model with robust error variance. No analysis for difference in adverse events was required because no adverse events were registered in the PNE-alone group.

A prespecified responder analysis was conducted to illustrate the proportion of participants in the 2 intervention groups who experienced a minimum clinically important difference of at least 10 points in KOOS 4 . The proportions were compared using a χ 2 test.

For all outcomes, 95% CIs are presented. A 95% CI, including 10 points or more for the primary outcome, KOOS 4 , was interpreted as a clinically meaningful difference. 22 A 2-sided P  < .05 was considered significant. All analyses were performed in Stata, version 18 (StataCorp LLC).

A total of 69 patients (median age, 67.2 years [IQR, 61.2-71.9 years]; 40 female [58%]) and 29 male [42%]) were recruited. Overall, 435 patients were assessed for eligibility ( Figure 1 ). Of these, 364 were excluded, leaving 71 eligible for inclusion; 2 patients withdrew before randomization. Thirty-six participants were randomized to receive neuromuscular exercises and PNE and 33 participants to receive PNE alone. The participants’ baseline characteristics were comparable ( Table 1 ). 31 The mean body mass index in our population was greater than 33 (calculated as weight in kilograms divided by height in meters squared), most participants had at least 1 comorbidity, and there was a group-average score in the Hospital Anxiety and Depression Scale 31 that indicated clinical depression.

All participants were included in the intention-to-treat analysis. Twenty-three participants (64%) in the neuromuscular exercises and PNE group and 26 (79%) in the PNE-alone group adhered to the intervention and were included in the per-protocol analysis. The completion rates for the 12-month follow-up assessment were 24 of 36 participants (67%) for the neuromuscular exercises and PNE group and 22 of 33 (67%) for the PNE-alone group. Dropout reasons are reported in Figure 1 . The baseline characteristics for the participants adhering to the 12-month assessment and the participants lost to follow-up were comparable (eTable 1 in Supplement 2 ).

The intention-to-treat analysis showed no between-group difference in improvement from baseline to the 12-month follow-up for the primary outcome KOOS 4 , illustrated by an adjusted mean difference of −1.33 (95% CI, −7.59 to 4.92; P  = .68) ( Figure 2 ). Both groups experienced significant improvements in KOOS 4 from baseline to the 12-month follow-up, with the neuromuscular exercise and PNE group improving 7.46 points (95% CI, 3.04-11.89; P  = .001) and the PNE-alone group improving 8.65 points (95% CI, 4.67-12.63; P  < .001) ( Table 2 ).

The responder analysis showed that 8 of 24 participants (33.3%) in the neuromuscular exercise and PNE group and 8 of 22 participants (36.4%) in the PNE-alone group (16 of 46 total participants [34.8%]) experienced clinically important improvements (10 points) from baseline to the 12-month follow-up for the primary outcome KOOS 4 . Individual changes in KOOS 4 from baseline to 12 months are shown in Figure 3 . There was no difference in the proportion of responders between the groups (relative risk, 1.09; 95% CI, 0.49-2.41; P  = .83).

There were no significant between-group differences in change in the 5 KOOS subscales of pain, symptoms, activity of daily living, sport and recreation, and knee-related quality of life; the global perceived effect; time to complete the 40-m fast-paced walk test and the stair-climb test; or numbers of repetitions in the 30-second chair-stand test ( Table 2 ). Nor was there a significant between-group difference for use of pain medication (relative risk, 1.02; 95% CI, 0.73-1.43; P  = .92) (eTable 2 in Supplement 2 ). Both groups experienced significant within-group improvements in all outcomes except use of pain medication, in which neither group showed an improvement; the KOOS subscale sport and recreation, in which the neuromuscular exercise and PNE group showed no improvement; and the 40-m fast-paced walk test, in which the PNE-alone group showed no improvement.

No serious adverse events were registered in either of the intervention groups during the trial. For the neuromuscular exercise and PNE group, 5 nonserious adverse events were registered during the trial: 4 participants experienced increased pain intensity, and 1 participant experienced swelling in the index knee following a neuromuscular exercise session, which subsided after a few days and did influence the next neuromuscular exercise session. No nonserious adverse events were registered in the PNE-alone group. No participants in either group reported that they had received other treatments during the trial period. The per-protocol analysis revealed no differences in changes from baseline to 12 months for neither the primary nor the secondary outcomes (eTables 3 and 4 in Supplement 2 ).

To our knowledge, the NEPNEP trial is the first randomized clinical trial evaluating exercise and education for patients with chronic pain after TKA. Our results revealed that neuromuscular exercise and PNE were not superior to PNE alone for the primary outcome KOOS 4 in patients with chronic pain after TKA or for any of the secondary outcomes. Consequently, the results did not support the hypothesis that neuromuscular exercises and PNE would lead to greater improvements in pain and function than would PNE alone. We observed clinically important improvements in approximately one-third (34.7%) of the participants with chronic pain after TKA, regardless of treatment allocation.

Studies evaluating the effect of treatments introduced in the early postoperative period 32 - 37 have not considered that patients who undergo TKA often experience spontaneous improvements in pain between 3 and 9 months after surgery. 38 Hence, the observed treatment effects could have been influenced by the natural course of improvement after TKA and are therefore not generalizable to patients with chronic pain more than 1 year after TKA. Our findings contribute insight into the treatment of the patients who do not experience spontaneous improvements postoperatively and still experience chronic pain for at least 1 year after their TKA surgery.

Qualitative research has shown that patients with chronic pain after TKA feel abandoned by the health care system and the lack of treatment options. Therefore, patients experience their pain as something they are stuck with and that nothing more can be done. 10 Our results challenge that perception. Given that both intervention groups experienced similar outcomes, the introduction of PNE as treatment could be of particular importance. By providing PNE, patients might realize the factors they can influence themselves, which could lead to improved self-management.

As illustrated in Figure 2 , the neuromuscular exercise and PNE group exhibited an improvement in KOOS 4 immediately after the 3-month supervised exercise therapy program. While the neuromuscular exercise and PNE-alone group largely maintained their improvements until the 12-month follow-up, the PNE group gradually improved from baseline to 12 months. This could indicate that exercising is effective when performed with effects diminishing over time, similarly to findings within hip and knee osteoarthritis. 39 , 40 Therefore, it would be valuable to investigate whether a longer period of exercise therapy or booster sessions could provide sustained improvements.

The KOOS was chosen as the primary outcome, as it is imperative to consider the patient perspective when evaluating treatment effect. 41 , 42 The psychometric properties of KOOS have been scrutinized, with some findings indicating the need for further validation 42 and other findings consolidating its validity and reliability. 23 , 41 However, the KOOS remains a frequently used patient-reported outcome measure for patients undergoing TKA. 17 , 43 , 44

As illustrated in Figure 3 , participants from both groups experienced large improvements in KOOS 4 , highlighting that some participants benefited substantially from neuromuscular exercise and PNE or PNE alone. On the contrary, other participants in both groups experienced little improvement or even a worsening in KOOS 4 . This supports the need for individualized approaches when seeking the best possible treatment. Future research should investigate which patient characteristics indicate a favorable response to exercises and PNE and who might not benefit from either. 45

The mean body mass index in our population was greater than 33, most participants had at least 1 comorbidity, and there was a group-average score in the Hospital Anxiety and Depression Scale 31 that indicated clinical depression. These factors have previously been associated with chronic pain after TKA 45 and emphasize the complexity of the studied population. Given the multiple factors influencing chronic pain and the characteristics of the population, a biopsychosocial and multimodal treatment approach should be considered for patients with chronic pain after TKA. 6 , 10

This trial has some limitations. The study was affected by the COVID-19 pandemic and failed in recruiting the target sample size. However, when taking the small between-group differences into consideration, it seems unlikely that a fully powered study would change the conclusion of no between-group differences. Moreover, considering that the study did not include a no-treatment control group, the true effects of neuromuscular exercises and/or PNE could not be determined. Therefore, the findings could represent fluctuations in pain intensity over time. Long-term follow-up studies have observed that some patients experience pain fluctuations after TKA, whereas other patients’ chronic pain remains stable over time. 38

The results of this randomized clinical trial suggest that neuromuscular exercises and PNE were not superior to PNE alone for the primary outcome on pain, symptoms, function, and knee-related quality of life or any of the secondary outcomes in participants with chronic pain after TKA. The study demonstrated clinically relevant improvements in approximately one-third of the participants, regardless of intervention group. This finding challenges the perception that nothing can be done to relieve pain in patients with chronic pain after TKA. Therefore, the results could have important implications for the future management of patients with chronic pain after TKA. Despite the contributions of this study, an evidence gap for the treatment and management of patients with chronic pain after TKA remains and should be further addressed in future research.

Accepted for Publication: March 15, 2024.

Published: May 24, 2024. doi:10.1001/jamanetworkopen.2024.12179

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Larsen JB et al. JAMA Network Open .

Corresponding Author: Jesper B. Larsen, PhD, Musculoskeletal Health and Implementation, Department of Health Science and Technology, Aalborg University, Selma Lagerløfs Vej 249, 9260 Gistrup, Denmark ( [email protected] ).

Author Contributions: Dr Larsen and Mr Bruun had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Larsen, Skou, Laursen, Arendt-Nielsen, Madeleine.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Larsen, Skou, Arendt-Nielsen, Madeleine.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Larsen, Bruun.

Obtained funding: Larsen, Skou, Arendt-Nielsen, Madeleine.

Administrative, technical, or material support: Larsen, Laursen, Madeleine.

Supervision: Skou, Laursen, Arendt-Nielsen, Madeleine.

Conflict of Interest Disclosures: Prof Skou reported receiving grants from the European Research Council as payment to the University of Southern Denmark and from Region Zealand (Exercise First) for payment to the Næstved-Slagelse-Ringsted Hospital, receiving personal fees from Munksgaard as royalties for book chapters and from TrustMe-Ed as royalties for online lectures, and receiving honoraria from Nestlé Health Science for 1 presentation at a webinar on osteoarthritis outside the submitted work and reported being cofounder of GLA:D, a not-for-profit initiative hosted at the University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice. No other disclosures were reported.

Funding/Support: This work was supported by grant R168-A5619 from the Danish Rheumatism Association and by the Svend Andersen Foundation and the Lions Club Danmark (Dr Larsen) and by grants 801790 for payment to the University of Southern Denmark and 945377 for payment to the Næstved-Slagelse-Ringsted Hospital from the European Union’s Horizon 2020 research and innovati on program (Prof Skou).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3 .

Additional Contributions: We thank the patients for their participation in the trial. We acknowledge the Department of Occupational Therapy and Physiotherapy, Aalborg University Hospital, Denmark, for administrative and logistic support and the Department of Orthopedic Surgery, Aalborg University Hospital, Denmark, for its involvement in recruiting patients.

• Register for email alerts with links to free full-text articles
• Access PDFs of free articles
• Manage your interests
• Save searches and receive search alerts

Aims and Scope

• Journal Information
• Advanced Online Publication
• Current Issue
• Welcome Message from Editor-in-Chief
• Editorial Board
• Copyright, Open Access License Policy
• Editorial and Peer Review Policy
• Conflicts of Interest
• Ethics Policies
• Instructions to Authors
• Publication Fees and Charges

Physical Therapy Research

Physical Therapy Research (PTR) is an Open Access journal that aims to foster important advances in physical therapy. PTR publishes a comprehensive and dynamic array of peer-reviewed articles and materials that are of interest to our broad global audience of researchers, practitioners, continuing-education students, and those interested in the field. The article types include Original Articles, Case Studies, Brief Reports, Reviews, and more. PTR is free to access for all readers and free to publish for most authors * .

ISSN 2189-8448 Current Issue 2022 Vol.26 Issue 1 -->

* A submission fee and a publication fee must be paid for by those who hold a physical therapy license in Japan but do not belong to Japanese Physical Therapy Associaation (JPTA)

Current lssue (2024 vol.27 lssue 1)

Physical Exercise-Induced Activation of NRF2 and BDNF as a Promising Strategy for Ferroptosis Regulation in Parkinson’s Disease

• Published: 24 May 2024

Cite this article

• Anand Thirupathi 1 ,
• Luis Felipe Marqueze 2 ,
• Tiago F. Outeiro 3 , 4 , 5 , 6 ,
• Zsolt Radak 7 &
• Ricardo A. Pinho 1 , 2  

73 Accesses

1 Altmetric

Explore all metrics

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Ferroptosis, an iron-dependent form of regulated cell death, may contribute to the progression of PD owing to an unbalanced brain redox status. Physical exercise is a complementary therapy that can modulate ferroptosis in PD by regulating the redox system through the activation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) and brain-derived neurotrophic factor (BDNF) signaling. However, the precise effects of physical exercise on ferroptosis in PD remain unclear. In this review, we explored how physical exercise influences NRF2 and BDNF signaling and affects ferroptosis in PD. We further investigated relevant publications over the past two decades by searching the PubMed, Web of Science, and Google Scholar databases using keywords related to physical exercise, PD, ferroptosis, and neurotrophic factor antioxidant signaling. This review provides insights into current research gaps and demonstrates the necessity for future research to elucidate the specific mechanisms by which exercise regulates ferroptosis in PD, including the assessment of different exercise protocols and their long-term effects. Ultimately, exploring these aspects may lead to the development of improved exercise interventions for the better management of patients with PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA) Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Rent this article via DeepDyve

Institutional subscriptions

Similar content being viewed by others

Does pgc1α/fndc5/bdnf elicit the beneficial effects of exercise on neurodegenerative disorders, exercise-induced increase in brain-derived neurotrophic factor in human parkinson's disease: a systematic review and meta-analysis, moderate-intensity physical exercise protects against experimental 6-hydroxydopamine-induced hemiparkinsonism through nrf2-antioxidant response element pathway, data availability.

No datasets were generated or analysed during the current study.

Cabreira V, Massano J (2019) Doença De Parkinson: Revisão Clínica E Atualização [Parkinson’s Disease: clinical review and update]. Acta Med Port 32(10):661–670

Article   CAS   PubMed   Google Scholar  

Riess O, Krüger R (1999) Parkinson’s disease–a multifactorial neurodegenerative disorder. J Neural Transm Suppl 56:113–125

Ramesh S, Arachchige ASPM (2023) Depletion of dopamine in Parkinson’s disease and relevant therapeutic options: a review of the literature. AIMS Neurosci 10(3):200–231

Article   PubMed   Google Scholar  

Puspita L, Chung SY, Shim JW (2017) Oxidative stress and cellular pathologies in Parkinson’s disease. Mol Brain 10(1):53

Article   PubMed   PubMed Central   Google Scholar  

Gleitze S, Paula-Lima A, Núñez MT, Hidalgo C (2021) The calcium-iron connection in ferroptosis-mediated neuronal death. Free Radic Biol Med 175:28–41

Sian-Hülsmann J, Mandel S, Youdim MB, Riederer P (2011) The relevance of iron in the pathogenesis of Parkinson’s disease. J Neurochem 118(6):939–957

Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P et al (2018) Molecular mechanisms of cell death: recommendations of the nomenclature Committee on Cell Death 2018. Cell Death Differ 25(3):486–541

Guiney SJ, Adlard PA, Bush AI, Finkelstein DI, Ayton S (2017) Ferroptosis and cell death mechanisms in Parkinson’s disease. Neurochem Int 104:34–48

Ko CJ, Gao SL, Lin TK, Chu PY, Lin HY (2021) Ferroptosis as a Major Factor and Therapeutic Target for Neuroinflammation in Parkinson’s Disease. Biomedicines. 2021 9(11):1679

Jolitha AB, Subramanyam MV, Asha Devi S (2006) Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol 41(8):753–763

Tuon T, Souza PS, Santos MF, Pereira FT, Pedroso GS, Luciano TF, De Souza CT, Dutra RC, Silveira PC, Pinho RA (2015) Physical Training Regulates Mitochondrial Parameters and Neuroinflammatory Mechanisms in an Experimental Model of Parkinson’s Disease. Oxid Med Cell Longev 2015:261809

Wong-Yu ISK, Mak MKY (2019) Multisystem balance training reduces injurious fall risk in Parkinson Disease: a Randomized Trial. Am J Phys Med Rehabil 98(3):239–244

Oliveira de Carvalho A, Filho ASS, Murillo-Rodriguez E, Rocha NB, Carta MG, Machado S (2018) Physical Exercise for Parkinson’s Disease: clinical and experimental evidence. Clin Pract Epidemiol Ment Health 14:89–98

Janssen Daalen JM, Schootemeijer S, Richard E, Darweesh SKL, Bloem BR (2022) Lifestyle interventions for the Prevention of Parkinson Disease: a recipe for action. Neurology 99(7 Suppl 1):42–51

Schootemeijer S, de Vries NM, Macklin EA, Roes KCB, Joosten H, Omberg L, Ascherio A, Schwarzschild MA, Bloem BR (2023) The STEPWISE study: study protocol for a smartphone-based exercise solution for people with Parkinson’s Disease (randomized controlled trial). BMC Neurol 23(1):323

Pinho RA, Aguiar AS Jr, Radák Z (2019) Effects of Resistance Exercise on Cerebral Redox Regulation and Cognition: an interplay between muscle and brain. Antioxid (Basel) 8(11):529

Article   CAS   Google Scholar  

Silva LAD, Tortelli L, Motta J, Menguer L, Mariano S, Tasca G, Silveira GB, Pinho RA, Silveira PCL (2019) Effects of aquatic exercise on mental health, functional autonomy and oxidative stress in depressed elderly individuals: a randomized clinical trial. Clin (Sao Paulo) 74:e322

Article   Google Scholar  

Secher NH, Seifert T, Van Lieshout JJ (2008) Cerebral blood flow and metabolism during exercise: implications for fatigue. J Appl Physiol (1985) 104(1):306–314

Radak Z, Pan L, Zhou L, Mozaffaritabar S, Gu Y, A Pinho R, Zheng X, Ba X, Boldogh I (2024) Epigenetic and redoxogenetic adaptation to physical exercise. Free Radic Biol Med 210:65–74

Radak Z, Suzuki K, Higuchi M, Balogh L, Boldogh I, Koltai E (2016) Physical exercise, reactive oxygen species and neuroprotection. Free Radic Biol Med 98:187–196

Tonelli C, Chio IIC, Tuveson DA (2018) Transcriptional regulation by Nrf2. Antioxid Redox Signal 29(17):1727–1745

Article   CAS   PubMed   PubMed Central   Google Scholar  

Song X, Long D (2020) Nrf2 and ferroptosis: a New Research Direction for neurodegenerative diseases. Front Neurosci 14:267

Koo JW, Chaudhury D, Han MH, Nestler EJ (2019) Role of mesolimbic brain-derived neurotrophic factor in Depression. Biol Psychiatry 86(10):738–748

Sada N, Fujita Y, Mizuta N, Ueno M, Furukawa T, Yamashita T (2020) Inhibition of HDAC increases BDNF expression and promotes neuronal rewiring and functional recovery after brain injury. Cell Death Dis 11(8):655

Ishii T, Mann GE (2018) When and how does brain-derived neurotrophic factor activate Nrf2 in astrocytes and neurons? Neural Regen Res 13(5):803–804

Ishii T, Warabi E, Mann GE (2019) Circadian control of BDNF-mediated Nrf2 activation in astrocytes protects dopaminergic neurons from ferroptosis. Free Radic Biol Med 133:169–178

Yao W, Lin S, Su J, Cao Q, Chen Y, Chen J, Zhang Z, Hashimoto K, Qi Q, Zhang JC (2021) Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents. Transl Psychiatry 11(1):140

Ferrazzoli D, Ortelli P, Cucca A, Bakdounes L, Canesi M, Volpe D (2020) Motor-cognitive approach and aerobic training: a synergism for rehabilitative intervention in Parkinson’s disease. Neurodegener Dis Manag 10(1):41–55

Noguchi-Shinohara M, Ono K (2023) The mechanisms of the roles of α-Synuclein, Amyloid-β, and tau protein in the Lewy Body diseases: Pathogenesis, early detection, and therapeutics. Int J Mol Sci 24(12):10215

Reichert CO, de Freitas FA, Sampaio-Silva J, Rokita-Rosa L, Barros PL, Levy D, Bydlowski SP (2020) Ferroptosis mechanisms involved in neurodegenerative diseases. Int J Mol Sci 21(22):8765

Fernandes JT, Tenreiro S, Gameiro A, Chu V, Outeiro TF, Conde JP (2014) Modulation of alpha-synuclein toxicity in yeast using a novel microfluidic-based gradient generator. Lab Chip 14(20):3949–3957

Ito K, Eguchi Y, Imagawa Y, Akai S, Mochizuki H, Tsujimoto Y (2017) MPP + induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells. Cell Death Discov. 2017 3:17013

Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014:360438

Lee KH, Cha M, Lee BH (2020) Neuroprotective effect of antioxidants in the brain. Int J Mol Sci 21(19):7152

Oswald MCW, Garnham N, Sweeney ST, Landgraf M (2018) Regulation of neuronal development and function by ROS. FEBS Lett 592(5):679–691

Radák Z, Kaneko T, Tahara S, Nakamoto H, Pucsok J, Sasvári M, Nyakas C, Goto S (2001) Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochem Int 38(1):17–23

Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga AM (2013) ROS and brain diseases: the good, the bad, and the ugly. Oxid Med Cell Longev 2013:963520

Sultana R, Perluigi M, Butterfield DA (2013) Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain. Free Radic Biol Med 62:157–169

Signorini C, De Felice C, Durand T, Oger C, Galano JM, Leoncini S, Pecorelli A, Valacchi G, Ciccoli L, Hayek J (2013) Isoprostanes and 4-hydroxy-2-nonenal: markers or mediators of disease? Focus on Rett syndrome as a model of autism spectrum disorder. Oxid Med Cell Longev 2013:343824

Sanyal J, Bandyopadhyay SK, Banerjee TK, Mukherjee SC, Chakraborty DP, Ray BC, Rao VR (2009) Plasma levels of lipid peroxides in patients with Parkinson’s disease. Eur Rev Med Pharmacol Sci 13(2):129–132

CAS   PubMed   Google Scholar  

Brekk OR, Honey JR, Lee S, Hallett PJ, Isacson O (2020) Cell type-specific lipid storage changes in Parkinson’s disease patient brains are recapitulated by experimental glycolipid disturbance. Proc Natl Acad Sci U S A 117(44):27646–27654

Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR (2016) Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci U S A 113(34):E4966–E4975

Serratos IN, Hernández-Pérez E, Campos C, Aschner M, Santamaría A (2022) An update on the critical role of α-Synuclein in Parkinson’s Disease and other synucleinopathies: from tissue to Cellular and molecular levels. Mol Neurobiol 59(1):620–642

Ambaw A, Zheng L, Tambe MA, Strathearn KE, Acosta G, Hubers SA, Liu F, Herr SA, Tang J, Truong A, Walls E, Pond A, Rochet JC, Shi R (2018) Acrolein-mediated neuronal cell death and alpha-synuclein aggregation: implications for Parkinson’s disease. Mol Cell Neurosci 88:70–82

Acosta G, Race N, Herr S, Fernandez J, Tang J, Rogers E, Shi R (2019) Acrolein-mediated alpha-synuclein pathology involvement in the early post-injury pathogenesis of mild blast-induced parkinsonian neurodegeneration. Mol Cell Neurosci 98:140–154

Dong-Chen X, Yong C, Yang X, Chen-Yu S, Li-Hua P (2023) Signaling pathways in Parkinson’s disease: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther 8(1):73

Wang J, Zhu Q, Wang Y, Peng J, Shao L, Li X (2022) Irisin protects against sepsis-associated encephalopathy by suppressing ferroptosis via activation of the Nrf2/GPX4 signal axis. Free Radic Biol Med 187:171–184

Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL (2009) Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 390(3):191–214

Wang YT, Lin HC, Zhao WZ, Huang HJ, Lo YL, Wang HT, Lin AM (2017) Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death. Sci Rep 7:45741

Taso OV, Philippou A, Moustogiannis A, Zevolis E, Koutsilieris M (2019) Lipid peroxidation products and their role in neurodegenerative diseases. Ann Res Hosp 3:2

Ochneva A, Zorkina Y, Abramova O, Pavlova O, Ushakova V, Morozova A, Zubkov E, Pavlov K, Gurina O, Chekhonin V (2022) Protein misfolding and aggregation in the brain: Common Pathogenetic pathways in Neurodegenerative and Mental disorders. Int J Mol Sci 23(22):14498

Shadfar S, Parakh S, Jamali MS, Atkin JD (2023) Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases. Transl Neurodegener 12(1):18

Nakabeppu Y, Tsuchimoto D, Yamaguchi H, Sakumi K (2007) Oxidative damage in nucleic acids and Parkinson’s disease. J Neurosci Res 85(5):919–934

Chang KH, Chen CM (2020) The role of oxidative stress in Parkinson’s Disease. Antioxid (Basel) 9(7):597

Parga JA, Rodriguez-Perez AI, Garcia-Garrote M, Rodriguez-Pallares J, Labandeira-Garcia JL (2021) NRF2 activation and downstream effects: Focus on Parkinson’s Disease and Brain Angiotensin. Antioxid (Basel) 10(11):1649

Doll S, Conrad M (2017) Iron and ferroptosis: a still ill-defined liaison. IUBMB Life 69(6):423–434

Dodson M, Castro-Portuguez R, Zhang DD (2019) NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol 23:101107

Chen X, Yu C, Kang R, Kroemer G, Tang D (2021) Cellular degradation systems in ferroptosis. Cell Death Differ 28(4):1135–1148

Sun Y, Chen P, Zhai B, Zhang M, Xiang Y, Fang J, Xu S, Gao Y, Chen X, Sui X, Li G (2020) The emerging role of ferroptosis in inflammation. Biomed Pharmacother 127:110108

Jiang X, Stockwell BR, Conrad M (2021) Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 22(4):266–282

Cabantchik ZI, Breuer W, Zanninelli G, Cianciulli P (2005) LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol 18(2):277–287

Cabantchik ZI (2014) Labile iron in cells and body fluids: physiology, pathology, and pharmacology. Front Pharmacol 5:45

Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y (2016) Regulators of Iron Homeostasis: New players in Metabolism, Cell Death, and Disease. Trends Biochem Sci 41(3):274–286

Zheng J, Conrad M (2020) The metabolic underpinnings of Ferroptosis. Cell Metab 32(6):920–937

Winterbourn CC (1995) Toxicity of iron and hydrogen peroxide: the Fenton reaction. Toxicol Lett 82–83:969–974

Liang C, Zhang X, Yang M, Dong X (2019) Recent progress in Ferroptosis Inducers for Cancer Therapy. Adv Mater 31(51):e1904197

Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtzer M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD (2017) Ferroptosis: a regulated cell death Nexus linking metabolism, Redox Biology, and Disease. Cell 171(2):273–285

Duan JY, Lin X, Xu F, Shan SK, Guo B, Li FX, Wang Y, Zheng MH, Xu QS, Lei LM, Ou-Yang WL, Wu YY, Tang KX, Yuan LQ (2021) Ferroptosis and its potential role in metabolic diseases: a curse or revitalization? Front Cell Dev Biol 9:701788

Cardoso BR, Hare DJ, Bush AI, Roberts BR (2017) Glutathione peroxidase 4: a new player in neurodegeneration? Mol Psychiatry 22(3):328–335

Conrad M, Friedmann Angeli JP (2015) Glutathione peroxidase 4 (Gpx4) and ferroptosis: what’s so special about it? Mol Cell Oncol 2(3):e995047

Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, Bassik MC, Nomura DK, Dixon SJ, Olzmann JA (2019) The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575(7784):688–692

Hadian K (2020) Ferroptosis Suppressor Protein 1 (FSP1) and Coenzyme Q 10 cooperatively suppress ferroptosis. Biochemistry 59(5):637–638

Ayton S, Lei P (2014) Nigral iron elevation is an invariable feature of Parkinson’s disease and is a sufficient cause of neurodegeneration. Biomed Res Int 2014:581256

Ding XS, Gao L, Han Z, Eleuteri S, Shi W, Shen Y, Song ZY, Su M, Yang Q, Qu Y, Simon DK, Wang XL, Wang B (2023) Ferroptosis in Parkinson’s disease: molecular mechanisms and therapeutic potential. Ageing Res Rev 91:102077

Do Van B, Gouel F, Jonneaux A, Timmerman K, Gelé P, Pétrault M, Bastide M, Laloux C, Moreau C, Bordet R, Devos D, Devedjian JC (2016) Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC. Neurobiol Dis 94:169–178

Frøyset AK, Edson AJ, Gharbi N, Khan EA, Dondorp D, Bai Q, Tiraboschi E, Suster ML, Connolly JB, Burton EA, Fladmark KE (2018) Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo. Redox Biol 16:237–247

Cao J, Chen X, Jiang L, Lu B, Yuan M, Zhu D, Zhu H, He Q, Yang B, Ying M (2020) DJ-1 suppresses ferroptosis through preserving the activity of S-adenosyl homocysteine hydrolase. Nat Commun 11(1):1251

Mahoney-Sánchez L, Bouchaoui H, Ayton S, Devos D, Duce JA, Devedjian JC (2021) Ferroptosis and its potential role in the physiopathology of Parkinson’s Disease. Prog Neurobiol 196:101890

Sharma N, Rao SP, Kalivendi SV (2019) The deglycase activity of DJ-1 mitigates α-synuclein glycation and aggregation in dopaminergic cells: role of oxidative stress mediated downregulation of DJ-1 in Parkinson’s disease. Free Radic Biol Med 135:28–37

Mihoub M, Abdallah J, Gontero B, Dairou J, Richarme G (2015) The DJ-1 superfamily member Hsp31 repairs proteins from glycation by methylglyoxal and glyoxal. Biochem Biophys Res Commun 463(4):1305–1310

Du Y, Guo Z (2022) Recent progress in ferroptosis: inducers and inhibitors. Cell Death Discov 8(1):501

Fu X, Qu L, Xu H, Xie J (2024) Ndfip1 protected dopaminergic neurons via regulating mitochondrial function and ferroptosis in Parkinson’s disease. Exp Neurol 375:114724

Belaidi AA, Masaldan S, Southon A, Kalinowski P, Acevedo K, Appukuttan AT, Portbury S, Lei P, Agarwal P, Leurgans SE, Schneider J, Conrad M, Bush AI, Ayton S (2022) Apolipoprotein E potently inhibits ferroptosis by blocking ferritinophagy. Mol Psychiatry. https://doi.org/10.1038/s41380-022-01568-w

Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L (2014) The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol 13:1045–1060

Devos D, Labreuche J, Rascol O, Corvol JC, Duhamel A, Guyon Delannoy P et al (2022) FAIRPARK-II study Group. Trial of Deferiprone in Parkinson’s Disease. N Engl J Med 387(22):2045–2055

Chen J, Zhu T, Yu D et al (2023) Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and cognitive impairments via suppressing STING pathway. Mol Neurobiol 60:4872–4896

Zhang X, Xu S, Hu Y, Liu Q, Liu C, Chai H, Luo Y, Jin L, Li S (2023) Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease. NPJ Parkinsons Dis 9(1):13

Tsou YH, Shih CT, Ching CH, Huang JY, Jen CJ, Yu L, Kuo YM, Wu FS, Chuang JI (2015) Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP + toxicity. Exp Neurol 263:50–62

Xiang Y, Song X, Long D (2024) Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases. Arch Toxicol 98(3):579–615

Tutakhail A, Nazary QA, Lebsir D, Kerdine-Romer S, Coudore F (2018) Induction of brain Nrf2-HO-1 pathway and antinociception after different physical training paradigms in mice. Life Sci 209:149–156

Monir DM, Mahmoud ME, Ahmed OG, Rehan IF, Abdelrahman A (2020) Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkinson’s disease in rotenone-treated rats. Behav Brain Funct. 2020 16(1):9

Camiletti-Moirón D, Aparicio VA, Aranda P, Radak Z (2013) Does exercise reduce brain oxidative stress? A systematic review. Scand J Med Sci Sports 23(4):e202–e212

Powers SK, Radak Z, Ji LL (2016) Exercise-induced oxidative stress: past, present and future. J Physiol 594(18):5081–5092

Shen H, Tong L, Balazs R, Cotman CW (2001) Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mitogen-activated protein kinase in the rat hippocampus. Neuroscience 107(2):219–229

Peng Y, Chi R, Liu G, Tian W, Zhang J, Zhang R (2022) Aerobic Exercise Regulates Apoptosis through the PI3K/Akt/GSK-3β Signaling Pathway to Improve Cognitive Impairment in Alzheimer’s Disease Mice. Neural Plast 2022:1500710

Li K, Gao ZK, Guo YS, Shen XY, Han Y, Yuan M, Bi X (2024) Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis. Exp Brain Res 242(4):869–878

Choi JW, Jo SW, Kim DE, Paik IY, Balakrishnan R (2024) Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation. Redox Biol 71:103101

Souza J, da Silva RA, da Luz Scheffer D, Penteado R, Solano A, Barros L, Budde H, Trostchansky A, Latini A (2022) Physical-Exercise-Induced Antioxidant Effects on the Brain and Skeletal Muscle. Antioxidants (Basel). 2022 1(5):826

Tang C, Liu M, Zhou Z, Li H, Yang C, Yang L, Xiang J (2023) Treadmill Exercise alleviates cognition disorder by activating the FNDC5: dual role of integrin αV/β5 in Parkinson’s Disease. Int J Mol Sci 24(9):7830

Matheus FC, Raisman-Vozari R, Latini A, Prediger RD (2016) Moderate-intensity Physical Exercise protects against experimental 6-Hydroxydopamine-Induced Hemiparkinsonism through Nrf2-Antioxidant response element pathway. Neurochem Res 41(1–2):64–72

PubMed   Google Scholar  

Piccinin E, Sardanelli AM, Seibel P, Moschetta A, Cocco T, Villani G (2021) PGC-1s in the spotlight with Parkinson’s Disease. Int J Mol Sci 22(7):3487

Ren B, Zhang T, Guo Q, Che J, Kang Y, Cui R, Wang Y, Ji X, Zhang G, Shi G (2022) Nrf2 Deficiency Attenuates Testosterone Efficiency in Ameliorating Mitochondrial Function of the Substantia Nigra in Aged Male Mice. Oxid Med Cell Longev 2022:3644318

Schaeffer E, Roeben B, Granert O, Hanert A, Liepelt-Scarfone I, Leks E, Otterbein S, Saraykin P, Busch JH, Synofzik M, Stransky E, Bartsch T, Berg D (2022) Effects of exergaming on hippocampal volume and brain-derived neurotrophic factor levels in Parkinson’s disease. Eur J Neurol 29(2):441–449

Bastioli G, Arnold JC, Mancini M, Mar AC, Gamallo-Lana B, Saadipour K, Chao MV, Rice ME (2022) Voluntary Exercise boosts striatal dopamine release: evidence for the necessary and sufficient role of BDNF. J Neurosci 42(23):4725–4736

Marino G, Campanelli F, Natale G, De Carluccio M, Servillo F, Ferrari E, Gardoni F, Caristo ME, Picconi B, Cardinale A, Loffredo V, Crupi F, De Leonibus E, Viscomi MT, Ghiglieri V, Calabresi P (2023) Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease restoring striatal synaptic plasticity. Sci Adv 9(28):eadh1403

Rafie F, Rajizadeh MA, Shahbazi M, Pourranjbar M, Nekouei AH, Sheibani V, Peterson D (2023) Effects of voluntary, and forced exercises on neurotrophic factors and cognitive function in animal models of Parkinson’s disease. Neuropeptides 101:102357

Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J (2018) BDNF: a key factor with multipotent impact on Brain Signaling and synaptic plasticity. Cell Mol Neurobiol 38(3):579–593

Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H (2009) Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 94(10):1062–1069

Palasz E, Wysocka A, Gasiorowska A, Chalimoniuk M, Niewiadomski W, Niewiadomska G (2020) BDNF as a Promising Therapeutic Agent in Parkinson’s Disease. Int J Mol Sci 21(3):1170

Cheng SM, Lee SD (2022) Exercise Training enhances BDNF/TrkB signaling pathway and inhibits apoptosis in Diabetic Cerebral cortex. Int J Mol Sci 23(12):6740

El Hayek L, Khalifeh M, Zibara V, Abi Assaad R, Emmanuel N, Karnib N, El-Ghandour R, Nasrallah P, Bilen M, Ibrahim P, Younes J, Abou Haidar E, Barmo N, Jabre V, Stephan JS, Sleiman SF (2019) Lactate mediates the effects of Exercise on Learning and Memory through SIRT1-Dependent activation of hippocampal brain-derived neurotrophic factor (BDNF). J Neurosci 39(13):2369–2382

PubMed   PubMed Central   Google Scholar  

Su G, Yang W, Wang S, Geng C, Guan X (2021) SIRT1-autophagy axis inhibits excess iron-induced ferroptosis of foam cells and subsequently increases IL-1Β and IL-18. Biochem Biophys Res Commun 561:33–39

Caruso GI, Spampinato SF, Costantino G, Merlo S, Sortino MA (2021) SIRT1-Dependent upregulation of BDNF in Human Microglia challenged with Aβ: an early but transient response rescued by Melatonin. Biomedicines 9(5):466

Mishra P, Mittal AK, Kalonia H, Madan S, Ghosh S, Sinha JK, Rajput SK (2021) SIRT1 promotes neuronal fortification in neurodegenerative diseases through attenuation of pathological hallmarks and Enhancement of Cellular Lifespan. Curr Neuropharmacol 19(7):1019–1037

CAS   PubMed   PubMed Central   Google Scholar  

Early increasing-intensity Treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury. Pain 156(9):1812–1825

Huang G, Xiang Z, Wu H, He Q, Dou R, Lin Z, Yang C, Huang S, Song J, Di Z, Wang S, Xiong B (2022) The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination. Int J Biol Sci 18(4):1415–1433

Download references

This study was supported by the National Council for Scientific and Technological Development (No: 442941/2023-4, MCTI/CNPq nº 14/2023 - Support for International Scientific Cooperation).

Author information

Authors and affiliations.

Faculty of Sports Science, Ningbo University, Ningbo, China

Anand Thirupathi & Ricardo A. Pinho

Graduate Program in Health Sciences, School of Life Sciences and Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil

Luis Felipe Marqueze & Ricardo A. Pinho

Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany

Tiago F. Outeiro

Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany

Faculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK

Scientific Employee with an Honorary Contract at Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen, Germany

Research Institute of Sport Science, University of Physical Education, Budapest, Hungary

Zsolt Radak

You can also search for this author in PubMed   Google Scholar

Contributions

A.T. and R.A.P. conceived the idea and wrote the manuscript; L.F.M., T.F.O., and Z.R. edited and proofread the manuscript. All the authors read the final version of the manuscript and approved it.

Corresponding author

Correspondence to Ricardo A. Pinho .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Conflict of interest

The authors declare that this review was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Thirupathi, A., Marqueze, L.F., Outeiro, T.F. et al. Physical Exercise-Induced Activation of NRF2 and BDNF as a Promising Strategy for Ferroptosis Regulation in Parkinson’s Disease. Neurochem Res (2024). https://doi.org/10.1007/s11064-024-04152-6

Download citation

Received : 26 February 2024

Revised : 19 April 2024

Accepted : 10 May 2024

Published : 24 May 2024

DOI : https://doi.org/10.1007/s11064-024-04152-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Parkinson´s disease
• Ferroptosis
• Physical exercise
• Antioxidants
• Oxidative stress
• Find a journal
• Publish with us
• Track your research

• Previous Article
• Next Article

“Can I Play Too?” A Qualitative Study of Outdoor Play and Participation Among Autistic Preschoolers

• Article contents
• Figures & tables
• Supplementary Data
• Peer Review
• Get Permissions
• Cite Icon Cite
• Search Site

Maeve Coughlan , Helen Lynch; “Can I Play Too?” A Qualitative Study of Outdoor Play and Participation Among Autistic Preschoolers. Am J Occup Ther July/August 2024, Vol. 78(4), 7804185130. doi: https://doi.org/10.5014/ajot.2024.050732

Download citation file:

• Ris (Zotero)
• Reference Manager

Importance: Outdoor play in homes, schools, and communities provides children with unique opportunities to explore their worlds, develop fundamental life skills, and experience belonging. However, few studies have explored outdoor free play among autistic preschoolers in natural settings from a neurodivergent-informed perspective.

Objective: To explore the play preferences, opportunities, and challenges in outdoor play for autistic preschoolers.

Design: In this qualitative study, the authors used a multimethod approach to data collection using visual, verbal, and projective techniques and thematic analysis to identify and describe outdoor play occupation as expressed by autistic preschoolers.

Setting: Home, community, and preschool environments in a city in Ireland.

Participants: Seven autistic children and their parents, from seven diverse preschool settings in Ireland.

Results: Two overarching themes were identified: (1) outdoor play preferences and meaning and (2) the physical and social environments of outdoor play. The findings suggest that autistic preschoolers demonstrate distinctive play styles and preferences when playing freely outdoors, with physical and social barriers to outdoor play existing in community and educational contexts.

Conclusions and Relevance: The findings suggest that autistic preschoolers’ outdoor play styles and preferences require support from adult advocates. Although the importance of relationships and social play cannot be overlooked, infrastructural accommodations for parents and schools are required if we are to create supportive and inclusive outdoor play environments and opportunities for freedom of expression for autistic children.

Plain-Language Summary: This study explored the distinctive outdoor play preferences, opportunities, and challenges for autistic preschoolers. The findings show that autistic preschoolers face physical and social barriers to outdoor play and that they need parents, schools, and communities to create supportive and inclusive play environments and opportunities for freedom of expression.

Citing articles via

Email alerts.

• Special Collections
• Conference Abstracts
• Browse AOTA Taxonomy
• AJOT Authors & Issues Series
• Online ISSN 1943-7676
• Print ISSN 0272-9490
• Author Guidelines
• Permissions
• Privacy Policy
• Cookie Policy
• Accessibility
• Terms of Use
• Copyright © American Occupational Therapy Association, Inc.

This Feature Is Available To Subscribers Only

Sign In or Create an Account

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List

Lifestyle Medicine: The Role of the Physical Therapist

Dear Editors, Authors, and Readers,

I applaud the authors of the article Lifestyle Medicine: A Brief Review of Its Dramatic Impact on Health and Survival by Bodai et al. 1 I would like to suggest an addition to the article. It cites the root cause of most chronic diseases as poor nutrition and physical inactivity. With regard to physical inactivity, physical therapists must be involved as a resource for healthy lifestyle recommendations, just as exercise coaches and lifestyle coaches are cited in the article.

As a pelvic health and manual physical therapist who has studied, practiced, and implemented patient education of a whole-food, plant-based diet, I am aware of the evidence-based benefit, have experienced personal change, as well as witnessed change in family, friends, and patients while on a whole-food, plant-based diet. My career, of course, is focused on the benefit and practice of exercise and overcoming movement impairment, but movement is not optimal without optimal nutrition.

With regard to physical inactivity, the article provides a box titled Moving Forward: Health Lifestyle Recommendations and Resources for Daily Practice , which provides 2 lists identifying team members engaged in promotion of a healthy lifestyle and promotion of exercise programs. Physical therapy should be included under both lists because we are experts in movement, and we daily address the causes and/or the manifestations of physical inactivity. We spend many years earning doctoral-level degrees, studying, and training to understand human movement from a molecular to a motivational level. Further, we are legally deemed wellness practitioners.

As in many medical school programs, nutrition is only briefly touched on in physical therapy programs. However, in June 2015, the American Physical Therapy Association adopted the motion RC 12–15, The Role of The Physical Therapist in Diet and Nutrition , which cites, “As diet and nutrition are key components of primary, secondary, and tertiary prevention of many conditions managed by physical therapists, it is the role of the physical therapist to evaluate for and provide information on diet and nutritional issues to patients, clients, and the community within the scope of physical therapists practice. This includes appropriate referrals to nutrition and dietary medical professionals when the required advice and education lie outside the education level of the physical therapist.” 2 The motion goes on to cite an article by Dean, 3 stating “a compelling argument can be made that clinical competencies in the 21st century physical therapy need to include assessment of smoking and smoking cessation (or at least its initiation), basic nutritional assessment and counseling, recommendations for physical activity and exercise, stress assessment and basic stress reduction recommendations, and sleep assessment and basic sleep hygiene recommendations.” Further, the motion cites the Commission on Accreditation in Physical Therapy Education’s Current Evaluative Criteria to meet education standards, that physical therapists “CC-5.50 provide culturally competent physical therapy services for prevention, health promotion, fitness and wellness to individuals, groups, and communities.” 4

The motion goes on to recommend that future physical therapy educational programming include the study of nutrition. Following motion RC 12–15, there has been an increase in physical therapy continuing education available for physical therapists to study and obtain continuing medical education units in nutrition. This leads me to plead that Lifestyle Medicine welcome physical therapy to help steer the proper evidence-based direction of education of physical therapists.

What is the case for physical therapy involvement? There are many implications for physical therapy involvement. I will touch on 3 general reasons:

What do we do with a patient whose obesity has contributed to osteoarthritis of the knee when they are being told to lose weight, exercise, and strengthen the knee before a surgery, but they have pain with movement?

Patients with lifestyle-induced, chronic-disease states may present with various neurofasciomusculoskeletal pathology, making movement difficult. How can we start to make movement easier to achieve the goal of physical activity? How can we maintain that movement? Screening for dietary involvement is necessary. For instance, food can be the catalyst for weight loss to initiate prehabilitation that may otherwise be laborious and painful. As we start to see more and more advanced stages of chronic disease, I think we will find more and more that our starting place is, in the very least, nutrition screening, nutrition conversation, nutrition referral, and nutrition leadership by example.

A general exercise program of walking for 30 minutes, 5x/wk may work for many people, but it won’t work for all. This could be because of movement impairment or simply motivation or interest. What brings meaning to movement for a patient? The answer will be different for everyone. Simply assigning an exercise coach may not be appropriate owing to impairment. Proper physical therapy evaluation, intervention, and communication with an exercise coach may be necessary. By the same token, asking a patient to join a walking program may not be a meaningful form of exercise to them, and physical therapy may need to assist in finding a safe alternative that gives meaning and maintains motivation.

Each contact is a potential moment to check if a patient is achieving and maintaining the nutrition goals set by other practitioners. There is a learning curve to implementing and following a whole-food, plant-based diet. It requires support from a team of practitioners, family, friends, and coworkers. Not every patient will get support from all of these sources. We can be one more person on the side of support.

How do physicians, dieticians, and other practitioners move forward with physical therapists as a team to help patients make dietary transitions for better function and health? I offer these simple suggestions: 1) when writing physical therapy referrals, add a note requesting the physical therapist follow-up with the dietary prescription; 2) volunteer to give an educational lecture to your local team of physical therapists highlighting the goals of your request to follow-up with patients on diet; 3) notify physical therapy clinics of any Lifestyle Medicine continuing education.

I look forward to seeing how these great groups of knowledgeable practitioners can impact health and survival. We are better together!

Re: Bodai BI, Nakata TE, Wong WT, et al. Lifestyle medicine: A brief review of its dramatic impact on health and survival. Perm J 2018;22:17-025. DOI: https://doi.org/10.7812/TPP/17-025

• Perm J. 2020; 24: 18.192.

Response to Dr Worman

On behalf of all of our coauthors, we wish to thank Dr Worman for reviewing our article regarding Lifestyle Medicine and for preparing such an insightful comment. She points out the importance of physical therapists as a significant part of the team that must be assembled as the messengers of a healthy lifestyle. She correctly identifies the role that physical therapists can play in our overall health.

It is correct, and sad to say, that most professional schools that offer health-related degrees largely ignore any education regarding nutrition. It is great to note that the American Physical Therapy Association has mentioned this and has recently adopted a motion to address this inadequacy. More professional associations must urgently take note of this and follow their lead.

Although we all recognize that not all forms of exercise are appropriate for each patient, perhaps because of other comorbid conditions, such as being wheelchair bound, this recognition adds further support to the important role of physical therapists with the knowledge to suggest alternative approaches to promote exercise and other physical activities that may achieve similar results.

Dr Worman addresses the unique opportunity that physical therapists have to access patients because they often provide long-term, follow-up care. This enables them to introduce lifestyle changes. As she correctly points out, there is a “learning curve” to implementing a whole-food, plant-based diet. Thus, they have the opportunity to progressively monitor their interventions, address ongoing challenges, and reinforce recommendations.

We are grateful for this important letter to the editor and greatly appreciate Dr Worman’s recommendations. It is our hope that her message will be resoundingly heard. v

• Search Menu
• Sign in through your institution
• Animal Research
• Cardiovascular/Pulmonary
• Health Services
• Health Policy
• Health Promotion
• History of Physical Therapy
• Implementation Science
• Integumentary
• Musculoskeletal
• Orthopedics
• Pain Management
• Pelvic Health
• Pharmacology
• Population Health
• Professional Issues
• Psychosocial
• Advance Articles
• COVID-19 Collection
• Featured Collections
• Special Issues
• PTJ Peer Review Academies
• Author Guidelines
• Submission Site
• Why Publish With PTJ?
• Open Access
• Call for Papers
• Self-Archiving Policy
• Promote your Article
• About Physical Therapy
• Editorial Board
• Advertising & Corporate Services
• Permissions
• Journals on Oxford Academic
• Books on Oxford Academic

Top Mentioned Articles of 2020

To mark another year of growth for the journal,  PTJ invites you to explore a collection of the most talked-about articles from 2020. 

Continue to engage with PTJ on Twitter  and Facebook  in 2021.

Manual Therapy Versus Surgery for Carpal Tunnel Syndrome: 4-Year Follow-Up From a Randomized Controlled Trial

The essential role of home- and community-based physical therapists during the covid-19 pandemic, blood pressure screening by outpatient physical therapists: a call to action and clinical recommendations, frequency of physical therapist intervention is associated with mobility status and disposition at hospital discharge for patients with covid-19, systematic review of changes and recovery in physical function and fitness after severe acute respiratory syndrome–related coronavirus infection: implications for covid-19 rehabilitation, physical therapist management of total knee arthroplasty, home and community-based physical therapist management of adults with post–intensive care syndrome, cost-effectiveness and outcomes of direct access to physical therapy for musculoskeletal disorders compared to physician-first access in the united states: systematic review and meta-analysis, italian physical therapists’ response to the novel covid-19 emergency, rhabdomyolysis after the use of percussion massage gun: a case report, integrating motivational interviewing in pain neuroscience education for people with chronic pain: a practical guide for clinicians, physical therapist roles during the opioid epidemic in rural appalachia: preparing students to educate communities, application of high-intensity functional resistance training in a skilled nursing facility: an implementation study, impact of physical training programs on physical fitness in people with class ii and iii obesity: a systematic review and meta-analysis, six lessons for covid-19 rehabilitation from hiv rehabilitation, be a part of ptj.

Are you in the fields of physical therapy and rehabilitation? Submit your research and reviews to  Physical Therapy and Rehabilitation . Learn more about the submission process in our  Author Guidelines .  

Listen with PTJ

The  PTJ  Podcast is hosted by Editor-in-Chief Alan Jette, who gets at the story behind the research with author interviews. The exclusive interviews include insights on clinical application, study design, and future directions.

Browse our  podcast hub  to explore the latest episodes, episode collections, and archives.

• Recommend to Your Librarian
• Advertising and Corporate Services
• Journals Career Network

Affiliations

• Online ISSN 1538-6724
• Copyright © 2024 American Physical Therapy Association
• About Oxford Academic
• Publish journals with us
• University press partners
• What we publish
• New features  
• Open access
• Institutional account management
• Rights and permissions
• Get help with access
• Accessibility
• Advertising
• Media enquiries
• Oxford University Press
• Oxford Languages
• University of Oxford

Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide

• Copyright © 2024 Oxford University Press
• Cookie settings
• Cookie policy
• Privacy policy
• Legal notice

This Feature Is Available To Subscribers Only

Sign In or Create an Account

This PDF is available to Subscribers Only

For full access to this pdf, sign in to an existing account, or purchase an annual subscription.