Abstract Mediation analysis is a useful research method that potentially allows identification of the mechanisms through which treatments affect patient outcomes. This chapter reviews the theoretical ...framework, research designs and statistical approaches used in mediation analysis. It describes what can be learnt from previous mediation research, much of which has investigated mediating factors of psychosocial interventions in other health conditions. It also summarises the few treatment-mediation studies of psychosocial interventions conducted in back pain. This chapter shows that there is emerging evidence about the role of some psychological factors as potential treatment mediators, such as self-efficacy and catastrophising. Mediation analysis can equally be applied to non-psychological factors. Pre-planned and appropriately conducted mediation analysis in adequately powered clinical trials would be a step forward in understanding treatment effects in back pain and improving patient management.
Abstract
Background
Many interventions for the treatment of low back pain exist, but the mechanisms through which such treatments work are not always clear. This situation is especially true for ...biopsychosocial interventions that incorporate several different components and methods of delivery.
Objective
The study objective was to examine the indirect effects of the Cognitive Patient Education (COPE) intervention via illness perceptions, back pain myths, and pain catastrophizing on disability outcome.
Design
This study was a secondary analysis of the COPE randomized controlled trial.
Methods
Mediation analysis techniques were employed to examine the indirect effects of the COPE intervention via residualized change (baseline – posttreatment) in the 3 variables hypothesized to be targeted by the COPE intervention on posttreatment disability outcome. Pain intensity at baseline, pain duration, clinician type, and a treatment-mediator interaction term were controlled for in the analysis.
Results
Preliminary analyses confirmed that changes in pain catastrophizing and illness perceptions (not back pain myths) were related to both allocation to the intervention arm and posttreatment disability score. The treatment exerted statistically significant indirect effects via changes in illness perceptions and pain catastrophizing on posttreatment disability score (illness perceptions standardized indirect effect = 0.09 95% CI = 0.03 to 0.16; pain catastrophizing standardized indirect effect = 0.05 95% CI = 0.01 to 0.12). However, the inclusion of an interaction term led to the indirect effects being significantly reduced, with the effects no longer being statistically significant.
Limitations
This study presents a secondary analysis of variables not identified a priori as being potentially important treatment targets; other, unmeasured factors could also be important in explaining treatment effects.
Conclusions
The finding that small indirect effects of the COPE intervention via changes in illness perceptions and pain catastrophizing on posttreatment disability could be estimated indicates that these variables may be viable treatment targets for biopsychosocial interventions; however, this finding must be viewed in light of the adjusted analyses, which showed that the indirect effects were significantly reduced through the inclusion of a treatment-mediator interaction term.
Interventions developed to improve disability outcomes for low back pain (LBP) often show only small effects. Mediation analysis was used to investigate what led to the effectiveness of the ...STarT Back trial, a large primary care-based trial that treated patients consulting with LBP according to their risk of a poor outcome. The high-risk subgroup, randomized to receive either psychologically-informed physiotherapy (n = 93) or current best care (n = 45), was investigated to explore pain-related distress and pain intensity as potential mediators of the relationship between treatment allocation and change in disability. Structural equation modeling was used to generate latent variables of pain-related distress and pain intensity from measures used to identify patients at high risk (fear-avoidance beliefs, depression, anxiety, and catastrophizing thoughts). Outcome was measured using the Roland–Morris Disability Questionnaire. Change in pain-related distress and pain intensity were found to have a significant mediating effect of .25 (standardized estimate, bootstrapped 95% confidence interval, .09–.39) on the relationship between treatment group allocation and change in disability outcome. This study adds to the evidence base of treatment mediation studies in pain research and the role of distress in influencing disability outcome in those with complex LBP.
Mediation analysis using structural equation modeling found that change in pain-related distress and pain intensity mediated treatment effect in the STarT Back trial. This type of analysis can be used to gain further insight into how interventions work, and lead to the design of more effective interventions in future.
•Identifying how treatments work is important in making them more effective in the future.•Changes in psychological distress and pain intensity are mediators of treatment effect.•This study adds to the evidence base for the role of mediators in pain research.
How much are the reductions in pain intensity and improvements in physical function from Pilates exercise mediated by changes in pain catastrophising and kinesiophobia?
This was a secondary causal ...mediation analysis of a four-arm randomised controlled trial testing Pilates exercise dosage (once, twice or thrice per week) against a booklet control.
Two hundred and fifty-five people with chronic low back pain.
All analyses were conducted in R software (version 4.1.2) following a preregistered analysis plan. A directed acyclic graph was constructed to identify potential pre-treatment mediator-outcome confounders. For each mediator model, we estimated the intervention-mediator effect, the mediator-outcome effect, the total natural indirect effect (TNIE), the pure natural direct effect (PNDE), and the total effect (TE).
Pain catastrophising mediated the effect of Pilates exercise compared with control on the outcomes pain intensity (TNIE MD –0.21, 95% CI –0.47 to –0.03) and physical function (TNIE MD –0.64, 95% CI –1.20 to –0.18). Kinesiophobia mediated the effect of Pilates exercise compared with control on the outcomes pain intensity (TNIE MD –0.31, 95% CI –0.68 to –0.02) and physical function (TNIE MD –1.06, 95% CI –1.70 to –0.49). The proportion mediated by each mediator was moderate (21 to 55%).
Reductions in pain catastrophising and kinesiophobia partially mediated the pathway to improved pain intensity and physical function when using Pilates exercise for chronic low back pain. These psychological components may be important treatment targets for clinicians and researchers to consider when prescribing exercise for chronic low back pain.
ObjectivesTo identify potentially modifiable factors that mediate the association between symptomatic osteoarthritis (OA) and premature mortality.MethodsA population-based prospective cohort study; ...primary care medical record data were linked to self-report information collected by questionnaire in adults aged 50 years and over (n=10 415). OA was defined by primary care consultation and moderate-to-severe pain interference in daily life. A Cox proportional hazards analysis determined the total effect (TE) of OA on mortality after adjustment for potential confounders. Within the Cox model, path analysis was used to decompose the TE to assess the indirect and direct effects for selected potential mediators (anxiety, depression, unrefreshed sleep and walking frequency). Results are expressed as HRs with 95% CIs derived from bootstrap resampling.ResultsOA was significantly associated with mortality (TE-adjusted HR 1.14; 95% CI 1.00 to 1.29). The indirect effects for walking frequency were 1.05 (95% CI 1.04 to 1.06), depression 1.02 (95% CI 1.02 to 1.03), anxiety 1.01 (95% CI 1.00 to 1.02) and unrefreshed sleep 1.01 (95% CI 1.00 to 1.01).ConclusionsThe analysis indicates that encouraging people to walk and ‘get out and about’ in addition to targeting OA could be protective against excessive mortality. The findings also suggest that depression, anxiety and unrefreshed sleep have a role in premature mortality for people with OA; however, this has low clinical significance.
IntroductionSelf-management and remaining physically active are first-line recommendations for the care of patients with low back pain (LBP). With a lifetime prevalence of up to 85%, novel approaches ...to support behavioural self-management are needed. Internet interventions may provide accessible support for self-management of LBP in primary care. The aim of this randomised controlled trial is to determine the clinical and cost-effectiveness of the ‘SupportBack’ internet intervention, with or without physiotherapist telephone support in reducing LBP-related disability in primary care patients.Methods and analysisA three-parallel arm, multicentre randomised controlled trial will compare three arms: (1) usual primary care for LBP; (2) usual primary care for LBP and an internet intervention; (3) usual primary care for LBP and an internet intervention with additional physiotherapist telephone support. Patients with current LBP and no indicators of serious spinal pathology are identified and invited via general practice list searches and mailouts or opportunistic recruitment following LBP consultations. Participants undergo a secondary screen for possible serious spinal pathology and are then asked to complete baseline measures online after which they are randomised to an intervention arm. Follow-ups occur at 6 weeks, 3, 6 and 12 months. The primary outcome is physical function (using the Roland and Morris Disability Questionnaire) over 12 months (repeated measures design). Secondary outcomes include pain intensity, troublesome days in pain over the last month, pain self-efficacy, catastrophising, kinesophobia, health-related quality of life and cost-related measures for a full health economic analysis. A full mixed-methods process evaluation will be conducted.Ethics and disseminationThis trial has been approved by a National Health Service Research Ethics Committee (REC Ref: 18/SC/0388). Results will be disseminated through peer-reviewed journals, conferences, communication with practices and patient groups. Patient representatives will support the implementation of our full dissemination strategy.Trial registration numberISRCTN14736486.
Background and objective
This systematic review synthesized evidence from European neck and low back pain (NLBP) clinical practice guidelines (CPGs) to identify recommended treatment options for use ...across Europe.
Databases and Data Treatment
Comprehensive searches of thirteen databases were conducted, from 1st January 2013 to 4th May 2020 to identify up‐to‐date evidence‐based European CPGs for primary care management of NLBP, issued by professional bodies/organizations. Data extracted included; aim and target population, methods for development and implementation and treatment recommendations. The AGREE II checklist was used to critically appraise guidelines. Criteria were devised to summarize and synthesize the direction and strength of recommendations across guidelines.
Results
Seventeen CPGs (11 low back; 5 neck; 1 both) from eight European countries were identified, of which seven were high quality. For neck pain, there were consistent weak or moderate strength recommendations for: reassurance, advice and education, manual therapy, referral for exercise therapy/programme, oral analgesics and topical medications, plus psychological therapies or multidisciplinary treatment for specific subgroups. Notable recommendation differences between back and neck pain included, i) analgesics for neck pain (not for back pain); ii) options for back pain‐specific subgroups—work‐based interventions, return to work advice/programmes and surgical interventions (but not for neck pain) and iii) a greater strength of recommendations (generally moderate or strong) for back pain than those for neck pain.
Conclusions
This review of European CPGs identified a range of mainly non‐pharmacological recommended treatment options for NLBP that have broad consensus for use across Europe.
Significance
Consensus regarding evidence‐based treatment recommendations for patients with neck and low back pain (NLBP) from recent European clinical practice guidelines identifies a wide range of predominantly non‐pharmacological treatment options. This includes options potentially applicable to all patients with NLBP and those applicable to only specific patient subgroups. Future work within our Back‐UP research team will transfer these evidence‐based treatment options to an accessible clinician decision support tool for first contact clinicians.
Background
Multiple cohort and systematic review studies exist, reporting independent predictive factors associated with outcome in musculoskeletal populations. These studies have found evidence for ...a number of “generic” factors that have been shown to predict outcome across musculoskeletal patient cohorts. This review provides a higher level review of the evidence with a focus on generic patient factors associated with functional musculoskeletal outcome with a view to informing predictive modelling.
Objectives
(a) Identify patient factors found to have evidence to support their association with functional outcome, and (b) review these findings across body areas/conditions to identify generic predictive factors.
Databases and Data Treatment
Electronic databases of MEDLINE, AMED, EMBASE, CINAHL and Cochrane were searched for eligible studies. Two reviewers independently extracted data and assessed quality using an established checklist for umbrella reviews.
Results
Twenty‐one systematic reviews met inclusion criteria, all were of moderate/high quality. Six independent predictors were found to have strong evidence of association with worse musculoskeletal functional outcome across anatomical body sites (worse baseline function, higher symptom/pain severity, worse mental well‐being, more comorbidities, older age and higher body mass index). Longer duration of symptoms, worse pain coping, presence of workers compensation, lower vitality and lower education were also found to have moderate evidence of association with worse functional outcome across body sites.
Conclusions
This study identifies a number of factors associated with musculoskeletal functional outcome. The generic predictive factors identified should be considered for inclusion into musculoskeletal prognostic models, including models used for case‐mix‐adjustment of patient reported outcome measure data.
Significance
This article identifies “generic” patient factors that predict functional outcome (measured using Patient Reported Outcome Measures (PROMs)) across musculoskeletal conditions. Findings provide support for the development and content of generic musculoskeletal prognostic models including models used to case‐mix adjust PROM data for baseline complexity. Generic musculoskeletal models and functional PROMs would facilitate more feasible comparison and benchmarking of musculoskeletal services in order to identify variation and address health inequalities.
Disability is an important outcome from a clinical and public health perspective. However, it is unclear how disability develops in people with low back pain or neck pain. More specifically, the ...mechanisms by which pain leads to disability are not well understood. Mediation analysis is a way of investigating these mechanisms by examining the extent to which an intermediate variable explains the effect of an exposure on an outcome. This systematic review and meta-analysis aimed to identify and examine the extent to which putative mediators explain the effect of pain on disability in people with low back pain or neck pain. Five electronic databases were searched. We found 12 studies (N = 2961) that examined how pain leads to disability with mediation analysis. Standardized regression coefficients (β) of the indirect and total paths were pooled. We found evidence to show that self-efficacy (β = 0.23, 95% confidence interval CI = 0.10 to 0.34), psychological distress (β = 0.10, 95% CI = 0.01 to 0.18), and fear (β = 0.08, 95% CI = 0.01 to 0.14) mediated the relationship between pain and disability, but catastrophizing did not (β = 0.07, 95% CI = -0.06 to 0.19). The methodological quality of these studies was low, and we highlight potential areas for development. Nonetheless, the results suggest that there are significant mediating effects of self-efficacy, psychological distress, and fear, which underpins the direct targeting of these constructs in treatment.
Self-management interventions for persistent low back pain (LBP) promote active involvement of the patient in managing their condition. Such interventions can be characterised as behaviour change ...interventions, in that they are designed to help the patient learn and adopt a set of health behaviours that they can use in everyday life to benefit their condition by reducing or managing their symptoms. Self-management interventions are recommended in several key guidelines for the treatment of persistent LBP, but the evidence for the effectiveness of these types of interventions is inconclusive. In this article, we discuss the existing literature within self-management interventions for persistent LBP and make suggestions for how research in this area can be improved, specifically addressing areas where evidence is currently lacking. Existing definitions of self-management are examined, and the importance of the choice of an underlying theory and appropriate outcome measures are discussed.
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