Introduction

Low back pain (LBP) is the world’s leading cause of disability [1] and is associated with enormous and escalating costs to society [2]. Most of this burden is attributed to the condition when LBP becomes persistent or recurrent. Why some individuals with acute LBP recover, whereas others do not [3, 4], is largely unknown.

Although psychosocial factors have generally been considered stronger predictors of long-term outcome than diagnostic or injury-related factors [5, 6], they only explain a small proportion of the variance in outcome [6, 7]. Biological factors have largely been dismissed and the few that have been comprehensively addressed (e.g., muscle strength/endurance [8]) have little relation to outcome [9]. With this incomplete understanding of factors related to LBP outcome, it is not surprising that most treatments have modest effects at best [10] and are generally unable to prevent recurrence/persistence of pain [11].

We argue that three issues underlie a fresh approach to this problem. First, novel biological factors that could plausibly contribute to LBP outcome have been identified in cross-sectional studies, e.g., systemic inflammation, trunk muscle morphology/function, and processing of pain. Up until now, these potentially modifiable factors had not been tested longitudinally from the initial onset of symptoms, and analyses of the early time-points from the cohort presented in this paper are providing promising results [12,13,14]. Second, although interaction between biological, psychological and social factors is implied in the biopsychosocial model of pain, this interaction has received little attention in past longitudinal studies of LBP outcome. Again, early analyses from the present cohort have revealed interaction between features such as depression, cytokines and poor LBP outcome [12,13,14,15,16]. Third, there is growing evidence that behavioural factors such as sleep interact with the “biopsychosocial” components of LBP, but their contribution to outcome is unknown. This too has been supported by early observations [12, 14]. Further, little is known of the time course of changes in each of the biopsychosocial domains over 12 months following an acute LBP episode. There is strong foundation to evaluate whether candidate biological factors, along with their possible interaction with psychosocial factors, contribute to the transition from acute LBP to that of persistent/recurrent symptoms.

The purpose of this paper is to provide a profile of a cohort study that aims to; (1) evaluate whether outcome after an acute episode of LBP can be predicted by the most promising bio-psycho-social factors and/or the interactions between them; (2) compare these factors between individuals with and without acute LBP; and (3) evaluate the time course of changes in these factors following LBP onset. This paper outlines the participants, measures and data collection schedule, and compares baseline characteristics between acute LBP and control, and follow-up and non-follow-up LBP participants.

Main text

Methods

Study design

This longitudinal cohort study involved measures of variables within the biological, psychological and social domains (Table 1) at multiple time-points for 12 months (Additional file 1: Table S1). Measures of sleep, physical activity, alcohol consumption and smoking were grouped separately in a “behavioural” domain as they cross between classical domains. Eligible participants completed a series of detailed online questionnaires related to their pain and disability level, health, demographics, behaviour, and psychosocial status within 24 h of undertaking a laboratory-based session (~ 4 h) at the University of Queensland to assess biological variables. Measures (laboratory-based biological measures and online questionnaires) were repeated at 3, 6 and 9 months for LBP participants, and at 3 months for control participants. At 12 months, questionnaires were completed by all participants in the LBP group in addition to a separate 12-month recall questionnaire relating to the trajectory of their LBP since initial assessment for the study. Participants were also instructed (and reminded) via email to report their pain and disability level every fortnight for 3 (controls) or 12 months (LBP) via an online survey. For some analyses that have been conducted to date, these pain and disability data have been used to classify LBP participants as either “unrecovered”, “partially recovered” or “recovered” at follow-up (for details see Additional file 1: Table S2).

Table 1 Detailed description of measures
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Participant recruitment

A total of 1849 individuals from Brisbane (and surrounds), Australia, were screened between April 2012 and September 2017 (Fig. 1). Participants were recruited through advertisements around the University campus and local community, social media, three nearby hospitals and via a professional recruitment agency (Trialfacts).

Fig. 1
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Cohort flow diagram

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Screening was conducted using two different methods. Initially, eligibility was determined via email and/or phone, and when this method was used the reason(s) for exclusion at this initial screening were not recorded. This was replaced with an automated online screening questionnaire from April 2014, with reasons for exclusion recorded. The inclusion and exclusion criteria for LBP participants are outlined in Additional file 1: Table S3. Participants did not need to be experiencing their first ever LBP episode. Previous LBP was recorded for inclusion as a covariate. Control participants were included if they had not experienced LBP within the last month in addition to meeting the exclusion criteria in Additional file 1: Table S3.

At the first laboratory testing session (after initial screening), eligibility for inclusion were confirmed using data from the baseline questionnaire (completed within 24 h of the first laboratory-based session), to ensure that the participant’s average level of pain and LBP-related disability in the past week exceeded the inclusion threshold (≥ 1/10 for pain; ≥ 1/24 for disability). Potential control participants who reported a score > 0 on a 0 (“no pain”) to 10 (“worst pain imaginable”) numerical rating scale (NRS) and/or the Roland Morris Disability Questionnaire (RMDQ [35], [for definition of measures see Table 1]), or provided no scores were excluded from the study (N = 14). Potential LBP participants who reported < 1 on the pain NRS and/or the RMDQ, or provided no scores in the past week were excluded from the study (N = 8). After data collection, criteria for exclusion were identified for two participants with LBP (multiple sclerosis [N = 1], duration of LBP > 14 days [N = 1]) and two control participants (no pain/disability data [N = 1], pain/injury in another body region [N = 1]). These participants were excluded from the dataset. The final cohort included 133 and 74 participants in the LBP and control groups, respectively, for analyses.

Measurements

Details of the measures and at what time-point(s) they were implemented are presented in Table 1 and Additional file 1: Table S1. All variables were measured in a standardised order for each participant. Biological measures were those we considered to be the most promising candidate factors for predicting LBP recurrence/persistence based on previous research and plausible rationales founded on clinical, epidemiological and fundamental research. For psychological measures, we considered three key domains of relevance in LBP: cognitive (expectations, beliefs, and perceptions concerning pain) [6, 36,37,38], emotional (distress, anxiety, and depression) [5], and behavioural (coping, pain behaviour, and activity/activity avoidance) [6, 36, 37]. Social measures were selected based on the Multinational Musculoskeletal Inception Cohort Study (MMICS) guidelines [39]. These guidelines were developed by an international expert team with review of the best available evidence from systematic/narrative reviews and expert consensus. As it was not our intention to withhold treatment over the study period, we collected information regarding health care and medication use so that treatment variables can be included as covariates. The total number of variables was restricted to limit the required participant sample size, minimise the potential for over-fitting, and for cost–benefit.

Sample size

A sample size of 217 was calculated based on power to detect predictor variables using complex multiple regression models (i.e., 28 predictor variables, 5 a priori selected interactions) and growth curve modelling methods, while allowing for loss to follow-up. The planned sample size was not achieved due to feasibility issues as outlined in the “limitations” section. Although the achieved sample size (N = 133) limits the ability to examine numerous interactions simultaneously, reduced model sizes and alternative methods (e.g., cluster analysis) have been applied successfully on data from this cohort [12,13,14,15,16].

Data analysis

All questionnaire-based measures (that could be quantitatively analysed) at baseline were compared between: (1) LBP and control participants, and (2) LBP participants who did and did not follow-up at 3, 6, 9 and 12 months.

Results

Participant characteristics at baseline

The characteristics of the study participants are described in Additional file 1: Table S4. Compared to controls, LBP participants were/had: taller and heavier, a higher BMI, a higher prevalence of comorbidities, a higher incidence of previous LBP, higher depressive and pain catastrophizing symptoms, higher self-reported job demands, more sick days (over the last 12 months), poorer sleep quality, more likely to have a history of cigarette smoking, and more likely to have performed vigorous physical activity on less days in the previous week.

Participant attrition

Of the 133 eligible acute LBP participants who were enrolled in the study and provided baseline data, 35 (26%) were lost to follow-up for their laboratory-based measures (i.e., did not attempt/complete any biological measures) at 3 months, a further 9 at 6 months (total lost to follow-up = 44, 33%), and a further 5 at 9 months (total lost to follow-up = 49, 37%). As biological measures were not performed at 12 months, all participants were invited to complete the standard 3-montly questionnaire in addition to a separate recall questionnaire at 12 months, irrespective of whether or not they had continued or dropped out earlier. One or both of these were fully/partly completed by all but 41 of the 133 LBP participants who started the study (follow-up at 12 months: N = 92). For participants that did follow-up, Additional file 1: Table S5 shows the number of those that provided valid data for each of the 3-monthly questionnaire-based measures at each respective time-point. Ten control participants did not return for follow-up at 3 months. With respect to the completion rate of fortnightly pain (NRS) and disability (RMDQ) questionnaires, 85% (1505 of 1770) were completed by LBP participants who were retained for follow-up (i.e., up to 3, 6, 9 or 12 months) within 7 days of each questionnaire being issued, and 91% (282 of 310) were completed by control participants (i.e., up to 3 months).

Comparison of follow-up and non-follow-up participants

Comparison of baseline characteristics between LBP participants who did and did not follow-up for laboratory-based measures at 3, 6 and 9 months, and questionnaire measures at 12 months, revealed some differences, as shown in Table 2.

Table 2 Comparison of baseline characteristics between participants with LBP who did (FU) and did not (NFU) follow-up at 3, 6, 9 and 12 months
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Discussion

This paper profiles the only acute LBP cohort in which detailed biological, psychological, social and behavioural factors have been longitudinally and frequently collected, to date. The cohort has great potential to provide unique insight into the features that may predict and/or mediate long-term outcome [40].

The findings of baseline (acute LBP) characteristics presented here provide a foundation for future longitudinal analyses. Whether the findings can be generalised to a larger or clinical sample of individuals with early-acute LBP requires further and detailed studies of the condition during the early-acute phase. Despite the rate of loss to follow-up, most occurred after the first session, and baseline characteristics were generally similar between those who did and not return for follow-up.

Initial analyses of this cohort have revealed specific immune and nervous system features associated with the transition to persistent/recurrent LBP, and that various psychological and behavioural factors shape these relationships [12,13,14,15,16]. Ongoing analyses focus on elucidating the role of trunk neuromuscular, kinematic, mechanical and morphological properties, along with their possible interactions with psychosocial/behavioural features, in predicting LBP outcome.

Limitations

  • The strict “acute LBP” inclusion criteria (i.e., within 2 weeks of onset of a LBP episode following 1 month without pain) rendered recruitment challenging – > 50% of screened individuals did not meet these criteria.

  • Study measures and follow-up procedures imposed substantial burden and explains the reported attrition.

  • Missing data due to attrition was high as is usual in longitudinal cohorts, and statistical approaches (e.g., mixed effects models) have been, and will continue to be, used to minimise bias.

  • The smaller than expected sample size limits the types of analyses to investigate interactions, and their interpretation; however, approaches such as cluster analyses have so far provided valuable insights.

  • It was not possible to collect blood samples at a standardised time during the day for each participant at each time-point. To account for the diurnal variations in cytokines [41], time of blood collection was recorded for inclusion as a potential confounder when interpreting cytokine levels.