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. 2022 Dec 29;17(12):e0278906. doi: 10.1371/journal.pone.0278906

Accumulation of health complaints is associated with persistent musculoskeletal pain two years later in adolescents: The Fit Futures study

Kaja Smedbråten 1,*, Margreth Grotle 2,3, Henriette Jahre 1,2, Kåre Rønn Richardsen 1,2, Pierre Côté 4, Ólöf Anna Steingrímsdóttir 5,6, Kjersti Storheim 1,3, Christopher Sivert Nielsen 7,8, Britt Elin Øiestad 1,2
Editor: Dong Keon Yon9
PMCID: PMC9799295  PMID: 36580469

Abstract

There is limited knowledge on the association between different health complaints and the development of persistent musculoskeletal pain in adolescents. The aims of this study were to assess whether specific health complaints, and an accumulation of health complaints, in the first year of upper-secondary school, were associated with persistent musculoskeletal pain 2 years later. We used data from a population-based cohort study (the Fit Futures Study in Norway), including 551 adolescents without persistent musculoskeletal pain at baseline. The outcome was persistent musculoskeletal pain (≥3 months) 2 years after inclusion. The following self-reported health complaints were investigated as individual exposures at baseline: asthma, allergic rhinitis, atopic eczema, headache, abdominal pain and psychological distress. We also investigated the association between the accumulated number of self-reported health complaints and persistent musculoskeletal pain 2 years later. Logistic regression analyses estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs). At the 2-year follow-up, 13.8% (95% CI [11.2–16.9]) reported persistent musculoskeletal pain. Baseline abdominal pain was associated with persistent musculoskeletal pain 2 years later (OR 2.33, 95% CI [1.29–4.19], p = 0.01). Our analyses showed no statistically significant associations between asthma, allergic rhinitis, atopic eczema, headache or psychological distress and persistent musculoskeletal pain at the 2-year follow-up. For the accumulated number of health complaints, a higher odds of persistent musculoskeletal pain at the 2-year follow-up was observed for each additional health complaint at baseline (OR 1.33, 95% CI [1.07–1.66], p = 0.01). Health care providers might need to take preventive actions in adolescents with abdominal pain and in adolescents with an accumulation of health complaints to prevent development of persistent musculoskeletal pain. The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research to understand the underlying patterns of persistent pain conditions in adolescents.

Introduction

Musculoskeletal pain is common already in young ages, with a prevalence of up to 40% among children and adolescents [1]. Adolescents with persistent musculoskeletal pain report difficulties in daily activities [2] and reduced health-related quality of life [3]. Furthermore, experiencing musculoskeletal pain in adolescence is a predictor of future pain [4], and of receiving sickness benefits [5] and long-term social welfare benefits [6] in adulthood. Given these consequences, it is important to draw attention to risk factors of persistent musculoskeletal pain onset in adolescence to be able to develop appropriate preventive strategies.

Importantly, also headache [1, 7], abdominal pain [1] and mental health problems [8] are common health complaints in children and adolescents. Furthermore, medical conditions, such as asthma, eczema [9, 10] and allergic rhinitis [9] are frequent. Several of these health complaints commonly co-occur with musculoskeletal pain [11–13], however, whether the presence of different health complaints increase the risk of developing musculoskeletal pain is unclear. A systematic review suggested that negative emotional symptoms might increase the risk of developing musculoskeletal pain in children and adolescents [14]. Studies have also indicated an association between abdominal pain [15] and headache [15–18] with later musculoskeletal pain. For the association between other health issues, including medical conditions, and musculoskeletal pain onset in children and adolescents, the existing findings are inconsistent [14].

A cross-sectional study by Dominick et al [19] demonstrated that several discrete chronic physical conditions, and the number of conditions, were independently associated with chronic pain in the general population aged 15 years and over. Furthermore, a cross-sectional study suggested that adolescents with two additional health complaints, were more likely to report low back pain compared to those with one additional health complaint [13]. Thus, investigating both specific and an accumulation of health complaints might be of interest in relation to persistent musculoskeletal pain. According to a previous cohort study of 9-12-year-olds, an increasing number of physical and psychological symptoms increased the odds of future neck pain [20]. Furthermore, a strong association between a combination of persistent low back pain, persistent headache and asthma in adolescence and future persistent low back pain has been reported [21]. To the best of our knowledge, no previous cohort studies have investigated the association between an accumulation of health complaints in adolescence, including medical diseases, psychological and somatic symptoms, and the onset of persistent musculoskeletal pain.

Hence, the aims of this study were to assess whether specific health complaints, and an accumulation of health complaints, in adolescents without persistent musculoskeletal pain in the first year of upper-secondary school, were associated with persistent musculoskeletal pain (≥ 3 months) 2 years later.

Material and methods

Study design and sample

This is a population-based cohort study using data from the Fit Futures study, which was conducted in the municipalities of Tromsø and Balsfjord in Northern Norway. The first wave of the study, Fit Futures 1 (FF1), was conducted in 2010–2011 and all first-year upper-secondary school students in the two municipalities were invited to participate. Two years later (2012–2013), all FF1 participants, and all other third-year students in the same upper-secondary schools, were invited to participate in the second wave of the study, Fit Futures 2 (FF2). In our sample we have included adolescents who participated in both waves. The assessments and data collection were conducted during school hours, at a research unit at the University Hospital of North Norway, and included an electronic questionnaire, clinical examinations and a clinical interview. Further details regarding the Fit Futures study have been presented earlier [22, 23].

Of 1117 adolescents invited to participate in FF1, 1038 (92.9%) responded. Thirty-six participants were excluded from our sample because they were older than 19 years of age at baseline. Moreover, 190 participants reported persistent musculoskeletal pain at baseline and were excluded from the sample. Finally, 23 participants were excluded because they had incomplete data on musculoskeletal pain at baseline (Fig 1). Of 789 respondents to the FF1 study that met the inclusion criteria, 551 (69.8%) participated in FF2 and had complete outcome data for the present study.

Fig 1. Flow chart of the study sample.

Fig 1

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All participants provided written informed consent prior to participation. For participants under the age of 16 years, written consent of one parent/guardian was also obtained. Our study protocol was approved by the Regional Committee for Medical and Health Research Ethics (2019/599/REK Nord) in Norway and approved by the Norwegian Centre for Research Data (954769). The protocol was registered at ClinicalTrials.gov (NCT05036746). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed to ensure the reporting quality of this study [24].

Persistent musculoskeletal pain

The outcome was persistent musculoskeletal pain assessed at the 2-year follow-up with the question “Do you have persistent or recurring pain that has lasted for 3 months or more?”. In addition, pain frequency and location were assessed. We defined persistent musculoskeletal pain as pain that persists or is recurring on a weekly basis for three months or more, in one or several of the following pain sites; “shoulder”, “arm/elbow”, “hand”, “hip”, “thigh/ knee/shin”, “ankle/foot”, “jaw/temporomandibular joint”, “neck”, “upper back”, “lower back” and/or “chest”.

Persistent musculoskeletal pain was also measured and defined as described above at baseline. The measurement of persistent musculoskeletal pain at baseline was only used to identify the sample in our cohort study.

Health complaints

The Fit Futures Study questionnaire included a section to measure health complaints. The presence of asthma, allergic rhinitis and atopic eczema were measured by the question “Has a doctor ever told you that you have…”, followed by “asthma”, “hay-fever or allergic rhinitis” and “children’s eczema or atopic eczema”. “Hay fever or allergic rhinitis” will in the following be termed “allergic rhinitis” and “children`s eczema or atopic eczema” will be termed “atopic eczema”. The response alternatives were “yes”, “no” and “don`t know”. Those who answered “yes” were categorized as having the disease of interest. For the main analyses the response alternatives “no” and “don’t know” were merged.

Psychological distress, including symptoms of depression and anxiety, was measured using the Hopkins Symptom Checklist– 10 (HSCL-10) [25, 26]. HSCL-10 has been validated in Norwegian adolescents [27]. The questionnaire includes ten items, in which each was rated on a four-point scale from 1 (not at all bothered) to 4 (extremely bothered). A mean score (range 1–4) was calculated. The variable was used as a continuous variable in the analysis of the association between psychological distress and persistent musculoskeletal pain, but also as a dichotomised variable to create the variable of the accumulated number of health complaints. When dichotomised, we used a well-established cut-off score of >1.85 to define the presence of psychological distress [25].

Abdominal pain was measured by the question “During the last two months: how often did you have pain or discomfort in your stomach?” The answer options were “never”, “1 to 3 times a month”, “once a week”, “several times a week” and “every day”. Participants who reported weekly or more frequent abdominal pain were categorised as having abdominal pain at baseline.

Headache was measured by the questions “Did you suffer from headaches the last year?” and “If you have suffered from headaches the last year; how many days per month do you suffer from headache?” The answer options were “less than 1 day”, “1 to 6 days”, “7 to 14 days” and “more than 14 days” per month. Participants who reported that they had suffered from headache for at least 1 to 6 days per month were categorised as having headache at baseline.

Other health complaints were measured by the question “Do you have any chronic or persistent disease?” The question was asked during a clinical interview and the reported health complaints were recoded to ICD-10 codes. The prevalence of the other health complaints, reported through this question, were too low to analyse as separate exposures, but they were included as separate health complaints when investigating the accumulated number of health complaints at baseline.

The accumulated number of health complaints was analysed as a continuous variable and included any health complaints reported at baseline (asthma, allergic rhinitis, atopic eczema, psychological distress, headache, abdominal pain and any other self-reported health complaints).

Potential confounders

Potential confounding factors in the association between health complaints and musculoskeletal pain 2 years later were selected based on theory and previous empirical findings. Socioeconomic status [14, 28, 29] and sex [6, 30] were considered as potential confounders. In the analyses of specific health complaints, we also adjusted for all the other health complaints by generating a new variable (yes = at least one other health complaint / no = no other health complaints). Parents`employment status was used as an indicator of socioeconomic status and was measured with the questions “Is your father currently employed?” and “Is your mother currently employed?” and the answer options “full time employed”, “part time employed”, “unemployed”, “disabled”, “working at home (housewife)”, “attends school / courses”, “retired”, “deceased”, “other” and “don`t know”. The variables were merged and categorized as “both parents are currently employed” (fulltime or part-time), “one/neither parent is currently employed” and “don’t know”. Parents´ education was used as a second indicator of socioeconomic status and categorised by the highest completed education by father or mother; “at least one parent with higher education”, “primary / secondary school” and “don’t know”. Due to a large proportion (23.8%) who did not know the educational level of their parents, parents’ employment status was used as the indicator of socioeconomic status in the final models.

Statistical analyses

Descriptive data was presented as median and range (due to skewed data) and categorical data as counts and percentages. Mann-Whitney U test (skewed data) and Chi-Square tests (categorical data) were used to compare baseline characteristics of the individuals lost to follow-up or with missing outcome data with the study sample.

Incidence rate with 95% confidence intervals (CIs) of persistent musculoskeletal pain was computed as the number of participants who reported persistent musculoskeletal pain at the 2-year follow-up divided by the total number of the study sample and reported as percentage.

Logistic regression analyses [31] were used to measure the association between baseline health complaints and the presence of persistent musculoskeletal pain at the 2-year follow-up. We analysed crude and adjusted associations with persistent musculoskeletal pain in separate models for specific health complaints (asthma, allergic rhinitis, atopic eczema, psychological distress, headache and abdominal pain) and the accumulated number of these and other reported baseline health complaints. In the adjusted models, all potential confounders were included (sex, parents`employment status and the presence of other health complaints in the analyses of specific complaints, and sex and parents`employment status in the analysis of the accumulated number of baseline health complaints). Due to low proportion of missing values in exposures and confounders (4.0% missing cases in the adjusted models), complete case analyses were conducted. The results from the logistic regression analyses are reported as odds ratios (ORs) with 95% CIs.

Sensitivity analyses investigating the associations between asthma, allergic rhinitis, atopic eczema and persistent musculoskeletal pain at the 2-year-follow-up, excluding participants who responded “don’t know” to the baseline health complaints questions, were conducted.

P-values < 0.05 were considered statistically significant. The analyses were conducted with STATA statistical software system, version 16 [32].

Results

The study included 286 girls (51.9%) and the median age was 16 years (range 15–19) at baseline. The median number of health complaints at baseline was 1 (range 0–5). Characteristics of the study sample are presented in Table 1.

Table 1. Baseline characteristics of the study sample.

Characteristics Total
(n = 551)
Age, y, median (min-max) 16 (15–19)
Sex, girls, n (%) 286 (51.9)
Parents`employment status, n (%)
    Both parents are currently employed 415 (75.3)
    One/neither parent is currently employed 113 (20.5)
    Don’t know 20 (3.6)
    Missing 3 (0.5)
Parents`education, n (%)
    At least one parent with higher education 281 (51.0)
    Primary / secondary school 126 (22.9)
    Don’t know 131 (23.8)
    Missing 13 (2.4)
Asthma, n (%)
    Yes 63 (11.4)
    No 459 (83.3)
    Don`t know 23 (4.2)
    Missing 6 (1.1)
Atopic eczema, n (%)
    Yes 73 (13.2)
    No 395 (71.7)
    Don`t know 79 (14.3)
    Missing 4 (0.7)
Allergic rhinitis, n (%)
    Yes 54 (9.8)
    No 441 (80.0)
    Don’t know 49 (8.9)
    Missing 7 (1.3)
Headache, yes a, n (%) 185 (33.6)
    Missing 0
Abdominal pain, yes b, n (%) 85 (15.4)
    Missing 1 (0.2)
Psychological distress c, median (min-max) 1.3 (1–3.5)
Psychological distress c (cat.), n (%)
    > 1.85 80 (14.5)
    ≤ 1.85 466 (84.6)
    Missing 5 (0.9)
Accumulated number of health complaints d, median (min-max) 1 (0–5)
    Missing, n (%) 19 (3.4)
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a Headache minimum 1–6 days a month the last year

b Abdominal pain minimum once a week the last two months

c Psychological distress, Hopkins Symptom Checklist-10 (HSCL-10), continuous (1–4), categorized (cut-off > 1.85 indicates the presence of psychological distress)

d This variable includes asthma, atopic eczema, allergic rhinitis, headache, abdominal pain, psychological distress and other reported health complaints (prevalence rates): diabetes type 1 (0.2%), ADHD (0.6%), psoriasis (0.4%), arthritis (0.2%), anaemia (0.4%), sleep disorder (0.2%), food allergy or intolerance (1.9%)

Compared to those completing the follow-up study, the group lost to follow-up or with incomplete outcome data had a lower proportion of girls, a lower proportion of adolescents with at least one parent with higher education and a higher proportion who did not know the educational level of their parents (S1 Table).

Associations between health complaints at baseline and persistent musculoskeletal pain at 2-year follow-up

The two-year incidence of persistent musculoskeletal pain was 13.8% (95% CI [11.2–16.9]), (n = 76). Participants with baseline abdominal pain had 2.33 (95% CI [1.29–4.19], p = 0.01) higher odds of persistent musculoskeletal pain at follow-up compared to those without abdominal pain (Table 2). We found no statistically significant associations between headache, psychological distress or doctor-diagnosed asthma, allergic rhinitis or atopic eczema and persistent musculoskeletal pain at the 2-year follow-up.

Table 2. Logistic regression analyses of the association between health complaints at baseline and persistent musculoskeletal pain a at 2-year follow-up.

Health complaints Exposed cases f Crude P-value Adjusted g P-value
OR (95% CI) OR (95% CI)
Asthma b 12 1.56 (0.79, 3.10) 0.20 1.71 (0.85, 3.43) 0.13
Atopic eczema b 12 1.26 (0.64, 2.47) 0.50 1.09 (0.53, 2.21) 0.82
Allergic rhinitis b 10 1.49 (0.71, 3.10) 0.29 1.34 (0.63, 2.83) 0.45
Headache c 31 1.44 (0.87, 2.36) 0.15 1.23 (0.72, 2.10) 0.45
Abdominal pain d 20 2.29 (1.29, 4.08) 0.01 2.33 (1.29, 4.19) 0.01
Psychological distress (1–4) e - 1.25 (0.75, 2.09) 0.39 1.03 (0.60, 1.79) 0.91
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Abbreviations: Odds ratio (OR), Confidence interval (CI). N = 529 in adjusted models

a Persistent musculoskeletal pain is defined as weekly musculoskeletal pain for three months or more

b The reference is “no” or “don`t know”

c Headache, defined as at least 1–6 days a month the last year, with less than 1–6 days a month as the reference

d Abdominal pain, defined as at least weekly pain the last two months, with less than once a week as the reference

e Psychological distress measured by the Hopkins Symptom Checklist– 10 (HSCL-10), used as a continuous variable (1–4).

f Number of participants with the specific health complaint at baseline and persistent musculoskeletal pain at follow-up

g Adjusted for sex, parents`employment status and other health complaints (yes/no)

Sensitivity analyses excluding individuals who answered “don`t know” to the questions of doctor-diagnosed asthma, allergic rhinitis and atopic eczema, revealed comparable results as the main analyses (S2 Table).

Association between accumulation of health complaints at baseline and persistent musculoskeletal pain at 2-year follow-up

Our analysis shows a higher odds of persistent musculoskeletal pain at the 2-year follow-up for each additional health complaint at baseline (OR 1.33, 95% CI [1.07–1.66], p = 0.01) (Table 3).

Table 3. Logistic regression analyses of the association between the number of health complaints at baseline and persistent musculoskeletal pain a at 2-year follow-up.

Crude P-value Adjusted c P-value
OR (95% CI) OR (95% CI)
Accumulated number of health complaints b 1.33 (1.07, 1.65) 0.01 1.33 (1.07, 1.66) 0.01
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Abbreviations: Odds ratio (OR), Confidence interval (CI). N = 529 in adjusted model

a Persistent musculoskeletal pain is defined as weekly musculoskeletal pain for three months or more

b Continuous variable including all reported health complaints at baseline (asthma, allergic rhinitis, atopic eczema, abdominal pain, headache, psychological distress, diabetes type 1, ADHD, psoriasis, arthritis, anaemia, sleep disorder, food allergy or intolerance)

c Analysis adjusted for sex and parents`employment status

Discussion

In this population-based cohort study of Norwegian adolescents, having abdominal pain in the first year of upper-secondary school was associated with persistent musculoskeletal pain 2 years later. Also, an accumulation of health complaints was associated with persistent musculoskeletal pain at the 2-year follow-up.

Abdominal pain was associated with future persistent musculoskeletal pain, which is in accordance with a systematic review on children, adolescents and young adults, reporting abdominal pain to be a potential risk factor for future back pain [15]. In previous research, an association between headache and future musculoskeletal pain has also been found across several studies [15–18]. In our study, adolescents with headache had a slightly increased odds of future persistent musculoskeletal pain, but the association was not statistically significant. A limited number of exposed cases might explain the non-significant result. Also, the response categories for headache were different than those for abdominal pain. Headache was classified as at least one to six episodes a month, while abdominal pain was classified as at least weekly pain. Hence, the frequency of pain episodes might be important in prediction of future musculoskeletal pain. Unfortunately, a cut-off with more frequent headache was not possible in our study due to few cases.

A previous systematic review reported that negative emotional symptoms might be associated with future musculoskeletal pain in children and adolescents [14]. No statistically significant association between psychological distress and future persistent musculoskeletal pain was found in our study. However, differences in populations, exposure measurement, outcome definitions and follow-up periods make direct comparison difficult. Our results revealed no statistically significant associations between allergic rhinitis or atopic eczema with future persistent musculoskeletal pain. Importantly, the number of exposed cases were small, so the results should be interpreted with caution. Nevertheless, the findings are in accordance with a previous study on 12-22-year-olds, investigating risk factors for low back pain after eight years [21]. The same study reported an association between asthma and low back pain eight years later [21]. Another study demonstrated that young adults with asthma had a non-significant increased odds for developing neck pain during a one-year follow-up [33], which is in line with our results. A potential lack of statistical power due to few exposed cases may explain the wide CI and the non-significant result in our data (OR 1.71, 95% CI [0.85–3.43]). It is not known whether different outcomes also influenced the results, as a statistically significant association was found in the study of low back pain [21], but not in our study of musculoskeletal pain in general.

We found that an accumulation of health complaints at baseline was associated with persistent musculoskeletal pain at the 2-year follow-up. To the best of our knowledge, this is the first cohort study to investigate the association between an accumulation of health complaints, including both medical diseases, psychological and somatic symptoms, and the onset of persistent musculoskeletal pain in adolescents. A few existing cohort studies have findings in accordance with our study. One former study of 12-22-year-olds found that a combination of persistent low back pain, persistent headache and asthma was strongly associated with persistent low back pain eight years later [21]. Another study of 9–12-year-olds found that for each additional physical and psychological symptom, including headache, abdominal pain, depressive mood, daytime tiredness, difficulty falling asleep and waking up during the night, the odds of weekly neck pain during a four-year follow-up increased [20]. Furthermore, previous research on adolescents have suggested that an accumulation of multiple factors in general predicts future outcomes of musculoskeletal pain more strongly than individual factors [16, 34].

The mechanisms behind the association between an accumulation of health complaints and onset of persistent musculoskeletal pain is not known. One theory is that repeated efforts to adapt to stressors over time (e.g. multiple health complaints) results in a cumulative physiological wear and tear, or allostatic overload, that disrupts physiological regulatory systems, which subsequently increase the risk of long-term health problems [19, 35], such as persistent musculoskeletal pain. Another theory might be that some health complaints share genetic mechanisms [36] or have other shared risk factors, such as childhood difficulties [37], making some individuals more vulnerable to a multitude of health complaints.

Strengths and limitations

A strength of the study is the cohort study design, in which allows a possible understanding of the temporal sequence between exposures and outcome. Furthermore, the results are based on data from a population-based sample with a high baseline response rate, in a period of life important for the onset of persistent musculoskeletal pain.

A limitation of our study was the self-reporting of health complaints, which may have caused misclassifications. For example, misclassification of “doctor-diagnosed” medical conditions might occur if adolescents do not recall whether they have been diagnosed with the condition. Furthermore, some of the health complaints were defined with umbrella terms. For example, we did not distinguish between migraine and other types of headaches, or between more and less frequent episodes of headache (cut-off used was ≥ 1–6 days a month). Furthermore, we did not have information on the severity of asthma, allergic rhinitis and atopic eczema. Thus, we do not know whether distinguishing between more specific complaints or only including adolescents with the most severe symptoms could have changed the results. The variable reflecting the number of health complaints was created by us on information of the different health complaints and is not formally validated. Another limitation of the study is low statistical power in the analyses of specific health complaints due to few exposed cases.

We adjusted for parents`employment status in the analyses as an indicator of socioeconomic status, despite some limitations. First, due to few cases in each category for those who were not employed (unemployed, disabled, working at home (housewife), attends school/courses, retired, deceased and other), all categories were merged and made up one category. However, for example unemployment and being a “housewife” might have different reasons and indicate different levels of resources. Second, 3.6% of the adolescents did not know their parents’ employment status. However, employment status was our best alternative as an indicator of socioeconomic status in the data. Almost one third of the participants were lost to follow-up or had incomplete outcome data. The group lost to follow-up or with incomplete outcome data had a lower proportion of girls, a lower proportion of adolescents with at least one parent with higher education, and a higher proportion who did not know the educational level of their parents. However, there were no statistically significant differences in prevalence of specific health complaints or in the number of health complaints between this group and the study sample. Persistent musculoskeletal pain was measured by a questionnaire developed for the Fit Futures study and is not formally validated.

Implications

Having abdominal pain was associated with persistent musculoskeletal pain onset in adolescents. Also, an accumulation of health complaints was associated with onset of persistent musculoskeletal pain. Health care providers consulting adolescents might need to take preventive actions in those with abdominal pain and/or an accumulation of health complaints, irrespective of type, to avoid development of persistent musculoskeletal pain.

This study contributes to knowledge of the relationship between health complaints and development of persistent musculoskeletal pain in adolescence. The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research to understand the underlying patterns of persistent pain conditions in youth. However, our study should be replicated by others. To enable development of appropriate preventive strategies, exploration of the mechanisms behind the associations are other potential topics for future research.

Conclusions

Having abdominal pain in the first year of upper-secondary school was associated with persistent musculoskeletal pain 2 years later. Also, an accumulation of health complaints was associated with persistent musculoskeletal pain after 2 years. Health care providers might need to take preventive actions in adolescents with abdominal pain, and in adolescents with an accumulation of health complaints, to prevent development of persistent musculoskeletal pain. The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research.

Supporting information

S1 Table. Comparison of baseline characteristics of respondents and non-respondents of the follow-up study (FF2).

(DOCX)

Click here for additional data file. (47.4KB, docx)
S2 Table. Logistic regression analyses of the associations between health complaints (asthma, atopic eczema, allergic rhinitis) at baseline and persistent musculoskeletal pain at follow-up, excluding participants who responded “don`t know” to the baseline health complaints questions.

(DOCX)

Click here for additional data file. (29KB, docx)

Acknowledgments

We thank all the participants in the Fit Futures Study, the research technicians at the Clinical Research Unit at the University Hospital of North Norway for conducting the data collection and the Fit Futures administration.

Data Availability

The data underlying the results presented in the study are available from the Fit Futures Study, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data can be made available from the Fit Futures Study upon application (fitfutures@uit.no).

Funding Statement

This study was supported by the Norwegian Fund for Post-Graduate Training in Physiotherapy (grant number 105597) to KS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Dong Keon Yon

13 Jul 2022

PONE-D-22-17250Adolescents with health complaints are more likely to develop persistent musculoskeletal pain: The Fit Futures StudyPLOS ONE

Dear Dr. Smedbråten,

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#1. The evidence level of no association is low due to the small event numbers of this study (i.e., Total=500 / Event=10~15, these sample may lead to small sample bias).

So please tone down the main results.

I.e.,

Our analyses showed no significant associations between asthma, allergic rhinitis, eczema, headache or psychological distress and persistent musculoskeletal pain onset.

-> Our analyses showed low evidence of potential associations between asthma, allergic rhinitis, eczema, headache or psychological distress and persistent musculoskeletal pain onset, although the event numbers were small.

#2. The authors have to cite the statistical guideline such as https://doi.org/10.54724/lc.2022.e3

Thank you.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: No

Reviewer #2: Yes

**********

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Reviewer #2: Yes

**********

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Reviewer #1: This study aims to assess whether specific health complaints and an accumulation of 33 health complaints were associated with the onset of persistent musculoskeletal pain 2 years later.

The work is systematically well done by analyzing the effect of each health complaints on musculoskeletal pain.

My main concern is the necessity of this research. Although it is interesting to note that Adolescents with health complaints are more likely to 2 develop persistent musculoskeletal pain, I still wonder what this research will lead us to.

I am also wondering if could self-reported questionnaire, “Do you have persistent or constantly recurring pain that has lasted for 3 months or more?” or “ Has a doctor ever told you that you have...”, work as a proper criterion. It would be great if the authors can provide some references to questions themselves to support the background.

P values should follow the reporting of comparisons of absolute numbers or rates and measures of uncertainty.

There is a lack of explanation for the reasons for the health complaints that have been linked to musculoskeletal pain. It would be nice to supplement it through an intensive literature review.

Reviewer #2: This paper is interesting and technically well performed. I think it needs only few corrections.

Abstract

Both in the abstract and in the text, it should be stated that health complaints such as asthma, allergic rhinitis, eczema, headache, abdominal pain, psychological distress, AND OTHERS are assessed. Otherwise, it seems that only 5 possible health complaints are assessed.

Materials and Methods

108-109: Moreover, 202 participants reported persistent musculoskeletal pain at baseline and were not at risk of developing the outcome of interest.

133-134: The measurement of persistent musculoskeletal pain at baseline was only used to identify the population at risk in our cohort study.

I think that saying “the population at risk” is not correct. The population is at risk of starting chronic musculoskeletal pain but those who are excluded already have chronic musculoskeletal pain. It is more understandable that the 202 patients with baseline pain are excluded from the sample and that the measurement of persistent pain was only used to define the study population, without pain at baseline.

173-176: The accumulated number of health complaints was analysed as a continuous variable and included the specific health complaints investigated in this study (asthma, allergic rhinitis, eczema, psychological distress, headache, and abdominal pain) and other complaints captured through “other health complaints”.

“Other health complaints” were collected as a yes or no variable. In the case of having more than one health complaint (apart from the 5 specific ones), was the number collected for analysis? If it did not occur in any case, indicate it in the results.

Results

245: The two-year incidence of persistent musculoskeletal pain was 13.8 % (95% CI 11.1, 17.0).

Adding the number of cases, not just the percentage, is not in the table either.

Discussion

283-286: An association between psychological distress and future musculoskeletal pain has been demonstrated in previous studies [13], but was not found in our study. Differences in populations, exposure measurement, outcome definitions and follow-up periods might explain the discrepancy in results.

The results may be influenced by the fact that patients who already have pain at baseline have been excluded from the study (202). This group probably has a higher percentage of health complaints, including psychological distress, and its inclusion would give more statistical power to the study.

It would be interesting to have the data of this group of patients with pain at the beginning, how many were still in pain at the end of follow-up and how many had other health complaints.

300-303: To the best of our knowledge, this is the first cohort study to investigate the association between an accumulation of health complaints and persistent musculoskeletal pain in adolescents, including both medical diagnoses, psychological and somatic symptoms.

You have to write … the association between an accumulation of health complaints and THE ONSET OF persistent musculoskeletal pain.

**********

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Reviewer #1: Yes: Gun Ahn

Reviewer #2: No

**********

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PLoS One. 2022 Dec 29;17(12):e0278906. doi: 10.1371/journal.pone.0278906.r002

Author response to Decision Letter 0

13 Nov 2022

Journal requirements:

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Author response: We have ensured that our manuscript meets PLOS ONE’s style requirements, including those for file naming.

Author action: Our manuscript is changed to meet PLOS ONE’s style requirements.

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research.

Author response: We have added information on the type of the participant consent in the ethics statement in the Methods and online submission information. Information on consent from parents or guardians was already described in the paper.

Author action:

Page 4, line 127 – 128: We have added information on the type of the participant consent: “All participants provided written informed consent prior to participation. For participants under the age of 16 years, written consent of one parent/guardian was also obtained.”

Editor comments

1. The evidence level of no association is low due to the small event numbers of this study (i.e., Total=500 / Event=10~15, these sample may lead to small sample bias).

So please tone down the main results. Our analyses showed no significant associations between asthma, allergic rhinitis, eczema, headache or psychological distress and persistent musculoskeletal pain onset.

-> Our analyses showed low evidence of potential associations between asthma, allergic rhinitis, eczema, headache or psychological distress and persistent musculoskeletal pain onset, although the event numbers were small.

Author response: Thank you for an important consideration. We agree on toning down the main results by including the following: 1) When referring to the associations which were not statistically significant, we describe that these were “not statistically significantly associated” instead of describing them as “not associated”. 2) We have toned down the non-significant results in the discussion and emphasised the low number of exposed cases as potential reasons for non-significant results. 3) The topic is emphasised in the limitation section.

Author action:

1) We have emphasised that the results which were not associated were not statistically significantly associated:

Page 1, line 48 – 50: “Our analyses showed no statistically significant associations between asthma, allergic rhinitis, atopic eczema, headache or psychological distress and persistent musculoskeletal pain at the 2-year follow-up.”

2) We have toned down the non-significant results in the discussion and emphasised the low number of exposed cases:

Page 12, line 290 – 294: “In previous research, an association between headache and future musculoskeletal pain has also been found across several studies [1-4]. In our study, adolescents with headache had a slightly increased odds of future persistent musculoskeletal pain, but the association was not statistically significant. A limited number of exposed cases might explain the non-significant result.”

Page 13, line 305 – 308: “Our results revealed no statistically significant associations between allergic rhinitis or atopic eczema with future persistent musculoskeletal pain. Importantly, the number of exposed cases were small, so the results should be interpreted with caution.”

Page 13, line 310 – 317:

“The same study reported an association between asthma and low back pain eight years later [5]. Another study demonstrated that young adults with asthma had a non-significant increased odds for neck pain at one-year follow-up [6], which is in line with our results. A potential lack of statistical power due to few exposed cases may explain the wide CI and the non-significant result in our data (OR 1.70, 95% CI [0.85 – 3.42]). It is not known whether different outcomes also influenced the results, as a statistically significant association was found in the study of low back pain [5], but not in our study of musculoskeletal pain in general.”

3) The topic is emphasized in the limitation section:

Page 15, line 345 – 347: “Another limitation of the study is low statistical power in the analyses of specific health complaints due to few exposed cases, particularly for asthma, allergic rhinitis and eczema.”

2. The authors have to cite the statistical guideline such as https://doi.org/10.54724/lc.2022.e3

Author response: Thank you for this suggestion. We have now added a reference to a statistical guideline.

Author action:

Page 8, line 222: A reference to a statistical guideline has been added: “Logistic regression analyses [7] were used to measure the association between baseline health complaints and the presence of persistent musculoskeletal pain at the 2-year follow-up.”

Reviewer #1:

1) My main concern is the necessity of this research. Although it is interesting to note that Adolescents with health complaints are more likely to 2 develop persistent musculoskeletal pain, I still wonder what this research will lead us to.

Author response: Thank you for this important comment. We will try to make it clearer why we consider this research as an important contribution to the field of musculoskeletal pain. Research on persistent musculoskeletal pain in adolescents is sparse and in contrast to the high prevalence of pain conditions and pain killer usage among younger people. We believe the results of this study add to the understanding of the overall picture of health in adolescence by investigating the associations between different prevalent health complaints and development of musculoskeletal pain. Recognized papers, such as the Lancet – series on low back pain, have emphasised that adults with other health complaints are more likely to report back pain than people in good health, but that the mechanisms behind the coexistence are not known [8], and a systematic review has asked for increased knowledge regarding this topic in youth [1]. We consider this study as a first step to contemplate persistent musculoskeletal pain in adolescence in a multimorbidity perspective. The next research step, with this study’s findings in mind, would be to investigate mechanisms of this connection to be able to find potential targets for preventive interventions. This is of particular importance, as we know multimorbidity in general is associated with poor outcomes and health care utilization later in life [9-11].

In a clinical perspective, we consider the findings in this paper important as it tells us that a broad assessment of health might be important in examination of adolescents. Adolescents with co-occurrent health complaints might be a subgroup with increased vulnerability of developing persistent pain, in which is important for future development of preventive strategies.

We have added a sentence in the conclusion of the abstract and in the main conclusion of the paper to make our argument of the importance of the knowledge from this paper clearer to the reader.

Author action:

Page 1, line 53 – 57: We have added information to the conclusion in the abstract:

“Health care providers might need to take preventive actions in adolescents with abdominal pain and in adolescents with an accumulation of health complaints, to prevent development of persistent musculoskeletal pain. The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research to understand the underlying patterns of persistent pain conditions in adolescents.”

Page 17, line 399 – 400: We have added a sentence in the main conclusion:

“The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research.”

2) I am also wondering if could self-reported questionnaire, “Do you have persistent or constantly recurring pain that has lasted for 3 months or more?” or “ Has a doctor ever told you that you have...”, work as a proper criterion. It would be great if the authors can provide some references to questions themselves to support the background.

Author response: Thank you for an important question. The question assessing persistent musculoskeletal pain; “Do you have persistent or recurring pain that has lasted for 3 months or more?”, is similar to the description of chronic pain in the ICD-11, defined as “persistent or recurrent pain lasting longer than 3 months” [12]. This specific question was, however, developed for the Fit Futures study and, unfortunately, it is not formally validated. The potential limitation of using an unvalidated outcome measure is emphasised in the limitation section:

Page 16, line 377 – 379: “Persistent musculoskeletal pain was measured by a questionnaire developed for the Fit Futures study and is not formally validated.”

Concerning the question assessing asthma, allergy and eczema; “ Has a doctor ever told you that you have...” is a well-used question on self-reported health complaints in observational health studies. For example, in the adolescent part of “the Trøndelag Health study (HUNT)”, an international well-recognised health study, similar questions have been used to measure self-reported health complaints [13]. Unfortunately, the question is not formally validated in adolescents. The potential limitation of self-reported health complaints is emphasised in the limitation section:

Page 14, line 349 – 351: “A limitation of our study was the self-reporting of health complaints, which may have caused misclassifications. For example, misclassification of “doctor-diagnosed” medical conditions might occur if adolescents do not recall whether they have been diagnosed with the condition.”

3) P values should follow the reporting of comparisons of absolute numbers or rates and measures of uncertainty.

Author response: We have added p-values in tables and text.

Author action:

We have added p-values in the abstract:

Page 1, line 47 - 48: “Baseline abdominal pain was associated with persistent musculoskeletal pain 2 years later (OR 2.31, 95% CI [1.29-4.17], p=0.01).

Page 1, line 50 – 53: “An accumulation of health complaints at baseline increased the odds for persistent musculoskeletal pain by 33% for each additional health complaint (OR 1.33, 95% CI [1.07-1.66], p=0.01).”

Page 11-12: We have added p-values in Table 1 and Table 2

We have added p-values in the text in the results chapter, following the OR-estimates:

Page 10, line 260 – 262: “Participants with baseline abdominal pain had 2.31 (95% CI [1.29 - 4.17], p = 0.01) times the odds of persistent musculoskeletal pain at follow-up compared to those without abdominal pain “

Page 11 - 12, line 276 – 278: “Specifically, for each additional reported complaint at baseline, the odds of reporting persistent musculoskeletal pain at the 2-year follow-up increased with 33% (OR 1.33, 95% CI [1.07 - 1.66], p=0.01).”

4) There is a lack of explanation for the reasons for the health complaints that have been linked to musculoskeletal pain. It would be nice to supplement it through an intensive literature review.

Author response: Thank you for a well-thought suggestion. Just to clarify; all health complaints reported by the adolescents are investigated against musculoskeletal pain in this study through the accumulated number of health complaints, but only the most common health complaints were also investigated as separate exposures. 1) To emphasise that all present health complaints are included in the variable of accumulated health complaints, we have rewritten the text regarding this variable. 2) To give a better explanation of why we have examined the six specific health complaints, we have now added information in the introduction to argue that these are six common health complaints in adolescence. 3) Literature on the association between the specific health complaints we have chosen to look specifically into, and musculoskeletal pain, is presented in the introduction, based on results from existing systematic reviews.

Author action:

1) Page 7, line 187-190: The text regarding the variable on the accumulated number of health complaints has been rewritten to better emphasise that all present health complaints are included:

“The accumulated number of health complaints was analysed as a continuous variable and included any health complaints reported at baseline (asthma, allergic rhinitis, atopic eczema, psychological distress, headache, abdominal pain and any other health complaints captured through the question “do you have any chronic or persistent disease?”).”

2) Page 2, line 71 – 76: We have added a section to the introduction to emphasise that the health complaints we assess individually in this study are common health complaints among adolescents:

“Importantly, also headache [14, 15], abdominal pain [15] and mental health problems [16] are all common health complaints in children and adolescents. Furthermore, medical conditions, such as asthma, eczema [17, 18] and allergic rhinitis [18] are frequent. Several of these health complaints commonly co-occur with musculoskeletal pain [19-21], however, whether the presence of different health complaints increase the risk of developing musculoskeletal pain is unclear.”

3) Page 2, line 76 - 81: Literature on the association between specific health complaints and musculoskeletal pain in adolescents is presented in the introduction:

“A systematic review suggested that negative emotional symptoms might increase the risk of developing musculoskeletal pain in children and adolescents [22]. Studies have also indicated an association between abdominal pain [1] and headache [1-4] with later musculoskeletal pain. For the association between other health issues, including medical conditions, and musculoskeletal pain onset in children and adolescents, the existing findings are inconsistent [22].”

Reviewer #2:

1) Abstract

Both in the abstract and in the text, it should be stated that health complaints such as asthma, allergic rhinitis, eczema, headache, abdominal pain, psychological distress, AND OTHERS are assessed. Otherwise, it seems that only 5 possible health complaints are assessed.

Author response: Thank you for making us aware that this was not clearly defined. We have rewritten the text in the abstract to make this clearer. We have also tried to make the definition of “the accumulated number of health complaints” clearer in other parts of the article.

Author action:

We have added “other reported health complaints” to the text to make it clearer that other health complaints than the 6 specific complaints are included in the “accumulated number of health complaints” – variable:

Page 1, line 40 - 45 (in the abstract):

“The following self-reported baseline health complaints were investigated as individual exposures: asthma, allergic rhinitis, atopic eczema, headache, abdominal pain and psychological distress. We also investigated the association between an accumulated number of these and other reported health complaints, and persistent musculoskeletal pain 2 years later.”

Page 8, line 224 – 227 (in the method section):

“We analysed crude and adjusted associations with persistent musculoskeletal pain in separate models for specific health complaints (asthma, allergic rhinitis, atopic eczema, psychological distress, headache and abdominal pain) and the accumulated number of these and other reported baseline health complaints.”

Page 7, line 187 – 190: We have rewritten the definition of “the accumulated number of health complaints”:

“The accumulated number of health complaints was analysed as a continuous variable and included any health complaints reported at baseline (asthma, allergic rhinitis, eczema, psychological distress, headache, abdominal pain and any other health complaints captured through the question “do you have any chronic or persistent disease?”).”

2) Materials and Methods

108-109: Moreover, 202 participants reported persistent musculoskeletal pain at baseline and were not at risk of developing the outcome of interest.

133-134: The measurement of persistent musculoskeletal pain at baseline was only used to identify the population at risk in our cohort study.

I think that saying “the population at risk” is not correct. The population is at risk of starting chronic musculoskeletal pain but those who are excluded already have chronic musculoskeletal pain. It is more understandable that the 202 patients with baseline pain are excluded from the sample and that the measurement of persistent pain was only used to define the study population, without pain at baseline.

Author response: Thank you for this comment. We have tried to rewrite to make this clearer.

Author action:

Page 4, line 117 - 122: We have rewritten the text:

“Of 1117 adolescents invited to participate in FF1, 1038 (92.9%) responded. Thirty-six participants were excluded from our sample because they were older than 19 years of age at baseline. Moreover, 190 participants reported persistent musculoskeletal pain at baseline and were excluded from the sample. Finally, 23 participants were excluded because they had incomplete data on musculoskeletal pain at baseline (Fig 1). Of 789 respondents to the FF1 Study that met the inclusion criteria, 549 (69.6 %) participated in FF2 and had complete outcome data for the present study.”

Page 5, line 144 – 146: We have rewritten the text:

“Persistent musculoskeletal pain was also measured and defined as described above at baseline. The measurement of persistent musculoskeletal pain at baseline was only used to identify the sample in our cohort study.”

Page 8, line 218 – 220: We have rewritten the text:

“Incidence rate with 95% confidence intervals (CIs) of persistent musculoskeletal pain was computed as the number of participants who reported persistent musculoskeletal pain at the 2-year follow-up divided by the total number of the study sample and reported as percentage.”

3) 173-176: The accumulated number of health complaints was analysed as a continuous variable and included the specific health complaints investigated in this study (asthma, allergic rhinitis, eczema, psychological distress, headache, and abdominal pain) and other complaints captured through “other health complaints”.

“Other health complaints” were collected as a yes or no variable. In the case of having more than one health complaint (apart from the 5 specific ones), was the number collected for analysis? If it did not occur in any case, indicate it in the results.

Author response: Thank you for making us aware that this was not clearly defined in the text. “Other health complaints” were not collected as a yes or no variable. The question “Do you have any chronic or persistent disease?” was asked, and all reported diseases / complaints were recoded to ICD-codes and reported separately. The variable of the accumulated number of health complaints includes the precise number of any reported health complaints at baseline. We have tried to rewrite the text to make this clearer. We have also changed Table 1 by removing the variable called “other health complaints”, as this variable description might confuse the reader to think other health complaints have only been treated as a yes/no variable.

Author action: We have rewritten the text:

Page 6 - 7, line 180 – 185:

“Other health complaints were measured by the question “Do you have any chronic or persistent disease?” The question was asked during an interview by a nurse and responses were recoded to ICD-10 codes. The prevalence of the other health complaints reported through this question, were too low to analyse as individual exposures, but they were included as separate health complaints when investigating the accumulated number of health complaints at baseline.”

Page 6-7, line 187 – 190:

“The accumulated number of health complaints was analysed as a continuous variable and included any health complaints reported at baseline (asthma, allergic rhinitis, eczema, psychological distress, headache, abdominal pain and any other health complaints captured through the question “do you have any chronic or persistent disease?”)”

Page 9 - 10, Table 1: The variable “other health complaints yes/no” was removed from Table 1. We have rather included a footnote on which other health complaints that have been reported and linked this footnote to the “accumulated number of health complaints” variable:

“f The variable includes asthma, atopic eczema, allergic rhinitis, headache, abdominal pain, psychological distress and other reported health complaints (prevalence rates): diabetes type 1 (0.2%), ADHD (0.6%), psoriasis (0.4%), arthritis (0.2%), anemia (0.4%), sleep disorder (0.2%), food allergy or intolerance (1.9%)”

4) Results

245: The two-year incidence of persistent musculoskeletal pain was 13.8 % (95% CI 11.1, 17.0). Adding the number of cases, not just the percentage, is not in the table either.

Author response: Thank you for this comment. The number of cases is now included.

Author action:

Page 10, line 259 – 260: We have rewritten the text to add information on the number of cases: “The two-year incidence of persistent musculoskeletal pain was 13.8 % (95% CI [11.2- 17.0]), (n=76).”

5) Discussion

283-286: An association between psychological distress and future musculoskeletal pain has been demonstrated in previous studies [13], but was not found in our study. Differences in populations, exposure measurement, outcome definitions and follow-up periods might explain the discrepancy in results.

The results may be influenced by the fact that patients who already have pain at baseline have been excluded from the study (202). This group probably has a higher percentage of health complaints, including psychological distress, and its inclusion would give more statistical power to the study. It would be interesting to have the data of this group of patients with pain at the beginning, how many were still in pain at the end of follow-up and how many had other health complaints.

Author response:

We agree that this would be interesting. However, to be able to say something about the temporal sequence between exposure and outcome, we find it important to exclude the group of individuals with baseline musculoskeletal pain in our analyses. In systematic reviews of risk factors, this is often a criterium for inclusion [2, 22, 23].

Regarding the association between psychological distress and persistent musculoskeletal pain, the results might indeed be different for studies including those with baseline pain or not. On the other hand, a systematic review, in which only studies on participants without baseline pain were included, concluded that emotional symptoms might be a risk factor for musculoskeletal pain in children and adolescents [22]. Hence, excluding participants with baseline pain cannot be the only reason why we do not find any association in our data.

If we understand the comment right, the reviewer also found it interesting to include the participants with baseline musculoskeletal pain for descriptive purposes. We agree that this would be interesting. However, as we have defined our population as those without persistent musculoskeletal pain at baseline, we find it a bit complicated to include this group for descriptive purposes in a clear way for the reader. Hence, we prefer not to include these participants to prevent misunderstandings on which sample we have analysed. Please let us know if these additional descriptive analyses are of particularly importance to present.

6) 300-303: To the best of our knowledge, this is the first cohort study to investigate the association between an accumulation of health complaints and persistent musculoskeletal pain in adolescents, including both medical diagnoses, psychological and somatic symptoms.

You have to write … the association between an accumulation of health complaints and THE ONSET OF persistent musculoskeletal pain.

Author response: We have now added “the onset of” in the text.

Author action:

Page 14, line 320 – 323: We have added “the onset of” in the text:

“To the best of our knowledge, this is the first cohort study to investigate the association between an accumulation of health complaints, including both medical diseases, psychological and somatic symptoms, and the onset of persistent musculoskeletal pain”

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Attachment

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Click here for additional data file. (91.7KB, docx)

Decision Letter 1

Dong Keon Yon

28 Nov 2022

Adolescents with health complaints are more likely to develop persistent musculoskeletal pain: The Fit Futures Study

PONE-D-22-17250R1

Dear Dr. Smedbråten,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Reviewer #2: All comments have been addressed

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Acceptance letter

Dong Keon Yon

16 Dec 2022

PONE-D-22-17250R1

Accumulation of health complaints is associated with persistent musculoskeletal pain two years later in adolescents: The Fit Futures Study

Dear Dr. Smedbråten:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Comparison of baseline characteristics of respondents and non-respondents of the follow-up study (FF2).

    (DOCX)

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    S2 Table. Logistic regression analyses of the associations between health complaints (asthma, atopic eczema, allergic rhinitis) at baseline and persistent musculoskeletal pain at follow-up, excluding participants who responded “don`t know” to the baseline health complaints questions.

    (DOCX)

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    Attachment

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    Data Availability Statement

    The data underlying the results presented in the study are available from the Fit Futures Study, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data can be made available from the Fit Futures Study upon application (fitfutures@uit.no).

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