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Does sedentary time and physical activity predict chronic back pain and morphological brain changes? A UK biobank cohort study in 33,402 participants

BMC Public Health volume 24, Article number: 2685 (2024) Cite this article

Abstract

Background

The relationship between sedentary time, physical activity, and chronic back pain remains unclear. The study aims to investigate whether sedentary time and physical activity predict chronic back pain and morphological brain changes.

Methods

This cohort study recruited adults aged 37–73 years enrolled between 2006 and 2010, with follow-up until 2014. The total cohort comprised 33,402 participants (mean age: 54.53). Data were collected on daily sedentary time, physical activity, lifestyle factors, and health outcomes.

Results

After nearly 8-year follow-up, 3,006 individuals (9.00%) reported chronic back pain in total. Individuals with daily sedentary time exceeding 6 h had a 33% higher risk of chronic back pain compared to those with sedentary time of 2 h or less (RR, 1.33, 95%CI, 1.17–1.52). Sedentary time was also associated with decreased grey matter volume in several brain regions, including bilateral primary somatosensory cortex (S1), secondary somatosensory cortex, putamen, primary motor cortex (M1), insula, hippocampus, amygdala, as well as right supplementary motor area, left medial frontal cortex, and right anterior cingulate cortex (FDR-corrected p-value < 0.05). Compared to individuals who sat for more than 6 h with light physical activity, those engaging in moderate physical activity with sedentary time of 2 h or less (RR, 0.71, 95%CI, 0.52–0.99) exhibited a significant decrease in chronic back pain risk. In addition, replacing sedentary time with equivalent amount of physical activity also demonstrated a reduction in the risk of chronic back pain (RR, 0.87, 95%CI, 0.77–0.99) and increased the reginal grey matter volumes including the amygdala, insula, M1, putamen and S1.

Conclusions

Prolonged sedentary time is associated with heightened risks of chronic back pain and deterioration in brain health.

Peer Review reports

Introduction

Research on sedentary time and its potentially harmful effects on health has grown exponentially in recent years. Prolonged sedentary time is considered an “independent” risk factor for chronic disease and may contribute to elevated risk and adverse consequences related to chronic conditions [1,2,3,4]. UK National Health Service (NHS) estimated the direct medical cost of prolonged sedentary time in the UK to be £ 800 million in 2016–2017 [5]. Regarding this issue, the WHO 2020 Guidelines for Physical Activity and Sedentary Behavior advocate for reducing sedentary time [6], aligning with the public health guidelines issued by Australia [7] and the United States [8]. However, due to the limited evidence on sedentary time, these guidelines are unable to offer specific quantitative recommendations, posing challenges for public adherence to the advice [9].

Chronic back pain is a worldwide health problem and is associated with a variety of factors such as individual characteristics, lifestyle and psychological factors [10, 11]. Currently, there are some studies exploring the relationship between sedentary time and the risk of chronic back pain. The results of two systematic reviews indicated that prolonged sedentary time is not linked to an elevated risk of developing new-onset low back pain [12, 13]. Another one-year longitudinal analysis also revealed no significant correlation between sedentary time and the likelihood of having a severe trajectory of chronic back pain [14]. However, the latest study reached the opposite conclusion, suggesting that increased sedentary time is inversely linked to the prevalence of low back pain [15]. These mixed findings regarding the relationship between sedentary time and the risk of chronic back pain may be attributed to heterogeneity in the definition of sedentary time, assessment of outcomes, and consideration of other covariates.

Another important issue is whether physical activity can counteract the risk of chronic back pain associated with sedentary time. Research has found that replacing 1 h of sedentary time with an equal duration of vigorous exercise every week might decrease the intensity of low back pain [16]. A cross-sectional study also found that the negative association between leisure-time physical activity and the prevalence of low back pain is influenced by sedentary time, specifically, this association is only observed among participants who spend less than 3 h per day in sedentary activities [17]. Another cross-sectional study indicated that the benefits of physical activity on pain are influenced by its intensity [18]. Preliminary evidence suggests that the protective effect of physical activity against chronic pain appears to be conditional. Further large-scale, longitudinal studies are warranted to confirm the association between sedentary time, physical activity, and chronic back pain. Furthermore, its potential mechanisms remain unclear.

Prolonged sedentary time may lead to changes in brain structures. Studies have demonstrated that physical activity is associated with increased volumes of the prefrontal cortex and hippocampus [19, 20], while sedentary time has the opposite effect [19]. Previous studies have identified an overlap between brain regions involved in pain processing and grey matters associated with prolonged sitting, such as the prefrontal cortex, posterior cingulate cortex, hippocampus, and thalamus [21]. Sedentary behaviour may lead to brain atrophy and subsequent risk of chronic pain. However, research on the specific changes in reginal brain area due to prolonged sedentary time is limited.

To address these gaps, we conducted a large-scale cohort study to: 1) assess whether sedentary time increases the risk of chronic back pain occurrence in the general population; 2) investigate whether physical activity mitigates this risk; and 3) examine changes in morphological brain structures related to pain to explore the potential mechanisms of sedentary time and physical activity.

Methods

Study population

This is a population-based cohort study. We utilized data from the UK Biobank, recruiting participants aged 40 to 70 between 2006 and 2010, followed by subsequent follow-up assessments conducted in 2014 and beyond. The inclusion criteria for participants were: 1) completion of questionnaires on sedentary time and pain assessment; 2) absence of chronic back pain at baseline; 3) consenting to participate in the study. Exclusion criteria involved: 1) sedentary time (TV viewing, computer use, and driving) ≥ 16 hours [22]; 2) total sum of sedentary time, sleep time, and physical activity time exceeding 24 hours [22]; 3) presence of missing data on variables of interest. The ethical approval and written informed consent were obtained and the rights of subjects were protected.

Measurement of sedentary time, physical activity, and outcomes

Sedentary time was determined by aggregating the self-reported durations of TV viewing, computer use, and driving each day at baseline. UK Biobank used a structured survey to inquire about the duration participants spent on viewing TV, using computers, and driving during a typical workday to obtain self-reported sedentary time. If the answer was “less than 1 h per day,” it was recorded as 0.5 h. If there was no answer or the answer was “do not know” or “prefer not to answer”, it was processed as a missing value.

UK Biobank employed the validated and widely utilized International Physical Activity Questionnaire (IPAQ) short form to evaluate the physical activity levels as reported by the participants [23]. The IPAQ short form assesses the duration (in minutes per day) and frequency (days per week) of three distinct intensities of activity (light, moderate, and vigorous) undertaken over the past 7 days through seven questions. All data were processed in accordance with the IPAQ official guidelines by UK Biobank team [24].

We also extracted data on chronic back pain assessed by a self-administered touchscreen questionnaire during follow-up. Participants were queried regarding whether back pain had interfered with their daily activities over the past month. If the answer was yes, then participants were asked if they had had back pain for more than 3 months. Individuals who responded “yes” to both questions were classified as suffering from chronic back pain.

After the baseline assessment, some participants were invited by UK Biobank team to participate in brain MRI scans in 2014. Brain structural volumes were collected using a standard Siemens Skyra 3T scanner running VD13A SP4, equipped with a standard Siemens 32-channel radiofrequency receiver head coil. The imaging protocols for the UK Biobank study can be accessed on their online showcase of resources. In the present study, regional gray matter volumes related to pain processing and physical activity were selected based on previous research [21, 25]. The gray matter volumes were processed by the UK Biobank team and made available to approved researchers. These regions include the primary somatosensory cortex (S1), medial frontal cortex (MFC), primary motor cortex (M1), hippocampus, thalamus, insula, amygdala, anterior cingulate cortex (ACC), caudate, putamen, supplementary motor cortex (SMA), and secondary somatosensory cortex (S2). Both left and right hemispheres of all brain structures were included in the analysis.

Covariates included age (y), sex (male/female), level of education (college or university degree/others), body mass index (BMI), ethnic background (white/non-white), the Townsend deprivation score, smoking and drinking status (never/previous/current), insomnia (never/sometimes/usually), engaging in social activities (more than once a month/once a month or less), anxious (yes/no), and loneliness (yes/no). The Townsend deprivation score was obtained based on postal code.

Statistical analyses

We described the baseline characteristics of the participants included in the study based on their sedentary time. The exposure variable, sedentary time, was categorized as ≤ 2 h/d [reference category], 2–4 h/d, 4–6 h/d, and > 6 h/d. Given the binary outcome measure (occurrence of chronic back pain), robust Poisson regression models were employed to explore the association between sedentary time and chronic back pain, aiming to obtain relative risks (RRs) and 95% confidence intervals (95%CI). Next, we replicated the analysis within subgroups. We also carried out sensitivity analyses to validate the robustness of our main findings. Initially, participants with a history of back pain at baseline were excluded for sensitive analysis. Subsequently, we replicated the analysis after employing multiple imputation to address missing values. We developed several models incorporating various covariates to estimate the RRs and 95% CI (see Supplementary material).

Additionally, to clarify the association between physical activity, sedentary time, and the risk of chronic back pain, we fitted a robust Poisson regression model comparing the RRs of the sitting-physical activity group with the prolonged sitting & light physical activity group (sedentary time > 6 h & light physical activity) as the reference. Furthermore, we utilized isotemporal substitution models (ISM) to examine whether replacing sedentary time with equal durations (0.5h, 1h, 2h) of various types of physical activity can offset the risk of chronic back pain. Given the finite total time available to individuals in a day, engaging in one type of physical activity necessarily displaces participation in another or reduces time spent on other activities. Thus, this model explored the impact of reallocating time from one activity type to another while maintaining total time constant on the health outcome.

All continuous brain structure volumes were standardized (mean = 0, SD = 1), and the standardized effect sizes (i.e., standardized β) and 95% CI were calculated for prolonged sedentary time (> 6 h) vs. non-prolonged sedentary time (≤ 6 h) using linear regression models adjusted age, sex, Townsend deprivation index, education, ethnic background, body mass index, smoking status, alcohol consumption, insomnia, anxiety, loneliness, social isolation, physical activity, as well as height and imaging assessment center. We employed the Benjamini–Hochberg approach to reduce the false discovery rate for multiple comparisons.

We performed an analysis on participants without any missing data after adjusting for the specific variables. Our statistical analyses and plotting were executed using R 4.2.2. A P-value < 0.05 denoted statistical significance.

Results

Sample characteristics

Initially, a total of 502,217 participants were recruited. Exclusions incorporated 1) 1,369 individuals with sedentary time ≥ 16 h; 2) 5,050 individuals with sum of sedentary time, sleep duration, and physical activity exceeding 24 h; 3) 33,755 individuals with chronic back pain at baseline, and 4) 278,656 individuals with missing data. Ultimately, the chronic back pain analysis dataset included 33,402 individuals, while the brain structure analysis dataset included 20,501 individuals (Figure S1). The average age of population was 54.53 ± 7.61 years (range: 40–70). Among them, 5,201 individuals (15.57%) reported sedentary time > 6 h per day (Table 1).

Table 1 Baseline characteristics of participants by sedentary time
Full size table

Sedentary time and chronic back pain

During the approximately 8-year follow-up period, a total of 3006 participants (9%) experienced chronic back pain, with 1,537 individuals (51.13%) reporting chronic back pain when sitting for more than 4 h. After adjusting for covariates in model 3, individuals sitting for 4–6 h and > 6 h per day had a 16% (RR, 1.16; 95% CI, 1.03–1.30) and 33% (RR, 1.33; 95% CI, 1.17–1.52) higher risk of chronic back pain, respectively, compared to those sitting for ≤ 2 h per day. Individuals sitting for 2–4 h per day did not exhibit an increased risk of chronic back pain (RR, 1.04; 95% CI, 0.93–1.17) (Table S1).

Subgroup analysis and sensitivity analysis results

In all subgroup analyses, we observed a significantly increased risk of chronic back pain among males (RR, 1.38, 95% CI, 1.12–1.69), females (RR, 1.29, 95% CI, 1.08–1.54), individuals under 60 years of age (RR, 1.38, 95% CI, 1.18–1.61), smokers (RR, 1.43, 95% CI, 1.16–1.76), never-smokers (RR, 1.28, 95% CI, 1.08–1.52), individuals with insomnia (RR, 1.34, 95% CI, 1.16–1.56), as well as those with anxiety (RR, 1.39, 95% CI, 1.17–1.65), loneliness (RR, 1.45, 95% CI, 1.04–2.04), and social isolation (RR, 1.40, 95% CI, 1.05–1.86) (Fig. 1). Excluding participants with a history of short-term back pain at baseline, sensitivity analysis revealed a significant increase in the risk of chronic back pain among individuals sitting for more than 6 h per day, observed across all populations (RR, 1.28, 95%CI, 1.11—1.48), including males (RR, 1.32, 95%CI, 1.05—1.66) and females (RR, 1.29, 95%CI, 1.06—1.56) (Table S3). After multiple imputation, the analysis of a total of 34498 participants indicated that sedentary time of 4–6 h and > 6 h increased the risk of chronic back pain by 15% and 32%, respectively, consistent with the above results (Table S4).

Fig. 1
figure 1

Adjusted relative risk (RR) for chronic back pain associated with prolonged sedentary time across different population characteristics

Full size image

Physical activity and chronic back pain

Across all stratifications of physical activity and sedentary time, except for individuals engaged in moderate physical activity with sedentary time ≤ 2 h (RR, 0.72, 95% CI, 0.52–0.99), those with less sedentary time and higher levels of physical activity did not exhibit a significantly reduced risk of chronic back pain compared to the reference group (Fig. 2). Isotemporal substitution analysis indicated that replacing 0.5 or 1 h of sedentary time with physical activity of any intensity did not reduce the risk of chronic back pain, except for 2 h of vigorous physical activity (RR, 0.87, 95% CI, 0.77–0.99) (Fig. 3).

Fig. 2
figure 2

Adjusted relative risk by sedentary time across 3 physical activity level. All RRs are adjusted for age, sex, Townsend deprivation index, education, ethnic background, body mass index, smoking status, alcohol consumption, insomnia, anxiety, loneliness, and social isolation. Abbreviation: SB: sedentary behavior; PA: physical activity; RR: relative risk

Full size image
Fig. 3
figure 3

Relative risk calculated by isotemporal substitution analysis. The analyses were adjusted for age, sex, Townsend deprivation index, education, ethnic background, body mass index, smoking status, alcohol consumption, insomnia, anxiety, loneliness, and social isolation. Abbreviation: PA: physical activity

Full size image

Sedentary time, physical activity, and morphological brain structure

After adjusting for covariates, we found that sedentary time was associated with decreased grey matter volume in several brain regions (Fig. 4), including bilateral S1, S2, putamen, M1, insula, hippocampus, amygdala, as well as right SMA, left MFC, and right ACC (FDR-corrected p-value < 0.05) (Table S5). The results of isotemporal substitution analysis indicate that physical activity is associated with increased volumes of regional brain structures, including the amygdala, insula, M1, putamen, and S1 (Table S6).

Fig. 4
figure 4

Regional gray matter volumes associated with prolonged sedentary time. The results showed that prolonged sedentary time was associated with decreased grey matter volume in several brain regions, including bilateral primary somatosensory cortex, secondary somatosensory cortex, putamen, primary motor cortex, insula, hippocampus, amygdala, as well as right supplementary motor area, left medial frontal cortex, and right anterior cingulate cortex (P_FDR value < 0.05). T-statistics are visualised here

Full size image

Discussion

Main findings

In this cohort study, sedentary time is predictive of future increased risk of chronic back pain and decreased reginal gray matter volume. Physical activity showed a tendency to mitigate this risk. Moreover, replacing sedentary time with an equivalent amount of physical activity each day can increase reginal brain volume.

Interpretation of results

Our study challenges previous meta-analytic findings, which suggested that sedentary time may yield no benefits to the onset of low back pain in adults [13]. Given the significant variability in sedentary time categorization across the nine cohort studies involved in this meta-analysis, and the limited number of articles in each subgroup for sedentary time exceeding 3 h, caution is advised when interpreting the results. In other musculoskeletal pain conditions such as neck pain, the link between sedentary time and elevated risk has been reported [26]. In our study, the correlation between sedentary time and heightened risk of chronic back pain was particularly significant among male participants, smokers, individuals experiencing insomnia, anxiety, loneliness, and social isolation. This suggests the need for action to reduce sedentary time, particularly among high-risk populations, to decrease the incidence of chronic back pain.

Our interaction analysis and isotemporal substitution analysis results indicate a trend of physical activity reducing the risk of chronic back pain. Previous research has found that risk of chronic low back pain can be reduced by 11%-16% through engaging in leisure time physical activity [27]. In the population with low back pain, substituting sedentary time with physical activity has also been found to reduce the severity of pain [16]. A study on U.S. adults also indicates that meeting the physical activity guidelines is associated with lower odds of reporting pain [28]. Physical activity has also been reported to have other health benefits, such as reducing the risk of various non-communicable diseases and mortality [22, 29, 30]. Although a potential protective effect was identified in our analysis, considering that only two results were statistically significant and the upper limit of their 95% confidence interval was 0.99, further research is necessary to confirm this finding.

Few studies have investigated the potential neurobiological mechanisms underlying the relationship between sedentary time, physical activity, and the risk of chronic back pain. Prior studies have emphasized the increase in back muscle stiffness due to prolonged sitting but have neglected the pathological changes in brain structure associated with chronic pain [31]. Changes in brain structures associated with pain processing represent a potential pathophysiological basis for chronic pain [21, 32]. We found that prolonged sitting is negatively correlated with the reginal brain volumes such as S1, S2, M1, putamen, SMA, ACC, MFC, insular, hippocampus, and amygdala. In neuroimaging studies, ACC, prefrontal cortex, insula, hippocampus, and amygdala are all important brain regions involved in pain processing [33]. S1 and S2 encode information related to sensory features, such as the location, nature, intensity, and duration of pain [34]. M1 is a crucial cortical region within the “pain matrix”, involved in processing various types of pain [35]. Meanwhile, M1 is also the region in the cerebral cortex responsible for executing voluntary movements. Previous studies have also found a positive correlation between physical activity and regional brain volume, including the hippocampus, parietal lobe, temporal lobe, and frontal lobe [36]. The increased volume of brain regions following physical activity may serve as a potential mechanism for the reduced risk of chronic back pain.

The relationship between chronic back pain, sedentary time, and brain morphological changes involves intricate physiological and pathological mechanisms. Prolonged sedentary time may contribute to a reduction in the volume of key brain regions, including the middle frontal gyrus, lingual gyrus, and postcentral gyrus [37], which in turn can adversely affect pain perception and processing. These structural brain changes are associated with the development of chronic pain, as these regions play crucial roles in the emotional and cognitive processing of pain, as well as in motor control [32]. Prolonged sedentary time may also induce neuroinflammation and reduce levels of neurotrophic factors, thereby exacerbating the risk of chronic pain [38]. In contrast, physical activity may help alleviate pain and enhance brain function by maintaining or increasing the volume of key brain regions [38].

Clinical significance

Our findings have several implications for clinical practice. First, we recommend limiting sedentary time to less than 6 h to enhance compliance with guidelines, given the significant increase in chronic back pain risk observed across various subgroups with sedentary time exceeding 6 h. Second, sedentary time can also accelerate brain degeneration. Finally, physical activity can reduce the risk of chronic back pain and brain degeneration, yet we still emphasize reducing sedentary time to reap health benefits.

Strengths and limitations

There are several strengths in our study. Firstly, this study benefits from a large sample size and utilizes a population-based cohort design, enhancing the credibility of its findings compared to previous smaller-scale and cross-sectional studies. Secondly, the data were obtained from a single cohort within the UK Biobank database, ensuring consistency in the definitions of sedentary time, physical activity, and chronic back pain across the entire cohort, which contrasts with the heterogeneity often observed in meta-analyses. Thirdly, we employed interaction analysis and isotemporal substitution models to examine the relationship between sedentary time, physical activity, and the risk of chronic back pain. Consistent results were obtained, ensuring the robustness of our conclusions. Lastly, we investigated the effect of sedentary time on brain structure changes, addressing a gap in understanding the potential neurobiological mechanisms linking sedentary time to chronic pain.

However, there are several constraints too. First, in our study, sedentary time and physical activity were self-reported rather than objectively measured with an accelerometer, which may introduce recall bias. However, the accessibility of survey questionnaires also allowed for a larger sample size to be included in the study. Second, our outcome measures are also subjective reports of participants without a medical diagnosis, which may lead to confusion between other pathological causes of pain and musculoskeletal pain. Third, our study only included participants from the UK, which limits the generalizability of the findings to other ethnicities. Finally, regarding the analysis of physical activity, only two results were statistically significant, and their confidence intervals were close to 1, making it difficult to draw a definitive conclusion about the protect effect of physical activity on chronic back pain. Although statistical significance was not achieved, the analysis of moderate and vigorous physical activity showed a trend towards reducing the risk of pain. In the future, perhaps this trend could be confirmed to be statistically significant if measured with more objective means such as accelerometers.

Conclusions

Sedentary behavior indicates an increased risk of future chronic back pain and brain degeneration, while engaging in physical activity may help reduce the risk of chronic back pain and promote brain health.

Availability of data and materials

The data that support the findings of this study are available from UK Biobank 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 are available from the corresponding author upon reasonable request and with permission of UK Biobank.

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Acknowledgements

We thank the participants of the UK Biobank. We would like to express our gratitude to Professor Jo Nijs for his assistance in providing feedback on the manuscript revisions.

Funding

This work was supported by the scientific and technological research program of the National Natural Science Foundation of China (82372578); the scientific and technological research program of the Shanghai Science and Technology Committee (Fund number: 19080503100；21S31902400); the Shanghai Key Lab of Human Performance (Shanghai University of Sport) (11DZ2261100); Shanghai Clinical Research Center for Rehabilitation Medicine (21MC1930200); Joint Research Project on Health and Family Planning of Pudong New Area Health Commission (PW2021D-07); Shanghai University of Medicine & Health Sciences Clinical Research Center (22MC2022002).

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Author notes

  1. Xue Jiang and Le Tang contributed equally to this work.

Authors and Affiliations

  1. School of Exercise and Health, Shanghai University of Sport, Shanghai, China

    Xue Jiang, Le Tang, Yonghui Zhang, Yiwen Bai, Rui Wang & Xueqiang Wang

  2. Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium

    Xue Jiang

  3. School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China

    Huihuan Luo & Renjie Chen

  4. Department of Rehabilitation Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

    Xia Bi

  5. Rehabilitation Medicine Center, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Xueqiang Wang

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  1. Xue Jiang
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Contributions

Xue Jiang: conceptualization, formal analysis, writing-original draft, writing-review & editing; Le Tang: data curation, formal analysis, writing-review & editing; Yonghui Zhang: data curation, investigation; Yiwen Bai: validation, visualization; Huihuan Luo: methodology; Rui Wang: visualization; Xia Bi: methodology, funding acquisition; Renjie Chen: validation, supervision; Xueqiang Wang: conceptualization, funding acquisition, project administration, resources, supervision, writing-review & editing.

Corresponding authors

Correspondence to Renjie Chen or Xueqiang Wang.

Ethics declarations

Ethics approval and consent to participate

UK Biobank received ethical approval from the North West Multi-centre Research Ethics Committee (REC reference: 11/NW/03820). All participants gave written informed consent before enrolment in the study, which was conducted in accord with the principles of the Declaration of Helsinki.

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Not applicable.

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The authors declare no competing interests.

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Supplementary Information

12889_2024_20188_MOESM1_ESM.docx

Supplementary material lists: Table S1. Overall and subgroup analysis results of the relationship between sedentary time and chronic back pain. Table S2. The risk of chronic back pain associated with sedentary behavior in different models. Table S3. Sensitivity analysis results excluded participants with short-term back pain at baseline. Table S4. Sensitivity analysis results from the 34498 participants after multiple imputation. Table S5. Overall and subgroup analysis results of the relationship between prolonged sedentary time and regional brain structure indices. Table S6. Brain structural changes induced by substituting prolonged sedentary behavior with varied intensity physical activities. Figure S1. Study flowchart.

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Jiang, X., Tang, L., Zhang, Y. et al. Does sedentary time and physical activity predict chronic back pain and morphological brain changes? A UK biobank cohort study in 33,402 participants. BMC Public Health 24, 2685 (2024). https://doi.org/10.1186/s12889-024-20188-3

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Keywords

BMC Public Health

ISSN: 1471-2458

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