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22 For the analysis of effect sizes of pain, the model included random effects at the level of trials and time points.
There was a large between-study variation in the sizes of pain improvement from baseline within both observational studies and RCT treatment arms demonstrated by the high I values (99%).
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Moreover, neither depression nor anxiety showed association with mean pain intensity, pain intensity in exacerbations, size of pain area, or pain frequency.
To test the association between mood state (i.e. depression and anxiety) and headache severity, linear regression analyses were done for continuous variables (mean pain intensity, pain intensity in exacerbations, and size of pain area) and discriminate analysis for categorical variables (pain frequency).
However, there was no distinct difference in the size of pain reduction between the three groups.
Sensitivity analysis according to potential risks of bias showed no significant difference between the effect size of pain (HT) at the end of treatment and risk of bias (see Additional file 7).
Statistical heterogeneity of analysis for the effect size of pain in the BT group (I = 63%) was substantially decreased (I = 0%) by removing the study of Ardiç et al. [ 69] (pharmacological co-therapies not allowed; non-intervention control group).
The mice were then awakened and their foot pad monitored for tumor size and signs of pain or ulceration twice a week.
Small effect sizes of chronic pain treatments were suspected to be due to unspecific treatment approaches, but different pain generating and maintaining mechanisms [ 19, 20].
Surprisingly, according to the second component, the above mentioned aspects also correlated with small area sizes of clinical pain.
Metaregression demonstrated no significant correlation between the magnitude of effect size on pain at final treatment and sample size.
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