Fig. 5: Assessing biopsychosocial synergy in the prognosis of pain-associated medical conditions.

a, An overview of the development of diagnosis risk stratification models based on pooled probabilities from biological (blood, brain and bone) and psychosocial modalities. (i) Biological and psychosocial risk scores were segmented into quantiles for stratification. (ii) A Sankey diagram visualizes the possible combinations blood and psychosocial risk quintiles; this operation is similarly conducted for bone and brain risk models. b, Top: diagnosis-associated ORs for each diagnosis are computed for participants within each risk quantile of blood assay risk scores, psychosocial risk scores and combined risk scores, in comparison with all other participants. Bottom: the ORs are transformed to log-odds to elucidate the protective effect associated with lower risk quantiles. c, The performance of the pooled risk scores for each diagnosis was measured against diagnosis-free participants using Cohen’s d effect size. The heat map displays the log-ORs of having a diagnosis across all risk quintile combinations, highlighting the synergistic impact of high combined biological and psychosocial risks and the protective effects conferred by lower combined risks. d,e, The analysis performed in c was replicated for diagnoses most accurately classified by the brain (d) and bone (e) modalities. f, log-ORs depict the synergy between blood assay biomarkers and psychosocial factors in disease prognosis 4 years later. g, Kaplan–Meier curves show the cumulative incidence of receiving a diagnosis up to 15 years after baseline, segregated into four groups according to combinations of blood and psychosocial risk quantiles (high–high, high–low, low–high and low–low). HRs are calculated using Cox-proportional hazard models, while the P value of the differences between groups is calculated using a two-sided log-rank test (P_HH < 0.001, P_HL = 0.047, P_LH = 0.055, P_LL < 0.001). h, Bar plots illustrate the association between biological and psychosocial risk scores for blood (left), bone (top right) and brain (bottom right) risks with categories of pain site spread (ranging from 1 to 4+ sites) The R² values indicate the strength of these associations, as determined by Spearman’s rank correlation. *P < 0.001.