RESUMO
The negative health consequences of loneliness have led to increasing concern about the economic cost of loneliness in recent years. Loneliness may also incur an economic burden more directly, by impacting socioeconomic position. Much of the research to date has focused on employment status which may not fully capture socioeconomic position and has relied on cross-sectional data, leaving questions around the robustness of the association and reverse causation. The present study used longitudinal data to test prospective associations between loneliness and multiple indicators of social position in young adulthood, specifically, whether participants who were lonelier at age 12 were more likely to be out of employment, education and training (NEET) and lower on employability and subjective social status as young adults. The data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 individuals born in England and Wales during 1994-1995. Loneliness and subjective social status were measured at ages 12, 18 and 26. Employability and NEET status were assessed at age 18. Findings indicate that greater loneliness at age 12 was prospectively associated with reduced employability and lower social status in young adulthood. The association between loneliness and lower social status in young adulthood was robust when controlling for a range of confounders using a sibling-control design. Results also indicate that loneliness is unidirectionally associated with reduced subjective social status across adolescence and young adulthood. Overall, our findings suggest that loneliness may have direct costs to the economy resulting from reduced employability and social position, underlining the importance of addressing loneliness early in life.
RESUMO
PURPOSE: Biologic heterogeneity is a feature of diffuse large B-cell lymphoma (DLBCL), and the existence of a subgroup with poor prognosis and phenotypic proximity to Burkitt lymphoma is well known. Conventional cytogenetics identifies some patients with rearrangements of MYC and BCL2 and/or BCL6 (double-hit lymphomas) who are increasingly treated with more intensive chemotherapy, but a more biologically coherent and clinically useful definition of this group is required. PATIENTS AND METHODS: We defined a molecular high-grade (MHG) group by applying a gene expression-based classifier to 928 patients with DLBCL from a clinical trial that investigated the addition of bortezomib to standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The prognostic significance of MHG was compared with existing biomarkers. We performed targeted sequencing of 70 genes in 400 patients and explored molecular pathology using gene expression signature databases. Findings were validated in an independent data set. RESULTS: The MHG group comprised 83 patients (9%), with 75 in the cell-of-origin germinal center B-cell-like group. MYC rearranged and double-hit groups were strongly over-represented in MHG but comprised only one half of the total. Gene expression analysis revealed a proliferative phenotype with a relationship to centroblasts. Progression-free survival rate at 36 months after R-CHOP in the MHG group was 37% (95% CI, 24% to 55%) compared with 72% (95% CI, 68% to 77%) for others, and an analysis of treatment effects suggested a possible positive effect of bortezomib. Double-hit lymphomas lacking the MHG signature showed no evidence of worse outcome than other germinal center B-cell-like cases. CONCLUSION: MHG defines a biologically coherent high-grade B-cell lymphoma group with distinct molecular features and clinical outcomes that effectively doubles the size of the poor-prognosis, double-hit group. Patients with MHG may benefit from intensified chemotherapy or novel targeted therapies.
