Spousal bereavement, mortality and risk of negative health outcomes among older adults: a population-based study

Lucas Morin; Jonas W Wastesson; Stefan Fors; Neda Agahi; Kristina Johnell

older spouses were linked together in a deterministic rather than probabilistic manner, which provides an unbiased classification of bereaved cases and non-bereaved controls. We were able to identify and measure a wide range of demographic, socioeconomic, and health-related baseline characteristics, thus allowing us to adjust our analyses for important confounders. Matching on sex and date of birth achieved good balance of measured covariates at baseline, which suggests strong empirical equipoise and supports our claim of a causal relationship between spousal bereavement and negative health outcomes. However, the lack of information with regard to important physical (e.g. body-mass index), functional (e.g. gait speed, ADL impairments), lifestyle (e.g. diet, smoking, alcohol use) or familyrelated factors (e.g. level of social support) represents a potential source of residual confounding, which could threaten the validity of our effect estimates. To alleviate this concern, we calculated E-values to evaluate how susceptible the observed associations were to unmeasured confounders. This sensitivity analysis showed that unmeasured confounders would need to be of substantial magnitude to fully explain the adjusted effect estimates. For instance, the observed incidence rate ratio for all-cause mortality (1.66, 95% CI 1.53-1.80) could only be moved to the null by an unmeasured confounder associated with both spousal loss and mortality by a risk ratio of at least 2.70 above and beyond measured confounders. The existence of such confounders is, to the best of our knowledge, highly unlikely. Negative control outcomes with presumed null effect sizes were used to assess the potential for residual systemic bias, which revealed no obvious prognostic imbalance at baseline. We also devised a cohort crossover design to measure within-individual change in the risk of experiencing adverse health outcomes before and after spousal loss among bereaved cases compared with the change among married controls. This approach offers the double advantage of eliminating between-person confounding (measured or otherwise) by using study subjects as their own controls while also attenuating the risk of bias due to left truncation and natural age-related trends. Another important strength of the present study is that all prespecified sensitivity analyses and non-prespecified post-hoc analyses are reported in a clear and transparent manner and explicitly linked to the corresponding hypotheses that we intended to test.