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

Third, we made use of negative control outcomes, namely conditions thought to be unrelated to bereavement and thus presumed to have null effect sizes, 44,45 to unravel potential sources of bias due to unmeasured confounders related to shared lifestyle and environmental factors. These negative control outcomes include the incidence of solid cancer, hallux valgus, Parkinson's disease and cataract during the first year of follow-up among individuals without these conditions at baseline. We reasoned that if the association between spousal loss and subsequent health events was truly causal, no association should be observed with biologically implausible health outcomes such as the risk of developing a new solid tumour or Parkinson's disease within one year. 46 A positive association would thus indicate the existence of residual confounding. Fourth, we calculated the E-value for each of the outcomes observed in our matched cohort design. This methodology has been proposed by VanderWeele and colleagues as a way to evaluate how susceptible an association is to potential unmeasured or uncontrolled confounding. 47 The E-value can be defined as the minimum strength of association that an unmeasured confounder would need to have with both the exposure and the outcome to fully explain away the observed association between them, conditional on the measured covariates. Finally, we expanded the definition of acute cardiovascular events to include a broader range of conditions than the ones included in the main analysis (e.g. acute endocarditis, non-rheumatic valve disorders, cardiomyopathies, deep vein thrombosis) and we extended the definition of fall-related injuries beyond hip fracture.