Table 5.

Summary of key findings from all follow-up of the Lothian cohort.

Study	No. patients	Follow-up time	Statistical measure	Key findings and comments
Logan et al.11	653	Date of clinical diagnosis of CD to 30 June 1986 (8823 person years at risk, 115 deaths)	Overall and cause-specific SMRs	• Mortality overall was 1.9-fold more for CD patients than that of the general population. The SMR was similar in men and women. • 10 deaths were directly attributable to CD, compared to 44 from malignancies (corresponding SMR of 3.0 fold for malignancies). • Only four deaths occurred in cases diagnosed in childhood (aged<15 years, total sample size of 292). All these deaths were from external causes. • Overall, there was a gradual decline in SMR with increased time from diagnosis. For 15+ years, there was an SMR of 1.2; however, this was based on just 11.64 expected deaths and was not statistically significant.
Solaymani-Dodaran et al.10	602a	Date of clinical diagnosis of CD or 1 January 1970 (whichever was later) to 31 December 2004 (14,926 person-years, 195 deaths)b	Overall and cause-specific SMRs	• All analyses in this paper were presented separately for child (0–14 years) and adult (15+ years) diagnosed cases. The overall raised mortality risk was higher in childhood-diagnosed cases (SMR = 2.6) than for adult-diagnosed cases (SMR = 1.6) • Among childhood-diagnosed cases there were 21 deaths, of which seven were due to external causes (SMR = 2.9) and five due to neoplasms (SMR = 3.6). Both these increases were statistically significant. • Due to the increased follow-up, the expected number of deaths 15 + years following diagnosis had increased to 68.71. In childhood-diagnosed cases there was a raised risk 25+ years after diagnosis (SMR = 3.5). For adult-diagnosed cases, no corresponding risk was observed but the confidence interval was wide (SMR = 1.26; 95% CI 0.86–1.77).
Current study	602	Date of clinical diagnosis of CD or 1 January 1970 (whichever was later) to 20 October 2016 (19,071 person years, 237 deaths)b	Overall and cause-specific SMRs	• In the current study, the overall increase in mortality was 2.1-fold in childhood-diagnosed cases and 1.4-fold in adult-diagnosed cases. The decrease in overall SMRs compared with the earlier reports reflects the decline in risk following increased time from diagnosis. • There were 32 deaths among childhood-diagnosed cases, of which the number of deaths from malignancy increased to eight and the number from external causes remained at seven. However, the expected number of deaths from external causes only increased slightly compared with the previous report (2.67 vs 2.39) as childhood-diagnosed participants are now at an age where deaths attributed to this cause are less common. • The expected number of deaths 15+ years following diagnosis has increased to 114.64. Among adult-diagnosed cases, the absence of an increased risk beyond 25 years reported previously remains but the confidence interval around this value has tightened considerably (SMR = 0.97; (95% CI 0.74–1.24). The equivalent SMR for childhood-diagnosed cases was reduced in this updated follow-up (SMR = 2.2) as the impact of deaths from external causes on this overall figure has been weakened. • There was a reduced risk of death from any malignancy more than 15 years after diagnosis in adult-diagnosed CD patients. Previously Grainge et al.17 reported no change in malignancy incidence in this group compared with the general population 15 years after diagnosis. In the previous mortality report, cause-specific results only stratified time since diagnosis into <5 years and 5+ years.

CD: coeliac disease; CI: confidence interval; SMR: standardised mortality ratio.

^aThe sample size reported in the paper was 625, however, the authors excluded 23 deaths (out of 218 deaths that had occurred in the 625 CD cases) that occurred before 1 January 1970 from the main analysis reported in the paper.

^bThe survival analysis commenced in 1970 in the analysis presented in this article, to circumvent the problem of survival bias and because population mortality estimates by cause were more reliable from this date onwards.