After a total of 169,463 person-years’ follow-up (39,550 person-years for the chronic insomnia group and 129,914 person-years for the comparison group) of the entire cohort, the chronic insomnia group that required sleep-inducing pills had a 1.8-fold increase in AID in terms of the incidence density rate as compared to people without chronic insomnia; moreover, there appeared to be an increased risk for a subsequent AID, representing a 70 % increase in the aHR (1.7; 95 % CI, 1.5–1.9; p < 0.0001) after controlling for age, sex, household insurance premium, urbanization, alcohol- and smoking-related diagnoses, morbid obesity, and comorbidities. Figure 2 demonstrates the curves of the cumulative incidence of AID over the follow-up period of the two compared groups. The log-rank test for the survival functions showed high statistical significance (p < 0.0001).
There were 5736 participants in the chronic insomnia group and 17,208 in the comparison group; 52 % of the participants were male. It is notable that 66.5 % of the insomniac subjects were aged 20 to 49 years. Eighty-five percent of the chronic insomnia group was recruited from the two lowest categories of income, indicating that the insomniac patients were more likely to be socioeconomically disadvantaged than the comparison subjects. Sixty-six percent of the subjects in this study lived in an urban area (Table 1).
Slightly more subjects in the chronic insomnia group had DM (6.14 vs 3.42 %), depression (5.58 vs 1.88 %), CKD (1.17 vs 0.53 %), and liver cirrhosis (0.71 vs 0.32 %) (Table 1).
Table 2 depicts the incidence of AID under specific person-years’ follow-up and analysis showing the univariate and multivariate aHRs as stratified by outcome, age group, sex, socioeconomic proxy, geographic urbanization level, smoking-related diagnoses, and comorbidities such as DM, CKD, liver cirrhosis, and depression. Compared with males, females had a statistically significant 70 % increased risk for AID, with an aHR of 1.7 (95 % CI, 1.4–2.1; p < 0.0001). Patients with DM and depression had increased risk for AID, with similar aHRs and 95 % CI of 1.4 (95 % CI, 1.0–2.0) (Table 2).
Among the various types of AID, pSS alone had a statistically significant association with chronic insomnia, and the results indicate that as compared with the population without chronic insomnia, the individuals with chronic insomnia had a 30 % increased risk of pSS (aHR, 1.3; 95 % CI, 1.1–1.6; p = 0.0073) (Table 3). The null hypothesis in this setting was therefore rejected, which was subsequently verified under FDR control using the BH procedure (Online Supplemental Table 1).
Sensitivity analysis was performed to assess the risk of AID over a longer follow-up period, which showed that AID risk was even stronger after 5 years of follow-up, with an aHR of 2.0 (95 % CI, 1.7–2.4) (Table 4).
Confirmation and validation of all cases of pSS were carried out by checking each individual’s medical claims record on information such as the median age at diagnosis, if they had ever undergone a sialoscintigraphy or salivary gland biopsy, if they had ever had anti-SSA/Ro and/or anti-SSB/La serologic tests, and subsequent treatment with hydroxychloroquine. Online Supplemental Table 2 demonstrates that the median age at diagnosis of pSS was 52 and 54 years in the chronic insomnia group and the comparison group, respectively. All patients with pSS in the chronic insomnia group had undergone sialoscintigraphy, whereas this rate was nearly 98 % in the comparison group. All but one patient with pSS had undergone at least one serologic test of anti-SSA/Ro or anti-SSB/La according to their claims record. These data provide convincing evidence that the diagnosis of pSS was reliable in this data set. In Taiwan, this study also demonstrated that approximately 60 % of the patients with pSS were treated with hydroxychloroquine, which is normally indicated for the management of extraglandular manifestations such as fatigue, arthralgia, and myalgia.