Table 4.

Hazard ratios (95% confidence intervals) of depression, anxiety, and stress-related disorders during the year after cancer diagnosis in relation to pre-diagnostic exclusive use of aspirin, stratified analysis by different factors

Characteristics	Any exclusive aspirin use	Current aspirin	Low-dose aspirin	Long-term aspirin
Calendar year at cancer diagnosis
2006–2009	0.82 (0.71–0.95)	0.74 (0.63–0.87)	0.82 (0.70–0.97)	0.77 (0.65–0.92)
2010–2013	0.93 (0.82–1.06)	0.90 (0.78–1.04)	0.93 (0.81–1.06)	0.89 (0.77–1.03)
P for interaction	0.72	0.36	0.66	0.70
Sex
Male	0.96 (0.83–1.11)	0.92 (0.79–1.07)	0.97 (0.83–1.12)	0.90 (0.77–1.06)
Female	0.80 (0.70–0.92)	0.74 (0.63–0.86)	0.80 (0.69–0.93)	0.77 (0.65–0.90)
P for interaction	< 0.01	< 0.01	< 0.01	0.01
Age at cancer diagnosis, years
< 50	0.80 (0.42–1.54)	0.80 (0.38–1.71)	0.86 (0.44–1.71)	0.87 (0.37–2.07)
50–59	0.89 (0.65–1.21)	0.79 (0.55–1.13)	0.87 (0.63–1.20)	0.71 (0.48–1.05)
60–69	0.89 (0.74–1.08)	0.88 (0.71–1.08)	0.91 (0.75–1.11)	0.84 (0.68–1.04)
≥ 70	0.90 (0.79–1.03)	0.84 (0.73–0.97)	0.91 (0.79–1.04)	0.89 (0.77–1.02)
P for interaction	0.82	0.92	0.93	0.32
Education level
Low	0.89 (0.76–1.03)	0.85 (0.72–1.01)	0.89 (0.76–1.05)	0.87 (0.74–1.03)
Medium	1.02 (0.87–1.20)	0.93 (0.78–1.12)	1.04 (0.88–1.23)	0.96 (0.80–1.15)
High	0.67 (0.53–0.84)	0.66 (0.51–0.85)	0.63 (0.49–0.81)	0.58 (0.45–0.77)
P for interaction	0.14	0.58	0.05	0.07
Marital status
Unmarried	0.72 (0.54–0.96)	0.76 (0.55–1.04)	0.78 (0.58–1.06)	0.72 (0.52–1.01)
Married/registered partnership	0.86 (0.74–0.99)	0.79 (0.67–0.93)	0.84 (0.72–0.98)	0.78 (0.66–0.91)
Divorced/separated	0.97 (0.78–1.20)	0.96 (0.75–1.22)	0.98 (0.78–1.23)	0.99 (0.77–1.26)
Widow(er)/surviving partner	0.97 (0.78–1.20)	0.88 (0.69–1.11)	0.98 (0.78–1.23)	0.95 (0.75–1.20)
P for interaction	0.82	0.78	0.76	0.27
Occupation
Blue-collar	0.89 (0.61–1.29)	0.80 (0.52–1.23)	0.88 (0.60–1.30)	0.86 (0.56–1.32)
White-collar	0.80 (0.58–1.11)	0.74 (0.51–1.07)	0.77 (0.55–1.09)	0.60 (0.40–0.91)
Not working	0.89 (0.80–1.00)	0.85 (0.75–0.95)	0.90 (0.81–1.01)	0.87 (0.77–0.97)
P for interaction	0.93	0.92	0.86	0.84
Place of residence
East	0.83 (0.71–0.97)	0.76 (0.64–0.91)	0.86 (0.73–1.01)	0.79 (0.67–0.94)
South	0.93 (0.81–1.08)	0.93 (0.79–1.10)	0.93 (0.80–1.09)	0.90 (0.76–1.06)
North	0.87 (0.69–1.12)	0.73 (0.56–0.97)	0.84 (0.65–1.09)	0.80 (0.61–1.05)
P for interaction	< 0.01	< 0.01	0.01	0.01
Chronic disease scorec
1–3	0.91 (0.79–1.04)	0.84 (0.72–0.98)	0.91 (0.79–1.05)	0.86 (0.74–1.01)
> 3	0.87 (0.75–1.00)	0.83 (0.71–0.97)	0.88 (0.75–1.02)	0.82 (0.70–0.96)
P for interaction	0.39	0.59	0.38	0.35
Cardiovascular disease
No	0.95 (0.84–1.07)	0.88 (0.76–1.01)	0.97 (0.85–1.10)	0.90 (0.78–1.03)
Yes	0.81 (0.68–0.95)	0.79 (0.66–0.94)	0.79 (0.66–0.93)	0.78 (0.66–0.93)
P for interaction	0.01	0.12	0.01	0.07
Inflammatory musculoskeletal condition
No	0.90 (0.81–1.01)	0.84 (0.74–0.95)	0.92 (0.82–1.03)	0.86 (0.76–0.97)
Yes	0.82 (0.66–1.02)	0.81 (0.64–1.03)	0.76 (0.60–0.96)	0.78 (0.61–0.99)
P for interaction	0.49	0.90	0.16	0.54
Inflammatory systemic disease
No	0.88 (0.80–0.97)	0.83 (0.74–0.93)	0.89 (0.80–0.98)	0.84 (0.75–0.94)
Yes	0.93 (0.51–1.69)	0.85 (0.43–1.67)	0.80 (0.41–1.57)	0.75 (0.37–1.54)
P for interaction	0.88	0.85	0.47	0.58
Pain and fever
No	0.88 (0.80–0.97)	0.83 (0.74–0.92)	0.88 (0.79–0.98)	0.84 (0.75–0.94)
Yes	0.98 (0.52–1.84)	1.04 (0.52–2.06)	0.92 (0.47–1.80)	0.61 (0.28–1.36)
P for interaction	0.90	0.66	0.98	0.42
Cancer stage
Localized limited	0.78 (0.63–0.95)	0.71 (0.56–0.89)	0.79 (0.64–0.97)	0.73 (0.58–0.92)
Localized advanced	1.06 (0.75–1.50)	1.12 (0.77–1.64)	0.95 (0.65–1.39)	0.82 (0.55–1.24)
Regional spread	0.78 (0.61–0.99)	0.72 (0.55–0.95)	0.77 (0.60–1.00)	0.73 (0.56–0.96)
Distant metastasis	1.01 (0.76–1.34)	0.98 (0.72–1.33)	1.10 (0.83–1.47)	1.08 (0.80–1.47)
P for interaction	0.57	0.45	0.23	0.14
Cancer type
Prostate cancer	0.94 (0.71–1.26)	0.88 (0.64–1.20)	0.93 (0.68–1.26)	0.77 (0.56–1.07)
Breast cancer	0.74 (0.56–0.98)	0.63 (0.46–0.87)	0.73 (0.54–0.97)	0.71 (0.52–0.98)
Gastrointestinal cancer	1.03 (0.84–1.27)	1.05 (0.84–1.32)	1.02 (0.82–1.27)	1.03 (0.82–1.29)
Lung cancer	0.78 (0.58–1.05)	0.70 (0.50–0.97)	0.82 (0.61–1.12)	0.73 (0.53–1.01)
Skin cancer excl. Melanoma	1.07 (0.66–1.74)	0.89 (0.52–1.53)	1.09 (0.65–1.84)	1.19 (0.71–1.99)
Melanoma	0.56 (0.30–1.03)	0.54 (0.28–1.05)	0.45 (0.23–0.91)	0.42 (0.20–0.89)
Kidney and bladder	0.86 (0.59–1.26)	0.80 (0.52–1.23)	0.85 (0.56–1.27)	0.92 (0.61–1.39)
Gynecologic cancer	0.76 (0.52–1.12)	0.83 (0.55–1.25)	0.78 (0.52–1.16)	0.68 (0.44–1.05)
Hematological malignancies	1.16 (0.82–1.66)	1.25 (0.85–1.83)	1.25 (0.87–1.80)	1.18 (0.79–1.76)
Other cancers	0.80 (0.62–1.05)	0.67 (0.49–0.91)	0.83 (0.63–1.09)	0.74 (0.55–1.01)
P for interaction	0.04	0.03	0.15	0.12

The columns refer to four definitions of exposure in separate models: any exclusive use of aspirin, current use of aspirin, low-dose use of aspirin, and long-term use of aspirin, where no use of NSAIDs was used as the reference in all models. Stratum-specific hazard ratios were estimated for each exposure by fitting separate Cox proportional hazard models for different levels of the stratification variable and are presented in different rows, adjusting for age, sex, calendar year at cancer diagnosis, educational level, occupation, region of residence, marital status, Chronic Disease Score, potential indications for NSAIDs, cancer type, cancer stage, and subtypes of hematological malignancies. To assess the interaction between the exposure and each stratification variable, multivariable models were fitted adjusting for the above covariates and including an interaction term for the exposure and each level of the individual stratification variable. P for interaction was then calculated through a Wald test of the null hypothesis that interaction parameter for the exposure and the individual stratification variable is equal to zero. P < 0.05 indicates a statistically significant interaction between the exposure and the stratification variable