Supplement Table 15: Unadjusted, adjusted# Cox regression and propensity score (PS) adjusted results for the intent-to-treat analyses
Exposure groups (reference=Short- acting hydrocodone)
Unadjusted HR (95% CI)
Adjusted HR (95%
CI)
PS adjusted HR (95% CI)
Opioid overdose (main measure)
Tramadol 1.13 (0.93–1.36) 1.08 (0.89–1.31) 1.05 (0.86–1.27) Short-acting oxycodone 1.74 (1.48–2.05) 1.62 (1.37–1.91) 1.58 (1.34–1.87)
Opioid overdose (broad measure 1)*
Tramadol 1.22 (1.04–1.44) 1.14 (0.97–1.35) 1.11 (0.94–1.31) Short-acting oxycodone 1.69 (1.46–1.95) 1.55 (1.33–1.79) 1.50 (1.30–1.74)
Opioid overdose (broad measure 2)**
Tramadol 1.15 (1.03–1.28) 1.11 (1.00–1.25) 1.07 (0.96–1.20) Short-acting oxycodone 1.53 (1.39–1.68) 1.44 (1.30–1.59) 1.40 (1.27–1.55)
Accidents
Tramadol 0.74 (0.72–0.75) 0.77 (0.75–0.79) 0.75 (0.74–0.77) Short-acting oxycodone 1.07 (1.05–1.09) 1.08 (1.06–1.10) 1.10 (1.08–1.12)
Self-inflicted injuries and poisoning
Tramadol 0.96 (0.83–1.11) 0.91 (0.78–1.05) 0.91 (0.78–1.05) Short-acting oxycodone 1.44 (1.28–1.63) 1.42 (1.25–1.61) 1.35 (1.19–1.53)
Violence-related injuries
Tramadol 0.65 (0.55 – 0.76) 0.75 (0.64–0.88) 0.72 (0.61–0.84) Short-acting oxycodone 0.92 (0.81–1.04) 1.04 (0.91–1.18) 1.03 (0.91–1.17)
Opioid use disorder
Tramadol 0.91 (0.84–0.99) 0.82 (0.76–0.89) 0.82 (0.76–0.89) Short-acting oxycodone 1.46 (1.37–1.57) 1.37 (1.28–1.47) 1.29 (1.20–1.38)
Non-opioid substance use disorder
Tramadol 1.06 (1.04–1.09) 1.00 (0.97–1.02) 1.05 (1.03–1.08) Short-acting oxycodone 0.95 (0.92–0.97) 1.00 (0.97–1.02) 0.94 (0.91–0.96)
Atopic dermatitis
Tramadol 0.99 (0.97–1.03) 1.04 (1.01–1.08) 1.01 (0.98–1.04) Short-acting oxycodone 0.95 (0.92–0.98) 0.94 (0.92–0.97) 0.97 (0.94–1.00) HR: Hazard Ratio; CI: Confidence Interval
# The models were adjusted for age, sex, region of residence, insurance type, index year, chronic back pain, chronic neck pain, chronic osteoarthritis, neuropathic pain, migraine, abdominal pain,
chest pain, other miscellaneous pain, major depressive disorder, anxiety disorders, mood disorders, personality disorders, post-traumatic stress disorder, nicotine dependence, Schizophrenia, any surgical procedure, Charlson comorbidity index, benzodiazepines, non- benzodiazepine hypnotics, gabapentinoids, skeletal muscle relaxants and antidepressants
* Opioid overdose diagnosis codes (main overdose definition) + Naloxone administration in the Emergency Department + Opioid-related adverse effects codes
** Opioid overdose diagnosis codes (main overdose definition) + Naloxone administration in the Emergency Department + Opioid-related adverse effects codes + Respiratory depression
(inpatient/outpatient/Emergency Department; age 50 years or less) + Central Nervous System depression (inpatient/outpatient/Emergency Department; age 50 years or less)
