Table 1.
Basic Characteristics of Tramadol Cohort Compared with Codeine Cohort
| Before propensity-score matched | Propensity-score matched | |||||
|---|---|---|---|---|---|---|
| Tramadol | Codeine | Standard difference | Tramadol | Codeine | Standard difference | |
| Participants, n | 202,003 | 170,369 | 146,956 | 146,956 | ||
| Demographics | ||||||
| Age, mean (SD), y | 65.9 (10.0) | 67.1 (10.3) | 0.112 | 66.5 (10.1) | 66.5 (10.1) | 0.001 |
| Socioeconomic deprivation index, mean (SD) † | 2.8 (1.4) | 2.6 (1.3) | 0.122 | 2.7 (1.3) | 2.7 (1.3) | 0.001 |
| Female (%) | 57.5 | 57.9 | 0.009 | 57.4 | 57.5 | 0.001 |
| BMI, mean (SD), kg/m2 | 28.5 (5.8) | 27.8 (5.4) | 0.126 | 28.1 (5.5) | 28.1 (5.5) | 0.001 |
| Lifestyle factors | ||||||
| Drinking (%) | 0.030 | 0.002 | ||||
| None | 21.1 | 19.9 | 20.1 | 20.2 | ||
| Past | 3.0 | 2.9 | 2.8 | 2.8 | ||
| Current | 75.9 | 77.2 | 77.1 | 77.0 | ||
| Smoking (%) | 0.132 | 0.003 | ||||
| None | 47.2 | 52.0 | 50.3 | 50.4 | ||
| Past | 31.8 | 31.9 | 32.1 | 32.1 | ||
| Current | 20.9 | 16.1 | 17.6 | 17.5 | ||
| Comorbidity (%) | ||||||
| Other fracture# | 8.3 | 7.7 | 0.022 | 7.9 | 7.8 | 0.001 |
| Fall | 11.2 | 12.6 | 0.044 | 11.9 | 11.8 | <0.001 |
| Osteoporosis | 9.0 | 7.9 | 0.038 | 8.2 | 8.2 | 0.001 |
| Seizure | 0.6 | 0.7 | 0.010 | 0.6 | 0.6 | 0.001 |
| Diabetes | 15.2 | 14.9 | 0.009 | 14.8 | 14.8 | 0.001 |
| Hypertension | 45.8 | 46.4 | 0.010 | 46.0 | 46.1 | 0.001 |
| Liver disease | 2.5 | 2.5 | 0.001 | 2.5 | 2.5 | 0.001 |
| Chronic kidney disease | 8.3 | 9.2 | 0.033 | 8.7 | 8.7 | 0.001 |
| Transient ischaemic attack | 3.2 | 3.5 | 0.013 | 3.3 | 3.3 | 0.001 |
| Ischaemic heart disease | 16.6 | 16.0 | 0.018 | 16.1 | 16.0 | 0.002 |
| Congestive heart failure | 3.6 | 3.9 | 0.017 | 3.6 | 3.6 | 0.001 |
| Myocardial infarction | 6.5 | 6.3 | 0.007 | 6.4 | 6.3 | 0.001 |
| Stroke | 4.0 | 4.4 | 0.025 | 4.1 | 4.1 | 0.001 |
| Angina | 10.5 | 10.2 | 0.010 | 10.2 | 10.2 | <0.001 |
| Peripheral vascular disease | 2.4 | 1.8 | 0.044 | 2.0 | 2.0 | 0.003 |
| Venous thromboembolism | 3.6 | 3.3 | 0.014 | 3.4 | 3.4 | 0.001 |
| Pneumonia or infection | 7.4 | 7.4 | 0.002 | 7.4 | 7.3 | 0.001 |
| Hyperlipidaemia | 15.3 | 14.6 | 0.020 | 14.7 | 14.8 | 0.001 |
| Dementia | 0.7 | 1.4 | 0.074 | 0.8 | 0.9 | 0.002 |
| Varicose veins | 10.2 | 10.3 | 0.001 | 10.3 | 10.3 | 0.001 |
| Other circulatory disease | 28.3 | 28.8 | 0.010 | 28.6 | 28.5 | 0.001 |
| Osteoarthritis | 33.9 | 28.5 | 0.116 | 30.4 | 30.5 | 0.001 |
| Rheumatoid arthritis | 2.8 | 1.9 | 0.057 | 2.2 | 2.1 | 0.004 |
| Depression | 15.1 | 13.0 | 0.062 | 13.5 | 13.5 | 0.001 |
| Chronic obstructive pulmonary disease | 7.2 | 6.0 | 0.046 | 6.4 | 6.3 | 0.003 |
| Atrial fibrillation | 5.3 | 6.4 | 0.046 | 5.8 | 5.8 | <0.001 |
| Anxiety | 15.8 | 15.0 | 0.023 | 15.1 | 15.1 | <0.001 |
| Sleep disorder or sleep apnea | 1.9 | 1.6 | 0.020 | 1.7 | 1.7 | <0.001 |
| Peptic ulcer | 7.8 | 6.6 | 0.047 | 7.0 | 6.9 | 0.003 |
| Alcohol abuse | 3.6 | 2.6 | 0.058 | 2.8 | 2.8 | 0.002 |
| Medication (%) | ||||||
| Other opioids* | 19.0 | 11.0 | 0.227 | 12.8 | 12.4 | 0.010 |
| Other NSAIDs* | 79.1 | 69.9 | 0.212 | 74.5 | 74.7 | 0.005 |
| Aspirin | 34.9 | 34.2 | 0.016 | 34.2 | 34.0 | 0.003 |
| Bisphosphonates | 8.1 | 6.7 | 0.052 | 7.1 | 7.0 | 0.004 |
| Statin | 40.6 | 38.2 | 0.050 | 38.8 | 38.8 | <0.001 |
| Glucocorticoids | 23.6 | 21.7 | 0.047 | 22.4 | 22.2 | 0.005 |
| Nitrates | 15.4 | 14.4 | 0.028 | 14.6 | 14.5 | 0.003 |
| Antihypertensive medicine | 64.7 | 63.1 | 0.035 | 63.4 | 63.4 | <0.001 |
| Antidiabetic medicine | 11.5 | 10.9 | 0.017 | 11.1 | 11.0 | 0.001 |
| ACE inhibitors | 34.3 | 34.8 | 0.010 | 34.5 | 34.5 | 0.001 |
| Beta receptor inhibitors | 35.2 | 35.3 | 0.001 | 35.1 | 35.1 | <0.001 |
| Calcium channel blockers | 32.0 | 31.3 | 0.015 | 31.4 | 31.3 | 0.001 |
| Loop diuretics | 19.2 | 17.5 | 0.044 | 17.7 | 17.6 | 0.002 |
| Thiazide diuretics | 33.0 | 32.7 | 0.006 | 32.7 | 32.8 | 0.001 |
| Potassium-sparing diuretics | 8.5 | 7.6 | 0.034 | 7.8 | 7.7 | 0.003 |
| Angiotensin receptor blocker | 12.4 | 12.0 | 0.011 | 12.3 | 12.0 | 0.009 |
| Insulin | 3.4 | 3.0 | 0.019 | 3.1 | 3.1 | <0.001 |
| Anticoagulants | 7.1 | 7.8 | 0.025 | 7.4 | 7.3 | 0.001 |
| Benzodiazepines | 41.0 | 32.5 | 0.178 | 35.2 | 35.1 | 0.002 |
| SSRI | 26.8 | 22.0 | 0.113 | 23.2 | 23.2 | <0.001 |
| SNRI | 7.9 | 5.7 | 0.085 | 6.2 | 6.2 | 0.002 |
| Antiepileptic medicine | 10.7 | 7.5 | 0.112 | 8.3 | 8.2 | 0.004 |
| Estrogen | 19.2 | 18.0 | 0.029 | 18.5 | 18.6 | 0.002 |
| PPIs | 54.0 | 46.7 | 0.148 | 49.3 | 49.2 | 0.003 |
| H2 blockers | 24.7 | 21.5 | 0.076 | 22.7 | 22.5 | 0.005 |
| Healthcare utilization, mean (SD) | ||||||
| Hospitalizations‡ | 0.5 (1.2) | 0.4 (1.1) | 0.037 | 0.4 (1.1) | 0.4 (1.1) | 0.005 |
| General practice visits‡ | 7.2 (6.6) | 6.9 (6.5) | 0.045 | 7.0 (6.6) | 7.0 (6.4) | 0.003 |
| Specialist referrals‡ | 0.6 (1.1) | 0.5 (1.0) | 0.095 | 0.6 (1.0) | 0.6 (1.0) | 0.004 |
BMI, body mass index; n, number; y, years; SD, standard deviation; NSAID, non-steroidal anti-inflammatory drug; ACE, angiotensin converting enzyme; SSRI, Selective serotonin reuptake inhibitor; SNRI, Serotonin-norepinephrine reuptake inhibitor; PPIs, proton pump inhibitor; H2 blockers, histamine-2 blockers.
†
The Socio-Economic Deprivation Index (i.e., Townsend Deprivation Index) was grouped into quintiles from 1 (least deprived) to 5 (most deprived).
#
Other fracture refers to spine and wrist fracture.
*
Other NSAIDs or opioids means other NSAIDs or opioids use prior to the index date.
‡
Frequency during the past one year.