Background
Methods
Study design and data source
Study population
Outcome | Definition |
---|---|
Bone-related conditions | Incident Read code of bone fracture (ankle, foot, toe, hand, finger, hip, femur, humerus, shoulder, clavicle, scapula, lower arm, elbow, wrist, vertebra or unspecific fracture) or osteoporosis. |
Hypertension | Incident Read code of hypertension preceded or followed within 180 days prior until 180 days after by a prescription for an antihypertensive drug (ACE inhibitor, ARB, dihydropyridine CCB or thiazide diuretic). The first record of either hypertension or antihypertensive treatment was assigned the date of outcome occurrence. |
Peptic ulcer | Incident Read code of peptic ulcer with or without haemorrhage. |
Severe infections | Main analysis: incident Read code of an infection preceded or followed within 1 month by a record suggesting hospitalisation or i.v. anti-infective treatment. Sensitivity analysis restricted to patients with IHS linkage (conducted in the nested-case control study only): incident Read code of an infection preceded or followed within 1 month by a hospitalisation whose reason was infection (ICD-10 code of infection in the IHS data). |
Herpes zoster | Incident Read code of herpes zoster |
DM2 | Incident Read code of DM2 and/or a first-time prescription for an oral antidiabetic drug, whichever came first. If a patient was prescribed insulin before any other antidiabetic drug during follow-up (and therefore likely was diagnosed with DM1), the event did not count as an outcome and the person was censored at the date of the insulin prescription. |
Cataract | Incident Read code of cataract or a procedure for lens replacement, whichever came first. |
Glaucoma | Incident Read code of glaucoma or a first-time prescription for intraocular pressure-lowering therapy, whichever came first. |
CKD | Incident Read code of CKD or ≥2 recorded values of an eGFR of < 60 ml/min/1.73m2 within 365 days and separated by ≥90 days (calculated based on the CKD-EPI equation). |
Affective disorders | Incident Read code of affective disorders (depression, bipolar affective disorder, manic episodes) preceded or followed within 180 days before or after by a prescription for an antidepressant or mood stabilizing drug, or a Read code indicating psychotherapy. The first record of either affective disorders or the respective treatment was assigned the date of outcome occurrence. |
Cardiovascular events | Incident Read code of myocardial infarction, ischaemic heart disease, or ischaemic stroke. |
Cohort analyses
Follow-up and definition of outcomes
Person-time analyses and definition of exposure
Nested case-control analyses
Definition of cases and controls
Definition of exposure
Definition of covariates
Statistical analysis
Cohort analyses
Nested case-control analyses
Sensitivity analysis
Results
Characteristics of the study population
Bone-related conditions | Hypertension | Peptic ulcer | Severe infections | Herpes zoster | DM2 | Cataract | Glaucoma | CKD | Affective disorders | Cardiovascular events | |
---|---|---|---|---|---|---|---|---|---|---|---|
Cohort analysis | |||||||||||
Individuals at cohort entry, n | 219,174 | 223,940 | 267,569 | 244,207 | 262,847 | 262,304 | 265,964 | 269,368 | 267,138 | 165,900 | 260,995 |
Individuals with cohort entry on 1 January 2000, n | 40,484 | 37,250 | 46,439 | 44,621 | 46,016 | 46,046 | 46,324 | 46,892 | 47,549 | 30,722 | 44,549 |
Individuals with cohort entry after 1 January 2000, n | 178,690 | 186,690 | 221,130 | 199,586 | 216,831 | 216,258 | 219,640 | 222,476 | 219,589 | 135,178 | 216,446 |
Cases, n | 8927 | 8162 | 836 | 16,192 | 4175 | 5195 | 5356 | 1473 | 8825 | 4965 | 4028 |
Total follow-up time, py | 682,398 | 653,565 | 850,874 | 744,410 | 824,689 | 820,055 | 830,289 | 854,208 | 825,108 | 525,577 | 816,959 |
Nested case-control analysis | |||||||||||
Casesa, n | 8907 | 8148 | 835 | 16 160b 2748c | 4163 | 5189 | 5327 | 1467 | 8778 | 4962 | 4014 |
Controls, n | 35,445 | 32,431 | 3328 | 64,316b 10839c | 16,605 | 20,715 | 21,019 | 5832 | 34,762 | 19,809 | 15,945 |
Mean age of cases, years (SD) | 54.3 (+/− 19.6) | 58.9 (+/− 12.9) | 63.1 (+/− 16.7) | 51.8 (+/− 19.7)b 58.6 (+/− 20.8)c | 57.3 (+/− 17.5) | 58.1 (+/− 15.3) | 72.7 (+/− 10.9) | 68.0 (+/− 13.0) | 71.3 (+/− 12.0) | 40.8 (+/− 16.7) | 67.4 (+/− 12.4) |
Females among cases, % | 69.1 | 57.4 | 60.2 | 67.7b 64.6c | 66.0 | 60.1 | 68.9 | 62.9 | 73.1 | 62.2 | 53.0 |
Cohort analyses
Use of oral prednisolone | Bone-related conditions | Hypertension | Peptic ulcer | Severe infections | Herpes zoster | DM2 | Cataract | Glaucoma | CKD | Affective disorders | Cardiovascular events |
---|---|---|---|---|---|---|---|---|---|---|---|
Non-use (reference) | |||||||||||
Cases, n | 6174 | 5867 | 591 | 10,115 | 2882 | 3534 | 3639 | 1057 | 6034 | 3602 | 2868 |
Person-years | 509,914 | 493,646 | 631,164 | 567,254 | 614,128 | 609,903 | 618,128 | 633,404 | 616,192 | 402,782 | 607,320 |
IR/ 1000 person-years (95% CI) | 12.1 (11.8–12.4) | 11.9 (11.6–12.2) | 0.9 (0.9–1.0) | 17.8 (17.5–18.2) | 4.7 (4.5–4.9) | 5.8 (5.6–6.0) | 5.9 (5.7–6.1) | 1.7 (1.6–1.8) | 9.8 (9.5–10.0) | 8.9 (8.7–9.2) | 4.7 (4.5–4.9) |
Ever use | |||||||||||
Cases, n | 2753 | 2295 | 245 | 6077 | 1293 | 1661 | 1717 | 416 | 2791 | 1363 | 1160 |
Person-years | 172,484 | 159,919 | 219,711 | 177,156 | 210,560 | 210,152 | 212,161 | 220,804 | 208,916 | 122,796 | 209,638 |
IR/1000 person-years (95% CI) | 16.0 (15.4–16.6) | 14.4 (13.8–14.9) | 1.1 (1.0–1.3) | 34.3 (33.4–35.2) | 6.1 (5.8–6.5) | 7.9 (7.5–8.3) | 8.1 (7.7–8.5) | 1.9 (1.7–2.1) | 13.4 (12.9–13.9) | 11.1 (10.5–11.7) | 5.5 (5.2–5.9) |
IRR (95% CI) | 1.3 (1.3–1.4) | 1.2 (1.2–1.3) | 1.2 (1.0–1.4) | 1.9 (1.9–2.0) | 1.3 (1.2–1.4) | 1.4 (1.3–1.4) | 1.4 (1.3–1.5) | 1.1 (1.0–1.3) | 1.4 (1.3–1.4) | 1.2 (1.2–1.3) | 1.2 (1.1–1.3) |
Current use | |||||||||||
Cases, n | 533 | 451 | 51 | 2268 | 257 | 398 | 272 | 62 | 541 | 269 | 236 |
Person-years | 29,141 | 27,032 | 36,864 | 29,074 | 35,586 | 35,468 | 35,723 | 37,125 | 35,364 | 19,803 | 35,269 |
IR/1000 person-years (95% CI) | 18.3 (16.7–19.8) | 16.7 (15.1–18.2) | 1.4 (1.0–1.8) | 78.0 (74.8–81.2) | 7.2 (6.3–8.1) | 11.2 (10.1–12.3) | 7.6 (6.7–8.5) | 1.7 (1.3–2.1) | 15.3 (14.0–16.6) | 13.6 (12.0–15.2) | 6.7 (5.8–7.5) |
IRR (95% CI) | 1.5 (1.4–1.6) | 1.4 (1.3–1.5) | 1.5 (1.1–2.0) | 4.4 (4.2–4.6) | 1.5 (1.4–1.7) | 1.9 (1.7–2.2) | 1.3 (1.1–1.5) | 1.0 (0.8–1.3) | 1.6 (1.4–1.7) | 1.5 (1.3–1.7) | 1.4 (1.2–1.6) |
Nested case-control analyses
Use of oral prednisolone | Bone-related conditions | Hypertension | Peptic ulcer | Severe Infectionsa | Herpes zoster | DM2 | Cataract | Glaucoma | CKD | Affective disorders | Cardiovascular events |
---|---|---|---|---|---|---|---|---|---|---|---|
No use (reference) | |||||||||||
Cases, n (%) | 4558 (51.2) | 4397 (54.0) | 416 (49.8) | 7642 (47.3) | 2056 (49.4) | 2571 (49.6) | 2582 (48.5) | 769 (52.4) | 4344 (49.5) | 2769 (55.8) | 2096 (52.2) |
Controls, n (%) | 19,038 (53.7) | 17,802 (54.9) | 1805 (54.2) | 36,039 (56.0) | 8875 (53.5) | 11,071 (53.4) | 10,641 (50.6) | 3048 (52.3) | 17,768 (51.1) | 12,016 (60.7) | 8827 (55.4) |
Current use (< 180 d before ID) | |||||||||||
Cases, n (%) | 846 (9.5) | 654 (8.0) | 80 (9.6) | 2227 (13.8) | 406 (9.8) | 596 (11.5) | 433 (8.1) | 119 (8.1) | 811 (9.2) | 434 (8.8) | 379 (9.4) |
Controls, n (%) | 2614 (7.4) | 2414 (7.4) | 225 (6.8) | 4489 (7.0) | 1307 (7.9) | 1617 (7.8) | 1612 (7.7) | 463 (7.9) | 2763 (8.0) | 1210 (6.1) | 1138 (7.1) |
OR crude (95% CI) | 1.36 (1.26–1.47) | 1.10 (1.01–1.20) | 1.57 (1.23–2.01) | 2.38 (2.26–2.50) | 1.36 (1.22–1.52) | 1.60 (1.46–1.75) | 1.11 (1.00–1.23) | 1.02 (0.84–1.24) | 1.21 (1.12–1.30) | 1.58 (1.42–1.75) | 1.41 (1.26–1.58) |
ORadjb (95% CI) | 1.27 (1.17–1.37) | 1.03 (0.94–1.12) | 1.47 (1.12–1.92) | 2.16 (2.05–2.27) | 1.32 (1.19–1.48) | 1.35 (1.22–1.49) | 1.03 (0.93–1.15) | 1.06 (0.87–1.29) | 1.14 (1.06–1.24) | 1.47 (1.32–1.63) | 1.33 (1.18–1.49) |
Recent use (180–365 d before ID) | |||||||||||
Cases, n (%) | 519 (5.8) | 405 (5.0) | 50 (6.0) | 1121 (6.9) | 267 (6.4) | 293 (5.7) | 310 (5.8) | 75 (5.1) | 478 (5.5) | 308 (6.2) | 212 (5.3) |
Controls, n (%) | 1858 (5.2) | 1608 (5.0) | 159 (4.8) | 3087 (4.8) | 889 (5.4) | 1036 (5.0) | 1102 (5.2) | 297 (5.1) | 1850 (5.3) | 871 (4.4) | 765 (4.8) |
OR crude (95% CI) | 1.18 (1.08–1.29) | 1.02 (0.92–1.13) | 1.36 (1.01–1.83) | 1.74 (1.63–1.86) | 1.32 (1.16–1.50) | 1.23 (1.09–1.39) | 1.17 (1.04–1.31) | 0.99 (0.75–1.26) | 1.06 (0.97–1.17) | 1.55 (1.38–1.75) | 1.18 (1.03–1.37) |
ORadjb (95% CI) | 1.12 (1.02–1.24) | 0.95 (0.85–1.05) | 1.19 (0.87–1.62) | 1.59 (1.49–1.70) | 1.29 (1.13–1.47) | 1.05 (0.92–1.19) | 1.12 (0.99–1.26) | 1.00 (0.79–1.28) | 1.00 (0.91–1.10) | 1.49 (1.32–1.69) | 1.11 (0.95–1.29) |
Past use (> 365 d before ID) | |||||||||||
Cases, n (%) | 2984 (33.5) | 2692 (33.0) | 289 (34.6) | 5170 (32.0 | 1434 (34.5) | 1729 (33.3) | 2002 (37.6) | 504 (34.4) | 3145 (35.8) | 1451 (29.2) | 1327 (33.1) |
Controls, n (%) | 11,935 (33.7) | 10,607 (32.7) | 1139 (34.2) | 20,701 (32.2) | 5534 (33.3) | 6991 (33.8) | 7664 (36.5) | 2024 (34.7) | 12,381 (35.6) | 5712 (28.8) | 5215 (32.7) |
OR crude (95% CI) | 1.05 (1.00–1.10) | 1.03 (0.98–1.08) | 1.11 (0.95–1.30) | 1.20 (1.16–1.25) | 1.13 (1.05–1.21) | 1.08 (1.01–1.15) | 1.08 (1.02–1.15) | 0.99 (0.88–1.11) | 1.04 (0.99–1.09) | 1.12 (1.05–1.19) | 1.08 (1.01–1.16) |
ORadjb (95% CI) | 1.03 (0.98–1.08) | 0.97 (0.92–1.02) | 1.05 (0.89–1.25) | 1.14 (1.10–1.19) | 1.13 (1.05–1.21) | 0.98 (0.92–1.05) | 1.04 (0.98–1.10) | 1.00 (0.89–1.13) | 1.01 (0.97–1.07) | 1.10 (1.02–1.18) | 1.06 (0.98–1.14) |