Article Figures & Tables
Figures
- Figure 1:
Percentage of persons in the combined immune-mediated inflammatory disease (IMID) cohort and the combined cohort of matched controls who received an influenza vaccination, stratified by psychiatric comorbidity status, fiscal years 1984 to 2015 (i.e., Apr. 1, 1984, to Mar. 31, 2016).
- Figure 2:
Age- and sex-standardized percentage of persons in the combined immune-mediated inflammatory disease (IMID) cohort, the individual disease cohorts and the combined cohort of matched controls who received an influenza vaccination, fiscal years 1984 to 2015 (i.e., Apr. 1, 1984, to Mar. 31, 2016). Arrows indicate changes in groups eligible for provincial (public) funding of vaccination: in 1999, age ≥ 65 years, chronic conditions, health care workers (A); in 2004, children aged 6–23 months and their families (B); in 2005, patients with chronic respiratory diseases (C); in 2007, pregnant women (D); in 2009, H1N1 epidemic (E); in 2010, coverage for entire provincial population (F); and in 2014, pharmacists able to administer influenza vaccine (G). Note: IBD = inflammatory bowel disease, MS = multiple sclerosis, RA = rheumatoid arthritis.
Tables
- Table 1:
Characteristics of prevalent disease cohorts at the time of diagnosis and matched controls at the matched index date
Characteristic Disease and cohort; no (%) of patients* Inflammatory bowel disease Multiple sclerosis Rheumatoid arthritis IMID† Controls
n = 50 704Cases†
n = 10 148Controls
n = 30 690Cases†
n = 6158Controls
n = 84 756Cases†
n = 16 975Controls
n = 164 152Cases†
n = 32 880Whole population, 1984–2015 Sex, female 27 663 (54.6) 5536 (54.6) 21 564 (70.3) 4322 (70.2) 61 231 (72.2) 12 263 (72.2) 109 065 (66.4) 21 841 (66.4) Age at diagnosis, yr, mean ± SD (range) 41.7 ± 17.0 (18 to 99) 41.7 ± 17.0 (18 to 99) 42.1 ± 13.5 (18 to 97) 42.1 ± 13.5 (18 to 96) 54.0 ± 16.1 (18 to 105) 54.0 ± 16.1 (18 to 103) 48.0 ± 17.1 (18 to 105) 48.0 ± 17.1 (18 to 103) Duration of follow-up from index date, yr, median (IQR) 11.9 (4.92 to 21.8) 13.3 (5.93 to 22.8) 13.9 (5.91 to 23.6) 13.9 (6.28 to 22.5) 11.1 (4.93 to 19.3) 11.4 (5.51 to 19.0) 11.9 (5.12 to 20.8) 12.4 (5.79 to 20.7) Urban region of residence 33 799 (66.7) 6763 (66.6) 20 685 (67.4) 4154 (67.5) 50 281 (59.3) 10 070 (59.3) 103 468 (63.0) 20 727 (63.0) Socioeconomic status,‡§ mean ± SD −0.23 ± 0.88 −0.26 ± 0.91 −0.22 ± 0.88 −0.25 ± 0.91 0.06 ± 1.01 0.03 ± 1.03 −0.08 ± 0.96 −0.11 ± 0.99 Physician visits in prior year 0–4 41 688 (82.2) 6569 (64.7) 24 637 (80.3) 3860 (62.7) 63 997 (75.5) 8416 (45.6) 128 760 (78.4) 19 997 (60.8) 5–9 6517 (12.9) 2172 (21.4) 4196 (13.7) 1313 (21.3) 14 230 (16.8) 3718 (21.9) 24 623 (15.0) 7297 (22.2) ≥ 10 2499 (4.9) 1407 (13.9) 1857 (6.0) 985 (16.0) 6529 (7.7) 4841 (28.5) 10 769 (6.6) 5586 (17.0) Comorbidity status at study start No. of ADGs 0 42 318 (83.5) 6749 (66.5) 26 373 (85.9) 4389 (71.3) 65 883 (77.7) 11 216 (66.1) 133 038 (81.0) 22 275 (67.7) 1 7246 (14.3) 2789 (27.5) 3763 (12.3) 1392 (22.6) 15 605 (18.4) 4643 (27.4) 26 227 (16.0) 8561 (26.0) ≥ 2 1140 (2.2) 610 (6.0) 554 (1.8) 377 (6.1) 3268 (3.9) 1116 (6.6) 4887 (3.0) 2044 (6.2) Any mood or anxiety disorder 10 979 (21.7) 3147 (31.0) 7431 (24.2) 2485 (40.4) 22 078 (26.0) 5735 (33.8) 39 911 (24.3) 11 171 (34.0) Depression 9590 (18.9) 2764 (27.2) 6546 (21.3) 2197 (35.7) 18 853 (22.2) 4864 (28.7) 34 480 (21.0) 9645 (29.3) Anxiety disorder 13 438 (26.5) 3453 (34.0) 8931 (29.1) 2378 (38.6) 25 922 (30.6) 6074 (35.8) 47 639 (29.0) 11 707 (35.6) Bipolar disorder 1562 (3.1) 548 (5.4) 1151 (3.8) 368 (6.0) 2963 (3.5) 716 (4.2) 5583 (3.4) 1602 (4.9) Population, 2006–2015 n = 40 364 n = 8458 n = 24 154 n = 4748 n = 64 510 n = 12 984 n = 127 310 n = 25 832 Sex, female 22 207 (55.0) 4623 (54.7) 17 247 (71.4) 3399 (71.6) 47 102 (73.0) 9458 (72.8) 85 349 (67.0) 8602 (33.3) Age at diagnosis, yr, mean ± SD (range) 41.2 ± 16.2 (18 to 99) 41.0 ± 16.2 (18 to 99) 40.9 ± 12.2 (18 to 97) 40.2 ± 11.9 (18 to 94) 51.8 ± 15.2 (18 to 105) 51.4 ± 15.4 (18 to 102) 46.4 ± 16.0 (18 to 105) 45.9 ± 16.0 (18 to 102) Urban region of residence 26 558 (65.8) 5574 (65.9) 15 925 (65.9) 3153 (66.4) 37 559 (58.2) 7609 (58.6) 78 949 (62.0) 16 104 (62.3) Socioeconomic status,‡ mean ± SD −0.22 ± 0.85 −0.26 ± 0.89 −0.21 ± 0.85 −0.25 ± 0.89 0.06 ± 1.0 0.04 ± 1.0 −0.08 ± 0.95 −0.11 ± 0.98 Physician visits in prior year 0–4 26 789 (66.4) 3810 (45.0) 15 224 (63.0) 2260 (47.6) 37 960 (58.8) 4745 (36.5) 78 891 (62.0) 10 716 (41.5) 5–9 8700 (21.6) 2358 (27.9) 5711 (23.6) 1313 (27.7) 16 064 (24.9) 3593 (27.7) 30 072 (23.6) 7171 (27.8) ≥ 10 4875 (12.1) 2290 (27.1) 3219 (13.3) 1175 (24.7) 10 486 (16.3) 4646 (35.8) 18 347 (14.4) 7945 (30.8) Comorbidity status at index date No. of ADGs 0 33 895 (84.0) 5546 (65.6) 20 903 (86.5) 3371 (71.0) 51 284 (79.5) 8594 (66.2) 104 753 (82.3) 17 434 (67.5) 1 5638 (14.0) 2390 (28.2) 2892 (12.0) 1089 (22.9) 11 140 (17.3) 3577 (27.5) 19 340 (15.2) 6827 (26.4) ≥ 2 831 (2.0) 522 (6.2) 359 (1.5) 288 (6.1) 2086 (3.2) 813 (6.3) 3217 (2.5) 1571 (6.1) Any mood and anxiety disorder 9108 (22.6) 2669 (31.6) 6119 (25.3) 1985 (41.8) 17 008 (26.4) 4490 (34.6) 31 739 (24.9) 8960 (34.7) Depression 7992 (19.8) 2343 (27.7) 5410 (22.4) 1742 (36.7) 14 548 (22.6) 3808 (29.3) 27 517 (21.6) 7723 (29.9) Anxiety disorder 11 444 (28.4) 2980 (35.2) 7543 (31.2) 1983 (41.8) 21 332 (33.1) 5063 (39.0) 39 735 (31.2) 9839 (38.1) Bipolar disorder 1326 (3.3) 465 (5.5) 968 (4.0) 301 (6.3) 2347 (3.6) 575 (4.4) 4559 (3.6) 1312 (5.1) Note: IMID = immune-mediated inflammatory disease (IMID cohort combines patients with inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis).
↵* Except where indicated otherwise.
↵† A small number of individuals met the case definitions for more than 1 of the IMIDs of interest. These were included in the analysis, to ensure generalizability of the findings, but they were counted only once in the combined IMID cohort. In this situation, they were classified on the basis of the IMID with the earliest index date in the coverage period. Some cases did not have 5 matched controls (IMID, n = 90; inflammatory bowel disease, n = 14; multiple sclerosis, n = 36; rheumatoid arthritis, n = 42).
↵‡ Socioeconomic status is reported as the Socioeconomic Factor Index score, incorporating information about average household income, percent of single-parent households, unemployment rate and high school education rate, with missing values imputed at the mean of 0. With this measure, values less than 0 indicate higher socioeconomic status.
↵§ Missing data: for multiple sclerosis, 20; for multiple sclerosis controls, 110; for inflammatory bowel disease, 21; for inflammatory bowel disease controls, 76; for rheumatoid arthritis, 40; for rheumatoid arthritis controls, 160; imputed at population mean = 0.
- Table 2:
Multivariable adjusted risk differences for the association of immune-mediated disease, any mood or anxiety disorder and uptake of influenza vaccination
Variable Cohort; adjusted risk difference,* % (95% CI)† Immune-mediated disease Inflammatory bowel disease Multiple sclerosis Rheumatoid arthritis No. flu shots/PYs at risk 402 542/1 235 712 111 983/401 123.6 72 424/248 553.6 223 725/601 042.5 Controls without a mood/anxiety disorder 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Immune-mediated disease effect without mood/anxiety disorder effect 6.44 (5.79 to 7.10) 7.19 (6.12 to 8.26) 6.70 (5.13 to 8.27) 5.61 (4.64 to 6.59) Mood/anxiety disorder effect without an immune-mediated disease effect 4.54 (4.20 to 4.89) 5.10 (4.52 to 5.68) 5.31 (4.53 to 6.09) 3.74 (3.23 to 4.26) Interaction contrast between case effect and mood/anxiety disorder effect‡ −1.38 (−2.26 to −0.50) −1.43 (−2.90 to 0.05) 0.08 (−1.97 to 2.13) −1.89 (−3.16 to −0.63) Age, yr 18–24 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) 25–44 6.12 (5.59 to 6.64) 5.61 (4.98 to 6.24) 6.94 (5.47 to 8.40) 5.56 (4.41 to 6.71) 45–64 15.10 (14.55 to 15.65) 13.97 (13.28 to 14.67) 15.15 (13.65 to 16.64) 14.96 (13.79 to 16.14) ≥ 65 33.33 (32.73 to 33.94) 33.77 (32.87 to 34.67) 32.61 (30.95 to 34.27) 32.32 (31.11 to 33.53) Sex Male 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Female 4.97 (4.64 to 5.29) 4.92 (4.41 to 5.43) 3.66 (2.90 to 4.42) 4.61 (4.09 to 5.13) Region Rural 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Urban 2.16 (1.83 to 2.49) 1.88 (1.35 to 2.40) 2.28 (1.52 to 3.04) 2.56 (2.06 to 3.06) Socioeconomic status Quintile 1 (lowest) −4.69 (−5.19 to −4.19) −4.66 (−5.48 to −3.84) −3.38 (−4.52 to −2.23) −6.03 (−6.82 to −5.25) Quintile 2 −3.74 (−4.25 to −3.23) −4.00 (−4.79 to −3.22) −3.45 (−4.57 to −2.34) −4.01 (−4.83 to −3.18) Quintile 3 −3.09 (−3.61 to −2.58) −3.40 (−4.18 to −2.61) −2.74 (−3.85 to −1.63) −3.39 (−4.23 to −2.55) Quintile 4 −2.25 (−2.75 to −1.75) −2.16 (−2.93 to −1.39) −2.21 (−3.30 to −1.12) −2.66 (−3.49 to −1.84) Quintile 5 (highest) 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Comorbidity 0 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) 1 4.77 (4.32 to 5.22) 3.43 (2.69 to 4.16) 3.78 (2.68 to 4.87) 5.66 (5.01 to 6.30) ≥ 2 8.67 (7.60 to 9.74) 8.64 (6.61 to 10.7) 8.96 (6.10 to 11.81) 8.34 (6.95 to 9.72) Immune-mediated disease-specific procedure 4.94 (4.21 to 5.67) 6.90 (5.58 to 8.22) – 4.00 (3.12 to 4.88) Immune therapy None 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Anti-inflammatory or immune-modulatory therapy 3.09 (2.73 to 3.46) 2.95 (2.39 to 3.52) 4.43 (2.53 to 6.32) 3.07 (2.58 to 3.56) Any biologic 9.08 (7.92 to 10.23) 9.11 (7.09 to 11.13) 5.60 (2.17 to 9.03) 9.45 (7.93 to 10.97) Note: CI = confidence interval, PY = person-year, Ref. = reference category.
↵* Adjusted for all other variables included in table.
↵† Except where indicated otherwise.
↵‡ A negative interaction contrast with a 95% CI that does not encompass 0 indicates a subadditive effect; that is, the joint effect of immune-mediated disease and a mood or anxiety disorder is less than the sum of their individual effects. A positive interaction with a 95% CI that does not encompass 0 indicates a superadditive effective that is greater than the sum of the individual immune-mediated disease and mood or anxiety disorder effects.
- Table 3:
Multivariable adjusted risk differences for the association of immune-mediated inflammatory disease, depressive disorder and uptake of influenza vaccination
Variable Cohort; adjusted risk difference,* % (95% CI)† Immune-mediated disease Inflammatory bowel disease Multiple sclerosis Rheumatoid arthritis No. flu shots/PYs at risk 402 542/1 235 712 111 983/401 123.6 72 424/248 553.6 223 725/601 042.5 Controls without depression 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Immune-mediated disease effect without depression effect 6.08 (5.49 to 6.66) 6.81 (5.82 to 7.80) 5.81 (4.45 to 7.18) 5.52 (4.65 to 6.38) Depression effect without immune-mediated disease effect 4.15 (3.75 to 4.56) 5.11 (4.40 to 5.82) 4.28 (3.39 to 5.17) 3.41 (2.82 to 4.00) Interaction contrast between case effect and depressive disorder effect‡ −0.98 (−1.93 to −0.04) −1.03 (−2.70 to 0.64) 2.43 (0.36 to 4.49) −2.53 (−3.88 to −1.18) Age, yr 18–24 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) 25–44 6.36 (5.83 to 6.89) 5.87 (5.24 to 6.51) 7.33 (5.90 to 8.77) 5.74 (4.58 to 6.90) 45–64 15.45 (14.90 to 16.00) 14.36 (13.66 to 15.05) 15.65 (14.19 to 17.11) 15.22 (14.04 to 16.40) ≥ 65 33.75 (33.14 to 34.35) 34.26 (33.36 to 35.15) 33.22 (31.59 to 34.86) 32.60 (31.39 to 33.82) Sex Male 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Female 5.19 (4.87 to 5.52) 5.12 (4.62 to 5.63) 3.96 (3.21 to 4.72) 4.80 (4.28 to 5.32) Region Rural 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Urban 2.28 (1.95 to 2.61) 1.99 (1.47 to 2.52) 2.47 (1.71 to 3.23) 2.67 (2.17 to 3.16) Socioeconomic status Quintile 1 (lowest) −4.71 (−5.21 to −4.20) −4.69 (−5.51 to −3.87) −3.41 (−4.56 to −2.27) −6.03 (−6.82 to −5.25) Quintile 2 −3.81 (−4.32 to −3.29) −4.15 (−4.94 to −3.36) −3.57 (−4.58 to −2.45) −4.02 (−4.85 to −3.19) Quintile 3 −3.14 (−3.65 to −2.62) −3.47 (−4.26 to −2.68) −2.83 (−3.94 to −1.72) −3.40 (−4.24 to −2.56) Quintile 4 −2.27 (−2.77 to −1.77) −2.19 (−2.97 to −0.64) −2.29 (−3.38 to −1.19) −2.66 (−3.48 to −1.84) Quintile 5 (highest) 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Comorbidity 0 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) 1 4.86 (4.41 to 5.31) 3.53 (2.80 to 4.27) 3.89 (2.79 to 4.98) 5.73 (5.09 to 6.37) ≥ 2 8.73 (7.65 to 9.80) 8.65 (6.62 to 10.68) 9.04 (6.18 to 11.90) 8.41 (7.02 to 9.79) Immune-mediated disease-specific procedure 4.96 (4.23 to 5.69) 6.95 (5.63 to 8.27) – 4.01 (3.13 to 4.89) Immune therapy None 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Anti-inflammatory or immune-modulatory therapy 3.10 (2.74 to 3.47) 2.97 (2.40 to 3.54) 4.40 (2.51 to 6.29) 3.06 (2.57 to 3.55) Any biologic 9.08 (7.92 to 10.23) 9.08 (7.06 to 11.10) 5.54 (2.11 to 8.96) 9.46 (7.94 to 10.98) Note: CI = confidence interval, PY = person-year, Ref. = reference category.
↵* Adjusted for all other variables included in table.
↵† Except where indicated otherwise.
↵‡ A negative interaction contrast with a 95% CI that does not encompass 0 indicates a subadditive effect; that is, the joint effect of immune-mediated disease and depressive disorder is less than the sum of their individual effects. A positive interaction with a 95% CI that does not encompass 0 indicates a superadditive effective that is greater than the sum of the individual immune-mediated disease and depressive disorder effects.
- Table 4:
Multivariable adjusted risk differences for the association of immune-mediated inflammatory disease, anxiety disorder and uptake of influenza vaccination
Variable Cohort; adjusted risk difference,* % (95% CI)† Immune-mediated disease Inflammatory bowel disease Multiple sclerosis Rheumatoid arthritis No. flu shots/PYs at risk 402 542/1 235 712 111 983/401 123.6 72 424/248 553.6 223 725/601 042.5 Controls without anxiety disorder 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Immune-mediated disease effect without anxiety disorder effect 6.58 (5.96 to 7.19) 6.89 (5.86 to 7.91) 7.78 (6.35 to 9.21) 5.72 (4.80 to 6.64) Anxiety effect without immune-mediated disease effect 4.41 (4.05 to 4.77) 4.93 (4.32 to 5.53) 4.95 (4.65 to 5.75) 3.75 (3.22 to 4.27) Interaction contrast between case effect and anxiety disorder effect‡ −1.74 (−2.62 to −0.86) −0.78 (−2.27 to 0.71) 2.43 (0.36 to 4.49) −2.35 (−3.62 to −1.07) Age, yr 18–24 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) 25–44 6.22 (5.70 to 6.74) 5.72 (5.09 to 6.35) 7.12 (5.67 to 8.58) 5.62 (4.47 to 6.77) 45–64 15.21 (14.67 to 15.76) 14.08 (13.39 to 14.78) 15.36 (13.88 to 16.85) 15.03 (13.86 to 16.20) ≥ 65 33.44 (32.83 to 34.04) 33.88 (32.98 to 34.77) 32.83 (31.17 to 34.48) 32.38 (31.18 to 33.59) Sex Male 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Female 5.10 (4.78 to 5.42) 5.06 (4.55 to 5.57) 3.86 (3.10 to 4.62) 4.69 (4.17 to 5.21) Region Rural 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Urban 2.20 (1.87 to 2.53) 1.91 (1.38 to 2.43) 2.32 (1.56 to 3.09) 2.59 (2.09 to 3.09) Socioeconomic status Quintile 1 (lowest) −4.70 (−5.21 to −4.20) −4.69 (−5.51 to −3.87) −3.30 (−4.44 to −2.15) −6.05 (−6.84 to −5.27) Quintile 2 −3.73 (−4.24 to −3.22) −4.04 (−4.82 to −3.25) −3.40 (−4.52 to −2.29) −4.00 (−4.82 to −3.17) Quintile 3 −3.06 (−3.57 to −2.54) −3.35 (−4.14 to −2.57) −2.70 (−3.81 to −1.58) −3.37 (−4.20 to −2.53) Quintile 4 −2.24 (−2.75 to −1.74) −2.15 (−2.92 to −1.38) −2.16 (−3.52 to −1.06) −2.67 (−3.49 to −1.84) Quintile 5 (highest) 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Comorbidity 0 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) 1 4.81 (4.36 to 5.26) 3.46 (2.72 to 4.20) 3.86 (2.76 to 4.96) 5.68 (5.04 to 6.33) ≥ 2 8.75 (7.68 to 9.83) 8.68 (6.65 to 10.71) 9.17 (6.31 to 12.04) 8.40 (7.02 to 9.79) Immune-mediated disease-specific procedure 4.98 (4.26 to 5.71) 6.91 (5.59 to 8.23) – 4.04 (3.17 to 4.92) Immune therapy None 0 (Ref.) 0 (Ref.) 0 (Ref.) 0 (Ref.) Anti-inflammatory/immune-modulatory therapy 3.09 (2.72 to 3.45) 2.97 (2.40 to 3.53) 4.48 (2.58 to 6.37) 3.06 (2.57 to 3.55) Any biologic 9.10 (7.95 to 10.30) 9.17 (7.15 to 11.20) 5.77 (2.31 to 9.24) 9.46 (7.93 to 10.98) Note: CI = confidence interval, PY = person-years, Ref. = reference category.
↵* Adjusted for all other variables included in table.
↵† Except where indicated otherwise.
↵‡ A negative interaction contrast with a 95% CI that does not encompass 0 indicates a subadditive effect; that is, the joint effect of immune-mediated disease and anxiety disorder is less than the sum of their individual effects. A positive interaction with a 95% CI that does not encompass 0 indicates a superadditive effective that is greater than the sum of the individual immune-mediated disease and anxiety disorder effects.
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