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3.42101 Tw 53.43 714 Td
(immune-suppressive medication, and when uncontrolled)Tj
0.25 Tw 0.017 -12 Td
(inflammation is debilitating the patient with RA.)Tj
/TT1 10 Tf
0 Tw -0.058 -24 Td
(REFERENCES)Tj
/TT0 8 Tf
6.986 -10 Td
[(1.)-875 (W)62.625 (orld Health Organization. Global tuberculosis control. WHO)]TJ
13.423 -10 Td
(report: Communicable diseases. Geneva: WHO; 2000.)Tj
-13.352 -10 Td
[(2.)-875 (Rajagopalan S. )-18 (T)]TJ
0.2 Tw 68.221 0 Td
(uberculosis and aging: a global health problem.)Tj
0 Tw -54.812 -10 Td
(Clin Infect Dis 2001;33:1034-9.)Tj
-13.494 -10 Td
[(3.)-875 (Johnson JL, Ellner JJ. Adult tuberculosis overview: African versus)]TJ
13.592 -10 Td
(W)Tj
0.2 Tw 6.551 0 Td
(estern perspectives. Curr Opin Pulm Med 2000;6:180-6.)Tj
0 Tw -20.077 -10 Td
(4.)Tj
0.10001 Tw 13 0 Td
(Bouza E, Moya JG, Mu\226oz P. Infections in systemic lupus )Tj
0 Tw 0.535 -10 Td
(erythematosus and rheumatoid arthritis. Infect Dis Clin North Am)Tj
-0.111 -10 Td
(2001;15:335-61.)Tj
-13.391 -10 Td
[(5.)-875 (Hernandez-Cruz B, Cardiel MH, )-67.875 (V)]TJ
-0.383 Tw 125.46 0 Td
(illa AR, Alcocer-Varela J.)Tj
0.2 Tw -112.158 -10 Td
(Development, recurrence, and severity of infections in Mexican)Tj
0 Tw 0.041 -10 Td
[(patients with rheumatoid arthritis. )-35.25 (A)-218.875 (nested case-control study)13.625 (.)]TJ
0.012 -10 Td
(J Rheumatol 1998;25:1900-7.)Tj
-13.522 -10 Td
[(6.)-875 (Bradley JD, Brandt KD, Katz BP. Infectious complications of)]TJ
13.561 -10 Td
(cyclophosphamide treatment for vasculitis. Arthritis Rheum)Tj
-0.043 -10 Td
(1989;32:45-53.)Tj
-13.391 -10 Td
(7.)Tj
0.14999 Tw 13 0 Td
(Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in)Tj
0.2 Tw 0.371 -10 Td
(patients taking glucocorticosteroids. Rev Infect Dis 1989;)Tj
0.075 -10 Td
(1)Tj
0 Tw 3.5 0 Td
(1:954-63.)Tj
-17.113 -10 Td
(8.)Tj
0.10001 Tw 13 0 Td
(Boerbooms AM, Kerstens PJ, van Loenhout JW, Mulder J, van de)Tj
0.2 Tw 0.723 -10 Td
(Putte LB. Infections during low-dose methotrexate treatment in)Tj
0 Tw -0.041 -10 Td
(rheumatoid arthritis. Semin Arthritis Rheum 1995;24:411-21.)Tj
-13.66 -10 Td
(9.)Tj
0.144 Tw 13 0 Td
[(Kurki PT. Safety aspects of the long term cyclosporin )64 (A)]TJ
0 Tw 182.511 0 Td
[(therapy)63 (.)]TJ
-182.012 -10 Td
(Scand J Rheumatol 1992;95 Suppl:35-8.)Tj
-17.399 -10 Td
[(10.)-875 (Cantwell MF, Snider DE Jr, Cauthen GM, Onorato IM.)]TJ
0.2 Tw 17.417 -10 Td
(Epidemiology of tuberculosis in the United States, 1985 through)Tj
1.95 Tw 0.018 -10 Td
(1992. JAMA1994;272:535-9.)Tj
-17.159 -10 Td
(1)Tj
0 Tw 3.75 0 Td
[(1.)-875 (Keane J, Gershon S, )-69 (W)31.375 (ise RP, et al. )25.625 (T)62.625 (uberculosis associated with)]TJ
0.2 Tw 13.54 -10 Td
(infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl)Tj
0 Tw -0.138 -10 Td
(J Med 2001;345:1098-104.)Tj
-17.463 -10 Td
(12.)Tj
0.2 Tw 17 0 Td
(Regidor E, Gutierrez-Fisac JL. Health indicators. Fourth Evaluation)Tj
0.172 Tw 0.427 -10 Td
(in Spain of the European Regional Program \322Health for All.\323)Tj
0.2 Tw -0.005 -10 Td
(Madrid: Ministerio de Sanidad y Consumo; 1999.)Tj
0 Tw -17.476 -10 Td
[(13.)-875 (Cabases JM, )-50.125 (V)62.375 (illalbi JR, Aibar C, editors. Sociedad Espa\226ola de)]TJ
17.655 -10 Td
(Salud P\234blica y Administraci\227n Sanitaria. 2002 SESPAS Report:)Tj
0.2 Tw 0.029 -10 Td
(Investing in health. Priorities for public health in Spain. Granada:)Tj
0 Tw -0.192 -10 Td
(Escuela Andaluza de Salud P\234blica; 2002.)Tj
-17.48 -10 Td
(14.)Tj
0.172 Tw 17 0 Td
(Arnett FC, Edworthy SM, Bloch DA, et al. American Rheumatism)Tj
0.2 Tw 0.577 -10 Td
(Association 1987 revised criteria for the classification of )Tj
0 Tw 0.096 -10 Td
(rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.)Tj
-17.555 -10 Td
[(15.)-875 (W)62.625 (olfe F, Flowers N, Anderson J, Urbansky K. )-13.375 (T)0.125 (uberculosis rates)]TJ
17.57 -10 Td
(are not increased in rheumatoid arthritis [abstract]. Arthritis Rheum)Tj
0.002 -10 Td
(2001; 44 Suppl:S105.)Tj
-17.534 -10 Td
(16.)Tj
0.2 Tw 17 0 Td
(Calpe J, Chiner E, Marin J, Martinez C, Lopez M, Sanchez E.)Tj
0.399 -10 Td
[(T)31.375 (uberculosis notification from 1987 to 1999 for the public health)]TJ
-0.079 -10 Td
[(area of the community of )32.875 (V)]TJ
0 Tw 88.636 0 Td
(alencia \(Spain\). Arch Bronconeumol)Tj
-88.662 -10 Td
(2001;37:417-23.)Tj
-17.391 -10 Td
[(17.)-875 (Cremades Romero MJ, Menendez )-99.125 (V)62.375 (illanueva R, Santos Durantez)]TJ
0.2 Tw 17.541 -10 Td
[(M, Martinez Garcia MA, Ferrando Garcia D, Perpina )32.5 (T)]TJ
0 Tw 178.343 0 Td
(ordera M.)Tj
0.2 Tw -178.257 -10 Td
(Characteristics of tuberculosis in a tertiary hospital during the years)Tj
-0.098 -10 Td
[(1993-1996. Influence of the coinfection with HIV)157.875 (.)]TJ
0 Tw 163.431 0 Td
(Arch)Tj
-163.508 -10 Td
(Bronconeumol 1998;34:333-8.)Tj
-17.394 -10 Td
[(18.)-875 (Labarga Echeverria P, Perucha Gonzalez M, Jimenez Gomez E, et)]TJ
17.398 -10 Td
[(al. )6.625 (T)]TJ
0.2 Tw 14.36 0 Td
(uberculosis in La Rioja from 1988 to 1993. Clinical course,)Tj
249.71 577.25 Td
(localization, influence of human immunodeficiency virus infection,)Tj
-0.12 -10 Td
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0 Tw 0.006 -10 Td
(104:81-4.)Tj
-17.363 -10 Td
[(19.)-875 (National Centre of Epidemiology. Diagnosis and treatment of)]TJ
0.2 Tw 17.435 -10 Td
(tuberculosis in Spain: results of the Multicenter Project for)Tj
0.061 -10 Td
(T)Tj
0 Tw 4.387 0 Td
(uberculosis Research. Med Clin \(Barc\) 2001;116:167-73.)Tj
-22.012 -10 Td
(20.)Tj
0.2 Tw 17 0 Td
[(Jalal H, Millar M, Linton C, Dieppe P)95 (.)]TJ
0 Tw 126.166 0 Td
(Absence of Mycobacterium)Tj
0.414 Tw -125.495 -10 Td
(tuberculosis DNAin synovial fluid from patients with rheumatoid)Tj
0 Tw -0.076 -10 Td
(arthritis. Ann Rheum Dis 1994;53:695-8.)Tj
-17.458 -9.75 Td
[(21.)-875 (Lai NS, Lan JL, )-37 (Y)93.625 (u CL, Lin RH. Antibody to Mycobacterium)]TJ
0.2 Tw 17.39 -9.75 Td
(tuberculosis 65 kDa heat shock protein in patients with rheumatoid)Tj
-0.051 -9.75 Td
(arthritis \321 a survey of antigen-specific antibody isotypes and)Tj
0.131 -10 Td
(subclasses in an endemic area of previous tuberculosis infection.)Tj
0 Tw -0.076 -9.75 Td
(Ann Rheum Dis 1995;54:225-8.)Tj
-17.541 -9.75 Td
(22.)Tj
0.164 Tw 17 0 Td
[(Pras E, Schumacher HR Jr, Kastner DL, )31.375 (W)]TJ
0 Tw 138.838 0 Td
(ilder RL. Lack of)Tj
0.2 Tw -138.115 -9.75 Td
(evidence of mycobacteria in synovial tissue from patients with)Tj
0 Tw -0.013 -9.75 Td
(rheumatoid arthritis. Arthritis Rheum 1996;39:2080-1.)Tj
-17.555 -10 Td
[(23.)-875 (van der Heijden IM, )-68.125 (W)]TJ
0.2 Tw 91.718 0 Td
(ilbrink B, Schouls LM, van Embden JD,)Tj
0 Tw -74.194 -9.75 Td
[(Breedveld FC, )13 (T)31.375 (ak PP. Detection of mycobacteria in joint samples)]TJ
0.2 Tw -0.192 -9.75 Td
(from patients with arthritis using a genus-specific polymerase chain)Tj
0.178 -9.75 Td
(reaction and sequence analysis. Rheumatology 1999;38:547-53.)Tj
0 Tw -17.633 -9.75 Td
(24.)Tj
0.144 Tw 17 0 Td
(Kempsell KE, Cox CJ, McColm AA, et al. Detection of)Tj
0.164 Tw 0.468 -10 Td
(Mycobacterium tuberculosis group organisms in human and mouse)Tj
0.2 Tw 0.193 -9.75 Td
(joint tissue by reverse transcriptase PCR: prevalence in diseased)Tj
-0.181 -9.75 Td
(synovial tissue suggests lack of specific association with )Tj
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-17.512 -10 Td
(25.)Tj
0.144 Tw 17 0 Td
(Martos A, Podzamczer D, Martinez-Lacasa J, Rufi G, Santin M,)Tj
0.125 Tw 0.523 -10 Td
(Gudiol F. Steroids do not enhance the risk of developing )Tj
0 Tw -0.195 -10 Td
(tuberculosis or other AIDS-related diseases in HIV-infected patients)Tj
0.22 -10 Td
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-17.507 -10 Td
[(26.)-875 (Andonopoulos AP, Safridi C, Karokis D, Bounas A. Is a purified)]TJ
0.2 Tw 17.485 -10 Td
(protein derivative skin test and subsequent antituberculous )Tj
-0.088 -10 Td
(chemoprophylaxis really necessary in systemic rheumatic disease)Tj
-0.093 -10 Td
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0 Tw -17.461 -10 Td
[(27.)-875 (Anon. )6.125 (T)]TJ
0.164 Tw 43.364 0 Td
(argeted tuberculin testing and treatment of latent )Tj
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(161:S221-47.)Tj
/TT1 10 Tf
-20.664 -24 Td
(APPENDIX)Tj
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0.858 Tw 0.165 -10 Td
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2.58501 Tw -109.835 -10 Td
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J.)Tj
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1.31599 Tw -0.043 -10 Td
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)Tj
0.71899 Tw 0.022 -10 Td
(Garc\222a-Meijide, Santiago de Compostela; H. G\227mez-Centeno, Barcelon\
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-0.36501 Tw 0.019 -10 Td
(C. G\227mez-Vaquero, Barcelona; M.J. Gonz\207lez-Fern\207ndez, Barcelona\
; M.L.)Tj
0.886 Tw 0.162 -10 Td
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0.778 Tw 0.012 -10 Td
[(\347lvaro, Madrid; )63 (Y)]TJ
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(. Grandal, Jerez; J. Gratacos, Barcelona; A. Hern\207ndez)Tj
0.91701 Tw -60.023 -10 Td
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-0.215 Tw -0.01 -10 Td
(Gim\216nez, Zaragoza; M. Jim\216nez-Palop, \347vila; A. Juan, Palma de M\
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2.394 Tw 0.213 -10 Td
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0.72501 Tw -0.084 -10 Td
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0.114 Tw -0.039 -10 Td
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0.483 Tw -0.033 -10 Td
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1.862 Tw 0.031 -10 Td
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/TT0 10 Tf
0.40199 Tw 53.304 328 Td
[(risk of TB in RA)-225 (by increasing the incidence in the general)]TJ
0 Tw 0.092 -12 Td
(population to 29 cases per 100,000, and the risk ratio would)Tj
2.091 Tw 0.017 -12 Td
(still be greater than 4-fold. It is also possible that some)Tj
1.77901 Tw 0.027 -12 Td
(patients in our cohort had undiagnosed TB disease or, if)Tj
0 Tw -0.154 -12 Td
[(diagnosed )-424.7 (and )-399.8 (treated )-424.2 (elsewhere, )-449.6 (that )-399.5 (the )-374.7 (patient )-424.2 (had)]TJ
1.94299 Tw 0.025 -12 Td
[(forgotten the episode when asked about infections, espe)2.09 (-)]TJ
0 Tw -0.05 -12 Td
(cially if mild. This means that errors may occur in both data)Tj
-0.3 Tw 0.198 -12 Td
(sources, and likely in the same direction; therefore obtaining)Tj
0 Tw 0.02 -12 Td
(a risk ratio is the optimal measure of the likelihood of TB in)Tj
-0.052 -12 Td
(patients with RA.)Tj
0.80299 Tw 12.023 -12 Td
(The number of TB cases in the cohort was too small to)Tj
3.34399 Tw -12.052 -12 Td
(draw any conclusion on the underlying reason for the)Tj
1.366 Tw 0.02 -12 Td
(increased risk, and no further analysis to test associations)Tj
3.16 Tw 0.032 -12 Td
(with any variable was attempted. This would be more)Tj
2.16 Tw -0.055 -12 Td
[(adequately addressed by a case-control study)77.2 (.)-450 (There are,)]TJ
1.216 Tw -0.06 -12 Td
(however, 2 possible explanations for the increased rate of)Tj
0.705 Tw -0.075 -12 Td
[(TB in RA. First, a causal relationship between mycobacte)-22.2 (-)]TJ
0.978 Tw 0.022 -12 Td
[(rial infection and RA)-298.8 (remains to be elucidated)]TJ
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 244.309 127.25 Tm
(20-24)Tj
/TT0 10 Tf
0.978 Tw 1 0 0 1 259.39 124 Tm
(. On the)Tj
1.213 Tw -206.105 -12 Td
(other hand, the debilitating and chronic nature of RA, the)Tj
0 Tw 0.012 -12 Td
(presence of comorbidity, the treatments used, or most likely)Tj
1.026 Tw 0.171 -12 Td
(a combined effect of all these factors, could predispose to)Tj
0.75999 Tw -0.047 -12 Td
(TB infection. All but 2 patients with TB in our cohort had)Tj
-0.13901 Tw 263.992 252 Td
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0 Tw -0.057 -12 Td
(one had diabetes and chronic obstructive pulmonary disease)Tj
0.442 Tw 0.017 -12 Td
(\(Table 2\). One patient developed a malignancy, but several)Tj
0 Tw 0.11 -12 Td
(years after the diagnosis of TB. No other known risk factors)Tj
0.85001 Tw -0.035 -12 Td
(such as recent infection, chronic renal disease, or acquired)Tj
0 Tw 0.024 -12 Td
[(immune )-399.3 (deficiency )-424.1 (syndrome )-424.8 (were )-374.9 (present. )-449.7 (Regarding)]TJ
1.205 Tw -0.187 -12 Td
(treatment, all TB cases in the cohort had received disease)Tj
1.91 Tw 0.195 -12 Td
(modifying antirheumatic drugs, although it is remarkable)Tj
2.16299 Tw 0.017 -12 Td
(that one patient had received only chloroquine as single)Tj
0.709 Tw -0.24 -12 Td
(treatment when TB was diagnosed, and 2 had not received)Tj
0.795 Tw 0.193 -12 Td
(prolonged or high doses of corticosteroids. The risk of TB)Tj
1.561 Tw -0.114 -12 Td
(attributable to corticosteroid use has not been determined)Tj
3.739 Tw 0.017 -12 Td
(and remains controversial)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 428.127 187.25 Tm
(7,25)Tj
/TT0 10 Tf
3.739 Tw 1 0 0 1 439.565 184 Tm
(, although most authorities)Tj
2.02299 Tw -122.129 -12 Td
[(consider that patients taking more than 15 mg/day pred)2.9 (-)]TJ
0 Tw 0.015 -12 Td
[(nisone )-399.8 (for )-425 (2\3204 )-400 (weeks )-400 (are )-399.7 (at )-374.7 (risk )-400 (for )-400 (developing )]TJ
-2.42799 Tw 227.276 0 Td
(T B)Tj
0 Tw -227.399 -12 Td
(disease)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 346.205 151.25 Tm
(26,27)Tj
/TT0 10 Tf
1 0 0 1 360.767 148 Tm
(.)Tj
0.149 Tw -31.5 -12 Td
(Patients with RAare at increased risk for developing TB.)Tj
2.326 Tw -11.926 -12 Td
(The potential reasons must be analyzed with a different)Tj
0.95599 Tw -0.052 -12 Td
(study design, although it is likely that immunosuppression)Tj
1.39999 Tw 0.017 -12 Td
(from medication and from debilitation secondary to long-)Tj
0 Tw 0.017 -12 Td
(standing RA)Tj
0.44099 Tw 53.261 0 Td
(are important risk factors. The implications of)Tj
0 Tw -53.24 -12 Td
[(this )-424.8 (risk )]TJ
0.15601 Tc 43.198 0 Td
(require )Tj
0.175 Tc 35.815 0 Td
(awareness )Tj
0 Tc 49.089 0 Td
[(both )-424.8 (when )]TJ
0.159 Tc 53.188 0 Td
(initiating )Tj
0 Tc 44.108 0 Td
(any)Tj
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0 Tw -370.352 -0.25 Td
(1438)Tj
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/TT1 8 Tf
125.318 714.75 Td
[(T)93.625 (able 1. )]TJ
/TT0 8 Tf
0.2 Tw 30.122 0 Td
(Sociodemographic and clinical characteristics of patients included in th\
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-30.058 -20 Td
(V)Tj
0 Tw 5.027 0 Td
(ariable)Tj
133.012 0 Td
[(Frequency, %)-3649.75 (Mean \261 SD)]TJ
150.612 0 Td
(Median*)Tj
-288.563 -20 Td
[(W)93.875 (omen)]TJ
152.824 0 Td
(72.1)Tj
-153 -10 Td
(Positive rheumatoid factor)Tj
153.017 0 Td
(73.7)Tj
-153 -10 Td
(Age at baseline visit, yrs)Tj
218.171 0 Td
(61 \261 13)Tj
67.041 0 Td
(64 \(54\32071\))Tj
0.783 Tw -285.222 -10 Td
(Age at RAonset, yrs)Tj
0 Tw 217.979 0 Td
(48 \261 15)Tj
67.291 0 Td
(49 \(37\32059\))Tj
-285.222 -10 Td
(Disease duration, yrs)Tj
213.966 0 Td
(10.1 \261 7.9)Tj
75.291 0 Td
(9 \(4\32013\))Tj
-289.222 -10 Td
(Early arthritis, < 2 yrs)Tj
153.046 0 Td
(14.4)Tj
-153 -10 Td
(Disease activity, DAS28 3)Tj
211.975 0 Td
[(4.09 \261 1.39)-3503.625 (4.06 \(3.12\3205.11\))]TJ
-211.931 -10 Td
(Functional status, HAQ)Tj
215.923 0 Td
[(1.6 \261 0.4)-4722.375 (1.6 \(1.2\3201.9\))]TJ
-215.931 -10 Td
(DMARD treatment)Tj
155.938 0 Td
(72)Tj
-0.35201 Tw -156 -20 Td
(* 25th\32075th percentile. DAS: Disease Activity Score. HAQ: Health Asse\
ssment Questionnaire. DMARD: disease)Tj
0 Tw -0.066 -10 Td
(modifying antirheumatic drug.)Tj
ET
125.25 708 360 0.5 re
f
126.25 689 358 0.5 re
f
125.25 588 362 0.5 re
f
BT
/TT1 8 Tf
54.466 540.25 Td
[(T)93.625 (able 2. )]TJ
/TT0 8 Tf
0.394 Tw 29.872 0 Td
(Characteristics of the 7 TB cases found in the RAcohort.)Tj
0 Tw -29.915 -20 Td
[(Sex)-1656.25 (Age at RA)-2299.875 (Age at TB)-1924.5 (Location )-1118 (RF)-1093.875 (Rheumatoid)-1155.375 (Extraarticular )-461.125 (Smoker )-1368.625 (T)0.125 (ime )6.75 (T)93.875 (aking )-3993.375 (DMARD)-3656.875 (Concomitant)]TJ
19.675 -10 Td
[(Diagnosis, yrs)-775.125 (Diagnosis, yrs)-1743.875 (of TB)]TJ
171.041 0 Td
[(Nodules)-4000 (RA)-3375.125 (\(yrs\))-2156.375 (CS if > 3 mo)]TJ
271.838 0 Td
(Disease)Tj
-462.621 -20 Td
[(F)-4281.375 (71)]TJ
90.699 0 Td
[(75)-4218.75 (Lung)-2437.375 (+)-3218.75 (No)]TJ
158.676 0 Td
[(Y)124.875 (es)-3656.25 (No)-3531.375 (5\32010yrs)-4468.875 (GSim, CLQ, )-3268.75 (Cytopenia)]TJ
134.95 -10 Td
(MTX, CF, CLO)Tj
-384.287 -10 Td
[(F)-4281.375 (67)]TJ
90.699 0 Td
[(74)-4218.75 (Lung)-2468.625 (\320)-3250 (No)]TJ
159.164 0 Td
[(No)-3781.375 (No)-3531.375 (5\32010yrs)-4468.875 (GSim, CLQ, )-2987.5 (Leukopenia)]TJ
120.665 -10 Td
(D-PEN, MTX, CF, CLO)Tj
-370.533 -10 Td
[(F)-4281.375 (55)]TJ
90.699 0 Td
[(75)-4218.75 (Lung)-2437.375 (+)-3218.75 (No)]TJ
158.426 0 Td
[(Y)93.625 (es)-3656.25 (No)-3531.375 (5\32010yrs)-4437.625 (GSim, CLQ,)-4025 (Anemia)]TJ
127.191 -10 Td
(MTX oral GS, GSim)Tj
-376.287 -10 Td
[(F)-4281.375 (51)]TJ
90.699 0 Td
[(65)-4562.5 (GD)-2781.625 (\320)-3250 (No)]TJ
158.582 0 Td
[(Y)93.625 (es)-3625 (No)-3625.125 (> 10yrs)-4681.375 (HCQ, MTX)-4619.25 (None)]TJ
-249.347 -10 Td
[(M)-3968.875 (33)]TJ
90.863 0 Td
[(63)-3875 (Pleural)-2030.75 (+)-3125 (Y)93.625 (es)-4906.25 (Y)93.625 (es)-2562.5 (Y)93.625 (es \(30\))-3837.5 (0)]TJ
311.273 0 Td
[(CLQ)-4718.75 (DM, COPD)]TJ
-402.07 -10 Td
[(M)-3937.625 (29)]TJ
90.613 0 Td
[(76)-4218.75 (Lung)-2437.375 (+)-3125 (Y)93.625 (es)-4906.25 (Y)93.625 (es)-2562.5 (Y)93.625 (es \(50\))-3806.25 (0)]TJ
310.25 0 Td
[(MTX)-3875.125 (Anemia, cancer)]TJ
-400.832 -10 Td
[(F)-4281.375 (42)]TJ
90.699 0 Td
[(45)-4218.75 (Lung)-2406.125 (+)-3125 (Y)93.625 (es)-4937.5 (Y)124.875 (es)-3656.25 (No)-3625.125 (> 10yrs)-4868.875 (SSZ, MTX)-4337.875 (Anemia)]TJ
0.138 Tw -90.866 -20 Td
(TB: tuberculosis; RF: rheumatoid factor, CS: corticosteroids, DMARD: dis\
ease modifying antirheumatic drugs, GS: gold salts \(oral or intramuscul\
ar\), CLQ:)Tj
0.899 Tw -0.015 -10 Td
(chloroquine, HCQ: hydroxychloroquine, MTX: methotrexate, CYC: cyclospori\
ne, CLO: chlorambucil, D-PEN: D-penicillamine, AZA: azathioprine, CF:)Tj
0.2 Tw 0.084 -10 Td
(cyclophosphamide, SSZ: sulfasalazine, GD: gastroduodenal, DM: diabetes m\
ellitus, COPD: chronic obstructive pulmonary disease.)Tj
ET
55.25 533.5 503 0.5 re
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53.25 503.5 506 0.5 re
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0 0 0 rg
/T1_0 8 Tf
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(Personal, non-commercial use only. The Journal of Rheumatology Copyrig\
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BT
/TT0 8 Tf
-0.24899 Tw 53.31 516.25 Td
(supported by the Spanish Society of Rheumatology. EMECAR\325s objectives\
)Tj
2.01401 Tw -0.02 -10 Td
(are to provide references of average measures of disease activity and)Tj
2.519 Tw 0.027 -10 Td
(progression of RA)Tj
2.425 Tw 68.394 0 Td
(in our country, and to describe the frequency of)Tj
0 Tw -68.429 -10 Td
[(comorbid diseases in rheumatoid patients, for comparison with other popu\
)48.875 (-)]TJ
0.481 Tw 0.025 -10 Td
(lations and to quantify the risk of specific comorbidity in RA. The coho\
rt)Tj
0.79201 Tw 0.162 -10 Td
(was assembled in 1998-99 by random selection of patients with RAfrom)Tj
-0.14999 Tw -0.127 -10 Td
[(the clinical registries of 34 centers throughout Spain. RApatients ever \
diag)3.7625 (-)]TJ
1.22099 Tw -0.01 -10 Td
(nosed and registered in the participating clinics were randomly selected\
)Tj
1.604 Tw 0.019 -10 Td
[(\(total eligible population 13,260\). )64.625 (A)-406.375 (minimum sample size of 673 was)]TJ
-0.27 Tw 0.04 -10 Td
(calculated after a pilot study. Clinical records were reviewed to confir\
m RA)Tj
1.25999 Tw 0.045 -10 Td
(classification criteria)Tj
/TT0 5 Tf
0 Tw 1.04 0 0 1.04 121.303 419 Tm
(14)Tj
/TT0 8 Tf
1 0 0 1 126.553 416.25 Tm
[(.)-375 (A)]TJ
1.25999 Tw 13.527 0 Td
(strict contact protocol was followed to ensure)Tj
0.207 Tw -86.705 -10 Td
(participation of eligible patients. Ineligible patients \(135 did not qu\
alify as)Tj
0.386 Tw 0.016 -10 Td
(having RAby the inclusion criteria, 96 had died, and 328 were impossible\
)Tj
0 Tw -0.022 -10 Td
(to locate\) were replaced by the next patients in the random list. Eight\
y-two)Tj
0.55299 Tw 0.018 -10 Td
(successfully contacted patients expressed unwillingness to participate a\
nd)Tj
0.66701 Tw 0.023 -10 Td
(were not replaced \(response rate 90.5%\). The study was approved by the\
)Tj
0.233 Tw -0.08 -10 Td
[(Ethics Committee of Hospital La Princesa, Madrid. Participant rheumatol)4.875 (-)]TJ
0.855 Tw 0.025 -10 Td
[(ogists were instructed in collecting the data and performing all measure\
)4.875 (-)]TJ
0.81599 Tw 0.023 -10 Td
(ments, according to standard definitions and procedures. Patients\325cli\
nical)Tj
0.457 Tw 0.085 -10 Td
(records were reviewed for all past and present relevant diseases includi\
ng)Tj
0 Tw 0.031 -10 Td
(infections \(by site and microorganism\) and date of diagnosis. All data\
were)Tj
0.2 Tw -0.141 -10 Td
(cross-checked with the patients in personal interviews.)Tj
0.73399 Tw 12.036 -10 Td
(The definition of a TB case in both data sources was based either on)Tj
0.41299 Tw -12.088 -10 Td
(documentation of a positive culture for )Tj
/TT1 8 Tf
0 Tw 129.104 0 Td
(Mycobacterium tuberculosis)Tj
/TT0 8 Tf
93.975 0 Td
(or on)Tj
0.16901 Tw -222.923 -10 Td
[(a compatible clinical picture responding solely to TB therapy)98.25 (.)]TJ
/TT1 8 Tf
0 Tw -0.208 -12.25 Td
(Statistical analysis.)Tj
/TT0 8 Tf
64.281 0 Td
(The mean standardized incidence of TB during the last)Tj
0.239 Tw -64.039 -10 Td
[(10 years \(1990 to 2000\) in the EMECAR cohort was calculated. The stan)3.25 (-)]TJ
0.57001 Tw -0.086 -10 Td
[(dardization of each year)-29.375 (\325)62.5 (s incidence by age and sex was performed using)]TJ
0 Tw -0.082 -10 Td
(the Spanish population over age 16 \(as no RApatients were below this ag\
e\))Tj
-0.121 Tw 0.111 -10 Td
(in year 2000 as a reference. This standardization permitted estimation o\
f an)Tj
0 Tw -0.086 -10 Td
(expected TB incidence rate if the patients were the same age and sex as \
the)Tj
-0.092 -10 Td
[(general population. )-40.625 (T)]TJ
0.168 Tw 68.48 0 Td
(o obtain each cohort year estimate, only patients who)Tj
0.81799 Tw -68.267 -10 Td
(had already been diagnosed with RAby that year and had not previously)Tj
0.2 Tw -0.183 -10 Td
(been diagnosed with TB were included in the calculations.)Tj
0 Tw 12.127 -10 Td
[(The relative risk of TB in RAand 95% confidence intervals were calcu)104.75 (-)]TJ
-0.258 Tw -11.98 -10 Td
(lated by dividing the standardized mean incidence of TB in the last 10 y\
ears)Tj
1.41499 Tw -0.096 -10 Td
(in EMECAR \(expected incidence\) by the mean incidence of TB in the)Tj
0.73 Tw 0.152 -10 Td
(general population over age 16 reported in the same period. All analyses\
)Tj
0.125 Tw -0.043 -10 Td
(were performed in Stata, v.7 \(Stata Corp., College Station, TX, USA\).)Tj
/TT2 10 Tf
0 Tw -0.129 -22 Td
(RESULTS)Tj
/TT0 10 Tf
0.076 -12 Td
[(Table )-324.4 (1 )-375 (shows )-400.5 (the )-399.7 (characteristics )-423.8 (of )-375 (the )-399.7 (788 )-375 (patients)]TJ
2.257 Tw 0.075 -12 Td
(included in the EMECAR cohort. Seven TB cases were)Tj
0.73599 Tw -0.052 -12 Td
[(identified after the diagnosis of RA. )26.7 (T)75.19 (able 2 gives data for)]TJ
0.11 Tw 263.9 638 Td
(the incident TB cases, most of whom were women over age)Tj
0.66 Tw -0.05 -12 Td
[(60 with few years of formal education. The mean TB inci)3.2 (-)]TJ
3.133 Tw 0.128 -12 Td
(dence in the EMECAR cohort \(1990-2000\) is 134 per)Tj
0 Tw 0.02 -12 Td
(100,000 patients \(95% CI 50\320218\). After standardization by)Tj
1.565 Tw 0.074 -12 Td
(age and sex, the mean incidence is 95 cases per 100,000)Tj
1.12399 Tw -0.238 -12 Td
[(patients. If only pulmonary cases are considered, the inci)-22.21 (-)]TJ
3.69299 Tw 0.024 -12 Td
(dence is 85 per 100,000. The mean incidence of TB)Tj
0.358 Tw 0.114 -12 Td
(\(pulmonary and meningeal\) in the 1990-2000 decade in the)Tj
-0.103 Tw 0.01 -12 Td
(general population over age 16 is 23 per 100,000 \(Figure 1\),)Tj
0 Tw 0.019 -12 Td
(with 94% corresponding to pulmonary TB. When compared)Tj
-0.126 -12 Td
(to the rate in the general population during the same period,)Tj
0.276 Tw 0.012 -12 Td
(the incidence risk ratio \(IRR\) of TB \(any location\) in RA)Tj
0 Tw 233.283 0 Td
(is)Tj
-233.33 -12 Td
(4.13 \(95% CI 2.59\3206.83\), and for pulmonary TB, the IRR is)Tj
0.2 -12 Td
(3.68 \(95% CI 2.36\3205.92\).)Tj
/TT2 10 Tf
-0.01 -24 Td
(DISCUSSION)Tj
/TT0 10 Tf
2.16701 Tw -0.117 -11.75 Td
(Our results reveal a 4-fold increased risk of tuberculous)Tj
0.409 Tw 0.037 -11.5 Td
[(disease in patients diagnosed with RA)-223.3 (compared to the risk)]TJ
1.80099 Tw -0.087 -11.75 Td
(in the general population of Spain. This quantification is)Tj
0.465 Tw 0.193 -11.5 Td
(particularly useful to estimate the risk of TB attributable to)Tj
0 Tw -0.05 -11.5 Td
(new therapies for RA. If we found that the risk of TB in RA)Tj
-0.27699 Tw -0.037 -11.75 Td
(patients undergoing biological therapies were greater than 4,)Tj
0.429 Tw -0.052 -11.5 Td
(and clearly if greater than 7, when compared to the general)Tj
0 Tw 0.017 -11.75 Td
(population rates, this should be interpreted as attributable to)Tj
0.25 Tw 0.02 -11.5 Td
(the new treatment, and not to RA.)Tj
12.023 -11.5 Td
(A)Tj
0.79601 Tw 9.972 0 Td
(better study design to investigate this question would)Tj
0 Tw -21.949 -11.75 Td
(have been either a prospective or a case-control study, but a)Tj
0.41299 Tw -0.081 -11.5 Td
(quantification of the risk of TB in a baseline RApopulation)Tj
-0.11301 Tw 0.054 -11.75 Td
(was needed urgently, following reports of the number of TB)Tj
0 Tw 0.033 -11.5 Td
[(cases in RA)-288 (patients taking TNF-)]TJ
/TT3 10 Tf
134.352 0 Td
(a)Tj
/TT0 10 Tf
9.059 0 Td
(blockers)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 494.96 374.75 Tm
(12)Tj
/TT0 10 Tf
1 0 0 1 501.46 371.5 Tm
[(.)-225 (Actually, the)]TJ
-0.185 Tw -184.034 -11.5 Td
(EMECAR initiative was undertaken before the marketing of)Tj
0.30901 Tw 0.022 -11.75 Td
(these drugs in Spain, and was designed to assess the risk of)Tj
0.261 Tw 0.034 -11.5 Td
[(TB, among other comorbidities, prospectively)77.8 (.)]TJ
0 Tw 189.446 0 Td
[(All risk esti)-51.6 (-)]TJ
0.286 Tw -189.484 -11.75 Td
(mations will very probably be compromised to some extent)Tj
-0.354 Tw 0.017 -11.5 Td
(in the coming years by the increasing use of TNF-)Tj
/TT3 10 Tf
197.596 0 Td
(a)Tj
/TT0 10 Tf
0 Tw 8.559 0 Td
(blockers)Tj
-206.123 -11.5 Td
(in rheumatoid patients.)Tj
11.924 -12 Td
(The strengths of a study rely on the country where it was)Tj
2.616 Tw -11.973 -12 Td
(carried out. Spain has universal coverage by the public)Tj
1.43401 Tw 0.017 -11.75 Td
(health system, thus any random selection of patients ever)Tj
0.15401 Tw 0.02 -12 Td
(registered at public centers will likely yield a representative)Tj
0.735 Tw -0.228 -11.75 Td
(sample of Spanish patients with RA. Moreover, the rate of)Tj
0.799 Tw 0.177 -12 Td
[(TB in Spain is higher than in other )26.4 (W)75.2 (estern countries, and)]TJ
1.47701 Tw -0.005 -12 Td
[(consequently the exposure of RA)-349.2 (patients to tuberculosus)]TJ
2.222 Tw -0.156 -11.75 Td
(bacilli is high as well, providing a sufficient number of)Tj
1.007 Tw 0.2 -12 Td
(events to allow quantification. This is probably the reason)Tj
0.416 Tw -0.052 -11.75 Td
(why a US study did not find a clear association of TB with)Tj
0 Tw -0.047 -12 Td
(RA)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 331.263 174.25 Tm
(15)Tj
/TT0 10 Tf
0.27 Tw 1 0 0 1 337.763 171 Tm
(, as the rate of TB reported in the US is low compared)Tj
0.25 Tw -20.436 -12 Td
(to the Spanish rate, only 6.8 cases per 100,000.)Tj
0 Tw 12.046 -12 Td
(The real incidence of TB in Spain may be slightly higher)Tj
2.58099 Tw -12.059 -12 Td
(than that reported, due to under-reporting of pulmonary)Tj
3.007 Tw -0.033 -12 Td
(cases and non-obligation to declare extrapulmonary TB)Tj
1.62801 Tw 0.193 -12 Td
(other than meningeal)Tj
/TT0 6.25 Tf
0 Tw 1.04 0 0 1.04 405.143 114.5 Tm
(16)Tj
/TT0 10 Tf
1.62801 Tw 1 0 0 1 411.643 111 Tm
(. In the EMECAR cohort, we take)Tj
0.504 Tw -94.155 -12 Td
(into account all cases of TB, irrespective of the location. If)Tj
1.23399 Tw -0.05 -12 Td
(the percentage of unreported extrapulmonary TB in Spain)Tj
0 Tw -0.055 -12 Td
(were around 20% as described)Tj
/TT0 6.25 Tf
1.04 0 0 1.04 439.954 78.5 Tm
(17-19)Tj
/TT0 10 Tf
1 0 0 1 455.036 75 Tm
(, we could recalculate the)Tj
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419.25 750.75 137 10.25 re
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0 g
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/Im0 Do
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BT
0 g
/TT1 8 Tf
55.324 568.25 Td
(Figure 1.)Tj
/TT0 8 Tf
0.52699 Tw 32.551 0 Td
(Incidence of pulmonary tuberculosis in adults from the general)Tj
0.722 Tw -32.512 -10 Td
(population in Spain over the last decade)Tj
/TT0 5 Tf
0 Tw 1.04 0 0 1.04 187.658 561 Tm
(12,13)Tj
/TT0 8 Tf
0.722 Tw 1 0 0 1 202.158 558.25 Tm
(\(and data from the National)Tj
0 Tw -146.703 -10 Td
(Centre of Epidemiology\).)Tj
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0 g
53.25 54.25 504 1 re
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BT
/TT1 8 Tf
53.835 36.75 Td
(Carmona, et al: Tuberculosis in RA)Tj
487.469 -0.25 Td
(1437)Tj
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(Personal, non-commercial use only. The Journal of Rheumatology Copyrig\
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