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A Nationwide Study of Connective Tissue Disease and Other Rheumatic Conditions Among Danish Women With Long-Term Cosmetic Breast Implantation

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A Nationwide Study of Connective Tissue Disease and Other Rheumatic Conditions Among Danish Women With Long-Term Cosmetic Breast Implantation
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  A Nationwide Study of Connective Tissue Disease and OtherRheumatic Conditions Among Danish Women With Long-TermCosmetic Breast Implantation  JON P. FRYZEK,  P H D , LISBET HOLMICH,  MD , JOSEPH K. MCLAUGHLIN,  P H D ,LOREN LIPWORTH,  S C D , ROBERT E. TARONE,  P H D , TRINE HENRIKSEN,  MD ,KIM KJØLLER,  MD , AND SØREN FRIIS,  MD PURPOSE:  Numerous epidemiologic studies have demonstrated that breast implants are not associatedwithconnectivetissuediseases(CTDs).However,manyCTDsarerare,andcontinuedfollow-upofwomenwith breast implants is warranted. METHODS:  Weextended by5 yearsthefollow-upofourearlier population-basedcohortstudy ofDanishwomen with cosmetic breast implants (n Z 2761) and comparison groups of women with other types of cosmetic surgery (n Z 8807). All women were followed from January 1977 through December 2001. Hos-pitalizationandoutpatientdataforCTDandill-definedandotherrheumaticconditionsintheimplantandcomparison groups were compared with those in the general Danish population. Additionally, CTDs andfibromyalgia were confirmed through medical chart review, and direct comparisons of the breast implantcohort with the comparison cohort were performed. RESULTS:  When compared with general population rates, CTDs were not statistically significantlyelevated in either the implant or the comparison cohorts. However, unspecified rheumatism was similarlyincreased in the implant (standardized rate ratio  Z  1.9; 95% confidence interval  Z  1.6 to 2.2) andcomparison (standardized rate ratio Z 1.5; 95% confidence interval Z 1.4 to 1.7) cohorts. In analysesof diagnoses validated by chart review, women with cosmetic breast implants compared with those havingother types of plastic surgery or consultation for plastic surgery had no statistically significant excess for anyspecific confirmed CTD or combined CTDs (hazard ratio Z 1.3; 95% CI Z 0.9 to 1.9). In addition, therewas no relation between breast implants and confirmed fibromyalgia (hazard ratio Z 1.2; 95% CI Z 0.6 to2.1). CONCLUSIONS:  This extension of our earlier cohort study further supports the consensus of epidemi-ologic research that breast implants are unrelated to the development of CTD.  Ann Epidemiol 2007;17:374–379 .   2007 Elsevier Inc. All rights reserved. KEY WORDS :  Breast Implants, Connective Tissue Disease, Rheumatic Conditions, Epidemiology, CohortStudy. INTRODUCTION Since their development in the 1960s, millions of womenaround the world have received breast implants (1). In2004, approximately 335,000 women in the United Statesaloneunderwentbreastimplantsurgery forcosmeticreasons(80%) or for reconstruction after surgery for breast cancer(20%) (2). In Denmark, breast implant surgery was intro-duced in the 1970s. Similar to that in the United States,most breast augmentations( > 70%) are currentlyperformedfor cosmetic reasons (3).To date, more than 20 epidemiologic studies have exam-ined the relation between breast implants and connectivetissue diseases (CTDs) (4). Herein, we report on an exten-sion of our earlier cohort study on the relation betweenbreast implants and CTDs in Denmark (5). The currentstudy updates the follow-up period by an additional 5 years,through2001,toprovidelongerfollow-upforCTDriskafterbreast implantation. MATERIALS AND METHODSStudy Cohorts The identification of the study cohorts is described in detailelsewhere(5).In brief, thestudywasconducted inDenmarkamong women who underwent cosmetic breast implant From the International Epidemiology Institute, Rockville, MD, and theDepartments of Medicine (J.P.F., J.K.M., R.E.T.) and Preventive Medicine(L.L.), Vanderbilt University Medical Center, Vanderbilt-Ingram CancerCenter,Nashville,TN;andInstituteofCancerEpidemiology,DanishCan-cer Society, Copenhagen, Denmark (L.H., T.H, K.K., S.F.).Addresscorrespondenceto:Dr.JosephK.McLaughlin,InternationalEp-idemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD20850. Tel.: 301-424-1054; fax: 301-424-1053. E-mail: jkm@iei.ws.Received June 7, 2006; accepted November 24, 2006.   2007 Elsevier Inc. All rights reserved. 1047-2797/07/$–see front matter360 Park Avenue South, New York, NY 10010 doi:10.1016/j.annepidem.2006.11.001  Selected Abbreviations and Acronyms CI Z Confidence intervalCTD Z Connective tissue diseaseHR Z Hazard ratio NHR Z  National Hospital RegisterSRR Z Standardized rate ratio surgery at public hospitals between 1977 and 1992 (n Z 1,135) and at eight private clinics between 1973 and 1995(n  Z  1,653). The public hospital cohort was identifiedthrough the Danish National Hospital Register (NHR),which, beginning in 1977, covers about 99% of all dis-charges from non-psychiatric hospitals in Denmark, withoutpatient data added in 1995. Surgical procedures in the NHR are coded according to a Danish classification system(6). The private clinic cohort was identified through medi-cal record review. The vast majority of the breast implantsweresilicone-gelfilledimplants(5,7).Accordingtoourear-lier sampling study of medical records of women with breastimplants (7), at least 84% of the women had silicone gel–filledimplants,whereasthetypeofimplantwasnotspecifiedin 16%.Two comparison groups were identified at the same hos-pitals and clinics as the women with breast implant surgery.The first included women who underwent breast reductionsurgery at Danish public hospitals between 1977 and 1992(n Z 7,071). The second group was ascertained from thefiles of the private clinics (n Z 1,736) and included womenwho attended the private clinics for reasons other thanbreast implantation (breast reduction and mastopexia[23%],facialsurgery[21%],skinexcisions[21%],liposuction[15%], other types of plastic surgery [1%], and consultationonly [19%]). They were matched on clinic, age ( G 3 years),and calendar year ( G 18 months) of procedure or consulta-tion to women who underwent breast augmentation.Thevariablesextractedfromclinicorhospitalrecordsin-cluded personal identification number, date of plastic sur-gery procedure (or consultation), indication for procedure,and type of implant. The personal identification number as-signed to all Danish residents by the Central PopulationRegisterallowedrecordlinkagesofcohortmembersbetweennationwide registries with little loss to follow-up. Connective Tissue Diseases Connectivetissuediseasesforallstudycohortmemberswereascertained through linkage with the NHR and the outpa-tient clinic database starting in 1995. Discharge diagnoseswere coded according to the Danish modified version of the International Classification of Diseases, 8th Revision(ICD-8), from 1977 through 1993, and according to a Dan-ishmodifiedversionoftheICD-10thereafter(5,8).Startingin 1995, the NHR also recorded information on outpatientcontacts,whichincludesambulatoryandemergencydepart-ment visits. Definite CTD was defined as rheumatoid arthri-tis (ICD-8: 712.09–712.39, 712.59; ICD-10: M05, M06,M08.0, M08.2–M08.9), dermato/polymyositis (716.09,716.19;M33),systemicsclerosis(734.00–734.09;M34),sys-temic lupus erythematosus (734.19; M32), or Sjo¨grens syn-drome (734.90; M35.0). Other and ill-defined rheumaticconditions included polyarteritis nodosa (446.09; M30.0),Wegener´s granulomatosis (446.29; M31.3), temporal arter-itis and polymyalgia rheumatica (446.30–446.39; M31.5,M31.6, M35.3), psoriatic arthritis (696.09; L40.5, M07.0–M07.3), ankylosing spondylitis (712.49; M45.9, M08.1), ar-thritis not further specified (715.99; M13.0, M13.1, M13.8,M13.9), unspecified rheumatism (including fibromyalgia andmyalgia) (717.90, 717.99, 718.99; M25.5, M25.6, M25.8,M25.9, M62.6, M62.8, M62.9, M79.0, M79.1, M79.8,M79.9), localized scleroderma (701.01-701.09; L94.0–L94.3),localized (discoid) lupus erythematosus (695.49; L93.0–L93.2), and CTD not further specified (734.91, 734.99;M35.1, M35.2, M35.4–M35.6, M35.8, M35.9, M79.3). Otherconditions considered included sarcoidosis (135.99; D86),Hashimoto’s thyroiditis (245.03; E06.3), and amyloidosis(276.00–276.09; E85).  Follow-up TheincidencesofCTDsforwomenintheimplantandcom-parison cohorts were compared with general populationrates (external comparison) and directly with each other(internal comparisons). For the external comparison,women were at risk for multiple CTDs throughout the studyperiod so the follow-up period was initiated on the date of the first breast implantation or other procedure or consulta-tion and continued until death, emigration from country, orDecember 31, 2001, whichever occurred first. Follow-up fortheinternalcomparisons commencedonthedate ofthefirstbreast implantation or other procedure or consultation andended on the date of hospitalization or outpatient diagnosisforspecificCTD,death,emigrationfromthecountry,orDe-cember 31, 2001, whichever occurred first. Follow-up for alldefinite CTDs combined ended at the time of the first CTDof any type. Data on emigration and death for women in thestudy cohorts were obtained through linkage with the Dan-ishCentralPopulationRegister,whichretainsdailyupdatedinformation on vital status and address of all Danish citizenssince 1968. Statistical AnalysisExternal comparisons.  Simple descriptive statistics, in-cluding frequencies, percentages, and means, were calcu-lated to describe the study cohorts. For each specific CTD,a standardized rate ratio (SRR Z observed/expected casesof CTD) was calculated as a measure of the relative  AEP Vol. 17, No. 5  Fryzek et al. May 2007: 374–379  CTD AND RHEUMATIC CONDITIONS IN BREAST IMPLANTATION 375  occurrence of the specific CTD under investigation com-pared with the general population. To calculate the ex-pected number of cases, national rates were firstconstructed by dividing the number of patients hospitalizedor identified in the outpatient database with the specificCTD by the corresponding mean person-years for womeninthegeneralpopulationin5-yearageandcalendarperiods.The expected number of cases of CTD in each cohort wasthen determined by multiplying the age and calendar pe-riod–specific person-years of follow-up in each cohort bythe national rates. For the calculation of both national ratesand observed numbers of cases, only the first diagnosis fora CTD in the above disease groups was counted. Ninety-five percent confidence intervals (95% CI) were calculatedfor each SRR assuming a Poisson distribution for the ob-served numbers of cases (9). Since the results for CTD inci-dence were not meaningfully different, the implant cohorts(publicandprivate)andthecomparisoncohorts(publicandprivate) were combined for the ease of presentation of theSRR results. Validation.  Medical charts of all patients with hospitaldischarges for any of the definite CTDs or for unspecifiedrheumatism, which includes fibromyalgia, were reviewedby two study physicians (SF and LH) to evaluate possiblemisclassification of these diseases in the study cohorts. Val-idationofthedefiniteCTDswaspossiblefortheentirestudyfollow-up period. As fibromyalgia is one among many diag-noses included in the term ‘‘unspecified rheumatism,’’ it wasseparately identified through medical record review. Suchvalidation was possible only for patients diagnosed after1993becausefibromyalgiawasfirstdefinedasadiseaseentity(within ICD-10 code M79) at that time. Internal comparisons.  The occurrence of confirmedCTDsamongwomeninthetwobreastimplantcohortscom-bined was directly compared with that among the combinedcohort of women with breast reduction and other forms of plasticsurgeryorconsultation,afterremovalofunconfirmedconditions. Cox regression models were used to calculatecrude and adjusted relative rates and 95% Wald CIs. Calen-dar year and time since first operation or consultation weretreated as linear covariates. RESULTS CharacteristicsofthefourstudycohortsareshowninTable1.A total of 2,761 women underwent breast implant surgery,1,653 at a private clinic, 1,135 at a public hospital, and 27at both places. The comparison cohort comprised 1,736women from the private clinics and 7,071 women fromthe public hospitals. There were 37,084 person-years of follow-up in the combined implant cohort and 128,437 per-son-years of follow-up in the combined comparison cohort.The median age of women in the private clinic comparisoncohort was slightly higher, 33 years, compared with 31 yearsof age for women in the other cohorts. The public hospitalimplantandthepublichospitalcomparisoncohortshadlon-ger mean follow-up periods than the private clinic cohorts,though all cohorts had more than a decade of follow-up,with long-term subjects having almost three decades.Overall,25(1%)womeninthecombinedimplantcohortand 79 (1%) women in the combined comparison cohorthad a subsequent hospitalization or outpatient diagnosisfor at least one definite CTD during the follow-up period(Table 2). There was no statistically significantly increasedSRR for any specific definite CTD in either combinedcohort. Further analyses were performed for those womenwith 10 or more years of follow-up. Given the small numberof definite CTDs observed after 10 years of follow-up, theseanalyses were conducted for all definite CTDs combined.There were significantly more CTDs than expected inboth the combined implant group (n Z 16, SRR Z 1.8;95% CI Z 1.0 to 2.9) and the combined control group (n Z 48, SRR Z 1.4; 95% CI Z 1.0 to 1.9). The majority of these CTDs were rheumatoid arthritis (n  Z  9 [56%] forthe combined implant cohort [SRR Z 1.4; 95% CI Z 0.7to 2.7] and n Z 32 [66%] for the combined control cohort[SRR Z 1.3; 95% CI Z 0.9 to 1.9]) (data not shown).With respect to other rheumatic conditions, unspecifiedrheumatism was similarly increased in both cohorts, withaSRRof1.9(95%CI Z 1.6to2.2)inthecombinedimplantcohort and a SRR of 1.5 (95% CI  Z  1.4 to 1.7) in thecombined comparison cohort (Table 2). We also examinedunspecifiedrheumatismbytimesinceoperationorconsulta-tion and found no statistically significant increasing or TABLE 1.  Characteristics of the study cohorts  No. of patientsAge atentryMedian(range),yearsTime atrisk y Person-yearsLength of follow-up y Mean,yearsBreast implant cohortsPrivate clinic 1653 31 (16–54) 19,198 11.6Public hospital 1135 31 (13–64) 18,204 16.0Combined implantcohort2761* 31 (13–64) 37,084 13.4Comparison cohortsPrivate clinic 1736 33 (13–54) 20,394 11.7Public hospital breastreduction7071 31 (11–79) 108,043 15.3Combined comparisoncohort8807 32 (11–79) 128,437 14.6 *Twenty-seven women were registered in both implant cohorts. y Since the women were at risk for multiple CTDs throughout the study period, thefollow-up period shown in this table commenced on the date of the first breast im-plantation or other procedure or consultation and continued until death, emigrationfrom country, or December 31, 2001, whichever occurred first. Fryzek et al.  AEP Vol. 17, No. 5 CTD AND RHEUMATIC CONDITIONS IN BREAST IMPLANTATION  May 2007: 374–379 376  decreasing trends(  p O .05) withincreasingtime since oper-ation or consultation for either study cohort (data notshown).A similar percentage of definite CTDs was validatedthrough medical chart review for women with breastimplants (22/26 Z 85%) and comparison women (74/84 Z 88%).Twocasesofrheumatoidarthritisandtwocasesofsys-temic lupus erythromatosus in the breast implant cohortcould not be confirmed. In three of these cases, the true di-agnosis was one or more other rheumatic conditions (fibro-myalgia; polymyalgia rheumatica and temporal arteritis;unspecified rheumatism and Raynaud’s disease), whereasin one woman no type of CTD could be confirmed fromthe medical chart. The 10 cases of unconfirmed definiteCTDs among women in the combined comparison cohortincluded one case of sarcoma (erroneously classified as der-mato/polymyositis), five cases of other rheumatic condi-tions, including ankylosing spondylitis, psoriatic arthritis,reactive arthritis, fibromyalgia, and ‘‘anti-cardiolipid-syndrome,’’ and four cases in whom definite CTDs couldnot be confirmed.Hazardratios(HRs)and95%CIsforconfirmedCTDsarepresented in Table 3. Women with breast implants were notsignificantly more likely to have CTDs compared withwomen in the comparison cohort (HR Z 1.3; 95% CI Z 0.9 to 1.9, adjusting for calendar year and time since opera-tion or consultation). Similarly, there was no statisticallysignificant increased risk for a confirmed diagnosis of fibro-myalgia among women with implants compared with com-parison women (HR Z 1.2; 95% CI Z 0.6 to 2.1). DISCUSSION The results of this extended follow-up study of breast im-plants and CTDs are consistent with the overwhelming ep-idemiologic evidence indicating that there is no associationbetween implants and CTDs either individually or incombination. Numerous meta-analyses, weight-of-the-evidence, and critical reviews are in agreement that thereis no evidence to support an association between breast im-plantsandCTD(1,4,10-18).Sincepublicationofthelatestliterature review (4), a retrospective US cohort study of 7,234 women with breast implants and 2,138 comparisonwomenwithothertypesofplasticsurgeryreportedincreasedoccurrences of self-reported rheumatoid arthritis, sclero-derma, systemic lupus erythematosus and Sjo¨gren’s syn-drome combined, and of self-reported rheumatoid arthritis TABLE 2.  Number of observed definite connective tissue diseases and other ill-defined rheumatic conditions, standardized rate ratios,and 95% confidence intervals for women in the study cohorts Combined implant cohorts Combined comparison cohortsRheumatic conditions Observed SRR 95% CI Observed SRR 95% CIDefinite connective tissue diseasesRheumatoid arthritis 17 1.3 0.8–2.2 53 1.1 0.8–1.4Dermato and polymyositis 2 4.4 0.5–15.8 4 2.5 0.7–6.4Systemic sclerosis 3 2.9 0.6–8.3 5 1.4 0.5–3.3Systemic lupus erythematosus 2 0.8 0.1–2.9 13 1.6 0.9–2.8Sjo¨gren’s syndrome 2 1.0 0.1–3.5 9 1.2 0.6–2.3Definite CTDs combined 26 1.4 0.9–2.0 84 1.2 1.0–1.5Other rheumatic conditionsPolyarteritis nodosa 0 0.0 0.0–15.2 4 3.5 0.9–9.0Wegener’s granulomatosis 0 0.0 0.0–13.6 0 0.0 0.0–3.2Temporal arteritis and polymyalgia rheumatica 3 1.5 0.3–4.4 22 1.1 0.7–1.7Psoriatic arthritis 1 0.4 0.0–2.0 11 1.3 0.6–2.3Ankylosing spondylitis 1 0.9 0.0–4.8 5 1.5 0.5–3.4Arthritis not further specified 4 0.7 0.2–1.9 24 1.3 0.8–1.9Unspecified rheumatism* 175 1.9 1.6–2.2 454 1.5 1.4–1.7Localized scleroderma 0 0.0 0.0–10.6 0 0.0 0.0–3.0Localized (discoid) lupus erythematosus 1 0.7 0.0–4.0 7 1.6 0.7–3.4CTD not further specified 5 1.8 0.6–4.1 16 1.7 1.0–2.7Sarcoidosis (Boeck) 1 0.3 0.0–1.6 14 1.1 0.6–1.9Hashimoto’s thyroiditis 0 0.0 0.0–1.9 2 0.3 0.0–1.2Amyloidosis 0 0.0 0.0–20.7 0 0.0 0.0–4.7Other rheumatic conditions combined 191 1.6 1.4–1.9 559 1.4 1.3–1.6Other rheumatic conditions combined, excluding unspecified rheumatism 16 0.7 0.4–1.2 105 1.2 1.0–1.5Definite and other rheumatic conditions combined 217 1.6 1.4–1.8 643 1.4 1.3–1.5Definite and other rheumatic conditions combined, excluding unspecified rheumatism 42 1.0 0.7–1.4 189 1.2 1.0–1.4  Note: Since the women were at risk for multiple CTDs throughout the study period, the follow-up period commenced on the date of the first breast implantation or otherprocedure or consultation and continued until death, emigration from country, or December 31, 2001, whichever occurred first.*Including fibromyalgia and myalgia.  AEP Vol. 17, No. 5  Fryzek et al. May 2007: 374–379  CTD AND RHEUMATIC CONDITIONS IN BREAST IMPLANTATION 377  alone among women with breast implants compared withwomen with other types of plastic surgery (19). The authorscould only confirm a minority of the self-reported CTDs ina medical record review; hence, caution should be observedin light of the study’s reporting bias (19).With the exception of unspecified rheumatism, no otherCTD or rheumatic condition was found in excess in ourstudy,confirmingtheconclusionsofearlierstudiesandinde-pendentreviewsthatbreastimplantsarenotassociatedwithany specific type of CTD (1, 4, 13, 14). Furthermore, no ev-idence has been found to support the existence of a newrheumatologic syndrome in women with silicone breast im-plants (4, 20, 21). In our study, unspecified rheumatism,which included fibromyalgia, was elevated in both theimplant and comparison cohorts. After validating thefibromyalgia diagnosis through medical records, directcomparison of the implant and comparison cohorts showedthattheriskratioforfibromyalgiawasconsistentwithnoin-creased risk (HR Z 1.2; 95% CI Z 0.6 to 1.2). The recentUS study (19) also found that women with breast implantswere no more likely to self-report fibromyalgia than womenwithotherformsofplasticsurgery(RR Z 1.3;95%CI Z 0.9to 1.7). Thus, the collective epidemiologic evidence doesnotsupportanassociationbetweencosmeticbreastimplantsand the subsequent occurrence of fibromyalgia (22). It hadbeen hypothesized that women with ruptured breast im-plants may be at an increased risk for the development of CTDs, particularly fibromyalgia (23), but rates of self-reported symptoms and CTDs, including fibromyalgia,were similar for women with ruptured implants comparedwith women with intact implants among a subgroup of women in our cohort who had undergone magnetic reso-nance imaging to detect rupture status (21).This study has a number of strengths. The study popula-tionwaswell-defined,withvirtuallycompletefollow-upandunbiaseddiseaseascertainment,duetotheuseofnationwidehospital and population registers. Earlier studies of this co-hort validated the information on breast implant and othersurgical procedures in public hospitals (7), and informationon private hospital procedures was gathered through medi-cal record review by two of the study investigators (KKand SF) (5). The outcome data had a high degree of validitybecause the CTDs were based on hospital records and med-ical chart reviews and not self-reports. Further, the additionof outpatient data from 1995 on increased the sensitivity of the data from the NHR and may reduce underreportingof less severe rheumatic conditions.Some misclassification exists in our study because out-comes of CTDs diagnosed and treated outside the hospitalor outpatient clinic setting (before 1995) were not includedin the analyses. However, most patients in Denmark withdefinite CTD or fibromyalgia will be referred to hospital oroutpatient clinic at some point along the course of their dis-ease. Further, the study had limited power to detect some of the rarer individual CTDs or other rheumatic conditions.In summary, the results of this study in conjunction withthe weight of the epidemiologic evidence to date should of-fer reassurance to women considering breast implant surgerythat breastimplants are unlikely to beassociated with eitherestablished or atypical CTDs. REFERENCES 1. Bondurant S, Ernster V, Herdman R. Safety of Silicone Breast Implants,Report of the Committee on the Safety of Silicone Breast Implants(IOM). Washington, DC: National Academy Press; 2000.2. American Society for Aesthetic Plastic Surgery, http://www.surgery.org.3. Henriksen TF, Holmich LR, Friis S, McLaughlin JK, Fryzek JP, PernilleHoyer A, et al. The Danish Registry for Plastic Surgery of the Breast:establishment of a nationwide registry for prospective follow-up, quality TABLE 3.  Number of observed definite connective tissue diseases and fibromyalgia, hazard rates, and 95% confidence intervalsfor women in the combined implant and comparison cohorts with verified diagnoses of the conditions Combined implant cohorts Combined comparison cohortsCrude Adjusted*Rheumatic conditions Observed Observed HR 95% CI HR 95% CIRheumatoid arthritis 15 49 1.4 0.8–2.6 1.3 0.7–2.5Dermato and polymyositis 2 3 3.0 0.4–22.5 2.8 0.4–20.4Systemic sclerosis 3 5 1.8 0.4–8.1 1.7 0.4–7.7Systemic lupus erythematosus 0 11 0.0 0.0Sjo¨gren’s syndrome 2 6 1.6 0.3–8.7 1.3 0.3–7.2All definite CTDs y 21 69 1.3 0.9–2.0 1.3 0.9–1.9Fibromyalgia z 17 37 1.2 0.6–2.1 1.2 0.6–2.1 *Adjustment for calendar year and time since operation or consultation. Age as underlying time scale. Calendar year and time since operation or consultation were treated aslinear covariates. y Follow-up for all definite CTDs combined ended at the time of the first CTD of any type. One woman in the implant cohort had rheumatoid arthritis and Sjo¨gren’s syndrome.In the comparison cohort, two women had systemic sclerosis and rheumatoid arthritis, one woman had Sjo¨gren’s syndrome and systemic lupus erythematosus, one woman hadrheumatoid arthritis and systemic lupus erythematosus, and one woman had rheumatoid arthritis and Sjo¨gren’s syndrome. z Fibromyalgia diagnosed after 1993 when an ICD code became available. Fryzek et al.  AEP Vol. 17, No. 5 CTD AND RHEUMATIC CONDITIONS IN BREAST IMPLANTATION  May 2007: 374–379 378
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