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A high body mass index was strongly and selectively associated with increased risk of anti-CCP-negative RA, a finding that has not been reported previously. A chance finding appears unlikely given the highly significant trend with increasing body mass index and its specificity to anti-CCP-negative RA. Theoretically, however, although we included only patients who fulfilled ACR 1987 diagnostic criteria for RA as cases in our study, we cannot exclude the possibility that some anti-CCP-negative patients actually had inflammatory osteoarthritis, which is positively associated with body mass index. Consequently, confirmatory findings in other settings are needed. Possibly, the lacking identification of other etiological candidates for anti-CCP-negative RA might reflect that this RA subtype comprises a heterogeneous group of etiologically distinct inflammatory arthritides.
The female predominance in RA has prompted suggestions that sex hormones and reproductive factors may be etiologically involved [ 16 – 18 ]. However, in the present study, the only interesting reproductive factor was age at menarche, a finding that accords well with prior findings that women with early menarche are at comparatively low RA risk [ 35 , 36 ]. We also searched for clues to a possible venereal etiology, but associations with all examined sexual behaviors and sexually transmitted diseases were consistently non-significant. There was also no indication that infection with parvovirus B19 or Epstein-Barr virus, two previously suggested etiological candidates [ 37 , 38 ], would have any bearing on the risk of either anti-CCP-positive or anti-CCP-negative RA.
The patients in our study, identified at hospital departments of rheumatology and internal medicine throughout Denmark over a 5-year diagnostic period, are likely to be representative of patients with RA in need of hospital care. Our findings may not necessarily apply to milder cases of RA managed in outpatient settings, although we have little reason to believe that associations would differ in other RA populations. Although the participation rate was high (83%) among RA cases, invited population controls were slightly more reluctant to participate (64%). Theoretically, such a difference might lead to biased associations for some of the studied risk factors, to the extent these factors were also associated with the decision to accept or decline our invitation to participate. If invited subjects who did not want to participate comprised more tobacco smokers than those who actually participated, such non-random self-selection might have contributed to the observed positive dose-response association with tobacco consumption. However, the supporting evidence for a genuine RA subtype-specific effect of tobacco smoking in anti-CCP-positive RA which has been described by other researchers [ 22 , 23 ] and the lack of a spurious positive association between smoking and anti-CCP-negative RA in our study, suggest that the hypothetical impact, if any, of a relative deficit of tobacco-smoking controls would be small. Additionally, because tobacco and alcohol consumption are positively correlated behaviors, the observed inverse association between alcohol intake and risk of anti-CCP-positive RA cannot plausibly be explained by the lower participation rate among controls. If influenced at all, the inverse and RA subtype-specific association with alcohol consumption reported here is likely to be conservative.
We assessed risk factors retrospectively by means of telephone interviews, so the possible influence of recall problems among study participants needs consideration. Because patients with RA are unlikely to be aware of their anti-CCP antibody status and because exposures covered by our questionnaire are not broadly recognised as RA risk factors, we believe that misclassification arising from recall problems would most likely have been non-differential and tended to produce conservative ORs and blur risk factor differences between the two RA subtypes. The RA subtype-specific risk factor associations we observed are therefore unlikely to be the result of recall problems among our study participants.
Our national case-control study addressed a large number of environmental factors potentially involved in the etiology of RA. Upon dichotomisation of patients with RA according to the presence or absence of anti-CCP-antibodies, we show that environmental risk factors differ considerably between anti-CCP-positive and anti-CCP-negative RA.
She was 13 when Roman Polanski sexually assaulted her. Forty years later, she wants a judge to drop the case against him.
Forty years ago, a 13-year-old girl clutched a heart charm her friend gave her as a prosecutor made her describe in explicit detail to a grand jury her alleged rape by director Roman Polanski.
On Friday, Samantha Geimer testified in the criminal case for the first time since that day, this time pleading with a judge to sentence Polanski, 83, to time served, so that her family can be released from the media spectacle that has haunted her life since that day.
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