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To estimate the prevalence of comorbidity among people with arthritis in the US adult population and to determine the role of comorbidity in accounting for the association of arthritis with days out of role (a measure of inability to work or carry out normal activities).Data come from the National Comorbidity Survey Replication (NCS-R), a nationally representative household survey of 9,282 respondents ages 18 and older carried out in 2001 to 2003. Arthritis was assessed by self-report in a chronic-conditions checklist, along with a wide range of other physical conditions. Mental and substance use disorders were ascertained with the World Health Organization Composite International Diagnostic Interview (CIDI). Number of days out of role was assessed for the 30 days before the interview.Arthritis was reported by 27.3% of respondents, 80.9% of whom also reported at least one other physical or mental disorder, including 45.6% with another chronic pain condition, 62.3% with another chronic physical condition, and 24.3% with a 12-month mental disorder. Arthritis was significantly associated with days out of role, but comorbidity explained more than half of this association. No significant interactions were found between arthritis and the other conditions in predicting days out of role.Comorbidity is the rule rather than the exception among people with arthritis. Comorbidity accounts for most of the days out of role associated with arthritis. The societal burden of arthritis needs to be understood and managed within the context of these comorbid conditions.NCS-R = National Comorbidity Survey Replication; WHO = World Health Organization; CIDI = Composite International Diagnostic Interview; WHO-DAS = WHO Disability Assessment Schedule; OR = odds ratio.