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We considered participants who reported using other antiinflammatory analgesics e. Participants with missing information on analgesic intake over any 2-year questionnaire period were excluded from that time period. Analgesic use assessed in this manner has been associated with colon cancer 16renal cell carcinoma 17Parkinson disease 18hypertension 1920and breast cancer survival Duration of medication use was categorized as less than 1 year, 1—2 years, 3—4 years, 5—6 years, and more than 6 years.

We were unable to ascertain information on duration of use of aspirin, NSAIDs, or acetaminophen before Ascertainment of hearing loss The outcome in the present study was self-reported hearing loss.

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The gold standard for evaluating hearing loss is pure-tone audiometry. From a logistical and financial standpoint, it is challenging to obtain audiograms in such a large cohort. It has been shown in previous studies that compared with hearing loss diagnosed by audiogram, self-reported hearing loss is a relatively reliable indicator of hearing loss 22 — In addition, significant associations between other factors and risk of self-reported hearing loss have been observed using this method of assessment in NHS I and NHS II 1426 — Ascertainment of covariates Covariates were selected based on previously reported risk factors for hearing loss.

Updated covariate data were obtained from the biennial questionnaires. The validity and reproducibility of the food frequency questionnaires have previously been reported 40 Many of the other covariates used in our models have been shown to be valid measures in this and other similar cohorts 42 — Calculation of the population attributable fraction In the event that duration of analgesic use was found to be associated with risk of hearing loss, we calculated the population attributable fraction PAF of hearing loss among women in our study using the method of Bruzzi et al.

This method has been shown to provide valid estimates of the population attributable fraction with multicategory exposures This calculation is based on the assumption that there is a causal relation. Statistical analysis All analyses were performed in a prospective manner. Person-time for each participant was assigned based on their responses to questions about aspirin, NSAID, and acetaminophen use on the questionnaire and was updated every 2 years subsequently.

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Participants were censored at the reported onset of hearing loss or cancer diagnosis. Multivariable-adjusted relative risks were calculated using Cox proportional hazards regression models. The Anderson-Gill data structure was used to deal with left truncation and time-varying covariates in an efficient manner To control for confounding by age as finely as possible, we stratified our analysis jointly by age at start of follow-up and calendar year of a given questionnaire cycle.

Age 60 years was chosen based on the distribution of participant ages and previous studies in which effect modification by age was investigated.