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We also included MS cases during 1993–2000 identified and validated in an earlier study.Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis.Another important question is what are the risk factors for the disease and what influence do they have on mortality.

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS.

Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001–2006 and validated using patients’ original records where possible.

We were unable to obtain information on use of interferon beta because, in the UK, it is mostly prescribed in secondary care and is not always captured in GP records.

For the 902 MS patients with original clinical records, we retrieved additional information on MS subtype [relapsing-remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS) or unknown], and MS symptoms at onset.

Where available, patients’ original clinical paper records containing clinical notes, consultation letters, specialist referrals, test results and hospital discharge letters were retrieved, and were reviewed by a neurologist (GJF) to validate the MS diagnosis and classify the case.

Each case was classified according to the Mc Donald criteria for MS [] and categorized as definite, possible or unlikely.

To supplement information on cause of death recorded in the GP records, we were able to link to death registry data for patients in practices in England, and we requested data from additional electronic GP notes where the cause of death was unknown, but there was an indication that additional electronic GP notes were available.

Information on the following variables was extracted from the database: age at first MS diagnosis, sex, and lifestyle factors closest to and before the first MS diagnosis including smoking, body mass index (BMI) and alcohol abuse.

The end of follow-up was the date of patient’s death, the date of transfer out of the practice, or the date of last data collection in the database (31 July 2012), whichever came first.

The cause of death was ascertained from electronic and/or original clinical paper records.

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