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All the investigators were trained on ISO-GCP standard before study start and on all study procedures during the site initiation visit by the sponsor.
Healthcare professionals were invited to participate in a workshop about diabetes before study start and to fill out an usability questionnaire at the end of the study.
Finally, we used the DNRP to identify hospital codes for oxygen treatment within the 12 months before study start and on lung volume reduction surgery between 1996 and study start.
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Selection of the patients based on specifically structured questionnaire that addressed certain areas of interest regarding the age, chronic medical illness, previous history of hospitalization within the last two months before study started and if there was any operative history together with antibiotic usage.
Patients in the INCO group were additionally separated in patients who had received any botulinum toxin treatment before study start ('BoNT/A-pretreated') and those who were BoNT/A naïve, since pretreatment may have an effect on the efficacy of the study treatment.
After removing the pregnancies conceived more than 19 weeks before the study start and less than 43 weeks before the study end, the adjusted cohort had 101,870 pregnancies (88.6% of the original sample).
A one-day study-specific course was given before study start, which included theory and hands-on-training in MA and EA.
Altogether, 26 patients were excluded from the Middle East cohort due to protocol violations (double entry [n = 1], final visit before study start [n = 23], and no follow-up visits documented [n = 2]), and three were excluded from the Morocco cohort because of no visits being documented.
The clinical characteristics before study start in the original study and in the replication study are listed in Table 1 and 2, respectively.
In the analyses of incident cases of ischaemic heart disease and stroke, we excluded people who were diagnosed as having ischaemic heart disease before the study start (n=1308) from the analyses of ischaemic heart disease and the combined endpoint, and we excluded those who were diagnosed as having stroke before study start from the analyses of stroke and the combined endpoint (n=676).
The clinical characteristics before study start are summarized in Table 1 and 2. In the original study, we selected 77 case subjects and 152 healthy control subjects from among 1803 Japanese male employees [ 5].
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