Third, the longitudinal nature of the medical information of general practitioners enables one to study trajectories in morbidity linked to environmental and occupational determinants. The main limitations of the study are those known to cohort studies sellekchem that use active and passive follow-up, in particular selection bias

and loss to follow-up related to future questionnaires, and the passive follow-up through EMRs in general practice, which will be truncated if cohort members move to another general practice. Of particular interest, related to selection bias and active follow-up is our choice to use online registration and (baseline) questionnaire(s). We argued that access to the internet is ubiquitous in the Netherlands, and that, owing to this online system, we could significantly cut costs such as printing and data entry, which enabled us to invite more participants. However, it requires from invitees the willingness and ability to access the internet and register and participate online. In time, as the cohort ages and to enhance the long-term participation of cohort participants, we will seek possibilities and pilot-test alternative modes such as also offering paper questionnaires on request or sending them along with reminder letters.

We anticipated this possibility in the design of the online questionnaire and made sure that it resembled paper questionnaires as much as possible, as detailed in the Methods section. With respect to selection bias at study entry, in our health-related participation bias analysis, we observed several statistically significant differences in general-practitioner recorded prevalence rates across several disorders and organ systems among cohort members compared with the source population. For example, 7 of the 10 studied disorders were statistically significantly more prevalent (most notably hypertension and migraine), while the other 3 were statistically significantly lower (most notably diabetes and COPD) in the total of cohort members compared with the source population. However, many of the statistically significant differences (in the total collective and some age and

Batimastat sex strata) were small. Moreover, we observed that the prevalence of one disorder in the same organ system is higher while another is less or similarly prevalent among the cohort members, which indicates that these differences are probably due to chance rather than differences in health or associated lifestyle. For example, while hypertension and COPD were more prevalent, cerebrovascular accidents and asthma, respectively, were less prevalent among cohort members, which does not seem to point at a participation bias based on smoking behaviour. Taken together, therefore, we found no consistent indications of systematic health-related participation bias based on these measures of morbidity or associated lifestyle such as smoking.