Semiparametric mixed models are increasingly popular for statistical analysis of medical device studies in which long sequences of repeated measurements are recorded. Monitoring these sequences at different periods over time on the same individual, such as before and after an intervention, results in nested repeated measures (NRM). Covariance models to account for NRM and simultaneously address mean profile estimation with penalized splines via semiparametric regression are considered with application to a prospective study of 24-hour ambulatory blood pressure and the impact of surgical intervention on obstructive sleep apnea.