Our study has important strengths. As far as we are aware, this is the largest study examining sex as a predictor of health services utilization following immunization. The use of the SCCS study design permitted us to adjust for fixed confounders. The use of relative incidence ratios to compare relative incidences of events between sexes allows us to adjust for temporal confounding such as the healthy vaccinee effect [8]. Our study also has limitations, which include the use of general vaccination codes. While we cannot be certain that the vaccinations administered at 2, 4, 6 and 12 months of age are those recommended

in Ontario’s Immunization Schedule, it would be highly unlikely that they represented other vaccinations. In our analysis we assume that the risk and control periods are consistent between males and Everolimus clinical trial females. While it is possible these may differ this is not evident in a visual inspection of the data. A limitation of all SCCS analyses

is the possibility of coincident temporal exposures. A possible example in this case could be day care exposure which theoretically could affect the sexes differently with respect to health services utilization. Finally, the main diagnoses associated with ER visits and hospital admissions were not validated. We observed that the relative incidence of ER visits and/or hospitalizations following the 12-month immunization during an at-risk period as compared Cytoskeletal Signaling inhibitor TCL to a control period was higher for females than for males. Our findings are hypothesis generating but raise the possibility that sex differences in short-term reactogenicity following routine MMR vaccination at 12 months may give insight into the far more severe sequelae of high titer measles vaccination. Given the importance of the measles vaccine to protect against natural infection, the observation that these events were mild and the fact that

increased reactogenicity in the girls may indicate less maternal protection, our findings support current measles vaccination programs. We also believe our findings point to a need for further studies to investigate pathophysiological reasons for the differential sex response to measles virus and measles-containing vaccines. This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent of the funding sources. No endorsement by ICES, or the Ontario MOHLTC is intended or should be inferred. Dr. Wilson is supported by the Canada Research Chair in public health policy. The authors have no conflicts of interest to declare. “
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