Epilepsy is one of the most common neurological disorders and requires long-term treatment with anti-seizure medication (ASM) which may cause adverse drug reactions (ADRs). Our aims were to investigate potential sex differences in reporting suspected ADR (sADRs) of ASMs through studying their seriousness, outcomes and Sudden Unexpected Death in Epilepsy (SUDEP). Using EudraVigilance database, reported sADRs with different ASMs over a ten year period were extracted. List of ASMs was compiled according to Anatomical Therapeutic Chemical Classification System. Reporting Odds Ratio (ROR), 95% confidence interval (95% CI), p-value were calculated. In general, more sADRs were reported from females (603,936, 57.46%). Males showed positive association with the following seriousness criteria: 'life threatening' (ROR=1.02, 95%CI: 1.01-1.04; p<0.001), 'caused/prolonged hospitalisation' (ROR=1.06, 95%CI: 1.05-1.07; p<0.001), 'results in death' (ROR=1.44, 95%CI: 1.43-1.46; p<0.001), and 'congenital anomaly' (ROR=2.43, 95%CI: 2.41-2.45; p<0.001). Only with 'not recovered / not resolved' outcome criteria showed negative association in males (ROR=0.72, 95%CI: 0.70-0.73; p<0.001), the other outcome criteria demonstrated positive association in the followings: 'fatal' (ROR=1.43, 95%CI: 1.41-1.45; p<0.001), 'recovered / resolved' (ROR=1.08, 95%CI: 1.07-1.09; p<0.001), 'recovered / resolved with sequelae' (ROR=1.06, 95%CI: 1.01-1.12; p<0.001), and 'recovering / resolving' (ROR=1.14, 95%CI: 1.12-1.15; p<0.001). Differences were observed between males and females, particularly in terms of seriousness criteria, worse outcomes but prone to recover, and associations with SUDEP to the detriment of males. When choosing an ASM for a patient or especially if the patient has previously experienced an adverse drug reaction. these aspects can also be taken into account and may be important.

Background: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD). Methods: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[¹⁸F]FDG and [⁶⁸Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts. Results: Due to a cellular adaptation to hypoxia, a gradual increase in [⁶⁸Ga]Ga-NOTA-c(NGR) and 2-[¹⁸F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups. Conclusions: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD.