COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Effect of urine pH on the stability of doxorubicin and its recovery from bladder instillations.

Doxorubicin (1 mg/ml) was shown to be stable when added to urine samples with a mean natural pH of 5.4 and in urine buffered to a mean pH of 4.6. However, at alkaline pH (mean = 8.1) there was a biphasic degradation of doxorubicin (mean t1/2 = 3.24 and 89 h respectively). The data indicate that buffering intravesical doxorubicin to pH 4.6 (acetate buffer) or pre-dosing of patients with ammonium chloride may minimise loss of active drug during the time for which the drug is retained in the bladder. Recovery of doxorubicin following 1 hour's retention in the bladder was similar (77%) for doses of 38/48 or 78 mg. It is suggested that a dose of 50 mg (1 mg/ml) is sufficient to ensure an adequate delivery of active drug to the bladder wall.

Differences in blood levels of androgens in female talapoin monkeys related to their social status.

Serum testosterone and androstenedione levels were lower in the subordinate female talapoin monkeys of four social groups than either dominant or intermediate-ranking females. This was found in both intact or ovariectomized (oestrogen-treated) animals, which suggests that androgen from the adrenals contributed to this rank-related endocrine effect. These differences disappeared when the females were housed singly, levels in all animals becoming similar to those in subordinates in the group cage. There were no rank-related differences in progesterone levels during either the follicular or luteal phase of the cycle in intact females, or in those of ovariectomized females of different rank, but cortisol was highest in dominant group-living animals in these experiments. Significant correlations were found between androgen levels in group-living females and the amount of sexual interest shown in them by males; the amount of aggressive interaction involving each female did not correlate with her androgen levels. Social rank is defined according to the direction, not the amount, of aggression. These findings suggest that the social hierarchy regulates androgen levels in these female monkeys; there may also be effects on the ability of females to respond to their own, or to administered, androgen. Similar findings have been made previously in male talapoins. Since androgens fill a critical role in the sexual behaviour of both sexes in primates, this may be a neuroendocrine mechanism of general significance relating behaviour to social rank.