Thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector COVID-19 vaccination in Canada.

INTRODUCTION: Identifying and monitoring adverse events following vaccination contributed to the safety and effectiveness of COVID-19 mass vaccination campaigns. In March 2021, international reports emerged of an adverse event following vaccination with adenovirus vector COVID-19 vaccines (ChAdOx1-S [recombinant] and Ad26.COV2.S) of thrombosis with low platelet counts, referred to as thrombosis with thrombocytopenia syndrome (TTS). We described TTS reports in Canada following adenovirus vector COVID-19 vaccines and investigated whether the observed number of events were higher than expected. METHODS: Reports of TTS following receipt of ChAdOx1-S [recombinant] or Ad26.COV2.S meeting the Canadian case definition for TTS and diagnostic certainty levels 1-3 of the Brighton Collaboration case definition, submitted to the Canadian Adverse Events Following Immunization Surveillance System and Canada Vigilance Database between February 26, 2021 and October 31, 2022 were included. Demographics and characteristics of the TTS reports are described along with an analysis comparing the observed number of reports to the expected number. RESULTS: As of October 31, 2022, 56 reports of TTS following administration of ChAdOx1-S [recombinant] and no reports following Ad26.COV2.S vaccines were reported in Canada, of which 37 had functionally positive anti-PF4 antibodies. The median age was 56 years; males accounted for 54 % of reports. Five deaths were reported. The observed number of reports exceeded the expected for all ages and sexes combined, as well as for males aged 30-49 and 60-69 years, and females aged 40-59 years. CONCLUSION: Based on international surveillance data, Canada evaluated a statistical signal of TTS following adenovirus vector vaccines. The investigation of this signal demonstrated how post-market vaccine safety surveillance systems were successful in investigating rare adverse events during the rollout of COVID-19 vaccines in Canada. As adenovirus vector vaccines continue to be administered, characterization of the association between the vaccine and TTS informs immunization programs and policies.

Status Report ­ The Cancer in Young People in Canada surveillance system.

TITRE: Rapport d'étape - Le système de surveillance Cancer chez les jeunes au Canada. INTRODUCTION: Même si le cancer infantile demeure la principale cause de décès lié à la maladie chez les enfants de moins de 14 ans, il est relativement rare. Chaque année au Canada, environ 910 enfants reçoivent un diagnostic de cancer et 139 meurent de la maladie. Sur le plan biologique, les cancers infantiles diffèrent de ceux habituellement observés chez les adultes. Chez ces derniers, la majorité des cancers sont des carcinomes du tissu épithélial qui tapisse les organes comme le sein, le poumon, le colon et la prostate. Chez les enfants, les carcinomes sont rares, et les tumeurs pédiatriques sont le plus souvent d'origine embryonnaire ou hématopoïétique. Les groupes de diagnostic les plus nombreux sont ceux de la leucémie, du lymphome et des cancers du système nerveux central. Comparativement aux cancers chez les adultes, les cancers chez les enfants ont des périodes de latence plus courtes et sont généralement plus agressifs, envahissants et avancés au moment du diagnostic. Malgré le rang élevé qu'occupe le cancer comme cause de décès chez les enfants, le taux de survie s'est grandement amélioré au cours des vingt dernières années, de sorte que les enfants survivent au cancer plus que jamais auparavant. Toutefois, plus de 60 % des survivants d'un cancer infantile sont confrontés aux effets secondaires physiques et psychologiques à long terme de la maladie et de son traitement, et presque 30 % d'entre eux éprouvent des effets tardifs graves ou potentiellement mortels. Les survivants d'un cancer infantile présentent un risque 11 fois plus élevé de décès, un risque accru de développer un second cancer jusqu'à 30 ans après le traitement ainsi qu'un large éventail de problèmes chroniques d'ordres physique, psychosocial et cognitif. La prise en compte de la nature particulière des cancers dans ce groupe d'âge et des effets tardifs à long terme d'ampleur considérable ont incité de nombreux pays à mettre sur pied des systèmes spécialisés de surveillance et de suivi du cancer chez les enfants. En 2009, l'Agence de la santé publique du Canada (ASPC) a lancé à l'échelle du pays un système spécialisé de surveillance du cancer chez les enfants qui assure un suivi actif des enfants de 14 ans et moins ayant été traités dans l'un des 17 centres d'oncologie pédiatrique du Canada. En fait, le programme Cancer chez les jeunes au Canada (CCJC) est le renouvellement du Programme canadien de surveillance et de lutte contre le cancer chez les enfants (PCSLCE) du gouvernement fédéral. Créé en 1992 dans le cadre de l'initiative Grandir ensemble, ce programme recueille des données exhaustives sur le diagnostic de cancer chez les enfants, les traitements, l'issue de la maladie et l'utilisation des services de santé. Dans cet article, nous décrivons les forces et les réussites de CCJC en mettant en lumière la rigueur appliquée dans les méthodes de collecte et de contrôle de la qualité des données, ses dernières réalisations et ses orientations futures.

Trends in incidence of childhood cancer in Canada, 1992-2006.

INTRODUCTION: Cancer is the leading cause of disease-related death in children aged 1 to 14 years in Canada. Despite the importance to public health of childhood cancer, there have been few reports on Canadian trends published in the peer-reviewed literature. This study examines childhood cancer trends by age, sex, and province of residence using the most current cancer registration data. METHODS: Data from the population-based Canadian Cancer Registry were used to compute incidence trends in primary cancers diagnosed between 1992 and 2006 in children (0-14 years) for the 12 major diagnostic groups of the International Classification of Childhood Cancer, 3rd Edition. RESULTS: Between 1992 and 2006, incidence rates for all cancers remained stable, although trends varied by cancer type. We observed a significant decrease in retinoblastoma in boys for the entire period (-6.5% per year) and an increase in leukemia from 1992 to 1999 (+3.5% per year). In girls, there was a significant decrease in renal tumours from 1998 to 2006 (-5.7% per year) and an increase in hepatic tumours from 1997 to 2006 (+8.1% per year). Differences by age and province were also apparent. Some caution should be exercised when interpreting trends involving a small number of cases per year and those with wide 95% confidence intervals. CONCLUSIONS: Our findings suggest an ongoing need for population-based surveillance and etiologic research.

Women's awareness of, and attitudes towards, hormone replacement therapy: ethnic differences and effects of age and education.

To investigate ethnic differences and the effect of age and education on awareness and attitudes of women towards hormone replacement therapy (HRT), we conducted a questionnaire survey of 180 women attending a gynaecology clinic, of whom 152 (84.4%) responded. Seventy-one of the women had heard of HRT. Awareness of HRT was higher in the 50-59 year age group and in women with higher education, but lower in Indo-Asian women than in white and black/Afro-Caribbean women. Friends, relatives and the media were important sources of information (apart from the doctor), especially among the younger age groups. The women themselves ranked their overall understanding of HRT as 'low'; 78% felt they did not know enough about the subject. A distorted perception of benefits/risks associated with HRT was also noted--cardiovascular protection was not appreciated, whereas there was an excessive fear of breast cancer. Twenty-eight per cent of the menopausal, postmenopausal and hysterectomised women surveyed were current HRT users. We conclude that factors such as ethnicity, age and educational level have an impact on women's awareness of and attitudes towards HRT. Some confusion about the real benefits/risks still exists, which probably accounts for low acceptance of this treatment, and suggests that clinicians prescribing HRT need to be aware of these problems.

Measurement of telomeric DNA content in human tissues.

Telomeres, nucleoprotein complexes at the ends of eukaryotic chromosomes, are 10-12 kbp in length in somatic cells, but as small as 1-2 kbp in rapidly growing cancer cells. Southern blot analysis is currently the standard method for the measurement of telomere length. However, accurate determinations are not possible when DNA is broken or scant. To avoid these problems, a slot blot assay that quantitates the relative content, instead of length, of telomere DNA was developed. The relative contents of telomere DNA determined by this slot blot assay were directly proportional to the relative lengths of telomere DNA determined in parallel by Southern blot analysis. Relative telomere DNA content could be measured in samples containing as little as 15 ng of total DNA. Relative telomere DNA content, but not length, also was unaffected by breakage of DNA into fragments 1 kbp or less in length.

Structure and function of the class C tetracycline/H+ antiporter: three independent groups of phenotypes are conferred by TetA (C).

The class C tetracycline/H+ antiporter, TetA(C), confers nine distinct phenotypes in Escherichia coli: resistance to tetracycline, reduced culture density at stationary phase (growth yield), increased supercoiling of plasmid DNA, delayed growth in succinate minimal medium, complementation of potassium uptake defects, increased susceptibility to cadmium, increased susceptibility to fusaric acid, increased susceptibility to bleomycin and increased susceptibility to several classes of cationic aminoglycoside antibiotics. These nine phenotypes were resolved into three 'linkage' groups based on their patterns of suppression by mutations of the tetA(C) gene of plasmid pBR322. Group I includes resistance to tetracycline, increased susceptibility to cadmium and reduced growth yield. Group II includes delayed growth in succinate minimal medium and complementation of potassium uptake defects. Group III includes increased supercoiling of plasmid DNA and increased susceptibilities to fusaric acid, bleomycin and cationic aminoglycosides. Phenotypes of Groups II and III, but not Group I, also were conferred by a chimeric gene encoding a fusion between the N-terminal 34 residues of TetA(C) and the C-terminal 429 residues of a structurally-similar protein, the E. coli galactose/H+ symporter, GalP. In contrast, none of these phenotypes was conferred by a chimeric gene encoding a fusion between the N-terminal 34 residues of TetA(C) and a structurally-dissimilar protein, TEM beta-lactamase. These results demonstrate that the three groups of linked phenotypes are dependent on different elements of the TetA(C) amino acid sequence, implying that TetA(C) confers these phenotypes by at least three independent mechanisms.