Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects

Conflits travail-famille et ajustement dyadique chez des couples d'aidants de la génération "sandwich" qui prennent soin d'un parent en perte d'autonomie fonctionnelle dans les activités de la vie quotidienne

Cette recherche s'attarde à l'examen des différences entre les conjoints sur les variables d'engagement dans les rôles, de conflits travail-famille et d'ajustement dyadique. Un autre objectif de la recherche est de vérifier s'il existe des conflits travail-famille vécus par les couples d'aidants qui prennent soin d'un parent âgé en perte d'autonomie fonctionnelle alors qu'ils ont des enfants à leur charge et qu'ils occupent un emploi rémunéré. Le lien entre les conflits travail-famille et l'ajustement dyadique des conjoints qui combinent ces rôles multiples est également observé. Pour ce faire, 45 couples d'aidants de la génération sandwich ont été sollicités pour participer à l'étude et ont rencontré un interviewer qui, après leur avoir expliqué les buts et le déroulement de l'étude, a recueilli leur consentement et leur a distribué un questionnaire autoadministré. Les participants ont répondu individuellement à des échelles portant, entre autres, sur l'engagement dans les rôles de vie, les conflits travail-famille et l'ajustement dyadique. Les résultats obtenus démontrent que les hommes et les femmes s'engagent dans certains rôles selon le modèle traditionnel des rôles sexuels. En effet, les femmes s'impliquent davantage dans leur rôle de mère et les hommes, dans celui de travailleur. Toutefois, les conjoints ne diffèrent pas significativement au plan de l'engagement dans le rôle d'aidant familial, de responsable de l'organisation de la maison ou de conjoint. De plus, contrairement à ce qui était attendu, les résultats indiquent que les niveaux de conflits travail-famille et d'ajustement dyadique des conjoints étaient comparables. Ces résultats permettent de porter un regard sur la situation des couples à double revenu et leur ajustement conjugal lorsqu'ils endossent le rôle de parent et prodiguent des soins à un parent âgé. Au niveau des implications sociales, les résultats de cette étude démontrent que des divergences ressortent entre les hommes et les femmes au plan de l'engagement dans les rôles de parent et de travailleur, mais pas pour les autres rôles. Toutefois, contrairement aux attentes, il semble qu'en général, les couples d'aidants de la génération sandwich ne soient pas victimes de hauts niveaux de conflits travail-famille ni d'insatisfaction conjugale. Le travail à temps partiel des femmes et le soutien conjugal et familial, ainsi que les services reçus pourraient expliquer ces résultats

Attachment insecurities and under-commitment in distressed couples : the role of positive and negative partner behaviors

Research has rarely considered intermediate variables in the association between attachment insecurities and relationship commitment. Based on attachment theory and Rusbult's Investment Model, we tested whether positive and negative partner behaviors explain this association in 91 distressed couples undergoing therapy. Path analyses based on the Actor–Partner Interdependence Model revealed that individuals with attachment avoidance reported perceiving fewer positive behaviors from their partner, which was associated with their own higher under-commitment. Partners of individuals with avoidance also reported perceiving fewer positive partner behaviors, which was in turn associated with their own higher under-commitment. Partners of individuals with attachment anxiety perceived more positive behaviors from their partner, which was associated to their own lower under-commitment. Perceived negative partner behaviors were only directly associated with higher under-commitment. These findings imply that perceived positive partner behaviors may be a key aspect to target in relationship therapy in couples who present with high attachment insecurities

Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality.

peer reviewedDespite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain–specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation. A three-variable model of vRNA, with predefined adjustment by age and sex, robustly identified patients with fatal outcome (adjusted hazard ratio for log-transformed vRNA = 3.5). This model remained robust in independent validation and confirmation cohorts. Since plasma vRNA’s predictive accuracy was maintained at earlier time points, its quantitation can help us understand disease heterogeneity and identify patients who may benefit from new therapies

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer

BackgroundThe traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.MethodsThis is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient’s choice. Our primary objective is to determine the rate of ‘failure’ of disease management in respective AS and surgical arms as defined by: i) AS arm – surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.DiscussionThe results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.Registration detailsThis prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Panel : Le codéveloppement en mode virtuel tout comme si vous étiez là!

Un panel d’experts de 120 minutes pendant lequel vous aurez l’occasion d’être conquis par le codéveloppement à distance, grâce à nos panélistes qui vous démontreront que l’animation en mode virtuel permet des apprentissages tout comme en présentiel et offre aussi des bénéfices. Des discussions animées où des experts Nathalie Lafranchise et Caroline Brassard mettront en lumière le fruit de leurs recherches, appuyées par les témoignages de nos praticiens invités Nathalie Sabourin et Anick Perron