Comparing Influenza Vaccine Efficacy Against Mismatched And Matched Strains: A Systematic Review And Meta-Analysis

Background: Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains. Methods: We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk x 100%). Results: We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I-2 < 50%) across all meta-analyses, except for the LAIV meta-analyses among children (I-2 = 79%). Conclusions: The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.Canadian Institutes for Health Research/Drug Safety and Effectiveness Network New Investigator Award in Knowledge Synthesi

Driver distraction impact assessment test : Design, development, administration, and partial evaluation

Cette thèse présente le produit d'un projet de recherche doctoral ambitieux qui a procédé à la réalisation des premières étapes cruciales de conception, développement et évaluation d'un test de mesure de l'impact de la distraction du conducteur (DDIAT). L'objectif de ce test est de mesurer l'impact que la distraction du conducteur a sur les performances de conduite et les comportements du conducteur. En outre, une présentation sera effectuée des étapes majeures qui restent encore à réaliser, et qui dépassent le cadre de cette thèse, pour entièrement valider et implémenter le test. Le DDIAT est composé de trois épreuves de conduite ou Drives (Drive 1, 2 et 3), qui ont été conçues à partir des principes de la littérature de la cognition et de l’attention. Les épreuves Drive 1 et Drive 2 ont été implémentées dans un environnement de conduite urbain et elles incluent des conditions de feux de circulation qui ont été conçues pour ressembler aux feux de circulation rencontrés dans des conditions de conduite réelles. De plus, l'épreuve Drive 1 inclut des scénarios de traversée d’une file de véhicules pour tourner à gauche à une intersection (gap acceptance), dans lesquels les participants doivent prendre la décision cruciale de sélectionner un intervalle entre deux véhicules pour traverser. L'épreuve Drive 2 inclut plusieurs instances de suivi de véhicule, dont certaines où le véhicule suivi freine brutalement et où le participant doit réagir de manière appropriée pour éviter une collision frontale. Enfin, l'épreuve Drive 3 a été conçue pour implicitement mesurer la conscience de la situation dans un environnement de conduite autoroutier, mais cette épreuve n'a pas été entièrement implémentée dans le cadre de cette thèse. Les épreuves Drive 1 et Drive 2 ont été évaluées dans une expérimentation sur un simulateur de conduite avancé. Les résultats de cette évaluation expérimentale ont montré que les deux épreuves Drive 1 et Drive 2 étaient capables de : a) représenter la conduite réelle (c.-à-d., elles vérifient la validité de contenu et la validité apparente), b) mesurer l'impact de la distraction du conducteur et c) de faire la distinction entre les deux tâches secondaires (l'une visuelle/manuelle, l'autre auditive/cognitive) à travers leur impact sur les performances de conduite. En conclusion, le travail complété dans le cadre de cette thèse constitue les premières étapes cruciales nécessaires au développement d'un DDIAT complet qui surpasse les limitations des outils et tests précédents et fournit également les bases d'une méthode standardisée pour aider à surpasser les incohérences qui existent entre les différentes études de mesure de l'impact de la distraction du conducteur.This thesis describes the outcomes of an ambitious doctoral research program that carried out the initial critical steps in the design, development, and evaluation of a driver distraction impact assessment test (DDIAT). The purpose of this test has been to assess the impact driver distraction has on driving performance and driver behaviour. The thesis also describes the critical steps, beyond the scope of this thesis, that remain to be carried out in order to fully validate and implement the complete DDIAT proposed in this thesis. As part of the DDIAT proposed in this thesis, three Drives (Drive 1, 2, and 3) were designed and created from basic attention principles and by using a complex experimental design. Drive 1 and Drive 2 were implemented in an urban driving environment and included traffic light conditions that were designed to resemble real world traffic light conditions. Furthermore, Drive 1 included gap acceptance events in which participants had to make a crucial and important decision when selecting a gap to turn left though an oncoming stream of vehicles. Drive 2 included various car following instances and lead vehicle braking events, whereby participants had to react suddenly to avoid a frontal collision. Lastly, Drive 3 was designed to implicitly measure situation awareness on a highway driving environment – but was outside of the scope of the thesis to investigate. Drive 1 and Drive 2 were evaluated in an experiment implemented in an advanced driving simulator. The results from this evaluation experiment showed that both Drive 1 and Drive 2: a) represent real world driving (i.e., have content and face validity); b) are capable of measuring the impact of driver distraction; and c) are capable of distinguishing between the impact on driving of two secondary tasks (one visual/manual, the other auditory/cognitive). In conclusion, the work completed as part of this thesis provided a first and important step towards the development of a complete DDIAT that overcomes the shortcomings of previous tests and tools and also provides the beginnings of a standardised method to assist in overcoming the inconsistencies that exist across studies in the measurement of driver distraction

Effect of influenza vaccines against mismatched strains: a systematic review protocol

Abstract Background Influenza vaccines are most effective when the antigens in the vaccine match those of circulating influenza strains. The extent to which the vaccine is protective when circulating strains differ from vaccine antigens, or are mismatched, is uncertain. We propose to systematically review the cross-protection offered by influenza vaccines against circulating influenza A or B viruses that are not antigenically well-matched to vaccine strains. Methods/Design This is a protocol for a systematic review and meta-analysis. Placebo-controlled randomized clinical trials (RCTs) reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of influenza strains that differed from those circulating will be included. The primary outcome is the incidence of laboratory-confirmed influenza (polymerase chain reaction (PCR) or viral culture). The secondary outcome is the incidence of laboratory-confirmed influenza through antibody assay (a less sensitive test than PCR or viral culture) alone or combined with PCR, and/ or viral culture. The review will be limited to RCTs written in English. We will search MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, previous influenza reviews, and the reference lists of included studies to identify potentially relevant RCTs. Two independent reviewers will conduct all levels of screening, data abstraction, and quality appraisal (using the Cochrane risk of bias tool). If appropriate, random effects meta-analysis of vaccine efficacy will be conducted in SAS (version 9.2) by calculating the relative risk. Vaccine efficacy will be calculated using the following formula: (1 - relative risk × 100). The results will be analyzed by type of vaccine (live attenuated, trivalent inactivated, or other). Subgroup analysis will include the effects of age (children, adults, older participants), and influenza A versus influenza B on the results. For influenza B we will also consider variable degrees of antigenic mismatch (lineage and drift mismatch). Discussion Our results can be used by researchers and policy-makers to help predict the efficacy of influenza vaccines during mismatched influenza seasons. Furthermore, the review will be of interest to patients and clinicians to determine whether to get immunized or support immunization for a particular influenza season

Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis

Abstract Background Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains. Methods We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%). Results We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%). Conclusions The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs

Density of the Waterborne Parasite Ceratomyxa shasta and Its Biological Effects on Salmon

The myxozoan parasite Ceratomyxa shasta is a significant pathogen of juvenile salmonids in the Pacific Northwest of North America and is limiting recovery of Chinook (Oncorhynchus tshawytscha) and coho (O. kisutch) salmon populations in the Klamath River. We conducted a 5-year monitoring program that comprised concurrent sentinel fish exposures and water sampling across 212 river kilometers of the Klamath River. We used percent mortality and degree-days to death to measure disease severity in fish. We analyzed water samples using quantitative PCR and Sanger sequencing, to determine total parasite density and relative abundance of C. shasta genotypes, which differ in their pathogenicity to salmonids. We detected the parasite throughout the study zone, but parasite density and genetic composition fluctuated spatially and temporally. Chinook and coho mortality increased with density of their specific parasite genotype, but mortality-density thresholds and time to death differed. A lethality threshold of 40% mortality was reached with 10 spores liter(⁻¹) for Chinook but only 5 spores liter(⁻¹) for coho. Parasite density did not affect degree-days to death for Chinook but was negatively correlated for coho, and there was wider variation among coho individuals. These differences likely reflect the different life histories and genetic heterogeneity of the salmon populations. Direct quantification of the density of host-specific parasite genotypes in water samples offers a management tool for predicting host population-level impacts.Keywords: Klamath River-basin, Infective stage, Rainbow trout, Myxosporean parasite, Oncorhynchus-tshawytscha, Coho salmon, Temperature, Host, Myxozoa, Juvenile Chinook salmo