| 1. |
- Boutry, Céline, et al.
(författare)
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The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster : Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 74:8, s. 1459-1467
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Tidskriftsartikel (refereegranskat)abstract
- Efficacy against herpes zoster and immune responses to the adjuvanted recombinant zoster vaccine plateaued at high levels between 5.1 and 7.1 years (mean) post-vaccination, suggesting that its clinical benefit in older adults is sustained for at least 7 years post-vaccination. Background This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age >= 50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after >= 2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. Methods Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing >= 2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. Results Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. Conclusions Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination.
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| 2. |
- Janssen, Samuel, et al.
(författare)
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Pharmacokinetics, biodistribution, and antitumor efficacy of a human glandular kallikrein 2 (hK2)-activated thapsigargin prodrug
- 2006
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 66:4, s. 358-368
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer cells secrete unique proteases such as prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) that represent targets for the activation of prodrugs as systemic treatment of metastatic prostate cancer. Previously, a combinatorial peptide library was screened to identify a highly active peptide substrate for hK2. The peptide was coupled to an analog of the potent cytotoxin thapsigargin, L12ADT, to generate an hK2-activated prodrug that was efficiently hydrolyzed by purified hK2, stable to hydrolysis in human and mouse plasma in vitro and selectively toxic to hK2 producing prostate cancer cells in vitro. METHODS: In the current study, toxicology, pharmacokinetics, prodrug biodistribution, and antitumor efficacy studies were performed to evaluate the hK2-activated prodrug in vivo. RESULTS: The single intravenous maximally tolerated dose of prodrug was 6 mg/kg (i.e., 3.67 micromole/kg) which produced peak serum concentration of approximately 36 microM and had a half-life of approximately 40 min. In addition, over a 24 hr period <0.5% of free L12ADT analog was observed in plasma. The prodrug demonstrated significant antitumor effect in vivo while it was being administered, but prolonged intravenous administration was not possible due to local toxicity to tail veins. Subcutaneous administration of equimolar doses produced lower plasma AUC compared to intravenous dosing but equivalent intratumoral levels of prodrug following multiple doses. CONCLUSIONS: The hK2-activated prodrug was stable in vivo. The prodrug, however, was rapidly cleared and difficult to administer over prolonged dosing interval. Additional studies are underway to assess antitumor efficacy with prolonged administration of higher subcutaneous doses of prodrug. Second-generation hK2-activated thapsigargin prodrugs with increased half-lives and improved formulations are also under development.
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| 3. |
- White, Marc, et al.
(författare)
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Identification, Control and Prevention of Work-related Psychosocial Hazards and Social Conditions Contributing to Mental Health Disorders and Prolonged Work Absence
- 2016
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Ingår i: CARWH 2016: Advancing Research to Improve Work and Health October 16-18, 2016.
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Konferensbidrag (refereegranskat)abstract
- Background & ObjectivesThis study is part of a series of projects arising from an academic stakeholder partnership (ASP) to facilitate the identification and translation of credible research to support and sustain safe, psychologically healthy, inclusive and productive workplaces. Prior work identified modifiable risk factors contributing to work absence, followed by a synthesis of workplace interventions that targeted these factors based on systematic reviews published between 2000 – 2012. This knowledge synthesis and translation project updates these findings with a specific focus on workplace interventions targeting psychological health and organizational culture. All projects in this series is associated with the content population of the Health and Work Productivity Web-Portal.MethodsParticipatory action research approach (problem identification, problem clarification, problem resolution), the utilization of a modified PRECEDE-PROCEED Model (predisposing, enabling, reinforcing factors); snowball methodology to expand team participants; collaborative survey development, discussions, and minutes as working documents to identify high priority issues relevant to stakeholders, to create PICO and search strategy. Following literature search pairs of researchers independently reviewed titles. Work continues on review of abstracts and full papers against a set of inclusion/exclusion criteria.ResultsParticpatory methods led to creation of a revised PICO statement, refinement of keywords and changes in search parameters to better meet the needs of organizational partners. Given changes in prior search terms a new search was conducted from 2000 to present across Medline, Embase, CDSR, DARE, CINAHL, PsycINFO, TRIP, NARIC, REHAB+ resulting in identification of 5644 citations. Following duplicate removal and administrative review of titles 1046 citations remained for scientific review. Administrative removal based on removal of pharmaceutical, clinical, non-work-related titles only. In the first round of scientific review there was poor congruence of title selection which has led to the creation of checklist and guide currently being tested.ConclusionsParticipatory approaches to knowledge synthesis and its translation creates opportunities for learning for all participants. Stakeholder participation has led to a better understanding of high priority needs across different stakeholders which has led to refinement PICO, and search strategy. Discussions with stakeholders has increased awareness of the need for root cause analysis. Preliminary results of the knowledge synthesis will be reported.
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| 4. |
- White, Marc, et al.
(författare)
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Planning, Implementing and Evaluating Successful Workplace Interventions for Psychologically Healthy and Productive Workplaces : A Pattern Analysis of 57 Systematic Reviews
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Mental health in the workplace is a key topic in British Columbia, across Canada and internationally with a growing focus on the importance of creating and sustaining safe, healthy, productive and inclusive workplaces. This stakeholder-centred best evidence-based synthesis of systematic reviews searched Medline, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, CINAHL, PsycINFO, TRIP, REHABDATA (NARIC), REHAB+ (McMaster), and Health-evidence.ca (McMaster) published between January 1, 2000 and February 2016 to identify interventions that addressed: mental health symptomatology (depression, anxiety, PTSD, etc.), job control, job demands, social support, stress management, and wellness (health promotion). Following deduplication 5,646 citations were reviewed by two or more independent reviewers. Following title and abstract review, 168 full text articles were reviewed against inclusion/exclusion criteria, resulting in 57 systematic reviews being included. Based on findings and trend analysis, the academic-stakeholder team proposed a framework for planning, implementing and evaluating interventions to mitigate psychosocial hazards in the workplace. Due to low quality evidence and experimental pre and post design of many studies recommendations should be considered with some caution noting the need for more rigorous monitoring of their implementation.
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