scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

2020 ◽  
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (Sanofi Pasteur) and DENVax (Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. While Dengvaxia resulted in serious adverse events and is restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods. Although better measurement over long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, we also compare the VE estimations for 12 and 18 months and we observe that the efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, bring up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 674
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV—Sanofi Pasteur) and DENVax (TAK 003—Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

Darbepoetin alfa improves quality of life in cancer patients undergoing radiation, final results of a multicenter, open study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18531-18531
Author(s):  
D. Antonadou ◽  
P. Varveris ◽  
P. Karageorgis ◽  
V. Papadopoulos ◽  
G. Georgakopoulos ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Darbepoetin Alfa ◽  
Well Being ◽  
Response To Treatment ◽  
Primary Study ◽  
Serious Adverse Events ◽  
Poor Prognostic Factor ◽  
Significant Difference ◽  
The Impact ◽  
Over Time

18531 Background: Anaemia is a poor prognostic factor for patients undergoing radiotherapy (XRT) and has been associated with decreased response to treatment. Darbepoetin alfa has been proven effective in treating anaemia and in improving QoL. The purpose of this study was to assess the efficacy, safety and the impact on QoL of darbepoetin alfa in these pts. Methods: Patients with Hb level 10–12 g/dl, PS ECOG <2, and life expectancy >6 mos were administered darbepoetin alfa SC 150 mcg once weekly during the 6 wk course of conventional XRT (2 Gy/5 days/week). All pts received iron supplem. Blood transfusion was given for Hb <9 g/dl. Complete blood counts, serum iron, folate, B12, ferritin, serum LDH, bilirubin and reticulocyte count were measured weekly. The primary study endpoints were changes in Hb level during XRT, number of transfusions and evaluation of QoL. Results: Between Mar 2002 and Feb 2004, 140 pts were entered, 116 were evaluable. Mean Hb at baseline was 10.95 ± 1.76. There was a significant increase (17.1%) in mean Hb levels from 2nd wks onwards with the peak value at wk 10 from XRT initiation. Hb significantly increased to 12.03 ± 2.39 (p < 0.001), 12.63 ± 2.10 (p < 0.001) and 12.96 ± 2.33 (p < 0.001) at 3,6 and 10 wks, respectively. Blood transfusion was necessary in 3 pts (2.6%). None of the pts experienced serious adverse events. There was a significant difference in physical well being score between Hb levels (p = .016) regardless the period of time (p = .17). Pts with high Hb levels had higher functional well being scores (p = .002) regardless time for the interaction (p = .24).There was a significant difference in mean fatigue score between Hb levels (p=.019) and a significant time by group interaction (p = .03).Pts with high Hb levels tend to have a higher social well being score than those with lower Hb (p = .08) while the differences were similar over time (p = .89).Those with Hb ≤ 12 g/dL had a tendency for increased emotional scores at 6 wks (p = .07) while the differences were similar over time (p = .138). Conclusion: Hb levels were significantly increased from baseline, irrespective of tumour localisation and stage. This increase reached the maximum value during wk 10 and remained significant 2 mos post XRT. QoL was significantly improved in these pts. No significant financial relationships to disclose.

scholarly journals Social Justice and Gender

Open Theology ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. 288-295
Author(s):  
William Loader
Keyword(s):  
Public Discourse ◽  
Value System ◽  
Greek Translation ◽  
Early Christian ◽  
Age At Marriage ◽  
Long Time ◽  
And Gender ◽  
The Impact ◽  
Creation Stories ◽  
Over Time

AbstractThis article examines the impact of the widespread pattern of unequal age at marriage which led men to conclude that not only were their wives less experienced and mature, they were also inferior by nature. It examines the ideological underpinning for the view of women’s inferiority in Plato and the Genesis creation stories, especially in their Greek translation. It then traces the way this value system found expression in the traditional allocation of gender roles, women taking responsibility for the internal affairs of the household and men for the external affairs, including public discourse. There were exceptions both within Judaism and within the early Christian movement. These and the egalitarian thoughts in Christian beginnings had the potential to subvert these norms, over time, but a long time.

scholarly journals Principal surrogates in context of high vaccine efficacy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Andrea Callegaro ◽  
Fabian Tibaldi ◽  
Dean Follmann
Keyword(s):  
Vaccine Efficacy ◽  
Meta Analysis ◽  
Principal Stratification ◽  
Simulation Experiments ◽  
Correlates Of Protection ◽  
Vaccine Trials ◽  
Simulation Results ◽  
The Impact ◽  
Statistical Solutions ◽  
Very High

Abstract Objectives The use of correlates of protection (CoPs) in vaccination trials offers significant advantages as useful clinical endpoint substitutes. Vaccines with very high vaccine efficacy (VE) are documented in the literature (95% or above). Callegaro, A., and F. Tibaldi. 2019. “Assessing Correlates of Protection in Vaccine Trials: Statistical Solutions in the Context of High Vaccine Efficacy.” BMC Medical Research Methodology 19: 47 showed that the rare infections observed in the vaccinated groups of these trials poses challenges when applying conventionally-used statistical methods for CoP assessment such as the Prentice criteria and meta-analysis. The objective of this work is to investigate the impact of this problem on another statistical method for the assessment of CoPs called Principal stratification. Methods We perform simulation experiments to investigate the effect of high vaccine efficacy on the performance of the Principal Stratification approach. Results Similarly to the Prentice framework, simulation results show that the power of the Principal Stratification approach decreases when the VE grows. Conclusions It can be challenging to validate principal surrogates (and statistical surrogates) for vaccines with very high vaccine efficacy.

scholarly journals The importance of time post-vaccination in determining the decrease in vaccine efficacy against SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Yinon M. Bar-On ◽  
Elad Noor ◽  
Noam Gottlieb ◽  
Alex Sigal ◽  
Ron Milo
Keyword(s):  
Vaccine Efficacy ◽  
Strong Dependence ◽  
Similar Efficacy ◽  
Mitigation Strategies ◽  
High Efficacy ◽  
Breakthrough Infection ◽  
Post Vaccination ◽  
Open Question ◽  
The Impact ◽  
Efficacy Studies

With the development of high-efficacy vaccines against SARS-CoV-2, an urgent open question is whether currently available vaccines protect with similar efficacy against infection with SARS-CoV-2 variants of concern (VOC). Recent reports quantifying the extent by which VOC can evade vaccine immunity resulted in a range of estimates for the same VOC, which makes them difficult to interpret. One possible explanation for the discrepancies between different studies is an inconsistency in terms of the time post-vaccination of the sampled population. Here we present a model based on the observed correlation between antibody neutralization levels and vaccine efficacy, which demonstrates the impact of time post-vaccination on the comparison of the vaccine efficacy for VOC versus non-VOC infections. Our model predicts and exemplifies several possible consequences for vaccine efficacy in VOC infections: 1) a delay in the onset of vaccine efficacy against VOC; 2) a transient increase in susceptibility to breakthrough infection with VOC compared to non-VOC as a function of time after vaccination. We review preliminary data indicating that such phenomena are observed in studies of the B.1.1.7 and B.1.351 variants. We find that ignoring the strong dependence on the time post-vaccination can lead to contradictory reports of relative efficacy against VOC versus non-VOC, with implications on mitigation strategies against VOC and the design of vaccine efficacy studies.

scholarly journals Three years efficacy and safety of Takeda’s dengue vaccine candidate (TAK-003)

2021 ◽  
Author(s):  
Luis Rivera ◽  
Shibadas Biswal ◽  
Xavier Sáez-Llorens ◽  
Humberto Reynales ◽  
Eduardo López-Medina ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Efficacy And Safety ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Safety Risks ◽  
Long Term Follow Up ◽  
To Receive

Abstract Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year post-vaccination. This exploratory analysis provides an update with cumulative and third year data. Methods Healthy 4–16 year-olds (n=20,099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific RT-PCR. Results Cumulative efficacy after three years was 62.0% (95% confidence interval: 56.6%, 66.7%) against virologically-confirmed dengue (VCD) and 83.6% (76.8%, 88.4%) against hospitalized VCD. Efficacy was 54.3% (41.9%, 64.1%) against VCD and 77.1% (58.6%, 87.3%) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9%, 70.1%) against VCD and 86.0% (78.4%, 91.0%) against hospitalized VCD in seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5%, 54.7%), while efficacy against hospitalized VCD was sustained at 70.8% (49.6%, 83.0%). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (i.e. second half of the three years following vaccination), but none were related. No important safety risks were identified. Conclusions TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.

scholarly journals Modeling COVID-19 vaccine efficacy and coverage towards herd-immunity in the Basque Country, Spain

2021 ◽  
Author(s):  
Nico Stollenwerk ◽  
Javier Mar ◽  
Joseba Bidaurrazaga Van-Dierdonck ◽  
Oliver Ibarrondo ◽  
Carlo Estadilla ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Basque Country ◽  
Severe Disease ◽  
Herd Immunity ◽  
Dose Administration ◽  
Vaccine Trials ◽  
The Impact ◽  
Sterilizing Immunity ◽  
Full Immunization

Vaccines have measurable efficacies, obtained first from vaccine trials. However, vaccine efficacy is not a static measure upon licensing, and the long term population studies are very important to evaluate vaccine performance and impact. COVID-19 vaccines were developed in record time and although the extent of sterilizing immunity is still under evaluation, the currently licensed vaccines are extremely effective against severe disease, with vaccine efficacy significantly higher after the full immunization schedule. We investigate the impact of vaccines which have different efficacies after first dose and after the second dose administration schedule, eventually considering different efficacies against severe disease as opposed to overall infection. As a proof of concept, we model the vaccine performance of hospitalization reduction at the momentary scenario of the Basque Country, Spain, with population in a mixed vaccination setting, giving insights into the population coverage needed to achieve herd immunity in the current vaccination context.

The Therapist’s Reaction to a Patient’s Suicide

Crisis ◽  
2011 ◽  
Vol 32 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Friedrich Martin Wurst ◽  
Isabella Kunz ◽  
Gregory Skipper ◽  
Manfred Wolfersdorf ◽  
Karl H. Beine ◽  
...  
Keyword(s):  
Emotional Responses ◽  
Well Being ◽  
Emotional Reaction ◽  
Emotional Reactions ◽  
Analog Scale ◽  
General Hospitals ◽  
Item Questionnaire ◽  
Retrospective Nature ◽  
The Impact ◽  
Over Time

Background: A substantial proportion of therapists experience the loss of a patient to suicide at some point during their professional life. Aims: To assess (1) the impact of a patient’s suicide on therapists distress and well-being over time, (2) which factors contribute to the reaction, and (3) which subgroup might need special interventions in the aftermath of suicide. Methods: A 63-item questionnaire was sent to all 185 Psychiatric Clinics at General Hospitals in Germany. The emotional reaction of therapists to patient’s suicide was measured immediately, after 2 weeks, and after 6 months. Results: Three out of ten therapists suffer from severe distress after a patients’ suicide. The item “overall distress” immediately after the suicide predicts emotional reactions and changes in behavior. The emotional responses immediately after the suicide explained 43.5% of the variance of total distress in a regression analysis. Limitations: The retrospective nature of the study is its primary limitation. Conclusions: Our data suggest that identifying the severely distressed subgroup could be done using a visual analog scale for overall distress. As a consequence, more specific and intensified help could be provided to these professionals.

The impact of price on preference consistency over time

2011 ◽  
Author(s):  
Ki Yeon Lee ◽  
Min Zhao
Keyword(s):  
The Impact ◽  
Over Time

Euratom and Brexit: Could the United Kingdom Maintain One Foot in the European Union? Current Scenarios and Future Prospects of British withdrawal from the EAEC

2018 ◽  
Vol 18 (2) ◽  
pp. 134-151
Author(s):  
Andrea Circolo ◽  
Ondrej Hamuľák
Keyword(s):  
European Union ◽  
United Kingdom ◽  
Independent Solution ◽  
Legal Regulation ◽  
The European Union ◽  
The United Kingdom ◽  
The Status ◽  
Long Time ◽  
Energy Community ◽  
The Impact

Abstract The paper focuses on the very topical issue of conclusion of the membership of the State, namely the United Kingdom, in European integration structures. The ques­tion of termination of membership in European Communities and European Union has not been tackled for a long time in the sources of European law. With the adop­tion of the Treaty of Lisbon (2009), the institute of 'unilateral' withdrawal was intro­duced. It´s worth to say that exit clause was intended as symbolic in its nature, in fact underlining the status of Member States as sovereign entities. That is why this institute is very general and the legal regulation of the exercise of withdrawal contains many gaps. One of them is a question of absolute or relative nature of exiting from integration structures. Today’s “exit clause” (Art. 50 of Treaty on European Union) regulates only the termination of membership in the European Union and is silent on the impact of such a step on membership in the European Atomic Energy Community. The presented paper offers an analysis of different variations of the interpretation and solution of the problem. It´s based on the independent solution thesis and therefore rejects an automa­tism approach. The paper and topic is important and original especially because in the multitude of scholarly writings devoted to Brexit questions, vast majority of them deals with institutional questions, the interpretation of Art. 50 of Treaty on European Union; the constitutional matters at national UK level; future relation between EU and UK and political bargaining behind such as all that. The question of impact on withdrawal on Euratom membership is somehow underrepresented. Present paper attempts to fill this gap and accelerate the scholarly debate on this matter globally, because all consequences of Brexit already have and will definitely give rise to more world-wide effects.

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