A randomized, double-blind, non-inferiority trial comparing the immunogenicity and safety of two seasonal inactivated influenza vaccines in adults.

BACKGROUND: To enhance the production and availability of influenza vaccines in different regions of the world is paramount to mitigate the global burden of this disease. Instituto Butantan developed and manufactured an embryonated egg-based inactivated split-virion trivalent seasonal influenza vaccine as part of a technology transfer partnership with Sanofi Pasteur. METHODS: This is a phase IV, randomized, double-blind, active-controlled, multicenter clinical trial including adults 18-60 and > 60 years recruited during the 2019 southern hemisphere influenza season. Subjects were randomized 1:1 to receive either the Sanofi Pasteur Trivalent Seasonal Influenza Vaccine (SP-TIV) or Instituto Butantan Trivalent Seasonal Influenza Vaccine (IB-TIV). Hemagglutinin inhibition antibody titers were assessed pre-vaccination and 21 days post-vaccination. RESULTS: 624 participants were randomized and vaccinated. In both intention-to-treat and per-protocol analysis, non-inferiority of the SP-TIV versus IB-TIV was demonstrated for the three influenza strains. In the per-protocol analysis, the SP-GMT/IB-GMT ratios for H1N1, H3N2, and B were 0.9 (95%CI, 0.7-1.1), 1.2 (95%CI, 1.0-1.4), and 1.1 (95%CI, 0.9-1.3), respectively. Across vaccination groups, the most common adverse reactions (AR) were limited to the injection-site, including pain and tenderness. The majority of the ARs were graded 1 and/or 2 and lasted less than one day. No serious adverse reaction was observed. CONCLUSION: This study demonstrated the non-inferiority of the immunogenicity of a single-dose of Instituto Butantan versus a single dose of the Sanofi Pasteur Seasonal Trivalent Influenza Vaccine in adults. Both vaccines were well tolerated and presented similar safety profiles.

Cervical cancer screening in low- and middle-income countries: A systematic review of economic evaluation studies.

Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.

Cervical cancer screening in low- and middle-income countries: A systematic review of economic evaluation studies

Abstract Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.

Simple but not simpler: a systematic review of Markov models for economic evaluation of cervical cancer screening.

The aim of this study was to critically evaluate the quality of the models used in economic evaluations of screening strategies for cervical cancer prevention. We systematically searched multiple databases, selecting model-based full economic evaluations (cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses) of cervical cancer screening strategies. Two independent reviewers screened articles for relevance and performed data extraction. Methodological assessment of the quality of the models utilized formal checklists, and a qualitative narrative synthesis was performed. Thirty-eight articles were reviewed. The majority of the studies were conducted in high-income countries (82%, n=31). The Pap test was the most used screening strategy investigated, which was present in 86% (n=33) of the studies. Half of the studies (n=19) used a previously published Markov model. The deterministic sensitivity analysis was performed in 92% (n=35) of the studies. The mean number of properly reported checklist items was 9 out of the maximum possible 18. Items that were better reported included the statement of decision problem, the description of the strategies/comparators, the statement of time horizon, and information regarding the disease states. Compliance with some items of the checklist was poor. The Markov models for economic evaluation of screening strategies for cervical cancer varied in quality. The following points require improvement: 1) assessment of methodological, structural, heterogeneity, and parameter uncertainties; 2) model type and cycle length justification; 3) methods to account for heterogeneity; and 4) report of consistency evaluation (through calibration and validation methods).

Influence of Prior Knowledge of Human Papillomavirus Status on the Performance of Cytology Screening.

OBJECTIVES: This study aimed to evaluate the influence of prior knowledge of human papillomavirus (HPV) status in cervical cytopathology readings. METHODS: Participants comprised 2,376 women who underwent parallel cytology and HPV-DNA testing. Smears were read twice by the same team, first with previous knowledge of HPV-DNA status. RESULTS: Overall, 239 (10.2%) smears had their cytology classification altered by the HPV-informed review. Cytology readings with prior knowledge of the HPV status revealed 10.5% of abnormal smears (atypical squamous cells of undetermined significance or higher), while without prior knowledge, this rate dropped to 7.6%. When HPV status was informed, a significant increase in all categories of altered smears was observed. Cytology with prior knowledge of HPV status detected more cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) compared with blinded: 86.7% vs 60.0%. CONCLUSIONS: Our data indicate that cytology interpreted with prior knowledge of the HPV status provides higher sensitivity for CIN 2+ lesions while marginally reducing the overall specificity compared with HPV status blinded cytology.

Simple but not simpler: a systematic review of Markov models for economic evaluation of cervical cancer screening

The aim of this study was to critically evaluate the quality of the models used in economic evaluations of screening strategies for cervical cancer prevention. We systematically searched multiple databases, selecting model-based full economic evaluations (cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses) of cervical cancer screening strategies. Two independent reviewers screened articles for relevance and performed data extraction. Methodological assessment of the quality of the models utilized formal checklists, and a qualitative narrative synthesis was performed. Thirty-eight articles were reviewed. The majority of the studies were conducted in high-income countries (82%, n=31). The Pap test was the most used screening strategy investigated, which was present in 86% (n=33) of the studies. Half of the studies (n=19) used a previously published Markov model. The deterministic sensitivity analysis was performed in 92% (n=35) of the studies. The mean number of properly reported checklist items was 9 out of the maximum possible 18. Items that were better reported included the statement of decision problem, the description of the strategies/comparators, the statement of time horizon, and information regarding the disease states. Compliance with some items of the checklist was poor. The Markov models for economic evaluation of screening strategies for cervical cancer varied in quality. The following points require improvement: 1) assessment of methodological, structural, heterogeneity, and parameter uncertainties; 2) model type and cycle length justification; 3) methods to account for heterogeneity; and 4) report of consistency evaluation (through calibration and validation methods).

All-Cause Mortality Attributable to Sitting Time: Analysis of 54 Countries Worldwide.

INTRODUCTION: Recent studies have shown that sitting time is associated with increased risk of all-cause mortality, independent of moderate to vigorous physical activity. Less is known about the population-attributable fraction for all-cause mortality associated with sitting time, and the gains in life expectancy related to the elimination of this risk factor. METHODS: In November 2015, data were gathered from one published meta-analysis, 54 adult surveys on sitting time distribution (from 2002 to 2011), in conjunction with national statistics on population size, life table, and overall deaths. Population-attributable fraction for all-cause mortality associated with sitting time >3 hours/day was estimated for each country, WHO regions, and worldwide. Gains in life expectancy related to the elimination of sitting time >3 hours/day was estimated using life table analysis. RESULTS: Sitting time was responsible for 3.8% of all-cause mortality (about 433,000 deaths/year) among those 54 countries. All-cause mortality due to sitting time was higher in the countries from the Western Pacific region, followed by European, Eastern Mediterranean, American, and Southeast Asian countries. Eliminating sitting time would increase life expectancy by 0.20 years in those countries. CONCLUSIONS: Assuming that the effect of sitting time on all-cause mortality risk is independent of physical activity, reducing sitting time plays an important role in active lifestyle promotion, which is an important aspect of premature mortality prevention worldwide.

Cost-effectiveness analysis of universal maternal immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Brazil.

BACKGROUND: Pertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants <4 months are most affected. This study aimed to evaluate the cost-effectiveness of introducing universal maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil. METHODS: Economic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed. RESULTS: Maternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness. CONCLUSION: The results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil.

Effect of physical inactivity on major noncommunicable diseases and life expectancy in Brazil.

BACKGROUND: In Brazil, one-fifth of the population reports not doing any physical activity. This study aimed to assess the impact of physical inactivity on major noncommunicable diseases (NCDs), all-cause mortality and life expectancy in Brazil, by region and sociodemographic profile. METHODS: We estimated the population attributable fraction (PAF) for physical inactivity associated with coronary heart disease, type 2 diabetes, breast cancer, colon cancer, and all-cause mortality. To calculate the PAF, we used the physical inactivity prevalence from the 2008 Brazilian Household Survey and relative risk data in the literature. RESULTS: In Brazil, physical inactivity is attributable to 3% to 5% of all major NCDs and 5.31% of all-cause mortality, ranging from 5.82% in the southeastern region to 2.83% in the southern region. Eliminating physical inactivity would increase the life expectancy by an average of 0.31 years. This reduction would affect mainly individuals with ≥ 15 years of schooling, male, Asian, elderly, residing in an urban area and earning ≥ 2 times the national minimum wage. CONCLUSIONS: In Brazil, physical inactivity has a major impact on NCDs and mortality, principally in the southeastern and central-west regions. Public policies and interventions promoting physical activity will significantly improve the health of the population.