ABSTRACT
We present the investigation and control of an extensively drug-resistant Serratia marcescens outbreak in a 30-bed intensive care unit (ICU). Within 6 weeks, 4 critically ill trauma patients were infected by the same strain. Intensive containment measures limited the spread of this strain while sustaining the capacity of the trauma ICU.
ABSTRACT
BACKGROUND: Influenza infection is a highly preventable transmissible viral disease associated with mild upper respiratory symptoms and more severe conditions such as lethal pneumonia. Studies have shown that a broader spectrum influenza vaccine could reduce influenza's burden of disease in low- and middle-income countries. A considerable number of systematic reviews reported that quadrivalent influenza vaccines are considered more effective compared to trivalent vaccines, hence, there is a need for an overview in order to synthesize the current evidence pertaining to the comparison between quadrivalent and trivalent inactivated influenza vaccines. OBJECTIVE: The aim was to summarize the evidence from systematic reviews that investigated the immunogenicity and safety of the Influenza's inactivated quadrivalent vaccine (QIV) compared to the trivalent vaccine (TIV), in the general population. METHODS: We searched articles up to December 2022 at: Web of Science, EMBASE, MEDLINE, Cochrane Library, and SCOPUS. The search strategy was conducted following the PICO model. We included systematic reviews comparing the primary outcomes of immunogenicity (seroprotection rate and seroconversion rate) and adverse events using risk ratios. The AMSTAR 2 and ROBIS were used for quality assessments, and GRADE was used for evidence certainty assessments. FINDINGS: We included five systematic reviews, totalling 47,740 participants. The Quadrivalent Inactivated Influenza Vaccine (QIV) exhibited enhanced immunogenicity in the context of B-lineage mismatch when compared to the Trivalent Inactivated Influenza Vaccine (TIV). While the safety profile of QIV was found to be comparable to that of TIV, the QIV showed a higher incidence of solicited local pain among children and adolescents, as well as an increased frequency of local adverse events within the adult population. CONCLUSION: Our findings suggest that the QIV provides a superior immunogenicity response compared to the TIV in all age groups evaluated, especially when a lineage mismatch occurred. The safety of QIV was considered similar to the TIV, with no serious or systemic solicited or unsolicited adverse events; tough pain at the injection site was greater for QIV. We recommend caution owing to the high risk of bias in the selection process and no protocol registration.
Subject(s)
Influenza Vaccines , Influenza, Human , Adolescent , Adult , Child , Humans , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Pain/etiology , Systematic Reviews as Topic , Vaccines, CombinedABSTRACT
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.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Adult , Humans , Antibodies, Viral , Double-Blind Method , Hemagglutination Inhibition Tests , Influenza A Virus, H3N2 Subtype , Influenza B virus , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Seasons , Vaccines, Inactivated/adverse effects , Adolescent , Middle Aged , Male , FemaleABSTRACT
Influenza infection is a highly preventable transmissible viral disease associated with mild upper respiratory symptoms and more severe conditions such as lethal pneumonia. Studies have shown that a broader spectrum influenza vaccine could reduce influenza’s burden of disease in low- and middle-income countries. A considerable number of systematic reviews reported that quadrivalent influenza vaccines are considered more effective compared to trivalent vaccines, hence, there is a need for an overview in order to synthesize the current evidence pertaining to the comparison between quadrivalent and trivalent inactivated influenza vaccines. Objective: The aim was to summarize the evidence from systematic reviews that investigated the immunogenicity and safety of the Influenza’s inactivated quadrivalent vaccine (QIV) compared to the trivalent vaccine (TIV), in the general population. Methods We searched articles up to December 2022 at: Web of Science, EMBASE, MEDLINE, Cochrane Library, and SCOPUS. The search strategy was conducted following the PICO model. We included systematic reviews comparing the primary outcomes of immunogenicity (seroprotection rate and seroconversion rate) and adverse events using risk ratios. The AMSTAR 2 and ROBIS were used for quality assessments, and GRADE was used for evidence certainty assessments. Findings We included five systematic reviews, totalling 47,740 participants. The Quadrivalent Inactivated Influenza Vaccine (QIV) exhibited enhanced immunogenicity in the context of B-lineage mismatch when compared to the Trivalent Inactivated Influenza Vaccine (TIV). While the safety profile of QIV was found to be comparable to that of TIV, the QIV showed a higher incidence of solicited local pain among children and adolescents, as well as an increased frequency of local adverse events within the adult population. Conclusion Our findings suggest that the QIV provides a superior immunogenicity response compared to the TIV in all age groups evaluated, especially when a lineage mismatch occurred. The safety of QIV was considered similar to the TIV, with no serious or systemic solicited or unsolicited adverse events; tough pain at the injection site was greater for QIV. We recommend caution owing to the high risk of bias in the selection process and no protocol registration.
ABSTRACT
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.
ABSTRACT
The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15µg H7N9, 1B) IB160 + 7.5µg H7N9, 1C) IB160 + 3.75µg H7N9, 2A) SE + 15µg H7N9, 2B) SE + 7.5µg H7N9, 2C) SE + 3.75µg H7N9, 3) unadjuvanted vaccine 15µg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.
Subject(s)
Influenza A Virus, H7N9 Subtype , Influenza Vaccines , Influenza, Human , Humans , Squalene , Pandemics/prevention & control , Polysorbates , Emulsions , Antibodies, Viral , Hemagglutination Inhibition Tests , Adjuvants, Immunologic , Adjuvants, Pharmaceutic , WaterABSTRACT
BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was detected in the psychiatric ward of a general hospital in Brasília, Brazil. METHODS: We report the investigation, clinical outcomes, viral sequencing, and control measures applied to outbreak containment. RESULTS: The overall attack rate was 95% (23/24) in a period of 13 days. Among the cases, 78% (18/23) were vaccinated and 17% (4/23) required intensive care. The Omicron variant was isolated from the 19 sequenced samples. CONCLUSIONS: The findings highlight the potential harm that highly transmissible variants may generate among hospitalized populations, particularly those with comorbidities.
Subject(s)
COVID-19 , SARS-CoV-2 , Brazil/epidemiology , Disease Outbreaks , Hospitals, General , Humans , Psychiatric Department, Hospital , SARS-CoV-2/geneticsABSTRACT
Objetivo: Avaliar a saúde mental, a adoção de medidas de prevenção de contágio e a percepção de risco de profissionais de saúde que atuavam em hospitais no estado de São Paulo, durante a pandemia de COVID-19, no período de 20 de julho a 25 de agosto de 2020. Métodos: estudo transversal com amostra de profissionais de 15 hospitais do estado que responderam a um formulário on-line. Para a avaliação da saúde mental, foi aplicado o Questionário de Saúde Geral (QSG-12), que gerou uma escala, variando de 0 a 12 (pior situação). Os resultados acima da mediana foram considerados indicativos de sofrimento psíquico. Utilizou-se modelo de regressão logística multivariada para a identificação de fatores associados ao sofrimento psíquico. Resultados: Participaram do estudo 627 profissionais, a maioria do sexo feminino, entre 40-59 anos, de cor branca; 45% estavam acima da mediana do QSG-12, que foi 6,3. Identificou-se maior chance de sofrimento psíquico entre mulheres; médicos; aqueles que responderam que o hospital não fornecia Equipamentos de Proteção Individual (EPIs) de boa qualidade; os que sentiam ter pouco controle sobre se infectar; os que tinham medo de não sobreviver à doença; aqueles cujas famílias tinham medo de se infectar através deles. Conclusão:O percentual de sofrimento psíquico na amostra foi expressivo, sendo possível atuar sobre alguns fatores associados para minimizar o problema.
Subject(s)
Mental Health , COVID-19 , Health PersonnelABSTRACT
Objetivo: Avaliar a saúde mental, a adoção de medidas de prevenção de contágio e a percepção de risco de profissionais de saúde que atuavam em hospitais no estado de São Paulo, durante a pandemia de COVID-19, no período de 20 de julho a 25 de agosto de 2020. Métodos: estudo transversal com amostra de profissionais de 15 hospitais do estado que responderam a um formulário on-line. Para a avaliação da saúde mental, foi aplicado o Questionário de Saúde Geral (QSG-12), que gerou uma escala, variando de 0 a 12 (pior situação). Os resultados acima da mediana foram considerados indicativos de sofrimento psíquico. Utilizou-se modelo de regressão logística multivariada para a identificação de fatores associados ao sofrimento psíquico. Resultados: Participaram do estudo 627 profissionais, a maioria do sexo feminino, entre 40-59 anos, de cor branca; 45% estavam acima da mediana do QSG-12, que foi 6,3. Identificou-se maior chance de sofrimento psíquico entre mulheres; médicos; aqueles que responderam que o hospital não fornecia Equipamentos de Proteção Individual (EPIs) de boa qualidade; os que sentiam ter pouco controle sobre se infectar; os que tinham medo de não sobreviver à doença; aqueles cujas famílias tinham medo de se infectar através deles. Conclusão: O percentual de sofrimento psíquico na amostra foi expressivo, sendo possível atuar sobre alguns fatores associados para minimizar o problema.
Subject(s)
Physicians , Delivery of Health Care , Personal Protective Equipment , HospitalsABSTRACT
The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15μg H7N9, 1B) IB160 + 7.5μg H7N9, 1C) IB160 + 3.75μg H7N9, 2A) SE + 15μg H7N9, 2B) SE + 7.5μg H7N9, 2C) SE + 3.75μg H7N9, 3) unadjuvanted vaccine 15μg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.
ABSTRACT
ABSTRACT Background: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was detected in the psychiatric ward of a general hospital in Brasília, Brazil. Methods: We report the investigation, clinical outcomes, viral sequencing, and control measures applied to outbreak containment. Results: The overall attack rate was 95% (23/24) in a period of 13 days. Among the cases, 78% (18/23) were vaccinated and 17% (4/23) required intensive care. The Omicron variant was isolated from the 19 sequenced samples. Conclusions: The findings highlight the potential harm that highly transmissible variants may generate among hospitalized populations, particularly those with comorbidities.
ABSTRACT
This cross-sectional seroepidemiological survey presents the seroprevalence of SARS-CoV-2 in a population living in 15 Long-Term Care Facilities (LTCFs), after two intra-institutional outbreaks of COVID-19 in the city of Botucatu, Sao Paulo State, Brazil. Residents were invited to participate in the serological survey performed in June and July 2020. Sociodemographic and clinical characterization of the participants as well as the LTCF profile were recorded. Blood samples were collected, processed and serum samples were tested using the rapid One Step COVID-19 immunochromatography test to detect IgM and IgG anti-SARS-CoV-2. Among 209 residents, the median of age was 81 years old, 135 (64.6%) were female and 171 (81.8%) self-referred as being white. An overall seroprevalence of 11.5% (95% CI: 7.5% - 16.6%) was found. The highest seroprevalences of 100% and 76.9% were observed in LTCFs that had experienced COVID-19 outbreaks. Most residents with positive immunochromatography tests (70.8%) referred previous contact with a confirmed COVID-19 case. Although there was a relatively low seroprevalence of COVID-19 in the total number of elderly people, this population is highly vulnerable and LTCFs are environments at higher risk for COVID-19 dissemination. A well-established test for COVID-19 policies, the adequate characterization of the level of interaction between residents and the healthcare provider team and the level of complexity of care are crucial to monitor and control the transmission of SARS-CoV-2 in these institutions.
Subject(s)
COVID-19/epidemiology , Long-Term Care , Nursing Homes , Aged , Aged, 80 and over , Antibodies, Viral/analysis , Brazil/epidemiology , COVID-19 Serological Testing , Cross-Sectional Studies , Disease Outbreaks , Female , Humans , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Male , Seroepidemiologic StudiesABSTRACT
INTRODUCTION: Active pharmacovigilance studies are pivotal to better characterize vaccine safety. METHODS: These are multicenter prospective cohort studies to evaluate the safety of the 2017 and 2018 seasonal trivalent influenza vaccines (TIVs) manufactured by Instituto Butantan, by means of active pharmacovigilance practices. Elderly, children, healthcare workers, pregnant women, and women in the puerperium period were invited to participate in the study during the 2017 and 2018 Brazilian national seasonal influenza vaccination campaigns. Following immunization, participants were observed for 30 minutes and they received a participant card to register adverse events information. All safety information registered were checked at a clinical site visit 14 days after immunization and by a telephone contact 42 days after immunization for unsolicited Adverse Events (AE) and Guillain-Barré Syndrome (GBS). RESULTS: A total of 942 volunteers participated in the two studies: 305 elderly, 109 children, 108 pregnant women, 32 women in the postpartum period, and 388 health workers. Overall, the median number of AR per participant ranged from 1 to 4. The lowest median number of AR per participant was observed among healthcare workers (1 AR per participant) and the highest among pregnant women (4 AR per participant). Overall, local pain (46.6%) was the most frequent solicited local AR. The most frequent systemic ARs were: headache (22.5%) followed by fatigue (16.0%), and malaise (11.0%). The majority of solicited ARs (96%) were mild, Grades 1 or 2), only 3% were Grade 3, and 1% was Grade 4. No serious AEs, including Guillain-Barré Syndrome, were reported up to 42 days postvaccination. CONCLUSION: The results from the two studies confirmed that the 2017 and 2018 seasonal trivalent influenza vaccines produced by Instituto Butantan were safe and that active pharmacovigilance studies should be considered, when it is feasible, as an important initiative to monitor vaccine safety in the post-marketing period.
Subject(s)
Influenza Vaccines/adverse effects , Pharmacovigilance , Aged , Brazil , Child , Child, Preschool , Female , Health Personnel/statistics & numerical data , Humans , Infant , Male , Pregnant WomenABSTRACT
Active pharmacovigilance studies are pivotal to better characterize vaccine safety. Methods: These are multicenter prospective cohort studies to evaluate the safety of the 2017 and 2018 seasonal trivalent influenza vaccines (TIVs) manufactured by Instituto Butantan, by means of active pharmacovigilance practices. Elderly, children, healthcare workers, pregnant women, and women in the puerperium period were invited to participate in the study during the 2017 and 2018 Brazilian national seasonal influenza vaccination campaigns. Following immunization, participants were observed for 30 minutes and they received a participant card to register adverse events information. All safety information registered were checked at a clinical site visit 14 days after immunization and by a telephone contact 42 days after immunization for unsolicited Adverse Events (AE) and Guillain-Barré Syndrome (GBS). Results: A total of 942 volunteers participated in the two studies: 305 elderly, 109 children, 108 pregnant women, 32 women in the postpartum period, and 388 health workers. Overall, the median number of AR per participant ranged from 1 to 4. The lowest median number of AR per participant was observed among healthcare workers (1 AR per participant) and the highest among pregnant women (4 AR per participant). Overall, local pain (46.6%) was the most frequent solicited local AR. The most frequent systemic ARs were: headache (22.5%) followed by fatigue (16.0%), and malaise (11.0%). The majority of solicited ARs (96%) were mild, Grades 1 or 2), only 3% were Grade 3, and 1% was Grade 4. No serious AEs, including Guillain-Barré Syndrome, were reported up to 42 days postvaccination. Conclusion: The results from the two studies confirmed that the 2017 and 2018 seasonal trivalent influenza vaccines produced by Instituto Butantan were safe and that active pharmacovigilance studies should be considered, when it is feasible, as an important initiative to monitor vaccine safety in the post-marketing period.
ABSTRACT
This cross-sectional seroepidemiological survey presents the seroprevalence of SARS-CoV-2 in a population living in 15 Long-Term Care Facilities (LTCFs), after two intra-institutional outbreaks of COVID-19 in the city of Botucatu, Sao Paulo State, Brazil. Residents were invited to participate in the serological survey performed in June and July 2020. Sociodemographic and clinical characterization of the participants as well as the LTCF profile were recorded. Blood samples were collected, processed and serum samples were tested using the rapid One Step COVID-19 immunochromatography test to detect IgM and IgG anti-SARS-CoV-2. Among 209 residents, the median of age was 81 years old, 135 (64.6%) were female and 171 (81.8%) self-referred as being white. An overall seroprevalence of 11.5% (95% CI: 7.5% – 16.6%) was found. The highest seroprevalences of 100% and 76.9% were observed in LTCFs that had experienced COVID-19 outbreaks. Most residents with positive immunochromatography tests (70.8%) referred previous contact with a confirmed COVID-19 case. Although there was a relatively low seroprevalence of COVID-19 in the total number of elderly people, this population is highly vulnerable and LTCFs are environments at higher risk for COVID-19 dissemination. A well-established test for COVID-19 policies, the adequate characterization of the level of interaction between residents and the healthcare provider team and the level of complexity of care are crucial to monitor and control the transmission of SARS-CoV-2 in these institutions.
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This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.
Subject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Antimalarials/administration & dosage , Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Severe acute respiratory syndrome-related coronavirus/drug effects , Severe acute respiratory syndrome-related coronavirus/isolation & purification , SARS-CoV-2 , Severe Acute Respiratory Syndrome/virology , COVID-19 Drug TreatmentABSTRACT
Objective: To discuss the importance of health technology assessment (HTA) to allow oral health policies to be planned to meet the needs of prevention, promotion and recovery of patients' health. Methods: It is an opinion article. Oral diseases can be a considerable economic burden for the individual and for society, leading to a global impact of US$ 544.41 billion in 2015. Results: Brazil has made great progress in terms of oral health care after the publication of the National Policy of Oral Health (PNSB). However, the current challenge is still great, especially with regard to the management of health technologies within the PNSB. Conclusion: The accomplishment of HTA to support decision-making on allocation of the financial resources used may prevent the Smiling Brazil program from becoming vulnerable to the waste of the scarce resources allocated to this are, which would result in low effectiveness, inefficiency and inequity of the health system.
Objetivo: Discutir a importância dos estudos de avaliação econômica em saúde para permitir que as políticas de saúde bucal possam ser planejadas para atender às necessidades de prevenção, promoção e recuperação da saúde dos pacientes. Métodos: Este artigo se trata de um ensaio. As doenças bucais podem ser um fardo econômico considerável para o indivíduo e para a sociedade. Estima-se que, globalmente, esse impacto tenha sido de 544,41 bilhões de dólares em 2015. Resultados: O Brasil avançou muito em termos de cuidados em saúde bucal após a publicação da Política Nacional de Saúde Bucal. Entretanto, o desafio atual ainda é grande, especialmente no que diz respeito à gestão de tecnologias em saúde na Política Nacional de Saúde Bucal (PNSB). Conclusão: A realização de avaliações econômicas, para subsidiar a tomada de decisão na alocação dos recursos financeiros utilizados, pode impedir que o programa Brasil Sorridente se torne vulnerável ao desperdício dos escassos recursos que são alocados na área, o que resultaria em baixa efetividade, ineficiência e iniquidade do sistema de saúde.
Subject(s)
Health Care Economics and Organizations , Unified Health System , Oral Health , Universal Access to Health Care ServicesABSTRACT
BACKGROUND: The Butantan Institute has manufactured a lyophilised tetravalent live-attenuated dengue vaccine Butantan-DV, which is analogous to the US National Institutes of Health (NIH) TV003 admixture. We aimed to assess the safety and immunogenicity of Butantan-DV. METHODS: We did a two-step, double-blind, randomised placebo-controlled phase 2 trial at two clinical sites in São Paulo, Brazil. We recruited healthy volunteers aged 18-59 years; pregnant women, individuals with a history of neurological, heart, lung, liver or kidney disease, diabetes, cancer, or autoimmune diseases, and individuals with HIV or hepatitis C were excluded. Step A was designed as a small bridge-study between Butantan-DV and TV003 in DENV-naive participants. In step A, we planned to randomly assign 50 dengue virus (DENV)-naive individuals to receive two doses of Butantan-DV, TV003, or placebo, given 6 months apart. In step B, we planned to randomly assign 250 participants (DENV-naive and DENV-exposed) to receive one dose of Butantan-DV or placebo. Participants were randomly assigned, by computer-generated block randomisation (block sizes of five); participants in step A were randomly assigned (2:2:1) to receive Butantan-DV, TV003, or placebo and participants in step B were randomly assigned (4:1) to receive Butantan-DV or placebo. Participants and study staff were unaware of treatment allocation. The primary safety outcome was the frequency of solicited and unsolicited local and systemic adverse reactions within 21 days of the first vaccination, analysed by intention to treat. The primary immunogenicity outcome was seroconversion rates of the DENV-1-4 serotypes measured 91 days after the first vaccination, analysed in the per-protocol population, which included all participants in step A, and all participants included in step B who completed all study visits with serology sample collection. This trial is registered with ClinicalTrials.gov, NCT01696422. FINDINGS: Between Nov 5, 2013, and Sept 21, 2015, 300 individuals were enrolled and randomly assigned: 155 (52%) DENV-naive participants and 145 (48%) DENV-exposed participants. Of the 155 DENV-naive participants, 97 (63%) received Butantan-DV, 17 (11%) received TV003, and 41 (27%) received placebo. Of the 145 DENV-exposed participants, 113 (78%) received Butantan-DV, three (2%) received TV003, and 29 (20%) received placebo. Butantan-DV and TV003 were both immunogenic, well-tolerated, and no serious adverse reactions were observed. In step A, rash was the most frequent adverse event (16 [845] of 19 participants in the Butantan-DV group and 13 [76%] of 17 participants in the TV003 group). Viraemia was similar between the Butantan-DV and TV003 groups. Of the 85 DENV-naive participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis and thus were included in the per-protocol analysis population, 74 (87%) achieved seroconversion to DENV-1, 78 (92%) to DENV-2, 65 (76%) to DENV-3, and 76 (89%) to DENV-4. Of the 101 DENV-exposed participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis, 82 (81%) achieved seroconversion to DENV-1, 79 (78%) to DENV-2, 83 (82%) to DENV-3, and 78 (77%) to DENV-4. INTERPRETATION: Butantan-DV and TV003 were safe and induced robust, balanced neutralising antibody responses against the four DENV serotypes. Efficacy evaluation of the Butantan-DV vaccine is ongoing. FUNDING: Intramural Research Program US NIH National Institute of Allergy and Infectious Diseases, Brazilian National Bank for Economic and Social Development, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Fundação Butantan.
Subject(s)
Dengue Vaccines/immunology , Dengue Virus/immunology , Immunogenicity, Vaccine , Vaccines, Attenuated/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Brazil , Double-Blind Method , Female , Humans , Male , Middle Aged , Seroconversion , Vaccination , Young AdultABSTRACT
Resorbable and titanium systems have been used in maxillary fixation. The aim of this review was to evaluate stability and morbidity of Le Fort I osteotomy by comparing both systems. It was performed in 11 databases, and reported according to preferred reporting items for systematic reviews and meta-analysis. Randomized and nonrandomized clinical trials, and retrospective comparative studies with patients who underwent nonsegmented Le Fort I osteotomy were included. Eleven articles were selected, with a total of 262 patients treated with resorbable and 252 with titanium fixation. The meta-analysis showed that when measured at point A, horizontal stability was 0.06 mm (95% confidence interval [CI] -0.19, 0.30), vertical stability for impaction was -0.43 mm (95% CI -0.94, 0.07), and for inferior repositioning was -1.29 mm (95% CI -2.62, 0.04). Morbidity was similar in the groups. Regarding infection, resorbable presented an absolute risk (AR)â=â0.032, and titanium an ARâ=â0.025 (Pâ=â1.0). For soft tissue reaction, an ARâ=â0.120 was shown for resorbable, and an ARâ=â0.132 for titanium (Pâ=â0.85). Removal of fixation showed an ARâ=â0.024 for resorbable, and an ARâ=â0.025 for titanium (Pâ=â1.0). Based on these results, resorbable and metal fixation systems seem to be equivalent with respect to stability and morbidity. This review was limited by the quality of the studies. Future studies should address these quality limitations to improve comparison between these 2 fixation approaches.