Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2-11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study.

Background: Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. Methods: In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE = (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. Findings: We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Interpretation: Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. Funding: National Fund for Science and Technology (FONCI-CITMA-Cuba).

Long-term therapy with itolizumab is safe and effective for patients with moderate to severe psoriasis: Results from an expanded-access program.

Itolizumab is a humanized monoclonal antibody that selectively targets the CD6-ALCAM pathway. This article reports on the safety and efficacy of itolizumab in the treatment of moderate-to-severe plaque psoriasis in a clinical study conducted in Cuba in the setting of an expanded-access program (EAP). The study included 84 patients who had previously received conventional anti-psoriatic systemic therapies but were either intolerant, had an inadequate response, or had contraindications to these therapies. It consisted of multiple phases, including a 12-week induction phase, a 40-week maintenance phase, and a 24-week off-treatment follow-up phase, using either a 0.4 or 1.6 mg/Kg dose. The results showed that itolizumab monotherapy was safe and effective during 52 weeks of continuous treatment and the subsequent 24 follow-up weeks. Itolizumab treatment resulted in a significant improvement (PASI 75) in 80 % of patients at the end of the induction phase, and this effect was sustained till week 52 during the maintenance phase. Moreover, 24 weeks after treatment stopped nearly two-thirds of patients still showed a PASI ≥ 75. The observed effects were dose-dependent, with 1.6 mg/kg being the most convenient dose. This study further supports the strategy of targeting the CD6-ALCAM signaling pathway for the treatment of psoriasis and the use of itolizumab as a valuable asset in the armamentarium of anti-psoriasis drugs.

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

Carcinoma neuroendocrino de vulva, una entidad poco frecuente. Reporte del primer caso en Venezuela / Neuroendocrine carcinoma of the vulva, a rare entity. Report of the first case in Venezuela

El cáncer de vulva representa 1 % de los cánceres en mujeres; el carcinoma neuroendocrino de vulva es extremadamente raro, con menos de 20 casos publicados. Su comportamiento es muy agresivo produciendo recurrencias locales tempranas, metástasis a ganglios linfáticos y a distancia. Se describe el caso de una paciente de 60 años de edad, quien consultó por lesión vulvar de 6 meses de evolución, con extensión a tercio inferior de uretra y vagina y plastrón ganglionar inguinal izquierda. La biopsia de vulva reportó neoplasia maligna de células redondas y el resultado de la inmunohistoquímica fue compatible con carcinoma neuroendocrino. Recibió quimioterapia y radioterapia concurrente, evidenciando respuesta completa en vulva y parcial en región inguinal, posteriormente se realizó linfadenectomía inguinofemoral bilateral. El carcinoma neuroendocrino de vulva debe ser considerado al momento de manejar patología vulvar maligna, el diagnóstico oportuno requiere histología e inmunohistoquímica para establecer un pronóstico y tratamiento adecuados(AU)

Vulvar cancer represents 1% of cancers in women; vulvar neuroendocrine carcinoma is extremely rare, with less than 20 published cases. Its behavior is very aggressive, producing early local recurrences, lymph node and distant metastases. The case of a 60-year-old patient who consulted for a vulvar lesion of 6 months of evolution, with extension to the lower third of the urethra and vagina and left inguinal nodal plastron is described. The vulvar biopsy reported malignant round cell neoplasm and the immunohistochemistry result was compatible with neuroendocrine carcinoma. She received concurrent chemotherapy and radiotherapy, evidencing a complete response in the vulva and a partial response in the inguinal region. Later, bilateral inguinofemoral lymphadenectomy was performed. Neuroendocrine carcinoma of the vulva should be considered when managing malignant vulvar pathology, timely diagnosis requires histology and immunohistochemistry to establish an adequate prognosis and treatment(AU)

Can suitability indices predict plant growth in the invaded range? The case of Acacias species.

Introduction: Forestry in many parts of the world depends on exotic species, making this industry a source of invasions in some countries. Among others, plantations of the genus Pinus, Eucalyptus, Acacia, Populus, and Pseudotsuga underpin the forestry industry and are a vital component of many countries economies. Among woody plants, the cosmopolitan genus Acacia includes some of the most commonly planted trees worldwide. In order to prevent, manage and control invasive plant species, one of the most used tools is species distribution models. The output of these models can also be used to obtain information about population characteristics, such as spatial abundance patterns or species performance. Although ecological theory suggests a direct link between fitness and suitability, this link is often absent. The reasons behind the lack of this relationship are multiple. Chile is one of the countries where Acacia species, in particular, A. dealbata and A. melanoxylon, have become invaders. Methods: Here, we used climatic and edaphic variables to predict thepotentially suitable habitats for A. dealbata and A. melanoxylon in continental Chile and evaluate if the suitability indices obtained from these models are associated with the observed performance of the trees along the country. Results: Our models show that variable importance showed significant similarities between the variables that characterize each species' niche. However, despite the high accuracy of our models, we did not observe an association between suitability and tree growth. Discussion: This disconnection between suitability and performance can result from multiple causes, from structural limitations, like the lack of biotic interactions in the models, to methodological issues, like the usefulness of the performance metric used. Whatever the scenario, our results suggest that plans to control invasive species should be cautious in assuming this relationship in their design and consider other indicators such as species establishment success.

Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-Plus: a double-blind, randomised, placebo-controlled phase 3 clinical trial.

Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralising IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralising antibodies. The aim of this study is to evaluate the safety and efficacy of two immunisation regimes: two doses of SOBERANA-02 and a heterologous three-dose combination with SOBERANA-Plus added to it. Methods: From March 8th to June 24th, 2021 we conducted in Havana, Cuba a multicentre randomised, double-blind, placebo-controlled, phase-3 trial evaluating a two doses SOBERANA-02 scheme and a heterologous scheme with one dose SOBERANA-Plus added to it (RPCEC00000354). Participants 19-80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose. Findings: We included 44,031 participants (52.0% female, 48.0% male; median age 50 years, range 19-80 years; 7.0% black, 24.0% mixed-race, 59.0% white) in a context of initial Beta VOC predominance, with this variant being partially replaced by Delta near the trial's end. Vaccine efficacy in the heterologous combination was 92.0% (95%CI 80.4-96.7) against symptomatic disease. There were no severe COVID-19 cases in the vaccine group against 6 in the placebo group. Two doses of SOBERANA-02 was 69.7% (95%CI 56.5-78.9) and 74.9% (95%CI 33.7-90.5) efficacious against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe adverse events (AE) was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient. Interpretation: Our results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC circulation, have a favourable safety profile, and may represent an attractive option for use in COVID-19 vaccination programmes. Funding: This study received funds from the National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020-20) of the Ministry of Science, Technology and Environment of Cuba.

Open-label phase I/II clinical trial of SARS-CoV-2 receptor binding domain-tetanus toxoid conjugate vaccine (FINLAY-FR-2) in combination with receptor binding domain-protein vaccine (FINLAY-FR-1A) in children.

OBJECTIVES: To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines. METHODS: A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results. RESULTS: Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval [CI] 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron. CONCLUSION: The heterologous scheme was safe and immunogenic in children 3-18 y/o. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000374.

Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 and SOBERANA Plus vaccines: Phase IIb clinical trial in adults.

BACKGROUND: SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- or three-dose heterologous scheme in adults. METHOD: Phase IIb was a parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled trial. Subjects (n = 810) aged 19-80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (IgG) concentration. Secondary outcomes were safety, reactogenicity, and neutralizing antibodies. FINDINGS: Seroconversion rate in vaccinees was 76.3% after two doses and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were detected 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE. CONCLUSIONS: Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000347 FUNDING: This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).

Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: Open label phase I and phase IIa clinical trials.

BACKGROUND: SOBERANA 02 is a COVID-19 vaccine based on SARS-CoV-2 recombinant RBD conjugated to tetanus toxoid (TT). SOBERANA Plus antigen is dimeric-RBD. Here we report safety and immunogenicity from phase I and IIa clinical trials using two-doses of SOBERANA 02 and three-doses (homologous) or heterologous (with SOBERANA Plus) protocols. METHOD: We performed an open-label, sequential and adaptive phase I to evaluate safety and explore the immunogenicity of SOBERANA 02 in two formulations (15 or 25 µg RBD-conjugated to 20 µg of TT) in 40 subjects, 19-59-years-old. Phase IIa was open-label including 100 volunteers 19-80-years, receiving two doses of SOBERANA 02-25 µg. In both trials, half of volunteers were selected to receive a third dose of the corresponding SOBERANA 02 and half received a heterologous dose of SOBERANA Plus. Primary outcome was safety. The secondary outcome was immunogenicity evaluated by anti-RBD IgG ELISA, molecular neutralization of RBD:hACE2 interaction, live-virus-neutralization and specific T-cells response. RESULTS: The most frequent adverse event (AE) was local pain, other AEs had frequencies ≤ 5%. No serious related-AEs were reported. Phase IIa confirmed the safety in 60 to 80-years-old subjects. In phase-I SOBERANA 02-25 µg elicited higher immune response than SOBERANA 02-15 µg and progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02-25 µg even in 60-80-years. Two doses of SOBERANA02-25 µg elicited an immune response similar to that of the Cuban Convalescent Serum Panel and it was higher after the homologous and heterologous third doses. The heterologous scheme showed a higher immunological response. Anti-RBD IgG neutralized the delta variant in molecular assay, with a 2.5-fold reduction compared to D614G neutralization. CONCLUSIONS: SOBERANA 02 was safe and immunogenic in persons aged 19-80 years, eliciting neutralizing antibodies and specific T-cell response. Highest immune responses were obtained in the heterologous three doses protocol. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000340, https://rpcec.sld.cu/trials/RPCEC00000347.

Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.

Bioconversion of Glycosidic Precursors from Sour Guava (Psidium friedrichsthalianum Nied.) Fruit by the Oral Microbiota into Odor-Active Volatile Compounds.

The ability of the human oral microbiota to hydrolyze the glycosidic aroma precursor extract isolated from sour guava (Psidium friedrichsthalianum Nied.) fruits was studied herein. The glycosidic extract (GP) was incubated with a mixture of the oral microbiota isolated from three individuals' saliva to evaluate the hydrolytic capacity of oral bacteria in the generation of odor-active compounds. The oral microbiota was able to release 1-hexanol from GP, under both aerobic and anaerobic conditions. Additionally, the aroma precursor extracts showed a decrease in the growth of harmful oral bacteria (Streptococcus and Actinomyces). This effect can be considered beneficial to human health because these bacteria have been related to different diseases of the bucco-respiratory tract.

A randomized, double-blind phase I clinical trial of two recombinant dimeric RBD COVID-19 vaccine candidates: Safety, reactogenicity and immunogenicity.

BACKGROUND: The Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase I clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD). METHODS: We performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 µg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 (50 µg d-RBD, three doses); 3) FINLAY-FR-1A-25 (25 µg d-RDB, three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction. RESULTS: Most adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more subjects with adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules. CONCLUSIONS: Vaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant. TRIAL REGISTRY: https://rpcec.sld.cu/en/trials/RPCEC00000338-En.

O processo de planejamento de uma proposta de intervenção educativa utilizando a Caderneta da Criança como ferramenta pedagógica para a qualificação profissional na Atenção Primária / The planning process of an education intervention proposal applying the Child's Health Booklet as a pedagogical tool for professional qualification in Primary Health

A Caderneta da Criança se destina ao acompanhamento do crescimento e desenvolvimento infantil pela sistematização das ações de cuidado integral, vigilância e diagnóstico precoce de problemas de desenvolvimento. Entretanto, a literatura revela a sua subutilização, despreparo técnico, lacunas no conhecimento e comprometimento dos profissionais de saúde. A emergência da síndrome congênita de Zika vírus, entre 2015 e 2017, afetou um número expressivo de crianças em puericultura no estado do Rio de Janeiro e reforçou a necessidade de estratégias para a qualificação do cuidado em rede. A Covid-19 mudou o paradigma metodológico para oferta de capacitações apoiadas por tecnologias de informação e comunicação visando maior capilaridade de qualificação nos territórios. O objetivo do estudo foi descrever o processo de planejamento de uma proposta educativa da Secretaria de Saúde do Estado do Rio de Janeiro para vigilância do crescimento e desenvolvimento infantil, utilizando a Caderneta da Criança para qualificação profissional na Atenção Primária à Saúde (APS). Elegeu-se o estudo de caso através de uma abordagem qualitativa, utilizando a pesquisa documental de um processo intrasetorial, inserido no planejamento estadual, entre 2017 e 2021, centrado na contextualização temática e conjuntural de surgimento e de condução político-administrativa do processo. A classificação de 145 documentos resultou em 34 unidades principais, cuja análise crítica permitiu mapear o "vai e vem" deste processo em correspondência com os processos administrativos e a mudança da proposta educativa inicial no molde semipresencial para o Ensino à distância, associada a um dispositivo digital, para orientar e potencializar o uso do instrumento. Os resultados evidenciaram a realidade de um processo submetido a uma instituição tradicional, vertical, de natureza burocrática com dificuldades traduzidas em desafios enfrentados em função da Crise pandêmica, inserção do modo remoto de trabalho, desabastecimento da Caderneta da Criança no Rio de Janeiro, crises de governo e de governabilidade institucional. Além disso, hipertrofia documental, lentidão na origem em contraponto com a celeridade de tramitação no Sistema eletrônico de informação, frágil integração do planejamento estratégico e do trabalho intrasetorial para executar ações educativas. Exigências formais e imprevisibilidade de execução impuseram o cancelamento da proposta digital e transferência de parte das ações para 2022. Constatou-se a limitação do método na impossibilidade de complementação de entrevistas com informantes-chave. Considera-se que o estudo possa inspirar novas pesquisas sobre processos de planejamento e estratégias de educação mediadas por tecnologias de inovação e comunicação no âmbito da Secretaria, criando uma cultura de inovação nos processos de qualificação profissional da APS do Rio de Janeiro.

The Child's Health Booklet is intended for monitoring children's growth and development through the systematization of comprehensive care actions, attentiveness and early detection of developmental problems. However, the literature reveals its underutilization, technical unpreparedness, gaps in knowledge and commitment of health professionals. The emergence of congenital Zika syndrome, between 2015 and 2017, affected a significant number of children in childcare in the state of Rio de Janeiro and reinforced the need for strategies aspiring the excellence of network care. Covid-19 changed the methodological paradigm for offering training supported by information and communication technologies, aiming at greater capillarity of qualification in the territories. The objective of the study was to describe the planning process of an educational proposal of the Health Secretariat of the State of Rio de Janeiro to monitor child growth and development, using the Child's Health Booklet for professional qualification in Primary Health Care (PHC). The case study was chosen through a qualitative approach, using the documentary research of an intra-sectoral process, inserted in the state planning, between 2017 and 2021, focused on the thematic and conjunctural contextualization of the emergence and political-administrative conduction of the process. The classification of 145 documents resulted in 34 main units, whose critical analysis allowed to map the "back and forth" of this process in correspondence with the administrative processes and the change from the initial educational proposal of blended learning to distance learning, associated with a digital device, to guide and enhance the use of the instrument. The results evidenced the reality of a process submitted to a traditional, vertical, of a bureaucratic nature institution with difficulties translated into challenges faced due to the Pandemic crisis, adoption of remote work, shortage of the Child's Health Booklet in Rio de Janeiro, government and institutional governance crises. In addition, documental hypertrophy, slowness at the origin in contrast to the fast processing in the electronic information System, fragile integration of strategic planning and of intra-sectoral work to carry out educational actions. Formal requirements and unpredictability of execution imposed the cancellation of the digital proposal and the transfer of part of the actions to 2022. The limitation of the method was noted considering the impossibility of completing interviews with key informants. It is considered that the study can inspire new research on planning processes and education strategies mediated by innovation and communication technologies within the Secretariat, creating a culture of innovation in the professional qualification processes of PHC in Rio de Janeiro.

A single dose of SARS-CoV-2 FINLAY-FR-1A vaccine enhances neutralization response in COVID-19 convalescents, with a very good safety profile: An open-label phase 1 clinical trial.

BACKGROUND: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. METHODS: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. FINDINGS: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-γ and TNF-α. INTERPRETATION: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. FUNDING: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. ANTECEDENTES: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfección, evaluamos la vacuna FINLAY-FR-1A en un ensayo clínico. MÉTODOS: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 años: convalecientes de COVID-19 leve y convalecientes asintomáticos, ambos con prueba PCR positiva al momento del diagnóstico; e individuos con infección subclínica detectada por IgG específica viral. Los participantes recibieron una dosis única por vía intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de unión al receptor recombinante dimérico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 días después de la vacunación. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y después de la vacunación, se evaluó por ELISA y mediante la prueba de neutralización del virus vivo. También se evaluó la respuesta de células T efectoras. Registro Público Cubano de Ensayos Clínicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. RESULTADOS: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los más comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimuló un incremento >21 veces de los anticuerpos IgG anti-RBD 28 días después de la vacunación. La mediana de los títulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron títulos de neutralización viral superiores a 1:160 en 24 (80%) de los participantes. También hubo un aumento en las células T específicas de RBD que producen IFN-γ y TNF-α. INTERPRETACIÓN: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzó eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. FINANCIAMIENTO: Se recibió un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministerio de Ciencia, Tecnología y Medio Ambiente, Cuba.

Biopsia de ganglio centinela con azul patente más impronta en el estadiaje axilar de cáncer de mama en un hospital de alta complejidad / Sentinel lymph node biopsy with blue patent more imprinted in the axillary stage of breast cancer in a hospital of high complexity

Objetivo: Analizar las principales características clínicopatológicas de pacientes con carcinoma de mama en quienes se realizó biopsia de ganglio centinela con azul patente más impronta en el estadiaje axilar. El estudio. Serie descriptiva, evaluó una serie de 20 casos con diagnóstico anatomopatológico de carcinoma ductal infiltrante atendidas en el área de Cirugía Oncológica del Hospital de Alta Complejidad "Virgen de la Puerta" EsSalud, La Libertad - Perú, durante el periodo febrero 2017 - enero 2018. Hallazgos: La sensibilidad y especificidad de la impronta de ganglio centinela fue de 75% respectivamente. El valor predictivo positivo y negativo fue de 67% y 82%. El cociente de probabilidad positivo y negativo fue de 3,0 y 0,33. El índice de Kappa fue 0,2 de considerado como un índice de concordancia. Conclusiones: La técnica del ganglio centinela es una buena alternativa para el manejo de cáncer de mama, ya que evita intervenciones quirúrgicas innecesarias.

Objetive:To analyze the main clinical-pathological characteristics of patients with breast carcinoma in whom a sentinel lymph node biopsy was performed with patent blue plus imprint in the axillary staging. . The studyThis descriptive series evaluated a series of 20 cases of patients with an anatomopathological diagnosis of infiltrating ductal carcinoma treated in the area of Oncological Surgery of the Hospital of High Complexity "Virgen de la Puerta" EsSalud, La Libertad - Peru, during the period February 2017 until January 2018. : The sensitivity and specificity of the sentinel lymph Findingsnode imprint was 75% respectively. The positive and negative predictive value was 67% and 82% respectively. The positive and negative likelihood ratio was 3.0 and 0.33. The Kappa index was 0.2 of considered as a concordance index. Conclusions. The sentinel lymph node technique is a good alternative for the management of breast cancer, since it avoids unnecessary surgical interventions

Animación interactiva en la administración segura de medicamentos / Interactive animation in secure administration of medications

Introducción: El objetivo de esta investigación fue fortalecer a estudiantes de enfermería en temática de la administración segura de medicamentos a través de una animación interactiva, orientado a maximizar el bienestar del sujeto de cuidado que requiera atención terapéutica en los diferentes servicios de salud. Metodología: Estudio cualitativo-cuantitativo (mixto), de cohorte transversal, con revisión de literatura en la primera fase y en la segunda fase ejecución cuasi experimental, aplicando consideraciones éticas como son: Validación de herramienta de recoleccion de datos pretest y postest por expertos. Resultados: La aplicabilidad de animación interactiva proporciona fortalecimiento en la percepción de los estudiantes de enfermería sobre la importancia de la adherencia en la práctica de manejo y la responsabilidad ético legal en administración segura de medicamentos en los servicios de salud. Aplicando en esta fase una herramienta tipo encuesta a estudiantes que cursan 8 semestres de enfermería en la jornada mañana y tarde. Resultados: se evidenció en la jornada mañana un 51.7% tenían conocimiento teórico y posterior a la socialización del video, el postest mejoró al 86.2%, en cuanto a la responsabilidad ético legal en el pretest un 62 % tenian adherencia a la ética en administración segura de medicamentos y que con el postest cambio a un 93 % mejorando la percepción de la adherencia a la ética en administración segura de medicamentos. En los resultados de estudiantes de la jornada tarde, el 52.6% tienen conocimiento teórico en el pre-test y con resultado del 89.4% en el post ­test; en cuanto a la responsabilidad ético legal se obtuvo en el pre-test un 68.4 % y un resultado en el post-test el 89.4%. Lo anteriormente descrito se mejoró con la animación interactiva, fortaleciendo los conocimientos teóricos y éticos en administración segura de medicamentos por vía intravenosa al sujeto que requiera atención terapéutica. Conclusión: Se concluye que la animación interactiva es un programa que ayuda a que la formación de enfermería reconozca y comprenda la labor y el deber de administrar tratamientos farmacológicos aplicando ética en la práctica de la misma, ya que el usuario que requiere un tratamiento tiene derecho a que se le proteja su integridad orgánica y sistémica. Adicionalmente, en relación al estudio realizado se evidencia que por medio de animación interactiva se logró fortalecer los conocimientos teóricos y prácticos en administración segura de medicamentos.

Introduction: The objective of this research was to strengthen the nursing staff in the safe administration of medicines through an interactive animation, oriented towards the welfare of the subject of care that requires therapeutic attention in the different health services. Methodology: Qualitative-quantitative cross-sectional study (mixed), with literature review in the first phase and in the second phase quasi-experimental execution, applying ethical considerations such as: Pre-test and post-test validation by experts. Results: The applicability of interactive animation provides strengthening in the perception of nursing staff about the importance of adherence in the practice of ethics in safe administration of medicines in health services. Applying in this part, the quantitative phase with quasi-experimental design type to the nursing student population of the University Foundation of the Andean Area, who study 8 semester and which is taken as a sample in the morning session 29 students and in the afternoon session 19 nursing students. Where it was evidenced in the day tomorrow with the students of nursing that 51.7% had theoretical knowledge and that with the realization of the posttest improved to 86.2%, as for the ethical ethical responsibility in the pretest 62% have adherence to the ethics in safe administration of medications and that with the post-test changed to 93% improving the perception of adherence to ethics in safe administration of medicines. In the pretest and posttest results made to the students of the afternoon session, 52.6% have theoretical knowledge in the pre-test and with a result of 89.4% in the post-test; in the part of ethical legal responsibility, 68.4% was obtained in the pre-test and 89.4% in the post-test. The above described was improved with interactive animation, strengthening the theoretical and ethical knowledge in safe administration of intravenous medications to the subject that requires therapeutic attention. Conclution: It is concluded that interactive animation is a program that helps the nursing profession know that it has the task and duty to administer pharmacological treatments applying ethics in the practice of the same, since the user that requires a treatment has the right to have its organic and systemic integrity protected. Additionally, in relation to the study carried out, it is evident that through interactive animation, the theoretical and practical knowledge in safe drug administration was strengthened.

Vivências de uma gestante em tratamento de hemodiálise no SUS / Experiences of a pregnant woman undergoing hemodialysis treatment in SUS

Este estudo pretendeu mostrar que a doença não é vista como sintoma, senão como alteração sistêmica do organismo que se expressa como sintoma, de modo que há um conjunto de doenças, dentre elas a renal crônica, nas quais tanto o modo de vida da pessoa, como a sua capacidade para lidar com seus conflitos são decisivos para sua prevenção e controle

Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers.

BACKGROUND: Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). METHODS: This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 µg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. RESULTS: There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(-1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]). CONCLUSION: BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. TRIAL REGISTRATION: This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 ). This trial was retrospectively registered in June 2013.

Beneficial effects of oral administration of C-Phycocyanin and Phycocyanobilin in rodent models of experimental autoimmune encephalomyelitis.

The only three oral treatments currently available for multiple sclerosis (MS) target the relapsing forms of the disease and concerns regarding efficacy, safety and tolerability limit their use. Identifying novel oral disease-modifying therapies for MS, targeting both its inflammatory and neurodegenerative components is still a major goal. AIM: The scope of this study was to provide evidence that the oral administration of C-Phycocyanin (C-PC), the main biliprotein of the Spirulina platensis cyanobacteria and its tetrapyrrolic prosthetic group, Phycocyanobilin (PCB), exert ameliorating actions on rodent models of experimental autoimmune encephalomyelitis (EAE). MAIN METHODS: EAE was induced in Lewis rats using the spinal cord encephalitogen from Sprague Dawley rats and in C57BL6 mice with MOG35-55 peptide. Clinical signs, motor function, oxidative stress markers, cytokine levels by ELISA and transmission electron microscopy analysis were assessed. KEY FINDINGS: Either prophylactic or early therapeutic administration of C-PC to Lewis rats with EAE, significantly improved clinical signs and restored the motor function of the animals. Furthermore, C-PC positively modulated oxidative stress markers measured in brain homogenate and serum and protected the integrity of cerebral myelin sheaths as shown by transmission electron microscopy analysis. In C57BL/6 mice with EAE, PCB orally improved clinical status of the animals and reduced the expression levels of brain IL-6 and IFN-γ proinflammatory cytokines. SIGNIFICANCE: These results, for the first time, support the fact that both C-PC and PCB administered orally could potentially improve neuroinflammation, protect from demyelination and axonal loss, which may be translated into an improved quality of life for MS patients.

Characterization of the communication resources used by patients in palliative care - an integrative review / Caracterização dos recursos de comunicação utilizados por pacientes em cuidados paliativos - revisão integrativa

ABSTRACT The aim of this study was to integrative review of publications concerning the role of speech and language therapists in regards to communication strategies in palliative care, as well as the characterization of the types of communication used in these cases. The search was conducted in the databases SciELO, LILACS and PubMed from 2001 to 2016. The studies selected included abstracts or full articles addressing aspects of communication in palliative care, especially those related to speech and language therapy, with an emphasis on communication. Ten articles focused on communication, and published after 2004, were selected, half being literature reviews, two, case reports, two others, quantitative exploratory studies, and one, a qualitative exploratory study, with only 3 specifically describing the communication strategies used by speech and language therapists in patients in palliative care. The descriptors found were: palliative care, communication, speech and language therapy, quality of life, dysphagia, swallowing and elderly. Four of the ten articles showed the importance of patients communication in palliative care. When described, it is up to the speech and language therapist to provide family support, evaluate the patient, favore patient-family and patient-team intervention, manage and intervene in communication and swallowing. Finally, the most used communication strategies were non-verbal communication, communication board, electronic equipment, verbal communication and speech valve. The analysis of the characterization of the communication in palliative care over the past 15 years allowed concluding that the attention to communication is recent and is only described in a few reports, includes non-verbal communication in different ways as the most frequent resource, but provides oral communication as an important factor for maintaining dignity and comfort in this scenario. Speech and language therapist are the main interlocutors for the maintenance, mediation and adaptation of communication, within the multidisciplinary team as well as among patients, their family and the care team.

RESUMO O objetivo foi realizar uma revisão integrativa das publicações referentes ao papel do fonoaudiólogo em relação às estratégias de comunicação em cuidados paliativos, bem como a caracterização das formas de comunicação utilizadas nesses casos. As buscas foram realizadas nos bancos de dados da SciELO, LILACS e PubMed no período de 2001 a 2016. Foram selecionados os estudos cujos resumos, ou textos na íntegra, abordavam aspectos da comunicação em cuidados paliativos, principalmente os relacionados com a atuação fonoaudiológica, com ênfase em comunicação. Foram selecionados 10 artigos, com enfoque em comunicação, a partir de 2004, sendo metade de revisão bibliográfica, dois relatos de caso, outros dois exploratórios quantitativos e um exploratório qualitativo, com apenas 3 deles descrevendo especificamente as estratégias de comunicação utilizadas por um fonoaudiólogo com pacientes em cuidados paliativos. Os descritores encontrados foram: cuidados paliativos (Palliative care), comunicação (communication), fonoaudiologia, qualidade de vida, disfagia, deglutição e idoso. Quatro dos dez artigos apontaram a importância da comunicação dos pacientes em cuidados paliativos. Quando descrito, compete ao fonoaudiólogo: oferecer suporte familiar, avaliar o paciente, favorecer a intervenção paciente-família e paciente-equipe, gerenciar e intervir na comunicação e deglutição. Finalmente, as estratégias de comunicação mais utilizadas foram: comunicação não verbal, prancha de comunicação, equipamentos eletrônicos, comunicação verbal e válvula de fala. A análise da caracterização da comunicação em cuidados paliativos nos últimos 15 anos permitiu concluir que a atenção à comunicação é recente, com poucos relatos ainda descritos, inclui a comunicação não verbal de diferentes maneiras como o recurso mais frequente, mas prevê a comunicação oral como um importante fator para a manutenção da dignidade e conforto nesse cenário. O fonoaudiólogo é o principal interlocutor para a manutenção, mediação e adaptação da comunicação, tanto entre equipe multiprofissional, quanto entre o paciente, sua família e a equipe de cuidado.