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The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.
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Comitês Consultivos , Vacinas Antimaláricas , Organização Mundial da Saúde , Humanos , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/imunologia , Análise Custo-Benefício , Vacinação/métodos , Malária/prevenção & controle , Imunização/métodosRESUMO
Evaluating vaccine-related research is critical to maximize the potential of vaccination programmes. The WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) provides an independent review of research that estimates the performance, impact and value of vaccines, with a particular focus on transmission and economic modelling. On 11-13 September 2023, IVIR-AC was convened for a bi-annual meeting where the committee reviewed research and presentations across eight different sessions. This report summarizes the background information, proceedings and recommendations from that meeting. Sessions ranged in topic from timing of measles supplementary immunization activities, analyses of conditions necessary to meet measles elimination in the South-East Asia region, translating modelled evidence into policy, a risk-benefit analysis of dengue vaccine, COVID-19 scenario modelling in the African region, therapeutic vaccination against human papilloma virus, the Vaccine Impact Modelling Consortium, and the Immunization Agenda 2030 vaccine impact estimates.
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Sarampo , Vacinas , Humanos , Comitês Consultivos , Organização Mundial da Saúde , Vacinas/uso terapêutico , Vacinação , ImunizaçãoRESUMO
The top 20 highest burdened countries (in disability-adjusted life years) account for more than 75% of the global burden of viral hepatitis. An effective response in these 20 countries is crucial if global elimination targets are to be achieved. In this update of the Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis, we convene national experts from each of the top 20 highest burdened countries to provide an update on progress. Although the global burden of diseases is falling, progress towards elimination varies greatly by country. By use of a hepatitis elimination policy index conceived as part of the 2019 Commission, we measure countries' progress towards elimination. Progress in elimination policy has been made in 14 of 20 countries with the highest burden since 2018, with the most substantial gains observed in Bangladesh, India, Indonesia, Japan, and Russia. Most improvements are attributable to the publication of formalised national action plans for the elimination of viral hepatitis, provision of publicly funded screening programmes, and government subsidisation of antiviral treatments. Key themes that emerged from discussion between national commissioners from the highest burdened countries build on the original recommendations to accelerate the global elimination of viral hepatitis. These themes include the need for simplified models of care, improved access to appropriate diagnostics, financing initiatives, and rapid implementation of lessons from the COVID-19 pandemic.
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Gastroenterologia , Hepatite A , Hepatite , Humanos , Pandemias , Hepatite/epidemiologia , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , ÍndiaRESUMO
This statement revises our earlier "WAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications" (January 20, 2023). The revision reflects the proliferation of chatbots and their expanding use in scholarly publishing over the last few months, as well as emerging concerns regarding lack of authenticity of content when using chatbots. These recommendations are intended to inform editors and help them develop policies for the use of chatbots in papers published in their journals. They aim to help authors and reviewers understand how best to attribute the use of chatbots in their work and to address the need for all journal editors to have access to manuscript screening tools. In this rapidly evolving field, we will continue to modify these recommendations as the software and its applications develop.
Esta declaración revisa las anteriores "Recomendaciones de WAME sobre ChatGPT y Chatbots en Relation to Scholarly Publications" (20 de enero de 2023). La revisión refleja la proliferación de chatbots y su creciente uso en las publicaciones académicas en los últimos meses, así como la preocupación por la falta de autenticidad de los contenidos cuando se utilizan chatbots. Estas recomendaciones pretenden informar a los editores y ayudarles a desarrollar políticas para el uso de chatbots en los artículos sometidos en sus revistas. Su objetivo es ayudar a autores y revisores a entender cuál es la mejor manera de atribuir el uso de chatbots en su trabajo y a la necesidad de que todos los editores de revistas tengan acceso a herramientas de selección de manuscritos. En este campo en rápida evolución, seguiremos modificando estas recomendaciones a medida que se desarrollen el software y sus aplicaciones.
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Inteligência Artificial , Editoração , HumanosRESUMO
Virtual clinical trials refer to clinical trials that take advantage of digital technologies, including computer and mobile device apps, web-based tools, and remote monitoring devices, for one or more of the trial processes, such as participant recruitment, counseling, informed consent, measurement of endpoints, and/or adverse event monitoring, to obviate or reduce the need for participant visits to the trial site. The advantages of such trials may include higher recruitment rates, better compliance, lower dropout rates, reduction in time for trial completion, and lower costs. The use of such trials increased manifold during the COVID-19 pandemic and is likely to continue in the future.
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Hepatitis E is a disease associated with acute inflammation of the liver. It is related to several dysregulated metabolic pathways and alterations in the concentration of several metabolites. However, longitudinal analysis of the alterations in metabolites and lipids is generally lacking. This study investigated the changes in levels of metabolites and lipids over time in sera from men with acute hepatitis E compared to healthy controls similar in age and gender. Untargeted measurement of levels of various metabolites and lipids was done using mass spectrometry on 65 sera sequentially sampled from 14 patients with acute hepatitis E and 25 serum samples from five controls. Temporal changes in intensities of metabolites and lipids were determined over different times at 3-day periods for the hepatitis E virus (HEV) group. In carbohydrate metabolism, glucose levels, fructose 1-6-bisphosphate and ribulose-5-phosphate were increased in the HEV-infected persons compared to the healthy controls. HEV infection is significantly associated with decreased levels of inosine, guanosine, adenosine and urate in purine metabolism and thymine, uracil and ß-aminoisobutyrate in pyrimidine metabolism. Glutamate, alanine and valine levels were significantly lower in the HEV group than in healthy individuals. Homogentisate of tyrosine metabolism and cystathionine of serine metabolism were increased, whereas kynurenate of tryptophan metabolism decreased in the HEV group. Metabolites of the bile acid biosynthesis, urea cycle (arginine and citrulline) and ammonia recycling (urocanate) were significantly altered. Co-enzymes, pantothenate and pyridoxal, and co-factors, lipoamide and FAD, were elevated in the HEV group. The acylcarnitines, sphingomyelins, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC and lysoPE tended to be lower in the HEV group. In conclusion, acute hepatitis E is associated with altered metabolite and lipid profiles, significantly increased catabolism of carbohydrates, purines/pyrimidines and amino acids, and decreased levels of several glycerophospholipids.
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Vírus da Hepatite E , Hepatite E , Masculino , Humanos , Estudos Longitudinais , LipídeosRESUMO
Background and Aims: Sofosbuvir (S), daclatasvir (D), ledipasvir, or velpatasvir (V) containing first-line hepatitis C virus (HCV) treatment regimens fail to cure viremia in 5-10%. We report our experience of HCV retreatment using these first-line drugs, in a setting where second-line anti-HCV drugs are not available. Methods: Adults, who had relapsed after first complete course of a sofosbuvir-containing first-line, pegylated interferon free, anti-HCV treatment regimen with or without ribavirin (Riba) were included. Retreatment regimen, tailored to the failed anti-HCV regimen, was based on principle of using first-line drugs for 24 weeks with ribavirin and swapping between pangenotypic and genotype-specific regimens. Retreatment outcome was categorized as successful (achieved undetectable HCV RNA at the end of treatment [ETR] and sustained viral response at week 12 [SVR12]), non-responder (failed to achieve ETR), or relapse (achieved ETR but not achieved SVR12). Results: Twelve patients (9 male; 7 cirrhosis; all genotype 3) who had relapsed to prior anti-HCV treatment (4 SD12, 4 SD24, 1 SDRiba12, 1 SDRiba24, 2 SV12) were included. Following retreatment (2 SDRiba24, 10 SVRiba24), all achieved ETR but only 9 (75%) achieved SVR12. Two among three, in whom retreatment failed, achieved SVR12 following another course of sofosbuvir/velpatasvir/ribavirin for 24 weeks. Overall, 11/12 (92%) patients achieved SVR12 following retreatment with the first-line anti-HCV drugs. Conclusion: HCV retreatment could be a treatment option if second-line anti-HCV drugs are not available. Successful retreatment could be achieved, in a large proportion, with the use of first-line drugs for 24 weeks with ribavirin and swapping of pangenotypic/genotype-specific regimens (NCT03483987).
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This statement revises our earlier "WAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications" (January 20, 2023). The revision reflects the proliferation of chatbots and their expanding use in scholarly publishing over the last few months, as well as emerging concerns regarding lack of authenticity of content when using chatbots. These recommendations are intended to inform editors and help them develop policies for the use of chatbots in papers published in their journals. They aim to help authors and reviewers understand how best to attribute the use of chatbots in their work and to address the need for all journal editors to have access to manuscript screening tools. In this rapidly evolving field, we will continue to modify these recommendations as the software and its applications develop.
Esta declaración revisa las anteriores "Recomendaciones de WAME sobre ChatGPT y Chatbots en Relation to Scholarly Publications" (20 de enero de 2023). La revisión refleja la proliferación de chatbots y su creciente uso en las publicaciones académicas en los últimos meses, así como la preocupación por la falta de autenticidad de los contenidos cuando se utilizan chatbots. Estas recomendaciones pretenden informar a los editores y ayudarles a desarrollar políticas para el uso de chatbots en los artículos sometidos en sus revistas. Su objetivo es ayudar a autores y revisores a entender cuál es la mejor manera de atribuir el uso de chatbots en su trabajo y a la necesidad de que todos los editores de revistas tengan acceso a herramientas de selección de manuscritos. En este campo en rápida evolución, seguiremos modificando estas recomendaciones a medida que se desarrollen el software y sus aplicaciones.
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OBJECTIVE: To report genotype data of the patients with Wilson disease (WD) hailing from across several parts of India to add to the available spectrum of causative variants in ATP7B gene (ATPase copper transporting beta polypeptide gene) and associated phenotypes in the Indian population. METHODS: The entire ATP7B gene was sequenced in 58 patients with WD and additional testing was also done by MLPA to look for intragenic deletions duplications and exome sequencing to rule out genetic variations with similar phenotypic overlap. RESULTS: Of all patients, 37 patients had a total of 33 distinct pathogenic variations, including 29 in the exonic regions and 4 at intronic splice sites. Of the variations identified, six were novel. The underlying genomic variations could be identified in nearly two-thirds of the patients by sequencing the entire gene. CONCLUSIONS: This study reports the genotype-phenotype data to add to the available spectrum of causative variants in ATP7B gene. The inability to detect a pathogenic variation in some patients and the existence of phenotypic variations in individuals with the same variation suggest that additional factors or genes may play a role in causation of the disease. Further, a marked genetic heterogeneity was found in the study patients, indicating ethnic diversity of the Indian population.
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Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , ATPases Transportadoras de Cobre/genética , Mutação , Genótipo , GenômicaRESUMO
This study aimed to determine lactoferrin (LF) in breast milk-based powders and formulas. Lactoferrin is an important whey protein in all mammalian milks and is responsible in large part for the known antimicrobial effects of human milk in particular. As breast feeding is not always possible, formulas based on cows milk have been developed in order to meet the nutritional needs of the newborn, while more recently human breast milk-based powders have been introduced to offer the biological functionality of human milk to pre-term and critically ill babies. In the present work, the amount of LF in commercial breast milk-based powders was tested by a validated RF-HPLC method for the determination of LF in breast milk in order to examine both the applicability of the method but at a second level the amount of LF in these commercial products. The detection of LF was possible but the complexity of the matrix lead us to the use the standard addition methodology in order to achieve quantification. The results indicated that breast milk-based powders had higher amount of LF than cows milk-based formulas, both non-fortified and fortified.
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Leite Humano , Leite , Lactente , Feminino , Humanos , Bovinos , Animais , Leite/metabolismo , Lactoferrina , Pós/metabolismo , Aleitamento Materno , Cromatografia Líquida de Alta Pressão/veterinária , Mamíferos/metabolismoRESUMO
As of November 2023, 140 World Health Organization (WHO) member states had introduced human papillomavirus (HPV) vaccination in their routine immunization schedules. Despite a continuously increasing demand from countries across all income groups, supply constraints, COVID-19 pandemic disruptions, and other factors have slowed the pace of introduction, particularly in low-resource settings. Using a population-based forecasting methodology and leveraging the WHO's yearly vaccine supply data collection, we updated global demand and supply projections for the HPV vaccine for the period of 2022-2031. The analysis aimed at clarifying the magnitude of the challenges to bringing in equitable access to HPV vaccines, which can hinder the achievement of the Global Strategy for the Elimination of Cervical Cancer. The results of this analysis show that the risk of HPV shortages has significantly decreased, and global supply is now, under normal circumstances, sufficient to meet global demand. In the long term, HPV supply will be more than sufficient to meet the Global Strategy's goal of 90% of girls fully vaccinated with the HPV vaccine by the age of 15 years. Nonetheless, paying attention to the formulation of policies and carefully managing demand and supply will be required to ensure the long-term sustainability of the HPV vaccine program.
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Hepatitis C virus (HCV) infection is one of the most common causes of liver cancer. HCV infection causes chronic disease followed by cirrhosis, which often leads to hepatocellular carcinoma (HCC). In this study, we investigated the roles of exosome-associated miRNAs in HCV-induced disease pathology. Small RNA sequencing was performed to identify miRNAs that are differentially regulated in exosomes isolated from patient sera at two different stages of HCV infection: cirrhosis and hepatocellular carcinoma. Among the differentially expressed miRNAs, miR-375 was found to be significantly upregulated in exosomes isolated from patients with cirrhosis and HCC. A similar upregulation was observed in intracellular and extracellular/exosomal levels of miR-375 in HCV-JFH1 infected Huh7.5 cells. The depletion of miR-375 in infected cells inhibited HCV-induced cell migration and proliferation, suggesting a supportive role for miR-375 in HCV pathogenesis. miR-375, secreted through exosomes derived from HCV-infected cells, could also be transferred to naïve Huh7.5 cells, resulting in an increase in cell proliferation and migration in the recipient cells. Furthermore, we identified Insulin growth factor binding protein 4 (IGFBP4), a gene involved in cell growth and malignancy, as a novel target of miR-375. Our results demonstrate the critical involvement of exosome-associated miR-375 in HCV-induced disease progression.
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Carcinoma Hepatocelular , Exossomos , Hepatite C , Neoplasias Hepáticas , MicroRNAs , Humanos , Hepacivirus/genética , Hepacivirus/metabolismo , Exossomos/metabolismo , Exossomos/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Insulina/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Hepatite C/genética , Hepatite C/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologiaRESUMO
Screening tests are done to diagnose asymptomatic disease in apparently healthy people with the aim to reduce mortality and morbidity from the disease. Certain criteria need to be fulfilled before we adopt population-level screening for any disease. Several biases exist in evaluating screening studies, and the ideal study design would be a randomized trial with hard endpoints such as mortality and morbidity.