Preparation and scale up of extended-release tablets of bromopride

A reprodutibilidade do processo de fabricação de comprimidos e o controle das suas propriedades farmacotécnicas depende da otimização dos aspectos de formulação e dos parâmetros de processo. O planejamento de experimentos como o Desenho de Experimentos (DOE) pode ser utilizado para acelerar a produção desta formulação, em particular, para a obtenção de comprimidos de liberação prolongada. Formulações de bromoprida são comercializadas sob a forma de péletes de liberação prolongada, o que torna o produto caro e de difícil fabricação. O objetivo deste estudo foi preparar novas formulações de bromoprida de liberação prolongada na forma de comprimidos e desenvolver modelos matemáticos visando ao escalonamento destas formulações, controlando o peso e a dureza dos comprimidos durante a fabricação, de acordo com a 34ª Edição da USP. Estudos de DOE foram realizados utilizando o software Minitab(tm). Diferentes combinações de excipientes foram avaliadas visando à obtenção dos comprimidos de liberação prolongada de bromoprida. No estudo de scale-up, coletaram-se e mediu-se a influência das variações nos parâmetros da máquina de compressão. Processaram-se os dados obtidos pelo software Minitab (tm), gerando equações matemáticas aptas para a previsão do comportamento de compactação do pó em escala industrial. Os comprimidos obtidos apresentavam características adequadas em termos de liberação sustentada, sendo a cinética de liberação estabelecida utilizando modelos matemáticos, indicando que esta formulação pode ser uma substituta aos péletes de bromoprida atualmente comercializados.Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE) can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm) software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm) software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed

COVID-19 outcomes in people living with HIV: Peering through the waves

Objective: To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. Methods: This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. Results: Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). Conclusions: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost