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

Sintomas depressivos entre idosos internados aumentam a chance de mortalidade após a alta hospitalar

Este estudo teve o objetivo de estimar a prevalência de sintomas depressivos em uma amostra de idosos hospitalizados, bem como a sua relação com o prognóstico do paciente 90 e 180 dias após a alta hospitalar. Trata-se de um estudo transversal, realizado com 213 idosos internados em um hospital geral-secundário da zona sul da cidade de São Paulo, durante os anos de 2016-2017. Os participantes foram solicitados a responder questionários sobre dados pessoais, sintomas depressivos e variáveis de confusão, tendo sido contatados novamente aos 90 e 180 dias após a alta. Um modelo de regressão logística foi ajustado individualmente para indicadores de saúde; a hipótese nula foi refutada quando p<0,05. Nesse sentido, um total de 42,5% dos idosos internados tinham sintomas depressivos. Aos 90 dias, 26% deles relataram piora do estado de saúde, 20,5% foram reinternados e 18,7% evoluíram para óbito, prevalências que aumentaram aos 180 dias. A presença de sintomas depressivos aumentou a chance de mortalidade depois de 180 dias da alta hospitalar. Dessa forma, concluímos que a prevalência de sintomas depressivos nessa amostra foi superior à encontrada em estudos anteriores. Desperta a atenção que esses sintomas interferem negativamente na chance de mortalidade após a alta hospitalar, de tal forma que sugerimos a identificação precoce e o tratamento desses sintomas durante a internação dos pacientes

Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers

Background: Nephrolithiasis has been associated with bone loss and vascular calcification (VC), reflecting abnormal extraosseous calcium deposition. Fetuin-A (Fet-A) acts as a potent inhibitor of ectopic mineralization. The aim of the present study was to evaluate the prevalence of VC in stone formers (SF) and non-stone formers (NSF) and to investigate potential determinants of VC among SF, including circulating levels of Fet-A and bone microarchitecture parameters. Methods: Abdominal aortic calcification (AAC) was assessed using available computed tomography in SF and in age-, sex-, and BMI-matched NSF (potential living kidney donors). Serum Fet-A was measured in stored blood samples from SF. Bone microarchitecture parameters were obtained as a post hoc analysis of a cross-sectional cohort from young SF evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: A total of 62 SF (38.0 [28.0-45.3] years old) and 80 NSF (40.0 [37.0-45.8] years old) were included. There was no significant difference in AAC scores between SF and NSF. However, when dividing SF according to mean AAC score, below = 5.8% (n = 29), SF with higher AAC presented significantly higher BMI and tibial cortical porosity (Ct.Po) and significantly lower serum HDL, klotho, Fet-A, and eGFR. Urinary calcium did not differ between groups, but fractional excretion of phosphate was higher in the former. Upon multivariate regression, BMI, serum Fet-A, and tibial Ct.Po remained independently associated with AAC. Conclusions: This study suggests an association between reduced circulating Fet-A levels and increased bone Ct.Po with VC in SF

The Genome of Anopheles darlingi, the main neotropical Malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector–human and vector–parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible a

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The Genome of Anopheles darlingi, the main neotropical malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vectorhuman and vectorparasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles- darlingi. © 2013 The Author(s)

Otimization of the block matching algorithm aplied to elastogtraphic studies.

Este trabalho apresenta uma análise sobre um novo método de formação de imagem, utilizando aparelhos de ultra-som a elastografia. Esta técnica baseia-se no fato de que quando um meio elástico, como o tecido, é deformado por uma tensão constante e uniaxial, todos os pontos no meio possuem um nível de deformação longitudinal cujo componente principal está ao longo do eixo de deformação. Se elementos do tecido possuem um módulo elástico diferente dos demais, a deformação nestes elementos será relativamente maior ou menor. Elementos mais rígidos geralmente deformam-se menos. Desta forma, pode-se mapear e identificar estruturas com diferentes níveis de dureza. A comparação entre os mapas de RF de pré e pós-deformação foi realizada pela técnica de block matching. Esta técnica consiste em comparar regiões, ou kernels, no mapa de pré-deformação com regiões de mesmo tamanho no mapa de pós-deformação. Esta comparação é feita pela minimização de uma função custo. Nesta técnica, o tamanho do kernel, é um dos principais parâmetros para melhorar a precisão das medidas de deslocamento. O principal objetivo neste trabalho é aperfeiçoar o algoritmo de block matching visando melhorar a precisão da determinação de deslocamento em técnicas de deformação dinâmica e estática, mantendo o custo computacional baixo. Para isto, foram utilizados phantoms com e sem inclusões mais duras que o meio. Os phantoms foram submetidos a deformações estáticas e dinâmicas. Foi possível determinar o comportamento destes phantoms sob estas formas de deformação, e as faixas de kernel e funções custo que forneceram os melhores resultados. Também foram gerados elastogramas do phantom com inclusão. Estas imagens permitiram avaliar a influência dos diferentes kernels sobre a resolução dos elastogramas e a capacidade em diferenciar a lesão do tecido circundante. Comparando os elastogramas obtidos sobre deformação dinâmica, utilizando os kernels que apresentaram o melhor desempenho, com as respectivas imagens em modo B, pôde-se observar que a inclusão estava clara e bem delimitada.This work provides an analysis about a new method for image formation using ultrasound devices elastography. This technique is based on the fact that when an elastic medium, as the tissue, is deformed under a constant and directional stress, all the points in the medium have a deformation level whose main component is along the deformation axis. If tissues elements have different elastic modules, the deformation in these elements will be higher or lower. Normally harder elements have lower deformations. In this way, one can detect and identify structures with different elastic levels. The comparisons between the pre and post-deformation RF maps were done by the block matching technique. This technique is based on the comparison of regions, or kernels, in the pre-deformation maps with regions of the same size in the post-deformation map. This is done by the minimization of a cost function. In this technique, the kernel size is one of the most important parameters to obtain better resolution and precision in the displacement measurements. The goal of this work is to optimize the block matching algorithm to improve the displacement estimates precision in both dynamic and static deformations, while keeping a low computational cost. To obtain this, we used phantoms with and without inclusions harder than the medium. These phantoms were submitted to both static and dynamic deformations. It was possible to estimate the behavior of these phantoms under these deformations, and the kernel range and cost functions that provided the best results. Also, we generated the elastograms of the phantom with the inclusion. These images allowed us to evaluate the influence of the different kernel sizes under the elastograms resolution and their capability in differentiate the lesion from the embedding tissue. Comparing the elastograms obtained under dynamic deformation that had the best performance, with the B mode images, we could conclude that the inclusion was well delimited and clear