Systematic evaluation of high-throughput PBK modelling strategies for the prediction of intravenous and oral pharmacokinetics in humans.

Physiologically based kinetic (PBK) modelling offers a mechanistic basis for predicting the pharmaco-/toxicokinetics of compounds and thereby provides critical information for integrating toxicity and exposure data to replace animal testing with in vitro or in silico methods. However, traditional PBK modelling depends on animal and human data, which limits its usefulness for non-animal methods. To address this limitation, high-throughput PBK modelling aims to rely exclusively on in vitro and in silico data for model generation. Here, we evaluate a variety of in silico tools and different strategies to parameterise PBK models with input values from various sources in a high-throughput manner. We gather 2000 + publicly available human in vivo concentration-time profiles of 200 + compounds (IV and oral administration), as well as in silico, in vitro and in vivo determined compound-specific parameters required for the PBK modelling of these compounds. Then, we systematically evaluate all possible PBK model parametrisation strategies in PK-Sim and quantify their prediction accuracy against the collected in vivo concentration-time profiles. Our results show that even simple, generic high-throughput PBK modelling can provide accurate predictions of the pharmacokinetics of most compounds (87% of Cmax and 84% of AUC within tenfold). Nevertheless, we also observe major differences in prediction accuracies between the different parameterisation strategies, as well as between different compounds. Finally, we outline a strategy for high-throughput PBK modelling that relies exclusively on freely available tools. Our findings contribute to a more robust understanding of the reliability of high-throughput PBK modelling, which is essential to establish the confidence necessary for its utilisation in Next-Generation Risk Assessment.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

Novel clinical phenotypes, drug categorization, and outcome prediction in drug-induced cholestasis: Analysis of a database of 432 patients developed by literature review and machine learning support.

BACKGROUND: Serum transaminases, alkaline phosphatase and bilirubin are common parameters used for DILI diagnosis, classification, and prognosis. However, the relevance of clinical examination, histopathology and drug chemical properties have not been fully investigated. As cholestasis is a frequent and complex DILI manifestation, our goal was to investigate the relevance of clinical features and drug properties to stratify drug-induced cholestasis (DIC) patients, and to develop a prognosis model to identify patients at risk and high-concern drugs. METHODS: DIC-related articles were searched by keywords and Boolean operators in seven databases. Relevant articles were uploaded onto Sysrev, a machine-learning based platform for article review and data extraction. Demographic, clinical, biochemical, and liver histopathological data were collected. Drug properties were obtained from databases or QSAR modelling. Statistical analyses and logistic regressions were performed. RESULTS: Data from 432 DIC patients associated with 52 drugs were collected. Fibrosis strongly associated with fatality, whereas canalicular paucity and ALP associated with chronicity. Drugs causing cholestasis clustered in three major groups. The pure cholestatic pattern divided into two subphenotypes with differences in prognosis, canalicular paucity, fibrosis, ALP and bilirubin. A predictive model of DIC outcome based on non-invasive parameters and drug properties was developed. Results demonstrate that physicochemical (pKa-a) and pharmacokinetic (bioavailability, CYP2C9) attributes impinged on the DIC phenotype and allowed the identification of high-concern drugs. CONCLUSIONS: We identified novel associations among DIC manifestations and disclosed novel DIC subphenotypes with specific clinical and chemical traits. The developed predictive DIC outcome model could facilitate DIC prognosis in clinical practice and drug categorization.

Repercussões da Covid-19 na percepção de mudanças de peso e satisfação corporal: comparação entre mulheres com e sem transtornos alimentares / Impacts of Covid-19 on weight change perception and body satisfaction: a comparison between women with and without eating disorders

Introdução: A pandemia da Covid-19 trouxe consequências diversas para a saúde mental e física das pessoas. O contexto de isolamento social potencializou problemas relacionados à imagem corporal, principalmente em pessoas com transtornos alimentares. Objetivo: Analisar as repercussões da Covid-19 em variáveis antropométricas em relação a percepção de peso e satisfação corporal, comparando mulheres com transtornos alimentares e aquelas sem essa condição. Métodos: Estudo observacional, descritivo, comparativo e transversal. Mulheres com transtornos alimentares em tratamento (GTA) foram recrutadas de cinco serviços nas regiões Sul e Sudeste. A contrapartida, o grupo controle (GCO) foi composto por mulheres sem TA, recrutadas on-line e com o escore negativo no teste EAT-26. Questionários on-line foram aplicados entre junho de 2020 e janeiro de 2021. Análises estatísticas incluíram Qui-quadrado de Pearson ou Exato de Fisher e regressões logísticas pelo SPSS 23.0. Resultados: Participaram 174 mulheres jovens (31,94±9,35 anos), com formação superior (71,3%) e companheiro (61,5%), que estavam em isolamento social. O GTA foi composto por 58 mulheres e GCO, 116. A maioria (55,2%) do GTA notou aumento do peso corporal, enquanto se mostrou pouco satisfeita com a imagem corporal (81%), resultado diferente estatisticamente do GCO. A associação entre mulheres com TA e pouca satisfação corporal foi significativa (p=0,0010). Aquelas em isolamento social e com sobrepeso ou obesidade tiveram maior probabilidade de percepção de aumento de peso. Conclusão: A pandemia da Covid-19 intensificou a insatisfação corporal, principalmente entre mulheres com transtornos alimentares. Aquelas em isolamento com sobrepeso ou obesidade perceberam mais aumento de peso, apontando a necessidade de estratégias de intervenção para esses grupos.

Introduction: The Covid-19 pandemic led to various consequences for people's mental and physical health. The context of social isolation exacerbated problems related to body image, especially in individuals with eating disorders. Objective: To analyze the repercussions of Covid-19 on anthropometric variables regarding weight perception and body satisfaction, comparing women with eating disorders to those without this condition. Methods: Observational, descriptive, comparative, and cross-sectional study. Women with eating disorders in treatment (EDG) were recruited from five services in the South and Southeast regions of Brazil. The counterpart, the control group (CG), consisted of women without eating disorders recruited online and with a negative score on the EAT-26 test. Online questionnaires were applied between June 2020 and January 2021. Statistical analyses included Pearson's Chi-square or Fisher's Exact test and logistic regressions, performed using the SPSS 23.0 program. Results: Participants were 174 young women (31.94±9.35 years of age), with higher education (71.3%) and with a partner (61.5%), who were in social isolation. The EDG consisted of 58 women, with116 in the CG. The majority (55.2%) of the EDG noticed an increase in body weight while being dissatisfied with body image (81.0%), a statistically different result from the CG. The association between women with eating disorders and low body satisfaction was significant (p=.0010). Those in social isolation and overweight or obese were more likely to perceive weight gain. Conclusion: The Covid-19 pandemic intensified body dissatisfaction, especially among women with eating disorders. Those in isolation who were overweight or obese perceived more weight gain, indicating the need for intervention strategies for these groups.

Influence of the dental arch and number of cutting-off and rescanning mesh holes on the accuracy of implant scans in partially edentulous situations.

OBJECTIVES: To evaluate the influence of the dental arch and cutting-off and rescanning procedures on the accuracy of complete-arch implant scans in partially edentulous arches. MATERIAL AND METHODS: A maxillary and a mandibular partially edentulous typodont with implant abutment analogs placed in the right and left first molar and right central incisor sites were digitized to create reference models by using an industrial optical scanner (7 Series Desktop Scanner; Dentalwings). Two experimental groups were scanned using an intraoral scanner (IOS) (TRIOS 4; 3Shape A/S): the Maxillary group (Mx) and the Mandibular group (Mb). Four subgroups were generated depending on the number of rescanned mesh holes: No holes (Mx-G0, Mb-G0), 1 hole (Mx-G1, Mb-G1), 2 holes (Mx-G2, Mb-G2) and 3 holes (Mx-G3, Mb-G3). A 3-dimensional metrology software (Geomagic Control X; 3D Systems) was used to measure the difference between the reference and the experimental scans computing the root mean square (RMS) error calculation. Two-way ANOVA and a post-hoc Tukey test were used to analyze the trueness data (α=0.05). Levene test was used to evaluate the prevision (α=0.05). RESULTS: The Mx group obtained a trueness mean value of 54 ± 17 µm and a mean precision value of 54 ± 17 µm, while the Mb group presented a trueness mean value of 67 ± 23 µm and a mean precision value of 66 ± 22 µm. The Mx group demonstrated significantly better trueness than the Mb group (P<.001). The G0 and G1 subgroups had the highest trueness values among the subgroups tested. No significant difference was observed between G0 and G1, G1 and G2, and G2 and G3 subgroups in trueness and precision. However, the G0 had significantly better trueness and precision values compared to G2 and G3 subgroups. In addition, the G1 had significantly better trueness values than the G3 subgroup. However, the Levene test revealed no difference in the precision mean values among the subgroups tested. CONCLUSIONS: Implant scanning trueness was affected by the dental arch and the number of rescanned mesh holes using the IOS tested. A higher number of rescanned mesh holes decreased the scanning trueness. The stitching algorithm of the IOS software tested after the mesh hole scan demonstrated a significant error, especially when multiples mesh holes are involved in the same arch. CLINICAL SIGNIFICANCE: Given that cutting-off and rescanning techniques can reduce trueness, clinicians should consider whether these techniques are necessary in complete digital workflows. This is particularly important when fabricating multiple single implant-supported restorations in the same arch.

Microfluidic-based prostate cancer model for investigating the secretion of prostate-specific antigen and microRNAs in vitro.

The study of prostate cancer in vitro relies on established cell lines that lack important physiological characteristics, such as proper polarization and expression of relevant biomarkers. Microphysiological systems (MPS) can replicate cancer microenvironments and lead to cellular phenotypic changes that better represent organ physiology in vitro. In this study, we developed an MPS model comprising conventional prostate cancer cells to evaluate their activity under dynamic culture conditions. Androgen-sensitive (LNCaP) and androgen-insensitive (PC3) cells were grown in conventional and 3D cultures, both static and dynamic. Cell morphology, the secretion of prostate-specific antigen, and the expression of key prostate markers and microRNAs were analyzed. LNCaP formed spheroids in 3D and MPS cultures, with morphological changes supported by the upregulation of cytokeratins and adhesion proteins. LNCaP also maintained a constant prostate-specific antigen secretion in MPS. PC3 cells did not develop complex structures in 3D and MPS cultures. PSA expression at the gene level was downregulated in LNCaP-MPS and considerably upregulated in PC3-MPS. MicroRNA expression was altered by the 3D static and dynamic culture, both intra- and extracellularly. MicroRNAs associated with prostate cancer progression were mostly upregulated in LNCaP-MPS. Overall dynamic cell culture substantially altered the morphology and expression of LNCaP cells, arguably augmenting their prostate cancer phenotype. This novel approach demonstrates that microRNA expression in prostate cancer cells is sensitive to external stimuli and that MPS can effectively promote important physiological changes in conventional prostate cancer models.

Delineating effects of angiopoietin-2 inhibition on vascular permeability and inflammation in models of retinal neovascularization and ischemia/reperfusion.

Introduction: Clinical trials demonstrated that co-targeting angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF-A) with faricimab controls anatomic outcomes and maintains vision improvements, with strong durability, through 2 years in patients with neovascular age-related macular degeneration and diabetic macular edema. The mechanism(s) underlying these findings is incompletely understood and the specific role that Ang-2 inhibition plays requires further investigation. Methods: We examined the effects of single and dual Ang-2/VEGF-A inhibition in diseased vasculatures of JR5558 mice with spontaneous choroidal neovascularization (CNV) and in mice with retinal ischemia/reperfusion (I/R) injuries. Results: In JR5558 mice, Ang-2, VEGF-A, and dual Ang-2/VEGF-A inhibition reduced CNV area after 1 week; only dual Ang-2/VEGF-A inhibition decreased neovascular leakage. Only Ang-2 and dual Ang-2/VEGF-A inhibition maintained reductions after 5 weeks. Dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 1 week. Both Ang-2 and dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 5 weeks. In the retinal I/R injury model, dual Ang-2/VEGF-A inhibition was statistically significantly more effective than Ang-2 or VEGF-A inhibition alone in preventing retinal vascular leakage and neurodegeneration. Discussion: These data highlight the role of Ang-2 in dual Ang-2/VEGF-A inhibition and indicate that dual inhibition has complementary anti-inflammatory and neuroprotective effects, suggesting a mechanism for the durability and efficacy of faricimab in clinical trials.

Effectiveness of a minimally processed food-based nutritional counselling intervention on weight gain in overweight pregnant women: a randomized controlled trial.

PURPOSE: This study aimed at evaluating the effectiveness of a nutritional counselling intervention based on encouraging the consumption of unprocessed and minimally processed foods, rather than ultra-processed products, and the practice of physical activities to prevent excessive gestational weight gain in overweight pregnant women. METHODS: This was a two-armed, parallel, randomized controlled trial conducted in primary health units of a Brazilian municipality from 2018 to 2021. Overweight, adult pregnant women (n = 350) were randomly assigned to control (CG) or intervention groups (IG). The intervention consisted of three individualized nutritional counselling sessions based on encouraging the consumption of unprocessed and minimally processed foods rather than ultra-processed products, following the NOVA food classification system, and the practice of physical activities. The primary outcome was the proportion of women whose weekly gestational weight gain (GWG) exceeded the Institute of Medicine guidelines. Adjusted logistic regression models were employed. RESULTS: Complete data on weight gain were available for 121 women of the IG and 139 of the CG. In modified intention-to-treat analysis, there was a lower chance of the IG women having excessive GWG [OR 0.56 (95% CI 0.32, 0.98), p = .04], when compared to the CG. No between-group differences were observed for the other maternal outcomes investigated. CONCLUSION: The present study was unprecedented in demonstrating that nutritional counselling based on the NOVA food classification system, together with encouraging the practice of physical activity, is effective in preventing excessive weight gain in overweight pregnant women. TRIAL REGISTRATION: Registered on July 30th 2018 at Brazilian Registry of Clinical Trials (RBR-2w9bhc).

Clinical recommendations for dry powder inhaler use in the management of COPD in primary care.

Over 1400 patients using dry powder inhalers (DPIs) to deliver COPD maintenance therapies were recruited across Europe and Australia. Their peak inspiratory flow (PIF) was measured, inhaler technique was observed, and adherence to treatment assessed. From relating the findings with patient health status, and thereby identifying critical errors, key clinical recommendations for primary care clinicians were determined, namely - measure PIF before prescribing a DPI to ensure inhalation manoeuvre ability is well-matched with the device. Some patients could benefit from inhalation training whereas others should have their DPI changed for one better suited to their inspiratory ability or alternatively be prescribed an active device (such as a soft mist inhaler or pressurized metered dose inhaler). Observing the inhalation technique was valuable however this misses suboptimal PIF (approaching one fourth of patients with a satisfactory observed manoeuvre had a suboptimal PIF for their DPI). Assess adherence as deliberate non-adherence can point to a mismatch between a patient and their inhaler (deliberate non-adherence was significantly associated with PIFs below the minimum for the DPI). In-person observation of inhalation technique was found to be inferior to video rating based on device-specific checklists. Where video assessments are not possible, observation training for healthcare professionals would therefore be valuable particularly to improve the ability to identify the critical errors associated with health status namely 'teeth and lips sealed around mouthpiece', 'breathe in' and 'breathing out calmly after inhalation'. However, it is recommended that observation alone should not replace PIF measurement in the DPI selection process.Trial registration: https://clinicaltrials.gov/ct2/show/NCT04532853 .

Development of melatonin-loaded, human-serum-albumin nanoparticles formulations using different methods of preparation for ophthalmic administration.

The use of proteins such as human serum albumin (HSA) to form nanometric systems seems very promising since they are non-toxic, biodegradable and have no antigenic activity. This molecule is ideal to transport insoluble drugs such as melatonin (Mel), which has antiapoptotic and antioxidant properties and appears promising for the treatment of neurodegenerative eye diseases. The objective of this study was to obtain nanoparticulate systems loaded with Mel, improving the conventional desolvation method. Systems were stabilised using two different strategies: one through the use of Eudragit S100 as a cross-linking agent and the other through thermal stabilisation. The systems thus obtained (Np-HSA-Eu-Mel and Np-HSA-Mel, respectively) were characterised and compared in terms of physicochemical and pharmacotechnical parameters. Whitish colloidal dispersions of nanometric size (≈170 nm), spherical shape, and monodisperse population were obtained. Besides, the pH was close to neutrality reaching 20 % drug encapsulation whereas the process performance was higher than 80 %. In FT-IR studies, thermal analysis and X-ray diffraction (XRD), the incorporation of the drug in the cavities of the nanoparticles could be evidenced. Regarding the physical stability of nanoparticles, for Np-HSA-Eu-Mel instability was observed at pH > 7. However, Np-HSA-Mel was able to remain stable at different pH levels. Mel release from these systems was consequently affected, where the former released faster than the active compared to the last. On the other hand, it was observed that the drying process (lyophilization in this case) applied to the nanoparticles suspensions does not affect their original properties after redispersion over a three months period. Likewise, the formulation did not produce irritation when administered topically, whereas when administered subconjunctivally, only slight irritation was observed 24 h after administration. According to the result of this study, the Np-HSA-Mel formulation could achieve advantageous properties as a vehicle for the transport of insoluble drugs for the treatment of neurodegenerative diseases at the ocular level.

Assessment of Haloferax mediterranei Genome in Search of Copper-Molecular Machinery With Potential Applications for Bioremediation.

Heavy metals are essential micronutrients at low concentrations, serving as cofactors for relevant microbial enzymes (i.e., respiratory nitrate and nitrite reductases NADH dehydrogenase-2, amine oxidase, etc.), but they become harmful cellular intoxicants at significant low concentrations compared to other chemical compounds. The increasing need to incorporate bioremediation in the removal of heavy metals and other contaminants from wastewaters has led extremophiles to the spotlight of research. The haloarchaeon Haloferax mediterranei has promising physiological characteristics regarding bioremediation. However, little is known about how haloarchaea manage to resist high concentrations of heavy metals in the environment. The aim of this work is to develop bioinformatics research as the first step for further omics-based studies to shed light on copper metabolism in haloarchaea by analyzing H. mediterranei genome (strain ATCC 33500). To reach this aim, genome and protein databases have been consulted, and copper-related genes have been identified. BLAST analysis has been carried out to find similarities between copper resistance genes described from other microorganisms and H. mediterranei genes. Plausible copper importer genes, genes coding for siderophores, and copper exporters belonging to P1B-type ATPase group have been found apart from genes encoding copper chaperones, metal-responsive transcriptional regulators, and several proteins belonging to the cupredoxin superfamily: nitrite reductase, nitrous oxide reductases, cytochrome c oxidases, multicopper oxidases, and small blue copper proteins from the amicyanin/pseudoazurin families as halocyanins. As the presence of heavy metals causes oxidative stress, genes coding for proteins involved in antioxidant mechanisms have been also explored: thioredoxin, glutaredoxin, peroxiredoxin, catalase, and γ-glutamylcysteine as an analog of glutathione. Bioinformatic-based analysis of H. mediterranei genome has revealed a set of genes involved in copper metabolism that could be of interest for bioremediation purposes. The analysis of genes involved in antioxidative mechanisms against heavy metals makes it possible to infer the capability of H. mediterranei to synthesize inorganic polyphosphate granules against oxidative stress.

Educational instrument for intervention in the lifestyle of overweight pregnant women / Instrumento educativo de intervenção no estilo de vida para gestantes com sobrepeso

Abstract Objectives: to conduct the semantic validation of the images and text in educational material about eating and lifestyle for overweight women in different stages of pregnancy. Methods: qualitative, descriptive, analytical, cross-sectional study with focus groups for adapting and semantically validating the messages and images of educational material for women in three moments of the pre-natal period, as well as the support scripts for healthcare providers. The Consolidated Criteria for Reporting Qualitative Research (COREQ - Portuguese acronym) were considered. Results: participants of this study were seven pregnant women aged 21 to 40 who were in pre-natal care and 17 nutritionists aged 25 to 51. The folder was validated over seven meetings with the focus group, with one-week intervals between the groups. For each folder there were at least two meetings with focus groups, and one meeting for each script. The language was adjusted for the messages, and two images were changed to improve the self-identification of pregnant women. Technical and didactic adaptations were suggested for the scripts. Conclusion: images and text were semantically adapted; the instrument is easy to use in primary and secondary healthcare, providing support for pregnant women and healthcare providers on the subject of eating habits and lifestyle for overweight women in different stages of pregnancy.

Resumo Objetivos: realizar validação semântica de imagem e texto de material educativo sobre alimentação e estilo de vida para diferentes etapas da gestação de mulheres com sobrepeso. Métodos:. estudo qualitativo, descritivo e analítico, transversal, para adaptação e validação semântica de mensagens e imagens, com grupos focais, de material educativo para gestantes em três períodos do pré-natal e de roteiros de apoio direcionados aos profissionais de saúde. Foram observados os Critérios Consolidados para Relatos de Pesquisa Qualitativa (COREQ) Resultados: participaram do estudo sete gestantes adultas entre 21 e 40 anos em atendimento de pré-natal e 17 nutricionistas entre 25 e 51 anos. A validação dos folders constituiu-se em sete sessões de grupo focal com intervalo de uma semana entre os grupos. Para cada folder, aconteceram pelo menos dois encontros com grupos focais e para a construção de cada roteiro foi realizado um encontro. Foram realizados ajustes da linguagem paras as mensagens e mudança de duas imagens para melhorar a autoidentificação das gestantes. Foram propostas adaptações textuais nos roteiros de conteúdo técnico e didático. Conclusão: o material educativo foi adaptado semântica e imageticamente, sendo um instrumento didático de fácil acesso para ser empregado na atenção primária e secundária à saúde, apoiando gestantes e profissionais da saúde sobre alimentação e estilo de vida.

Inclusão digital e suas relações com o empoderamento, a qualidade de vida e o bem-estar / Digital inclusion and its relationship with empowerment, quality of life and well-being

RESUMO O crescente desenvolvimento das Tecnologias de Informação e Comunicação (TIC) vem trazendo mudanças significativas nas tarefas realizadas no cotidiano. O presente estudo tem como objetivo identificar como a inclusão digital pode favorecer o empoderamento, a qualidade de vida e o bem-estar das pessoas. Constitui uma revisão integrativa da literatura, realizada em bases de dados científicas. Como critérios de inclusão, optou-se por artigos publicados nos últimos 10 anos (2011 - 2020), em português, inglês e espanhol. O levantamento bibliográfico localizou 47 artigos, dentre os quais nove atenderam aos critérios de inclusão e foram analisados. Os resultados indicaram que a inclusão digital está positivamente associada à qualidade de vida, e essa a índices mais elevados de educação, saúde e segurança econômica. Identificou-se também fatores limitantes ao empoderamento das mulheres e idosos

ABSTRACT The growing technological development and Information and Communication Technologies (ICT) has brought significant changes in daily tasks. This study aims to identify how digital inclusion can favor people's empowerment, quality of life and well-being. It consists of an integrative literature review done in scientific databases. As inclusion criteria, we chose articles published in the past 10 years (2011-2020), in Portuguese, English and Spanish. The bibliographic survey found 47 articles, among which nine met the inclusion criteria and were analyzed. The results indicated that the digital inclusion is positively associated with quality of life, which is associated with higher levels of education, health and economic security. It was also identified limiting factors for empowerment of women and the elderly

Leptospirose grave com envolvimento cardíaco: um relato de caso / Severe leptospirosis with cardiac involvement: a case report

Introdução: A leptospirose é uma doença zoonótica aguda causada por espiroquetas patogênicas do gênero Leptospira. Trata-se de uma condição subnotificada com maior incidência em áreas urbanas. Possui curso clínico variável, apresentando-se como infecção assintomática a doença fulminante, com possibilidade de acometimento múltiplos de órgãos. Objetivo: Relatamos o caso de um homem HÍGIDO de 22 anos que se apresentou no departamento do Hospital Municipal Dr. Moysés Deutsch (HMMD) com acometimento miocárdico agudo secundário à leptospirose . Considerações finais: Diante deste caso clínico, concluímos que a história exposicional nem sempre é bem estabelecida, assim como o curso clínico que pode manifestar-se com grande heterogeneidade de sinais e sintomas. Assim, um alto índice de suspeição deve ser mantido para o diagnóstico de leptospirose, levando-se em conta o contexto epidemiológico do país e da região sudeste. Por vezes o diagnóstico confirmatório não será imediato, contudo, diversas decisões terapêuticas deverão ocorrer de forma precisa para administrar a melhor terapêutica no decorrer da construção diagnóstica.

DIFFICULT BILIARY CANNULATION: SHOULD WE ALWAYS TRY A SECOND ERCP AFTER A FAILED NEEDLE-KNIFE FISTULOTOMY?

BACKGROUND: A successful bile duct cannulation is a prerequisite for the realization of endoscopic retrograde cholangiopancreatography (ERCP). When biliary cannulation is not possible, needle-knife fistulotomy (NKF) can be performed. However, when biliary access is not successfully achieved even after performing NKF, it is possible to interrupt the procedure, and repeat the ERCP after a short interval. OBJECTIVE: The aim of this study is to analyze if repeating an ERCP after a short interval of 48 hours is effective in achieving biliary access after an initial NKF was unsuccessfully performed. METHODS: A total of 1024 patients with a naive papilla, that underwent ERCP between the years of 2009-2019, were retrospectively reviewed. Difficult biliary cannulation was identified in 238 of these cases and NKF was performed. Success of biliary cannulation, NKF success at the first and second ERCPs, the associations between the type of the papilla, biliary dilatation, and overall success of NKF and adverse events rates were evaluated. RESULTS: Biliary access was initially achieved in 183 (76.8%) cases. Of the 55 (23.1%) remaining cases a second attempt was performed after 48 hours, and biliary access was successfully achieved in 46 (83.6%) of them. The overall success of NKF after the first and second ERCP, the success rate was 96.2%. Papilla located out of its normal position was related to a minor chance of success at NKF (P<0.05). CONCLUSION: We conclude that when biliary access is not achieved after the performance of a NKF, a second attempt is safe and effective and should be attempted.

Canulação biliar difícil: devemos tentar uma segunda CPRE após uma fistulotomia papilar mal-sucedida? / Difficult biliary cannulation: should we always try a second ercp after a failed needle-knife fistulotomy?

ABSTRACT BACKGROUND: A successful bile duct cannulation is a prerequisite for the realization of endoscopic retrograde cholangiopancreatography (ERCP). When biliary cannulation is not possible, needle-knife fistulotomy (NKF) can be performed. However, when biliary access is not successfully achieved even after performing NKF, it is possible to interrupt the procedure, and repeat the ERCP after a short interval. OBJECTIVE: The aim of this study is to analyze if repeating an ERCP after a short interval of 48 hours is effective in achieving biliary access after an initial NKF was unsuccessfully performed. METHODS: A total of 1024 patients with a naive papilla, that underwent ERCP between the years of 2009-2019, were retrospectively reviewed. Difficult biliary cannulation was identified in 238 of these cases and NKF was performed. Success of biliary cannulation, NKF success at the first and second ERCPs, the associations between the type of the papilla, biliary dilatation, and overall success of NKF and adverse events rates were evaluated. RESULTS: Biliary access was initially achieved in 183 (76.8%) cases. Of the 55 (23.1%) remaining cases a second attempt was performed after 48 hours, and biliary access was successfully achieved in 46 (83.6%) of them. The overall success of NKF after the first and second ERCP, the success rate was 96.2%. Papilla located out of its normal position was related to a minor chance of success at NKF (P<0.05). CONCLUSION: We conclude that when biliary access is not achieved after the performance of a NKF, a second attempt is safe and effective and should be attempted.

RESUMO CONTEXTO: A canulação biliar de sucesso é pré-requisito para a realização da colangiopancreatografia retrógrada endoscópica (CPRE). Quando a canulação biliar não é possível, a fistulotomia com auxílio do cateter Needle-Knife (NKF) pode ser realizada. Entretanto, quando o acesso biliar não é atingido mesmo após a realização de um NKF, é possível optar-se pela interrupção do procedimento, e pela repetição da CPRE após curto intervalo de 48 horas. OBJETIVO: O objetivo desse estudo é analisar se a repetição da CPRE após um curto intervalo de 48 horas é efetivo em atingir o acesso biliar, quando um NKF foi realizado inicialmente sem sucesso. MÉTODOS: Um total de 1024 pacientes com papila virgem de tratamento, submetidos à CPRE entre os anos de 2009-2019, foram retrospectivamente analisados. Canulação biliar difícil foi identificada em 238 deles, e NKF foi então realizado. Foram avaliadas as taxas de sucesso durante a canulação biliar, assim como durante a realização de NKF na primeira e segunda CPREs. A associação entre o tipo de papila, dilatação biliar e o sucesso final na realização do NFK também foi avaliada, assim como a presença de eventos adversos associados à realização do NKF. RESULTADOS: Dentre todos os NKF realizados, acesso biliar foi inicialmente atingido em 183 (76,8%) casos. Os 55 (23,1%) casos restantes, foram submetidos a uma segunda CPRE após 48 horas e o acesso biliar foi atingido em 46 (83,6%) deles, resultando em uma taxa final de sucesso, após a primeira e segunda CPREs, de 96,2%. Papila localizada fora da sua posição habitual foi relacionada a menor chance de sucesso durante a realização de NKF (P<0,05). CONCLUSÃO: Concluiu-se que quando o acesso biliar não pode ser atingido após a realização de um NKF, uma segunda CPRE é segura, efetiva e deve ser realizada.

Iniciativas para a integração ensino-serviço na SESAB: desafios e oportunidades em tempos de pandemia / Initiatives for the integration of teaching-service in SESAB: challenges and opportunities in pandemic times / Iniciativas para la integración del servicio docente en SESAB: desafíos y oportunidades en tiempos de pandemia

A suspensão imediata dos estágios curriculares e opcionais de nível médio técnico e de graduação na rede de serviços do Sistema Único de Saúde da Bahia foi necessária para evitar a disseminação do coronavírus nos estabelecimentos de saúde da Secretaria da Saúde do Estado da Bahia (Sesab) e na comunidade onde os atores da integração ensino-serviço circulam. Novas estratégias foram desenvolvidas para garantir que se cumprisse o papel ordenador e formador do SUS nesse cenário, na Bahia, com o intuito de evitar a exposição ao vírus. Para evitar um possível colapso, a rede foi reinventada com medidas que variaram da alteração do perfil de unidades à criação e reorganização dos serviços. Este relato tem como objetivo descrever os desafios da Coordenação de Integração da Educação e Trabalho na Saúde (CIET) para apoiar a implantação das estratégias preconizadas pelo Ministério da Saúde, pela Sesab e Rede de Educação no cenário emergente. A partir de notas técnicas, boletins epidemiológicos, normativas e legislações vigentes e referenciadas, foram elaborados planos de ação com base nos desafios identificados em cada estratégia. Os maiores ganhos gerados pela pandemia são, sem dúvida, o encurtamento de distâncias pelo uso das tecnologias comunicacionais e a possibilidade de viabilizar agendas. A CIET/ESPBA apoiou iniciativas interinstitucionais, assim como desenvolveu ações estratégicas, com o intuito de promover a integração ensino-serviço. O novo contexto instalado exigirá o desenvolvimento de competências e habilidades para os atores envolvidos no processo de ensino-aprendizagem profissional, bem como da capacidade de adaptabilidade ao mundo do trabalho em saúde.

In the Health Department of the State of Bahia (SESAB), the coronavirus pandemic led to an interruption of the curricular and optional internships in the Junior College/Certificate and undergraduate degree programs. Internal and external academic activities were suspended to avoid exposure to the virus, and new strategies have been developed to guarantee the SUS' ordering and forming role in the state. To prevent a possible health system collapse, new statements were done such as changing the profile of units to creating and reorganizing services. This report shows the challenges of CIET to support the implementation of the strategies recommended by the Brazilian Ministry of Health, SESAB and the Education Network in that emerging situation. Supported by technical notes, epidemiological bulletins, regulations and current and referenced legislation, action plans were developed based on the challenges identified in each strategy. The biggest gains generated by the pandemic are the shortening of distances by the use of communication technologies and the possibility of making the agenda viable. CIET/ESPBA had supported inter-institutional initiatives and developed strategic actions to promote teaching-service integration. The new context installed will require the development of new skills and abilities for the actors involved in the teaching proceedings of the professional learning, along with their ability to adapt to the world of health work.

La suspensión inmediata de las pasantías curriculares y opcionales a nivel técnico y de grado en la red de servicios del Sistema Único de Salud (SUS) de Bahía fue una necesidad para prevenir la propagación del coronavirus en los establecimientos de salud de la Secretaria Estadual de Salud de Bahía (Sesab) y en la comunidad donde los actores de la integración docencia-servicio circulan. Se han desarrollado nuevas estrategias para garantizar el rol ordenador y formador del SUS en Bahía para evitar la exposición al virus. Para impedir un posible colapso, la red se reinventó con medidas que iban desde cambiar el perfil de las unidades hasta crear y reorganizar los servicios. Este informe tiene como objetivo describir los desafíos de la Coordinación de Integración de Educación y Trabajo (CIET) para apoyar la implementación de las estrategias recomendadas por el Ministerio de Salud, la Sesab y la Red Educativa en el escenario emergente. Con base en notas técnicas, boletines epidemiológicos, normativas y legislaciones vigentes y referenciadas, se desarrollaron planes de acción a partir de los desafíos identificados en cada estrategia. Los mayores logros que genera la pandemia son, sin duda, el acortamiento de distancias por el uso de tecnologías de la comunicación y la posibilidad de viabilizar agendas. La CIET/ESPBA apoyó iniciativas interinstitucionales, así como desarrolló acciones estratégicas para promover la integración docencia-servicio. El nuevo contexto instalado requerirá el desarrollo de nuevas competencias y habilidades para los actores involucrados en el proceso de enseñanza-aprendizaje profesional, así como la capacidad de adaptación al mundo laboral de la salud.

O Programa Primeiro Emprego na pandemia: desafios da Escola de Saúde Pública da Bahia Professor Jorge Novis / The Programa Primeiro Emprego in pandemia: challenges of the Public Health School Professor Jorge Novis / El Programa Primeiro Emprego en la pandemia: desafíos de la Escuela de Salud Pública de Bahia Profesor Jorge Novis

O Programa Primeiro Emprego (PPE) é responsável, atualmente, pela contratação formal de cerca de 1.200 jovens pela Secretaria da Saúde do Estado da Bahia (Sesab), que atuam em mais de 80 unidades de saúde, distribuídas em 35 municípios. Entretanto, o cenário de emergência em saúde pública gerado pelo novo coronavírus trouxe a necessidade de avaliação e adequação das ações da Coordenação de Integração da Educação e do Trabalho (CIET), na Escola de Saúde Pública da Bahia Professor Jorge Novis (ESPBA), que assume o papel de ordenar as vagas de estágio e da contratação formal pelo PPE na Sesab. Assim, foi necessário promover uma reflexão sobre a nova realidade posta, para traçar estratégias de enfrentamento e suporte. A experiência foi revisitada por meio de consulta documental às fontes de informação do PPE, instituído em 2015, até o ano de 2020. Os desafios enfrentados pelo programa nesse período foram: escassez de recursos humanos no quadro da Sesab; incompatibilidade entre a oferta de egressos formados e a demanda dos serviços de saúde; paralisação do estágio de nível médio técnico; e necessidade de qualificação dos profissionais na pandemia. Dessa forma, avalia-se que o PPE se destacou durante a pandemia não apenas como programa social, mas também como apoio importante de recursos humanos para o setor de saúde, garantindo postos de trabalho temporários capazes de dotar esses indivíduos de capacidade técnica dentro da área da sua formação, atendendo ao escopo das atividades do serviço público.

The Programa Primeiro Emprego (PPE) is currently responsible for the formal hiring of about 1,200 young people at the Health Department of the State of Bahia (SESAB). These opportunities are settled in more than 80 health units and distributed in 35 municipalities. However, the public health emergency scenario generated by the new coronavirus brought the need to evaluate and adapt the actions of the Coordenação de Integração da Educação e do Trabalho (CIET), at the School of Public Health, which assumes the role of ordering vacancies of internships and formal contracting of PPE at SESAB. Thus, it was necessary to promote a reflection on the new reality to outline coping and support strategies. The experience was revisited through documentary consultation of information sources of the PPE instituted from 2015 to 2020. The challenges faced by the Program in this period were lack of human resources in SESAB framework, incompatibility between the offer of undergraduate students and the demand for health services, the interruption of the internship of Junior College degree, and a requirement for qualification of professionals in the pandemic. During the pandemic, the Program stood out not only as a social program, but also as an important support of human resources for the health sector. Besides, guaranteeing temporary jobs capable of providing these individuals with technical capacity within the area of their training, attending the scope of public service activities.

El Programa Primeiro Emprego (PPE) se encarga actualmente de la contratación formal de cerca de 1.200 jóvenes en la Secretaría de la Salud del Estado de Bahía (Sesab) para trabajar en más de 80 unidades de salud, distribuidas en 35 municipios. Sin embargo, el contexto de emergencia de salud pública generado por el nuevo coronavirus conllevó la necesidad de evaluar y adecuar las acciones de la Coordinación de Integración de la Educación y del Trabajo (CIET), en la Escuela de Salud Pública de Bahia Profesor Jorge Novis (ESPBA), quien asume el rol de ordenar las vacantes de pasantías y de contratación formal del PPE en la Sesab. Esto llevó a la reflexión sobre la nueva realidad para diseñar estrategias de afrontamiento y apoyo. La experiencia fue revisada mediante consulta documental de las fuentes de información del PPE, creado en el 2015, hasta el año 2020. Los desafíos que enfrentó el Programa en este período fueron: escasez de recursos humanos en el plantel de la Sesab; incompatibilidad entre la oferta de egresados capacitados y la demanda por servicios de salud; suspensión de la pasantía de nivel técnico; y la necesidad de capacitación de los profesionales en la pandemia. El Programa se destacó durante la pandemia no solo como un programa social, sino también como un importante sostén de recursos humanos para el sector de la salud, garantizando puestos de trabajo temporales capaces de proveerles a estos individuos capacidad técnica dentro del ámbito de su formación y facilitando la ejecución de las actividades del servicio público.