A Pilot, Predictive Surveillance Model in Pharmacovigilance Using Machine Learning Approaches.

INTRODUCTION: The identification of a new adverse event (AE) caused by a drug product is one of the key activities in the pharmaceutical industry to ensure the safety profile of a drug product. Machine learning (ML) has the potential to assist with signal detection and supplement traditional pharmacovigilance (PV) surveillance methods. This pilot ML modeling study was designed to detect potential safety signals for two AbbVie products and test the model's capability of detecting safety signals earlier than humans. METHODS: Drug X, a mature product with post-marketing data, and Drug Y, a recently approved drug in another therapeutic area, were selected. Gradient boosting-based ML approaches (e.g., XGBoost) were applied as the main modeling strategy. RESULTS: For Drug X, eight true signals were present in the test set. Among 12 potential new signals generated, four were true signals with a 50.0% sensitivity rate and a 33.3% positive predictive value (PPV) rate. Among the remaining eight potential new signals, one was confirmed as a signal and detected six months earlier than humans. For Drug Y, nine true signals were present in the test set. Among 13 potential new signals generated, five were true signals with a 55.6% sensitivity rate and a 38.5% PPV rate. Among the remaining eight potential new signals, none were confirmed as true signals upon human review. CONCLUSION: This model demonstrated acceptable accuracy for safety signal detection and potential for earlier detection when compared to humans. Expert judgment, flexibility, and critical thinking are essential human skills required for the final, accurate assessment of adverse event cases.

Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials.

BACKGROUND: Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene-related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. METHODS: This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). RESULTS: The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. CONCLUSIONS: Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309).

Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial.

BACKGROUND: Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed. METHODS: ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18-80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with ClinicalTrials.gov (NCT04740827) and EudraCT (2019-003448-58), and is completed. FINDINGS: Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were -1·9 (SE 0·4) with placebo and -4·2 (0·4) with atogepant (least squares mean difference -2·4, 95% CI -3·2 to -1·5; adjusted p<0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants (vs four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group vs none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group vs two [1%] in the placebo group. INTERPRETATION: Atogepant 60 mg once a day was safe, well tolerated, and showed significant and clinically relevant reductions in mean monthly migraine days compared with placebo across 12 weeks in patients with episodic migraine who had previously been failed by two to four classes of conventional oral preventive treatments. Atogepant might be an effective preventive treatment option for patients in this difficult-to-treat population. FUNDING: Allergan (now AbbVie).

Heterogeneous photosensitization for water reuse in cellars: evaluation of silica, spongin, and chitosan as carrier material.

Photosensitization, a powerful oxidation reaction, offers significant potential for wastewater treatment in the context of industrial process water reuse. This environmentally friendly process can be crucial in reducing water consumption and industrial pollution. The ultimate goal is to complete process water reuse, creating a closed-loop system that preserves the inherent value of water resources. The photosensitized oxidation reaction hinges on three essential components: the photosensitizer, visible light, and oxygen. In this study, we assess the performance of three distinct materials-silica, chitosan, and spongin-as carrier materials for incorporating the phthalocyanine photosensitizer (ZnPcS4) in the heterogenous photosensitization process. Among the three materials under study, chitosan emerged as the standout performer in reactor hydrodynamic performance. In the photooxidation process, the photosensitizer ZnPcS4 exhibited notable efficacy, resulting in a significant reduction of approximately 20 to 30% in the remaining COD concentration of the cellar wastewater. Chitosan demonstrated exceptional hydrodynamic characteristics and displayed a favorable response to pH adjustments within the range of 8 to 10, outperforming the other two carrier materials. To further enhance the efficiency of continuous operation, exploring methods for mitigating photosensitizer bleaching within the reaction medium and investigating the impact of different pH values on the process optimization would be prudent.

Formação da identidade profissional de enfermeiros para o trabalho no sistema prisional / Development of the professional identity of nurses to work in the prisonal system / Formación de la identidad profesional de los enfermeros para trabajar en el sistema penitenciario

Objetivo:analisar elementos motivadores da construção da identidade profissional de enfermeiros do sistema prisional. Método: estudo histórico-social, qualitativo, sob o método de triangulação de fontes orais e documentais coletados de maio a dezembro de 2020, iluminado pelo referencial foucaultiano. Protocolo de pesquisa aprovado pelo Comitê de Ética e Pesquisa da instituição signatária. Resultados: a realização de concurso público para o sistema prisional foi motivada pela aquisição de estabilidade. Os enfermeiros concursados eram despreparados para cuidar de pessoas presas. A disciplina e os poderes exercidos pelos guardas e presos surpreenderam estes enfermeiros, que precisaram se adaptar ao sistema num contexto social marcado pela violência urbana. Considerações finais: destaca-se, na construção da identidade destes profissionais, a capacidade para contornar medos e inseguranças, exercício de poder disciplinar e normatização do cuidado para o enfrentamento do cotidiano do trabalho. Emerge a necessidade de capacitação de enfermeiros nesta área na formação profissional.

Objective: to analyze elements that motivate the construction of the professional identity of nurses in the prison system. Method: historical-social, qualitative study, under the method of triangulation of oral and documental sources collected from May to December 2020, illuminated by the Foucaultian reference. Approved by the Ethics and Research Committee. Results: the holding of a public tender for the prison system was motivated by the acquisition of stability. The registered nurses were unprepared to take care of prisoners. The discipline and powers exercised by guards and prisoners surprised these nurses, who had to adapt to the system in a social context marked by urban violence. Final considerations: in the construction of the identity of these professionals, the ability to overcome fears and insecurities, exercising disciplinary Power and standardizing care for coping with daily work is highlighted. The need to train nurses in thisarea in professional training emerges.

Objetivo: analizar elementos que motivan la construcción de la identidad profesional de las enfermeras en el sistema penitenciario. Método: estudio histórico-social, cualitativo, iluminado por el referente foucaultiano, que utiliza el método de triangulación de fuentes orales y documentales recolectadas de mayo a 20 de diciembre. El Comité de Ética en Investigación de la institución firmante aprobó el protocolo de investigación. Resultados: la realización de un concurso público para el sistema penitenciario estuvo motivada por la adquisición de estabilidad. Los enfermeros aprobados por ese concurso público no estaban preparados para cuidar a los presos. La disciplina y los poderes que ejercían los guardias y presos sorprendieron a estos enfermeros, que debieron adaptarse al sistema en un contexto social marcado por la violencia urbana. Consideraciones finales: en la construcción de la identidad de estos profesionales se destaca la capacidad de superación de miedos e inseguridades, ejercicio de poder disciplinario y estandarización de los cuidados para hacer frente al cotidiano del trabajo. Surge la necesidad de capacitar a enfermeros en esta área en la formación profesional.

Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In this study, we aimed to evaluate the efficacy, safety, and tolerability of atogepant for the preventive treatment of chronic migraine. METHODS: We did this randomised, double-blind, placebo-controlled, phase 3 trial at 142 clinical research sites across the USA, the UK, Canada, China, Czech Republic, Denmark, France, Germany, Italy, Japan, South Korea, Poland, Russia, Spain, Sweden, and Taiwan. Adults aged 18-80 years with a 1-year or longer history of chronic migraine were randomly assigned (1:1:1) to receive oral atogepant 30 mg twice a day, oral atogepant 60 mg once a day, or placebo. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) across the 12-week treatment period. The primary analysis was done in the modified intent-to-treat population and included all randomly assigned participants who received at least one dose of study intervention, had an evaluable baseline period of electronic diary (eDiary) data, and had at least one evaluable post-baseline 4-week period (weeks 1-4, 5-8, and 9-12) of eDiary data during the double-blind period. The safety population consisted of all participants who received at least one dose of study intervention. This trial is registered with ClinicalTrials.gov (NCT03855137). FINDINGS: Between March 11, 2019 and Jan 20, 2022, 1489 participants were assessed for eligibility. 711 were excluded, and 778 participants were randomly assigned to atogepant 30 mg twice a day (n=257), atogepant 60 mg once a day (n=262), or placebo (n=259). Participants in the safety population were aged 18-74 years (mean 42·1 years). 459 (59%) of 773 patients were White, 677 (88%) patients were female, and 96 (12%) were male. 84 participants discontinued treatment during the trial, and 755 comprised the modified intent-to-treat population (atogepant 30 mg twice a day n=253, atogepant 60 mg once a day n=256, and placebo n=246). Baseline mean number of MMDs were 18·6 (SE 5·1) with atogepant 30 mg twice a day, 19·2 (5·3) with atogepant 60 mg once a day, and 18·9 (4·8) with placebo. Change from baseline in mean MMDs across 12 weeks was -7·5 (SE 0·4) with atogepant 30 mg twice a day, -6·9 (0·4) with atogepant 60 mg once a day, and -5·1 (0·4) with placebo. Least squares mean difference from placebo was -2·4 with atogepant 30 mg twice a day (95% CI -3·5 to -1·3; adjusted p<0·0001) and -1·8 with atogepant 60 mg once a day (-2·9 to -0·8; adjusted p=0·0009). Most common adverse events for atogepant were constipation (30 mg twice a day 28 [10·9%]; 60 mg once a day 26 [10%]; and placebo 8 [3%]) and nausea (30 mg twice a day 20 [8%]; 60 mg once a day 25 [10%]; and placebo 9 [4%]). Potentially clinically significant weight decrease (≥7% reduction at any time post-baseline) was observed in each treatment group (atogepant 30 mg twice a day 14 [6%]; atogepant 60 mg once a day 15 [6%]; and placebo 5 [2%]). INTERPRETATION: Atogepant 30 mg twice a day and 60 mg once a day showed clinically relevant reductions in MMDs across 12 weeks in chronic migraine patients. Both atogepant doses were well tolerated, consistent with the known safety profile of atogepant. FUNDING: Allergan (now AbbVie).

A model of zinc dynamics evoked by intense stimulation at the cleft of hippocampal mossy fiber synapses.

Zinc is a transition metal that is particularly abundant in the mossy fibers of the hippocampal CA3 area. Despite the large number of studies about the zinc role in mossy fibers, the action of zinc in synaptic mechanisms is only partly known. The use of computational models can be a useful tool for this study. In a previous work, a model was developed to evaluate zinc dynamics at the mossy fiber synaptic cleft, following weak stimulation, insufficient to evoke zinc entry into postsynaptic neurons. For intense stimulation, cleft zinc effluxes must be considered. Therefore, the initial model was extended to include postsynaptic zinc effluxes based on the Goldman-Hodgkin-Katz current equation combined with Hodgkin and Huxley conductance changes. These effluxes occur through different postsynaptic escape routes, namely L- and N-types voltage-dependent calcium channels and NMDA receptors. For that purpose, various stimulations were assumed to induce high concentrations of cleft free zinc, named as intense (10 µM), very intense (100 µM) and extreme (500 µM). It was observed that the main postsynaptic escape routes of cleft zinc are the L-type calcium channels, followed by the NMDA receptor channels and by N-type calcium channels. However, their relative contribution for cleft zinc clearance was relatively small and decreased for higher amounts of zinc, most likely due to the blockade action of zinc in postsynaptic receptors and channels. Therefore, it can be concluded that the larger the zinc release, the more predominant the zinc uptake process will be in the cleft zinc clearance.

Phase Ib, open-label, fixed-sequence, drug-drug interaction, safety, and tolerability study between atogepant and ubrogepant in participants with a history of migraine.

OBJECTIVE: To evaluate potential drug-drug interactions of ubrogepant and atogepant. BACKGROUND: Ubrogepant and atogepant, calcitonin gene-related peptide (CGRP) receptor antagonists, are recently approved drugs for acute and preventive treatment of migraine, respectively. For patients with migraine who are prescribed atogepant for the preventive treatment of migraine, health care providers could prescribe ubrogepant for the acute treatment of breakthrough migraine attacks. METHODS: A phase Ib, multi-center, open-label, fixed-sequence study was conducted in participants diagnosed with migraine for at least 1 year. To assess the primary objective of pharmacokinetic interactions in this phase I trial, the highest United States Food and Drug Administration-approved individual dose strengths of atogepant (60 mg once daily) and ubrogepant (100 mg) were utilized, with ubrogepant being administered on a fixed-dose schedule every 3 days, regardless of whether a participant was experiencing a migraine attack. Secondary endpoints included safety and tolerability. Clinical safety measurements were monitored throughout the study. RESULTS: Of the 31 participants enrolled, 26 completed the study. A single dose of ubrogepant had no statistically significant effect on atogepant pharmacokinetics. Co-administration of ubrogepant with atogepant resulted in a 19% increase (geometric mean ratio 118.80, 90% confidence interval [CI] 108.69-129.84) in the ubrogepant area under the plasma concentration-time curve and a 26% increase (geometric mean ratio 125.63, 90% CI 105.58-149.48) in the ubrogepant maximum plasma concentration. These statistically significant changes in ubrogepant exposure were not clinically meaningful, and no new safety concerns were identified for the combination. CONCLUSION: The combination use of atogepant and ubrogepant was safe and well tolerated in adult participants with a history of migraine enrolled in the study. Pharmacokinetic changes during co-administration were not clinically meaningful.

Phase 1 study of safety, pharmacokinetics, and antiviral activity of SARS-CoV-2 neutralizing monoclonal antibody ABBV-47D11 in patients with COVID-19.

ABBV-47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS-CoV-2. This first-in-human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID-19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double-blind, and placebo-controlled single ascending dose study of ABBV-47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non-hospitalized (confined) adults with mild to moderate COVID-19. Primary outcomes were grade 3 or higher study drug-related adverse events and infusion-related reactions. Secondary outcomes were pharmacokinetic parameters and concentration-time profiles to Day 29, immunogenicity (anti-drug antibodies), and antiviral activity (change in RT-PCR viral load) from baseline to Days 15 and 29. ABBV-47D11 single doses up to 2400 mg were safe and tolerated and no safety signals were identified. The pharmacokinetics of ABBV-47D11 were linear and showed dose-proportional increases in serum concentrations with ascending doses. The exploratory anti-SARS-CoV-2 activity revealed a reduction of viral load at and above the 600 mg dose of ABBV-47D11 regardless of patient demographics and baseline characteristics, however; because of the high inter-individual variability and small sample size a statistical significance was not reached. There is potential for anti-SARS-CoV-2 activity with ABBV-47D11 doses of 600 mg or higher, which could be evaluated in future clinical trials designed and powered to assess viral load reductions and clinical benefit.

Residência multiprofissional em saúde mental: atuação de enfermeiros no processo de ensino-aprendizagem / Residencia multiprofesional en salud mental: el papel del enfermero en el proceso de enseñanza-aprendizaje / Multiprofessional residence in mental health: nursing of the nurses in the teaching-learning process

Na saúde mental nos deparamos com desafios ao longo dos anos, avançamos com políticas públicas direcionadas ao atendimento dos pressupostos da Reforma Psiquiátrica Brasileira. Com a ampliação de redes substitutivas a psiquiatria, novas práticas foram produzidas, influenciando o processo de formação de enfermeiros desde a graduação quanto na pós-graduação. Objetivo: analisar estratégias de enfermeiros para a integração ensino-assistência junto à residentes multiprofissionais em Saúde Mental. Métodos: Estudo qualitativo, descritivo, com dez enfermeiros de uma instituição psiquiátrica universitária. Os dados foram coletados de fevereiro/17 a maio/17, por entrevista semiestruturada e submetidos à análise de conteúdo, na modalidade temática. Resultados: Identificamos como estratégias: interação interprofissional; trabalho em equipe; estímulo ao cuidado psicossocial. Conclusão: Os enfermeiros atuam como facilitadores do processo de ensino-aprendizagem independentemente de serem preceptores ou não, porquanto permanentemente atuam na assistência. Sugerimos a formalidade no preparo de enfermeiros-preceptores utilizadores de metodologias de ensino apropriadas para o campo da saúde mental.(AU)

In mental health we have faced challenges over the years, we have advanced with public policies aimed at meeting the assumptions of the Brazilian Psychiatric Reform. With the expansion of substitutive networks for psychiatry, new practices were produced, influencing the process of training nurses from undergraduate and graduate levels. Objective: to analyze nurses' strategies for teaching-care integration with multiprofessional residents in Mental Health. Methods: Qualitative, descriptive study with ten nurses from a university psychiatric institution. Data were collected from February/17 to May/17, through semi-structured interviews and submitted to content analysis, in the thematic mode. Results: We identified as strategies: interprofessional interaction; team work; stimulus to psychosocial care. Conclusion: Nurses act as facilitators of the teaching-learning process regardless of whether they are preceptors or not, as they permanently work in care. We suggest formality in the preparation of nurse-preceptors who use appropriate teaching methodologies for the field of mental health.(AU)

En salud mental hemos enfrentado desafíos a lo largo de los años, hemos avanzado con políticas públicas dirigidas a cumplir con los presupuestos de la Reforma Psiquiátrica Brasileña. Con la expansión de las redes sustitutivas de la psiquiatría, se produjeron nuevas prácticas que influyeron en el proceso de formación de enfermeros de pregrado y posgrado. Objetivo: analizar las estrategias de los enfermeros para la integración enseñanza-cuidado con residentes multiprofesionales en Salud Mental. Métodos: Estudio cualitativo, descriptivo con diez enfermeras de una institución psiquiátrica universitaria. Los datos fueron recolectados del 17/02 al 17/05, por medio de entrevista semiestructurada y sometidos a análisis de contenido, en la modalidad temática. Resultados: Identificamos como estrategias: interacción interprofesional; trabajo en equipo; estímulo a la atención psicosocial. Conclusión: Los enfermeros actúan como facilitadores del proceso de enseñanza-aprendizaje independientemente de que sean preceptores o no, ya que actúan permanentemente en el cuidado. Sugerimos formalidad en la preparación de enfermeros-preceptores que utilicen metodologías de enseñanza adecuadas al campo de la salud mental.(AU)

Predator fear memory depends on glucocorticoid receptors and protein synthesis in the basolateral amygdala and ventral hippocampus.

Previous studies have suggested that the basolateral amygdala (BLA) and the ventral hippocampus (VH) are critical sites for predator-related fear memory. Predator exposure is an intense emotional experience and should increase plasmatic corticosterone likely to modulate the emotion-related memories. However, it is unclear whether the BLA and VH harbor plastic events underlying predator-related fear memory storage and how molecular and endocrine mechanisms interact to modulate memory to the predatory threat. Here, we first examined the effects of protein synthesis inhibition in the BLA and VH on fear memory to a predatory threat. We next evaluated how exposure to a predatory threat impacts the corticosterone release and how the inhibition of corticosterone synthesis can influence predator-related fear memory. Finally, we examined how predator exposure triggers the activation of glucocorticoid and mineralocorticoid receptors in the BLA and VH and whether the GR antagonist injection affects predator-related fear memory. We showed that predator-related contextual fear is dependent on protein synthesis in the BLA and VH. Moreover, we described the impact of rapid glucocorticoid release during predatory exposure on the formation of contextual fear responses and that GR-induced signaling facilitates memory consolidation within the BLA and VH. The results are relevant in understanding how life-threatening situations such as a predator encounter impact fear memory storage and open exciting perspectives to investigate GR-induced proteins as targets to deciphering and manipulating aversive memories.

Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension.

INTRODUCTION: High efficacy and safety of 8-week glecaprevir/pibrentasvir (G/P) therapy was seen in hepatitis C (HCV)-infected, treatment-naïve (TN), compensated cirrhosis (CC) patients in EXPEDITION-8. To provide further understanding of the efficacy of G/P treatment in HCV-infected TN patients with CC and clinical evidence of portal hypertension (PHT), this analysis focused on differences in sustained virologic response at post-treatment week 12 (SVR12) between 8-week and 12-week G/P treatment groups in patients with PHT, and on differences in safety outcomes between PHT and non-PHT groups. METHODS: Data were derived from an ad hoc subgroup analysis of the EXPEDITION-8 study for patients receiving 8 weeks of G/P therapy, and pooled patient-level data from nine clinical studies for patients receiving 12 weeks of therapy. Evidence of PHT included at least one of the following at baseline: FibroScan ≥ 20 kPa, platelets < 100 × 109/L, or medical history consistent with PHT. The primary efficacy endpoint was SVR12; adverse events (AEs) consistent with hepatic decompensation were assessed. RESULTS: PHT was identified in 60.6% (208/343) and 57.1% (224/392) of the 8- and 12-week groups, respectively. For those with PHT, SVR12 was 97.6% (203/208) and 98.7% (221/224) with 8- and 12-week treatment, respectively (intention-to-treat population). For those without PHT, 97.8% (132/135) in the 8-week group and 97.6% (164/168) in the 12-week group achieved SVR12. Eight patients with PHT, and seven without, did not achieve SVR12. Similar rates of AEs were observed in the PHT and non-PHT groups. Three cases of hepatic decompensation in the PHT group, unrelated to G/P according to the investigators, were reported. CONCLUSION: G/P treatment for 8 or 12 weeks was equally efficacious in HCV patients with features of PHT. Safety outcomes were similar between PHT and non-PHT groups, with G/P treatment well tolerated across groups. NCTS: NCT03089944, NCT02642432, NCT02738138, NCT02243293, NCT02651194, NCT03235349, NCT02707952, NCT02966795, NCT03069365, NCT03219216.

Protocolos para atendimento de saúde mental na atenção primária: subsídios para transformação da assistência / Protocols for mental health care in primary-level services: subsidies for transforming the assistance provided / Protocolos para la atención de la salud mental en la atención primaria: contribuciones para transformar la atención

RESUMO Objetivo: analisar as repercussões no atendimento em saúde mental pela implantação de Protocolos de Conduta Assistencial em Unidade Básica de Saúde, em Juiz de Fora - MG - BR. Método: estudo histórico-social, realizado no ano de 2018, tendo por fontes diretas, documentos escritos e depoimentos orais, analisadas pelos pressupostos da Reforma Psiquiátrica. Resultados: apresentam-se as categorias: a) Reorganização da assistência em saúde mental por implantação de Protocolos de Conduta; b) Processo de referência e contrarreferência entre Unidade Básica de Saúde e serviços de atenção especializada em saúde mental; c) Transformação da assistência em saúde mental. Conclusão: protocolos organizaram a rede de atenção em saúde mental, sustentando a capacitação multiprofissional, introduzindo atenção primária à saúde como porta de entrada para acolhimento, tratamento e acompanhamento em saúde mental territorial.

ABSTRACT Objective: to analyze the repercussions on mental health care due to the implementation of Care Conduct Protocols in a Basic Health Unit from Juiz de Fora (Minas Gerais - Brazil). Method: a historical-social study carried out in 2018, having as direct sources written documents and oral testimonies analyzed according to the assumptions of the Psychiatric Reform. Results: the following categories are presented: a) Reorganization of mental health care through the implementation of Conduct Protocols; b) Referral and counter-referral process between Basic Health Units and specialized mental health care services; and c) Transformation of mental health care. Conclusion: the protocols organized the mental health care network, supporting multiprofessional training, introducing Primary Health Care as a gateway to welcoming, treatment and monitoring in territorial mental health.

RESUMEN Objetivo: analizar las repercusiones que tiene sobre la atención en salud mental la implantación de Protocolos de Conducta Asistencial en una Unidad Básica de Salud de Juiz de Fora (Minas Gerais - Brasil). Método: estudio histórico-social, realizado en 2018, cuyas fuentes directas son los documentos escritos y testimonios orales analizados según los presupuestos de la Reforma Psiquiátrica. Resultados: se presentan las categorías: a) Reorganización de la atención en salud mental a través de la implantación de Protocolos de Conducta; b) Proceso de derivación y contraderivación entre la Unidad Básica de Salud y los servicios de atención especializada en salud mental; c) Transformación de la atención en salud mental. Conclusión: los protocolos organizaron la red de atención en salud mental, apoyando la formación multidisciplinaria, instaurando la Atención Primaria de la Salud como puerta de entrada para la recepción, el tratamiento y seguimiento de la salud mental del territorio.

Working conditions of a nursing team in mental health facility.

OBJECTIVE: To analyze how the nursing team from a Psychosocial Care Center II relates its insertion in the service with the work process. METHODS: Descriptive, analytical research outlined as a case study with a qualitative approach. The data were collected through semi-structured interviews with nursing professionals and went through content analysis subsidized by Bardin's work. RESULTS: Two thematic categories emerged: a) Ways of intake in the nursing services at the Psychosocial Care Center; b) Setbacks in nursing routine at the Psychosocial Care Center. FINAL CONSIDERATIONS: The fact that the professionals have not planned to work in mental health nor have training impacts the rhythm of psychosocial care development at the Psychosocial Care Center, forcing them to seek training in the field after admission. Unmotivated by the working conditions, the nursing team suffers from the absence of an interdisciplinary partnership and goes to great lengths to approach psychosocial care.

Analysis of the prevalence of musculoskeletal disorders and occupational stress in professors of a higher education institution in the state of Pernambuco.

INTRODUCTION: The consequences of technological innovations and current ways of work organization have prompted the appearance of various health conditions, namely repetitive strain disorders, work-related musculoskeletal disorders, and burn-out; these can emotionally and physically overload workers. OBJECTIVES: To evaluate the prevalence of musculoskeletal disorders and occupational stress in professors of the Serra Talhada campus of Instituto Federal do Sertão Pernambucano. METHODS: Participants signed a free and informed consent form and answered to the Nordic Musculoskeletal Questionnaire. Subsequently, we applied the Maslach Burnout Inventory-Human Services Survey and evaluated the participants' postures during teaching by using the Rapid Upper Limb Assessment tool (Ergolândia software). RESULTS: We observed that 82% of the participants presented musculoskeletal symptoms, mainly in the lower back and lower limbs. Professors presented high scores for the burn-out syndrome, and posture evaluation indicated action levels of 3-4 (suggesting immediate intervention). CONCLUSIONS: The implementation of an occupational physical therapist in this higher education institution is recommended in order to promote ergonomic adaptations and to elaborate a protocol for workplace physical activity, ultimately aiming to prevent musculoskeletal disorders and occupational stress.

Electrochemical degradation of psychotropic pharmaceutical compounds from municipal wastewater and neurotoxicity evaluations.

Contaminants of emerging concern (CECs) are released daily into surface water, and their recalcitrant properties often require tertiary treatment. Electrochemical oxidation (EO) is often used as an alternative way to eliminate these compounds from water, although the literature barely addresses the neurotoxic effects of residual by-products. Therefore, this study investigated the performance of EO in the removal of five CECs (alprazolam, clonazepam, diazepam, lorazepam, and carbamazepine) and performed neurotoxicity evaluations of residual EO by-products in Wistar rat brain hippocampal slices. Platinum-coated titanium (Ti/Pt) and boron-doped diamond (BDD) electrodes were studied as anodes. Different current densities (13-75 A m-2), pH values (3-10), electrolyte dosages (NaCl), and matrix effects were assessed using municipal wastewater (MWW). The drugs were successfully degraded after 5 min of reaction for both the Ti/Pt and BDD electrodes when a current density of 75 A m-2 was applied. For Ti/Pt and BDD, neutral and acidic pH demonstrated better CEC removal performance, respectively. Compound degradation using MWW achieved 40% removal after 120 min for Ti/Pt and ranged between 33 and 52% for the BDD anode. For Ti/Pt, neurotoxicity studies using MWW indicated a decrease in reactive oxygen species (ROS) signals. However, when an artificial cerebrospinal fluid (ACSF) medium was reapplied, the signal recovered and increased to a value above the baseline, indicating that cells recovered part of their normal activity but remained in a different condition. For the BDD anode, the treated MWW did not cause significant ROS production variations, suggesting that he EO was effective in eliminating the toxicity of the treated solution.

Plano de alta hospitalar em saúde mental como estratégia de cuidado integrado à família: uma pesquisa convergente assistencial / Hospital discharge plan in mental health as a family-integrated care strategy: a convergent care research

A família do usuário de serviços de saúde mental apresenta-se, no proposto pela Reforma Psiquiátrica, como elemento essencial, no que diz respeito às intervenções ampliadas, junto ao usuário e à equipe multidisciplinar. Este estudo tem como objeto, a proposição de um plano de orientação intermediário para a alta da internação psiquiátrica para uso como um guia para o cuidado de enfermagem à família do usuário com transtorno mental e anseia: Redimensionar saberes e práticas do Enfermeiro no referente à orientação dada à família do egresso da internação psiquiátrica, no processo de alta; Descrever o conhecimento da família do usuário em práticas cotidianas de vida e saúde mental, no referente à alta da internação psiquiátrica; Elaborar um plano de orientação intermediário para a alta, construído pelos usuários, pela família e pelos Enfermeiros, buscando a reabilitação psicossocial. Apresentamos como pressuposto, o fato de que a integração dos saberes e práticas de Enfermeiros, usuários e família, para a construção de um plano de orientação de alta é um recurso que subsidia cada categoria no desenvolvimento de correspondentes papéis na reinserção social. Pesquisa subsidiada pelos conceitos de família, território, reabilitação psicossocial, ao olhar conceitual da Teoria da Relação Interpessoal de Joyce Travelbee. Sustentada no método da PCA, a investigação no cenário das enfermarias de internação psiquiátrica, onde os 16 participantes Enfermeiros, 10 usuários de serviço e seus 10 familiares vivenciam a internação, trouxe a confecção de um produto tecnológico de cuidado orientado à perspectiva do convívio familiar e seu usuário em comunidade, contribuindo para a permanência em território, diminuição de internações e gestão consciente do cuidado, pela família, apresentando a tese de que a elaboração e aplicação de um plano intermediário de orientação para alta da internação, dirigido à família do usuário em processo de alta da internação psiquiátrica, construído a partir da integração dos saberes e práticas de Enfermeiro, usuário e família, é um recurso potencialmente capaz de aprimorar o relacionamento interpessoal, facilitando o processo de reabilitação psicossocial, mantendo o usuário, no seu território.

The family of patients with mental disorders presents itself, as proposed by the Psychiatric Reform, as an essential element, with regard to expanded interventions, with the user and the multidisciplinary team. This study aims to develop an intermediary guidance plan for discharge from psychiatric hospitalization to be used as a guide for nursing care to the family of users with mental disorders and who want to: Resize nurses' knowledge and practices regarding guidance given to the family of the person discharged from the psychiatric hospital, during the discharge process; Describe the knowledge of the user's family in daily life and mental health practices, with regard to discharge from psychiatric hospitalization; Develop an intermediate guidance plan for discharge, built by the users, the family and the nurses, seeking psychosocial rehabilitation. We present as a premise the fact that the integration of knowledge and practices of nurses, users and families, for the construction of a discharge guidance plan, is a resource that supports each category in the development of corresponding roles in social reintegration. Qualitative, descriptive and exploratory research, supported by the concepts of family, territory, psychosocial rehabilitation, from the conceptual perspective of Joyce Travelbee's Theory of Interpersonal Relationship. Based on the PCA method, the investigation in the scenario of psychiatric inpatient wards, where nursing participants, service users and their families experience hospitalization, brought about the creation of a technological care product oriented to the perspective of family life and its user in the community, contributing to the permanence in the territory, reduction of hospitalizations and conscientious management of care by the family.

La familia de pacientes con trastornos mentales se presenta, como propone la Reforma Psiquiátrica, como un elemento imprescindible, en cuanto a intervenciones ampliadas, con el usuario y el equipo multidisciplinar. El presente estudio tiene como objetivo desarrollar un plan de orientación intermedio para el alta de la hospitalización psiquiátrica que sirva de guía para el cuidado de enfermería a la familia de los usuarios frente a los trastornos mentales y aquellos que deseen: Redimensionar los conocimientos y prácticas de la orientación del enfermero a la familia de la persona dada de alta de la hospitalización psiquiátrica, durante el proceso de alta; Describir el conocimiento de la familia del usuario en las prácticas de la vida diaria con la salud mental, en relación al alta de la hospitalización psiquiátrica; Desarrollar un plan de orientación intermedio para el bachillerato, construido por los usuarios, la familia y las enfermeras, en busca de rehabilitación psicosocial. Presentamos como premisa que la integración de conocimientos y prácticas de enfermeros, usuarios y familias, para la construcción de un plan de alta orientación, es un recurso que apoya a cada categoría en el desarrollo de roles correspondientes en la rehabilitación psicosocial. Investigación cualitativa, descriptiva y exploratoria, sustentada en conceptos de familia, territorio, rehabilitación psicosocial, desde la perspectiva conceptual de la Teoría de la Relación Interpersonal de Joyce Travelbee. Con base en el método PCA, la investigación en el escenario de las salas de hospitalización psiquiátrica, desde donde los participantes de enfermería, los usuarios del servicio y sus familias experimentando con la hospitalización, propició la creación de un producto de atención tecnológica orientado a la perspectiva de su vida familiar. y tu usuario en la comunidad. , contribuyendo a la permanencia en el territorio, reducción de hospitalizaciones y gestión concienzuda de los cuidados por parte de la familia.

Working conditions of a nursing team in mental health facility / Condiciones de trabajo del equipo de enfermería en dispositivo de salud mental / Condições de trabalho da equipe de enfermagem em dispositivo de saúde mental

ABSTRACT Objective: To analyze how the nursing team from a Psychosocial Care Center II relates its insertion in the service with the work process. Methods: Descriptive, analytical research outlined as a case study with a qualitative approach. The data were collected through semi-structured interviews with nursing professionals and went through content analysis subsidized by Bardin's work. Results: Two thematic categories emerged: a) Ways of intake in the nursing services at the Psychosocial Care Center; b) Setbacks in nursing routine at the Psychosocial Care Center. Final considerations: The fact that the professionals have not planned to work in mental health nor have training impacts the rhythm of psychosocial care development at the Psychosocial Care Center, forcing them to seek training in the field after admission. Unmotivated by the working conditions, the nursing team suffers from the absence of an interdisciplinary partnership and goes to great lengths to approach psychosocial care.

RESUMEN Objetivo: Analizar como equipo de enfermería de un Centro de Atención Psicosocial II relaciona su inserción en el servicio con el proceso de trabajo. Métodos: Investigación descriptiva, analítica, delineada como estudio de caso, con abordaje cualitativo. Datos recogidos por entrevista semiestructurada con profesionales de enfermería y pasaron por análisis de contenido subsidiada en Bardin. Resultados: Emergieron dos categorías temáticas: a) Formas de ingreso en el servicio de enfermería del Centro de Atención Psicosocial; b) Contratiempos en el cotidiano de la enfermería en Centro de Atención Psicosocial. Consideraciones finales: El hecho de los profesionales no tener planeado actuar en salud mental ni disponer de preparación, impacta considerablemente el ritmo del desarrollo del cuidado psicosocial en Centro de Atención Psicosocial, forzándolos a buscar capacitación en el área después admisión. Desmotivada por condiciones de trabajo, el equipo de enfermería sufre por la ausencia de colaboración interdisciplinar y redoblarse para aproximarse del cuidado psicosocial.

RESUMO Objetivo: Analisar como a equipe de enfermagem de um Centro de Atenção Psicossocial II relaciona sua inserção no serviço com o processo de trabalho. Métodos: Pesquisa descritiva, analítica, delineada como estudo de caso, com abordagem qualitativa. Os dados foram coletados por entrevista semiestruturada com profissionais de enfermagem e passaram pela análise de conteúdo subsidiada pela obra de Bardin. Resultados: Emergiram duas categorias temáticas: a) Formas de ingresso no serviço de enfermagem do Centro de Atenção Psicossocial; b) Contratempos no cotidiano da enfermagem em Centro de Atenção Psicossocial. Considerações finais: O fato de os profissionais não terem planejado atuar na saúde mental nem disporem de preparação impacta consideravelmente o ritmo do desenvolvimento do cuidado psicossocial no Centro de Atenção Psicossocial, forçando-os a buscar capacitação na área após admissão. Desmotivada pelas condições de trabalho, a equipe de enfermagem sofre pela ausência de parceria interdisciplinar e desdobra-se para aproximar-se do cuidado psicossocial.

Removal of a mixture of pharmaceuticals sulfamethoxazole and diclofenac from water streams by a polyamide nanofiltration membrane.

Wastewater treatment plants are not specially designed to remove pharmaceutically active compounds (PhACs), since these substances are toxic and bio-refractory. This paper aims to investigate and optimize the performance of the Trisep TS80 nanofiltration (NF) membrane for the removal of a mixture of two of the most detected PhACs in municipal wastewaters worldwide, sulfamethoxazole and diclofenac. Several NF tests were carried out to study the rejections of these contaminants both spiked in demineralized water, filtrated water taken from Mondego River and secondary effluent coming from a municipal wastewater treatment plant. Among the several studied operating variables, pH was the one that most affected the contaminant rejection and membrane permeability. In the case of synthetic effluent, an applied pressure of 10 bar and pH 7 were determined as the best operating conditions, which allowed almost total chemical oxygen demand retention and a global contaminant rejection of 96.3% to be achieved. The application of different water matrices (river water and secondary municipal effluent) had no relevant impact on process efficiency. Vibrio fischeri luminescence inhibition tests revealed that treatment by nanofiltration reduced acute toxicity of all studied effluents.

Disseminated Bacillus Calmette-Guérin (BCG) infection with pulmonary and renal involvement: A rare complication of BCG immunotherapy. A case report and narrative review.

Intravesical Bacillus Calmette-Guérin (BCG) instillation is a mainstay of adjunctive therapy for superficial bladder cancer that increases length of disease progression-free survival. Although usually well tolerated, moderate to severe local and systemic infectious complications can occur with this immunotherapy. Diagnosis is difficult and often based on high clinical suspicion since in many cases Mycobacterium bovis is not isolated. Treatment is not fully standardized but the combination of anti-tuberculosis drugs and corticosteroids is advocated in severe cases. The authors present an unusual case of a severe infectious complication following intravesical BCG instillation with pulmonary and kidney involvement. Prompt anti-tuberculosis treatment associated to corticosteroid resulted in a marked clinical and radiological improvement, supporting the diagnosis of disseminated BCG infection. Based on this, the authors aimed to review the literature on this exceptional complication of this immunotherapy.