Remission after CAR T-cell therapy: Do lymphoma patients recover a normal life?

Chimeric antigen receptor T cells (CAR T cells) can induce prolonged remission in a substantial subset of patients with relapse/refractory lymphoma. However, little is known about patients' life after CAR T-cell therapy. We prospectively assessed the multidimensional recovery of lymphoma patients in remission, before leukapheresis, before CAR T-cell infusion, and 3, 6, and 12 months thereafter. Validated tools were used to measure lymphoma-related and global health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy-Lymphoma [FACT-Lym] and EQ-5D-5L), cognitive complaint (FACT-Cognition), fatigue (FACIT-Fatigue subscale), psychological status (Hospital Anxiety and Depression Scale, Post-Traumatic Check List Scale), and sexuality (Relationship and Sexuality Scale). Beyond 12 months of remission, we also surveyed physical, professional, sexual, and general life status. At 3, 6, and 12 months, 53, 35, and 23 patients were evaluable, respectively. Improvement in lymphoma-related HRQoL was clinically relevant at 3, 6, and 12 months with a mean change from baseline of 10.9 (95% confidence interval [CI]: 5.8; 16.1), 12.2 (95% CI: 4.2; 20.1), and 11.72 (95% CI: 2.06; 21.38), respectively. Improvement in global HRQoL, fatigue, and anxiety was clinically relevant, but 20%-40% of patients experienced persistent fatigue, psychological distress, and cognitive complaints over time. Beyond 12 months after CAR T cells, 81.8% of 22 evaluable patients were satisfied with their daily life. Physical activity, professional, sexual, and global well-being had returned to prediagnosis levels in nearly half of the patients. We found an improvement in HRQoL after CAR T-cell therapy including anxiety, depression, sexual satisfaction, and general well-being. However, not all patients recover a "normal life." Further research is needed to determine which patients are at risk of quality-of-life impairment to improve recovery after CAR T-cell infusion.

The Effect of Upper Eyelid Blepharoplasty on Corneal Tomography and Epithelial Profile.

Introduction: Upper tarsal mechanical forces influence corneal epithelial thickness profile, which could modulate corneal astigmatism. Upper eyelid blepharoplasty reduces upper tarsal strength and may have an impact on ocular surface. The aim of this study is to evaluate the effect of upper eyelid blepharoplasty on corneal epithelial thickness profile, astigmatism and aberrations. Methods: Patients with dermatochalasis underwent bilateral upper eyelid blepharoplasty. Anterior segment optical coherence tomography (AS-OCT) (Zeiss Cirrus 5000 HD-OCT) and Pentacam (Oculus, Wetzlar Germany) were performed before surgery and in the 8th postoperative week. Corneal epithelial thickness, keratometry, aberrations and asphericity were considered for statistical purposes. Only right eyes were considered. A p-value lower than 0.05 was considered significant. Results: Thirty eyes of 30 patients were included. The degree of astigmatism did not change after surgery (0.95D vs 0.83D, p=0.23). The difference between preoperative and postoperative steepest axis was 3.1° (p=0.04) with a tendency to change toward the vertical meridian. Mean epithelial thickness was higher in the inferior region both pre- and postoperatively and did not change. ET in the superior octant was lower (42 µm vs 45 µm, p<0.01) and the difference between inferior and superior octants (I-S) was higher (7 µm vs 3 µm, p<0.001) before surgery. There were no statistically significant changes in corneal aberrations (p=0.52) and asphericity (p=0.41) after surgery. Conclusion: Our results support that upper tarsus pressure influences epithelial thickness profile and, consequently, the corneal steepest keratometry. These results lead us to postulate that upper eyelid blepharoplasty may influence biometric and keratometric measurements.

Vigilância e elevada cobertura vacinal: como Portugal superou o colapso e retomou o controle da pandemia / Surveillance and high vaccination coverage: how Portugal overcame the collapse and regained control of the pandemic

Resumo As incertezas sobre a COVID-19 requerem avaliação das respostas nacionais, visando identificar sucessos e fracassos no seu controle. Este artigo analisou a resposta portuguesa, particularmente a contribuição dos seus sistemas de saúde e de vigilância no enfrentamento à pandemia. Foi realizada uma revisão integrativa da literatura, sendo incluídas consultas a observatórios, documentos e sites institucionais. A resposta portuguesa foi ágil e revelou uma coordenação técnica e política unificada. Contou com estrutura de vigilância e uso de telemedicina. A reabertura foi amparada na alta testagem, baixa positividade e regras rígidas. Contudo, o relaxamento das medidas a partir de novembro/2020 resultou em aumento de casos com colapso do sistema de saúde. A resposta a esta situação envolveu estratégia de vigilância consistente, com instrumentos de monitoramento inovadores, que, aliados à alta adesão da população à vacinação, levaram à superação daquele momento e mantiveram baixos índices de hospitalizações e óbitos em novas ondas. Nesse sentido, o caso português evidenciou os riscos de recrudescimento com a flexibilização, a exaustão da população em relação a medidas restritivas e novas variantes, mas também a importância da articulação entre a coordenação técnica, a esfera política e o comitê científico.

Abstract The uncertainties about COVID-19 require evaluating national responses to identify successes and failures in the pandemic control. This article analyzes Portugal´s response, particularly the contribution of its health and surveillance systems in dealing with the pandemic. An integrative literature review was conducted, including consultations of observatories, documents, and institutional websites. Portugal´s response was agile and showed unified technical and political coordination, including surveillance structure using telemedicine. The reopening was supported by high testing and low positivity rates and strict rules. However, the relaxation of measures as of November/2020 resulted in an increase in cases, collapsing the health system. The response involved a consistent surveillance strategy with innovative monitoring tools, which, combined with high population adherence to vaccination, led to overcoming that moment and kept hospitalization and death rates at new disease waves at low levels. Thus, the Portuguese case discloses the risks of disease resurgence with the flexibility of measures and the population´s exhaustion in the face of restrictive measures and new variants, but also the importance of articulation between technical coordination, the political sphere, and the scientific committee.

Tobacco effects on ocular surface, meibomian glands, and corneal epithelium and the benefits of treatment with a lipid-based lubricant.

PURPOSE: Our aim was to evaluate the ocular surface in chronic smokers and to assess the benefit of sodium hyaluronate (SH) versus semi-fluorinated alkane (SFA) eyedrops on tear film, meibomian glands, and corneal epithelial thickness (CET). METHODS: This prospective randomized single-blinded study included smokers, who applied one eyedrop of Hyabak® on one eye (SH group) and one eyedrop of EvoTears® on the fellow eye (SFA group) 4 times daily for 2 months, and age-matched non-smokers. Ocular surface parameters, including tear film break-up time (TBUT) test and corneal fluorescein staining (CFS) score, lipid layer thickness (LLT), meibography (LipiView®), and CET measurements (Zeiss Cirrus HD-5000®), were assessed at baseline and after treatment. RESULTS: Seventy-eight eyes were included in the smokers group (39 in the SH subgroup and 39 in the SFA subgroup) and 42 eyes in the control group. At baseline, the smokers group had a higher prevalence of dry eye (100% vs 0%, p < 0.001) and of meibomian gland dysfunction (MGD) and lower CET measurements than controls (p < 0.05). TBUT, CFS, and LLT (controls vs SFA group: 64.02 ± 1.87 nm vs 49.56 ± 4.33 nm, p = 0.05) improved in the SFA subgroup after treatment, but not in the SH subgroup, and became equivalent to those of controls. Prevalence of dry eye decreased in the smokers group after treatment (controls vs SH group vs SFA group: 0% vs 12.82% vs 16.26%, p > 0.05). Meibomian gland morphological parameters and CET did not improve after treatment (p < 0.05). CONCLUSIONS: Smoking is associated with dry eye, MGD, and corneal epithelial thinning that seem to be only partially reversible with topical lubricants, preferably SFA.

The social construction of the PrEP1519 study: conditions of possibility for advances in HIV/AIDS prevention / A construção social do estudo PrEP1519: possíveis condições para os avanços na prevenção do HIV/aids / La construcción social del estudio PrEP1519: posibles condiciones para avances en la prevención del VIH/sida

This paper analyzed the genesis of the PrEP1519 study and feasibility conditions for its construction. A qualitative-approach study was conducted using the Bourdieusian sociology framework to reconstruct the dynamics of the social environment where PrEP1519 emerged during 2015-2018. A document analysis and ten in-depth interviews were carried out to analyze the trajectory of the project. Pre-exposure prophylaxis (PrEP) was introduced in Brazil as a public policy in 2017. The lack of scientific evidence available among the adolescent population led to the development of a demonstrative cohort study, associated with an intervention, aimed at combining the prevention and treatment of sexually transmitted infections at three sites in Brazil. PrEP1519 sought to generate evidence for global use and to help the Brazilian Ministry of Health apply PrEP among adolescents. The articulation of bureaucratic, scientific, and activist stakeholders enabled this study. The feasibility conditions for developing PrEP1519 included a favorable relationship of national organizations with international organizations, the favorable approach that public administrators had at the time towards new technologies and prevention strategies, the researchers' previous experience in studies with the target population or with PrEP, articulation efforts with social movements, civil society organizations, and other public agencies, and the integration between scientific institutions, which allowed using international resources and developing a response to the problem. Completing this study at a moment when conservatism advances in Brazil demands that the scientific community and activists closely monitor and take stances on PrEP to ensure its availability for adolescents as a public policy.

Este trabalho analisou a gênese do estudo PrEP1519 e as condições de possibilidade para sua construção. Um estudo qualitativo foi realizado, utilizando a estrutura sociológica de Bourdieu para reconstruir a dinâmica do ambiente social onde surgiu o estudo PrEP1519, de 2015 a 2018. Foram realizadas uma análise documental e 10 entrevistas aprofundadas, com análise de suas trajetórias. A pofilaxia pré-exposição (PrEP) foi introduzida no Brasil como política pública em 2017. A escassez de evidências científicas disponíveis entre a população adolescente levou ao desenvolvimento de um estudo de coorte demonstrativo, associado a uma intervenção, visando combinar a prevenção e o tratamento de infeccções sexualmente transmissíveis em três localidades no Brasil. O objetivo era gerar evidências para uso global, e apoiar o Ministério da Saúde com a incorporação da PrEP entre adolescentes. Este trabalho resultou da articulação de atores burocráticos, científicos e ativistas. As possibilidades de desenvolvimento deste estudo permearam uma relação favorável com organizações internacionais, a abordagem favorável dos administradores públicos da época para com as novas tecnologias e estratégias de prevenção, a experiência anterior dos pesquisadores em estudos com a população-alvo ou com a PrEP, os esforços de articulação com movimentos sociais, organizações da sociedade civil e outros órgãos públicos, e a integração entre instituições científicas que possibilitaram recursos internacionais e uma resposta ao problema. A conclusão deste estudo em cenário no qual o conservadorismo avança no país, exige que os campos científico e ativista acompanhem de perto e tomem posições, para garantir a disponibilidade da PrEP para adolescentes como política pública.

Este trabajo analizó la génesis del estudio PrEP1519 y las posibles condiciones para su desarrollo. Se realizó un estudio cualitativo a partir del marco sociológico de Bourdieu para reconstruir la dinámica del entorno social donde surgió el estudio PrEP1519, de 2015 a 2018. Se llevó a cabo un análisis documental y 10 entrevistas en profundidad, con análisis de sus trayectorias. La profilaxis pre-exposición (PrEP) se introdujo en Brasil como política pública en 2017. La escasez de evidencia científica disponible entre la población adolescente llevó al desarrollo de un estudio de cohorte demostrativo, asociado a una intervención, con el objetivo de combinar la prevención y el tratamiento de las enfermedades de transmisión sexual en tres localidades de Brasil. El objetivo fue generar evidencia de uso global y apoyar al Ministerio de Salud con la incorporación de la PrEP entre los adolescentes. Este trabajo resultó de la articulación de actores burocráticos, científicos y activistas. Las posibilidades para desarrollar este estudio permearon una relación favorable con organismos internacionales, el enfoque favorable de los administradores públicos hacia las nuevas tecnologías y estrategias de prevención, la experiencia previa de los investigadores en estudios con la población objetivo o con PrEP, los esfuerzos de articulación con movimientos sociales, organizaciones de la sociedad civil y otros organismos públicos, y la integración entre instituciones científicas que posibilitaron recursos internacionales y una respuesta al problema. La conclusión de este estudio en un escenario en el que avanza el conservadurismo en el país requiere que los campos científicos y activistas vigilen y tomen posiciones para asegurar la disponibilidad de la PrEP para adolescentes como política pública.

The social construction of the PrEP1519 study: conditions of possibility for advances in HIV/AIDS prevention / A construção social do estudo PrEP1519: possíveis condições para os avanços na prevenção do HIV/aids / La construcción social del estudio PrEP1519: posibles condiciones para avances en la prevención del VIH/sida

This paper analyzed the genesis of the PrEP1519 study and feasibility conditions for its construction. A qualitative-approach study was conducted using the Bourdieusian sociology framework to reconstruct the dynamics of the social environment where PrEP1519 emerged during 2015-2018. A document analysis and ten in-depth interviews were carried out to analyze the trajectory of the project. Pre-exposure prophylaxis (PrEP) was introduced in Brazil as a public policy in 2017. The lack of scientific evidence available among the adolescent population led to the development of a demonstrative cohort study, associated with an intervention, aimed at combining the prevention and treatment of sexually transmitted infections at three sites in Brazil. PrEP1519 sought to generate evidence for global use and to help the Brazilian Ministry of Health apply PrEP among adolescents. The articulation of bureaucratic, scientific, and activist stakeholders enabled this study. The feasibility conditions for developing PrEP1519 included a favorable relationship of national organizations with international organizations, the favorable approach that public administrators had at the time towards new technologies and prevention strategies, the researchers' previous experience in studies with the target population or with PrEP, articulation efforts with social movements, civil society organizations, and other public agencies, and the integration between scientific institutions, which allowed using international resources and developing a response to the problem. Completing this study at a moment when conservatism advances in Brazil demands that the scientific community and activists closely monitor and take stances on PrEP to ensure its availability for adolescents as a public policy.

Este trabalho analisou a gênese do estudo PrEP1519 e as condições de possibilidade para sua construção. Um estudo qualitativo foi realizado, utilizando a estrutura sociológica de Bourdieu para reconstruir a dinâmica do ambiente social onde surgiu o estudo PrEP1519, de 2015 a 2018. Foram realizadas uma análise documental e 10 entrevistas aprofundadas, com análise de suas trajetórias. A pofilaxia pré-exposição (PrEP) foi introduzida no Brasil como política pública em 2017. A escassez de evidências científicas disponíveis entre a população adolescente levou ao desenvolvimento de um estudo de coorte demonstrativo, associado a uma intervenção, visando combinar a prevenção e o tratamento de infeccções sexualmente transmissíveis em três localidades no Brasil. O objetivo era gerar evidências para uso global, e apoiar o Ministério da Saúde com a incorporação da PrEP entre adolescentes. Este trabalho resultou da articulação de atores burocráticos, científicos e ativistas. As possibilidades de desenvolvimento deste estudo permearam uma relação favorável com organizações internacionais, a abordagem favorável dos administradores públicos da época para com as novas tecnologias e estratégias de prevenção, a experiência anterior dos pesquisadores em estudos com a população-alvo ou com a PrEP, os esforços de articulação com movimentos sociais, organizações da sociedade civil e outros órgãos públicos, e a integração entre instituições científicas que possibilitaram recursos internacionais e uma resposta ao problema. A conclusão deste estudo em cenário no qual o conservadorismo avança no país, exige que os campos científico e ativista acompanhem de perto e tomem posições, para garantir a disponibilidade da PrEP para adolescentes como política pública.

Este trabajo analizó la génesis del estudio PrEP1519 y las posibles condiciones para su desarrollo. Se realizó un estudio cualitativo a partir del marco sociológico de Bourdieu para reconstruir la dinámica del entorno social donde surgió el estudio PrEP1519, de 2015 a 2018. Se llevó a cabo un análisis documental y 10 entrevistas en profundidad, con análisis de sus trayectorias. La profilaxis pre-exposición (PrEP) se introdujo en Brasil como política pública en 2017. La escasez de evidencia científica disponible entre la población adolescente llevó al desarrollo de un estudio de cohorte demostrativo, asociado a una intervención, con el objetivo de combinar la prevención y el tratamiento de las enfermedades de transmisión sexual en tres localidades de Brasil. El objetivo fue generar evidencia de uso global y apoyar al Ministerio de Salud con la incorporación de la PrEP entre los adolescentes. Este trabajo resultó de la articulación de actores burocráticos, científicos y activistas. Las posibilidades para desarrollar este estudio permearon una relación favorable con organismos internacionales, el enfoque favorable de los administradores públicos hacia las nuevas tecnologías y estrategias de prevención, la experiencia previa de los investigadores en estudios con la población objetivo o con PrEP, los esfuerzos de articulación con movimientos sociales, organizaciones de la sociedad civil y otros organismos públicos, y la integración entre instituciones científicas que posibilitaron recursos internacionales y una respuesta al problema. La conclusión de este estudio en un escenario en el que avanza el conservadurismo en el país requiere que los campos científicos y activistas vigilen y tomen posiciones para asegurar la disponibilidad de la PrEP para adolescentes como política pública.

Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis.

Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.

Safety of biological therapy in patients with rheumatoid arthritis in administrative health databases: A systematic review and meta-analysis.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the synovial fluid of joints, tendons, and some extra-articular sites. Biologic agents have been highly effective and are comparable in reducing RA symptoms, slowing disease progression, and improving physical function; however, concerns have been raised about the risks of several potential adverse effects. Thus, this study aimed to assess the safety of biological therapy in patients with rheumatoid arthritis in observational studies using administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science were searched from inception to 21 October 2021. The analysis was divided into five groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus csDMARDs; bDMARDs versus csDMARDs; abatacept versus bDMARDs; and TNFi versus Janus kinase inhibitors (JAKi). The adverse events were cancer, cardiovascular events, infection, herpes zoster, tuberculosis, and death. The methodological quality of the studies was assessed by the Newcastle-Ottawa Scale. A random-effects model estimated risk ratios with 95% confidence intervals. Results: Thirty-one studies were eligible for inclusion in the present systematic review, published from 2014 to 2021. A total of 1,039,398 RA patients were assessed. The 31 studies evaluated eleven different biological drugs. No significant differences were found regarding safety between TNFi versus non-TNFi (RR 1.08; 95% CI 0.92-1.28; p < 0.01; I2 = 93.0%), TNFi versus csDMARDs (RR 0.91; 95% CI 0.75-1.10; p < 0.01; I2 = 87.0%), bDMARDs versus csDMARDs (RR 0.99; 95% CI 0.82-1.20; p < 0.01; I2 = 93.0%), abatacept versus bDMARDs (RR 0.80; 95% CI 0.54-1.18; p < 0.01; I2 = 90.0%), and TNFi versus JAKi (RR 3.54; 95% CI 0.30-42.09; p = 0.01; I2 = 81.0%). In the subgroup analysis, among studies comparing abatacept to TNFi, a lower risk of cardiovascular events was associated with abatacept (RR 0.37; 95% CI 0.24-0.55). Conclusion: Our results do not suggest an increased risk of adverse events associated with biological therapy in treating RA patients, indicating a lower risk of cardiovascular events with abatacept than TNFi. However, these findings must be interpreted with caution given the limitations of this study and the low/very low certainty of the evidence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier [CRD42020190838].

Sphingosine Kinase-1 Is Overexpressed and Correlates with Hypoxia in Osteosarcoma: Relationship with Clinicopathological Parameters.

The Sphingosine kinase-1/Sphingosine 1-Phosphate (SphK1/S1P) signaling pathway is overexpressed in various cancers, and is instrumental for the adaptation to hypoxia in a number of solid tumor models, but no data are available in osteosarcoma. Here we report that SphK1 and the S1P1 receptor are involved in HIF-1α accumulation in hypoxic osteosarcoma cells. FTY720 (Fingolimod), which targets SphK1 and S1P1, prevented HIF-1α accumulation, and also inhibited cell proliferation in both normoxia and hypoxia unlike conventional chemotherapy. In human biopsies, a significant increase of SphK1 activity was observed in cancer compared with normal bones. In all sets of TMA samples (130 cases of osteosarcoma), immunohistochemical analysis showed the hypoxic marker GLUT-1, SphK1 and S1P1 were expressed in tumors. SphK1 correlated with the GLUT-1 suggesting that SphK1 is overexpressed and correlates with intratumoral hypoxia. No correlation was found between GLUT-1 or SphK1 and response to chemotherapy, but a statistical difference was found with increased S1P1 expression in patients with poor response in long bone osteosarcomas. Importantly, multivariate analyses showed that GLUT-1 was associated with an increased risk of death in flat bone, whereas SphK1 and S1P1 were associated with an increased risk of death in long bones.

Influence of Sociodemographic Determinants on the Hodgkin Lymphoma Baseline Characteristics in Long Survivors Patients Enrolled in the Prospective Phase 3 Trial AHL2011.

INTRODUCTION: Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10-15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. METHODS: This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events-SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data-marital status, living area, level of education, socio-professional category, and professional situation-were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. RESULTS: Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0-2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area's inhabitants and TMTV (R Pearson = -0.29, p = 0.0004) was observed. CONCLUSION: This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

Comparative evaluation of visual outcomes after bilateral implantation of an advanced or conventional monofocal intraocular lens.

PURPOSE: To assess the clinical outcomes and patient satisfaction of the Tecnis Eyhance, an advanced monofocal intraocular lens (IOL), compared to a conventional monofocal IOL. DESIGN: Retrospective case-control study. METHODS: This study included 120 eyes of 60 patients (30 patients in each group) who underwent bilateral cataract surgery either with the implantation of conventional monofocal IOLs (Tecnis PCB00), as a control group, or advanced monofocal IOLs (Tecnis Eyhance ICB00). Ophthalmological evaluation included the measurement of binocular corrected distance visual acuity (CDVA), monocular and binocular uncorrected distance visual acuity (UDVA), and uncorrected intermediate VA (UIVA). In addition the binocular defocus curve was analyzed. Furthermore a subjective questionnaire (Catquest-9SF) was used to assess vision and life quality. RESULTS: The average binocular UDVA was 20/22 in the ICB00 group and 20/20 in the PCB00 model (p = 0.62). The average monocular UIVA was 20/32 in the ICB00 group and 20/40 in the control group (p < 0.001). We found the binocular UIVA, had a mean value of 20/30 in the ICB00, compared to 20/40 in the control group (p < 0.001). The reported dysphotopsia was not significantly different between both groups (p = 0.56). Regarding the life quality questionnaire, the ICB00 group showed less difficulty in activities requiring intermediate vision. CONCLUSION: Our results demonstrated a significant improvement in visual acuity for intermediate distance in the ICB00 group compared to the control group, without compromising distance visual acuity. We also found a greater capability for intermediate distance activities (namely for computer use and reading price tags) when comparing ICB00 patients with the control group.

The legislative and the regulation of dental assistants professions in Brazil / O poder legislativo e a regulamentação das profissões auxiliares em saúde bucal

ABSTRACT Objective: To analyze the conditions of possibilities and contributions of the legislative power to the regulation of oral health assistants (in Portuguese "Auxiliar de Saúde Bucal" - ASB) and oral health technicians (in Portuguese "Técnico de Saúde Bucal" - TSB) in Brazil. Methods: This socio-historical study used Bourdieu´s theoretical framework. Twelve legislative processes were included. Information about their objects, similarities and differences, main stakeholders, their social and professional trajectories and their relationship with oral health were sought. An interview with two key informants was conducted. The multiple correspondence analysis investigated the association between the variables and their intensity of contribution. Results: This issue remained in dispute between 1977-2008 and was regulated by Law 11.889/2008, after the incorporation of Oral Health Teams in the Family Health Strategy. The restrictive practice was related to parliamentarians from the southeast region, linked to the pole of the private market, without training in the health area. The defense of clinical practice under dentist´ supervision was related to health and human sciences agents. Conclusion: The ASB profession has always been a consensus in regulation. The issue in dispute was the activities of Oral Health Technicians. It prevailed in the Law text a more progressive and broader view.

RESUMO Objetivo: Analisar as condições de possibilidade e contribuições do poder legislativo para regulamentação das profissões de auxiliar em saúde bucal (ASB) e técnico em saúde bucal (TSB) no Brasil. Métodos: Estudo sócio-histórico que utilizou o referencial teórico bourdieusiano. Foram incluídos 12 processos legislativos sobre o tema. Buscou-se informações sobre seus objetos, similaridades e diferenças, principais envolvidos, suas trajetórias social e profissional e relação com a saúde bucal. Realizou-se entrevista com dois informantes-chave. A análise de correspondência múltipla investigou a associação entre variáveis e intensidade de contribuição. Resultados: Essa questão permaneceu em disputa entre 1977-2008, sendo regulamentada pela Lei 11.889/2008, após a incorporação da Saúde Bucal na Estratégia Saúde da Família. A prática restritiva esteve relacionada a parlamentares do Sudeste, vinculados ao pólo privado, sem formação na área de saúde. A defesa da atuação clínica sob supervisão do dentista relacionou-se a agentes das áreas de saúde e ciências humanas. Conclusão: A regulamentação da profissão de ASB sempre foi um consenso, sendo a questão em disputa as atividades pertinentes ao TSB, prevalecendo no texto da Lei a visão mais progressista e de atuação mais ampliada.

Population PK-PD Modeling of Circulating Lymphocyte Dynamics in Chronic Lymphocytic Leukemia Patients Under Ibrutinib Treatment.

Ibrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL). Absolute lymphocyte count (ALC) is a clinical criterion used for the monitoring of CLL. Ibrutinib has several effects on lymphocytes, and has highly variable pharmacokinetics (PK). The objective of this work was to build a PK-pharmacodynamic (PD) model describing ALC dynamics under ibrutinib treatment in patients with CLL. ALC observations before and after ibrutinib treatment initiation in patients with CLL were included in the analysis. A population PK-PD model was developed based on physio-pharmacological knowledge. Individual PK concentrations at each hospital visit were included in the model. The association between PD parameters and lymphocytosis, and between PD parameters and response to treatment were assessed. A total of 94 patients, 658 ALC and 1,501 PK observations were included in model development. The final PK-PD model accurately described ALC dynamics for different patient profiles. It consisted in two compartments (tissues and blood circulation) with ibrutinib plasmatic concentration inducing two drug effects: stimulation of lymphocyte redistribution and death. Patients with hyperlymphocytosis had significantly higher tissues to circulation baseline lymphocyte count ratio, and lower death effect. Patients who progressed under ibrutinib had significantly lower baseline lymphocyte counts in tissues (2-fold lower) and blood (3-fold lower). The first PK-PD model for ALC in patients with CLL under ibrutinib treatment was developed. This model suggests that estimated lymphocyte counts in tissues and blood could be used as an early predictor of response in patients with CLL.

Preliminary Clinical Outcomes of a New Enhanced Depth of Focus Intraocular Lens.

PURPOSE: To assess the preliminary clinical outcomes and patient satisfaction of the new enhanced depth of focus (EDOF) LuxSmart™ intraocular lens IOL and to compare with a conventional monofocal IOL (Akreos™) in patients who had undergone bilateral cataract surgery. METHODS: Twelve patients underwent bilateral LuxSmart IOL implantation, and twelve underwent bilateral Akreos IOL implantation. Best-corrected distance (CDVA) and uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA) at 66cm, uncorrected near visual acuity (UNVA) at 40cm and defocus curve were assessed. Patients-reported visual function was inquired by Catquest-9SF. The presence of photic phenomena was evaluated. A p-value lower than 0.05 was considered for statistical significance. RESULTS: The mean IOL power was +21.90D in LuxSmart group and +22.30D in Akreos. Monocular UDVA (p = 0.32) and CDVA (p = 0.52) did not differ between groups. The average binocular UIVA (0.18 ± 0.12 logMAR vs. 0.30 ± 0.13 logMAR, p < 0.001) and UNVA (0.38 ± 0.14 logMAR vs. 0.44 ± 0.17 logMAR, p = 0.02) were higher in LuxSmart IOL group. No patients reported disabling photic phenomena in either group. CONCLUSION: This study shows that new LuxSmart EDOF IOL achieved higher performance for intermediate and near vision compared with a conventional monofocal IOL, without increasing the risk of dysphotopsias. LuxSmart may be an attractive and safe option for patients who desire spectacle independence for distance and intermediate vision after cataract surgery.

Population Pharmacokinetics of Ibrutinib and Its Dihydrodiol Metabolite in Patients with Lymphoid Malignancies.

BACKGROUND AND OBJECTIVE: Ibrutinib is used for the treatment of chronic lymphocytic leukemia and other lymphoid malignancies. The aim of this work is to develop a population pharmacokinetic model for ibrutinib and its dihydrodiol metabolite to quantify pharmacokinetic inter- and intra-individual variability, to evaluate the impact of several covariates on ibrutinib pharmacokinetic parameters, and to examine the relationship between exposure and clinical outcome. METHODS: Patients treated with ibrutinib were included in the study and followed up for 2 years. Pharmacokinetic blood samples were taken from months 1 to 12 after inclusion. Ibrutinib and dihydrodiol-ibrutinib concentrations were assessed using ultra-performance liquid chromatography tandem mass spectrometry. A population pharmacokinetic model was developed using NONMEM version 7.4. RESULTS: A total of 89 patients and 1501 plasma concentrations were included in the pharmacokinetic analysis. The best model consisted in two compartments for each molecule. Absorption was described by a sequential zero first-order process and a lag time. Ibrutinib was either metabolised into dihydrodiol-ibrutinib or excreted through other elimination routes. A link between the dosing compartment and the dihydrodiol-ibrutinib central compartment was added to assess for high first-pass hepatic metabolism. Ibrutinib clearance had 67% and 47% inter- and intra-individual variability, respectively, while dihydrodiol-ibrutinib clearance had 51% and 26% inter- and intra-individual variability, respectively. Observed ibrutinib exposure is significantly higher in patients carrying one copy of the cytochrome P450 3A4*22 variant (1167 ng.h/mL vs 743 ng.h/mL, respectively, p = 0.024). However, no covariates with a clinically relevant effect on ibrutinib or dihydrodiol-ibrutinib exposure were identified in the PK model. An external evaluation of the model was performed. Clinical outcome was expressed as the continuation or discontinuation of ibrutinib therapy 1 year after treatment initiation. Patients who had treatment discontinuation because of toxicity had significantly higher ibrutinib area under the curve (p = 0.047). No association was found between cessation of therapy due to disease progression and ibrutinib area under the curve in patients with chronic lymphocytic leukemia. For the seven patients with mantle cell lymphoma studied, an association trend was observed between disease progression and low exposure to ibrutinib. CONCLUSIONS: We present the first population pharmacokinetic model describing ibrutinib and dihydrodiol-ibrutinib concentrations simultaneously. Large inter-individual variability and substantial intra-individual variability were estimated and could not be explained by any covariate. Higher plasma exposure to ibrutinib is associated with cessation of therapy due to the occurrence of adverse events within the first year of treatment. The association between disease progression and ibrutinib exposure in patients with mantle cell lymphoma should be further investigated. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT02824159.

Psychotropic drug initiation in patients diagnosed with chronic myeloid leukemia: a population-based study in France.

Psychotropic drugs (PD) are often used close to a cancer diagnosis and may be considered as a way of coping. We aimed to determine the incidence of anxiolytics, hypnotics, antidepressants, and antipsychotics initiation around a diagnosis of chronic myelogenous leukemia (CML). Population-based cohort: Data were extracted from Systeme National des données de Santé (SNDS, the French health insurance database) at the regional level (Midi-Pyrenees area, 2.9 million inhabitants). All newly diagnosed patients treated by a CML tyrosine kinase inhibitor (TKI) between 10/01/2011 and 04/01/2014 were included. Pre-CML (9 months before to 3 months before first TKI prescription-F-TKI) and CML (3 months before to 9 months after F-TKI) phases were defined. The main evaluation criterion was the initiation of PD during CML phase. Determinants associated with this incident PD use were studied through a logistic regression model. We compared pre-CML and CML healthcare consumption. The cohort included 103 patients (mean age of 60.8 years). PD initiation rate was 35.9%, anxiolytics being the most initiated PD (59.5%). Advanced age was associated with PD initiation (adjusted OR = 1.029, 95% CI = 1.001-1.056). The number of consultations during the pre-CML phase and female gender tended to be associated with increased risk of PD initiation in univariate analysis. For PD initiators, healthcare consumption was greater in CML but not in pre-CML phase. PD initiation is a frequent finding around a CML diagnosis. Its risk increases with age. It could be a way to identify a subgroup with higher healthcare consumption.

Decurso histórico das políticas de fluoretação como estratégia de enfrentamento à cárie dentária no Poder Legislativo brasileiro, de 1963 a 2019 / History of fluoridation policies as a strategy by the Brazilian Legislative Branch to fight dental caries, 1963 to 2019 / Recorrido histórico de las políticas de fluoración como estrategia de combate a la caries dental en el Poder Legislativo brasileño, de 1963 a 2019

Resumo: O objetivo deste trabalho foi analisar os processos legislativos sobre políticas de fluoretação no Brasil, de 1963 a 2019. Utilizou-se o referencial teórico de Pierre Bourdieu. Foi realizada uma pesquisa documental sobre os processos legislativos que abordam o tema da fluoretação no Brasil como medida de saúde pública e as discussões que ocorreram no Congresso Nacional. As fontes de pesquisa para a construção do artigo foram os sítios eletrônicos oficiais da Câmara dos Deputados e do Senado Federal, para consultar os atos legislativos relacionados à fluoretação no Brasil. De 1963 a 2001 e em 2017, foi constatada uma disputa entre os métodos de fluoretação das águas de abastecimento, água mineral e fluoretação do sal. Entretanto, permeava a compreensão da importância e benefícios acerca da utilização do flúor sistêmico. De 2003 a 2013, os projetos contestavam a utilização do flúor sistêmico, propondo sua utilização apenas em meio tópico. Nos anos 1960, 1970 e em 2017, os atos legislativos apresentavam mais aproximação ao campo científico e foram propostos por parlamentares da oposição. Diferentemente do tema da fluoretação das águas, dos 6 atos legislativos favoráveis à fluoretação do sal, apenas um era proveniente de um profissional da saúde e apenas dois de legisladores do eixo Sudeste. Houve maior participação de projetos de legisladores do Centro-oeste e do Nordeste. Aqueles com formação na saúde apresentaram tomadas de posição em defesa de algum método de fluoretação sistêmica. Esta análise possibilita interpretar o processo histórico de construção em resposta ao problema constituído e suas distintas estratégias de enfrentamento.

Abstract: The aim of this study was to analyze legislative proceedings on fluoridation policies in Brazil from 1963 to 2019. The theoretical reference was Pierre Bourdieu. A document search was performed on legislative proceedings that address the theme of fluoridation in Brazil as a public health measure and the discussions in the National Congress. The sources for the article were the official websites of the Chamber of Deputies (lower house) and the Senate to consult the legislative acts related to fluoridation in Brazil. The study showed that from 1963 to 2001 and in 2017 there was a dispute between fluoridation methods for the water supply, mineral water, and table salt fluoridation. However, there was a crosscutting understanding of the importance and benefits of systemic fluoride use. From 2003 to 2013, the bills challenged the use of systemic fluoride, proposing its use only in topical applications. In the 1960s, 1970, and 2017, the legislative bills showed a closer approach to the scientific field and were submitted by opposition members of Congress. Unlike the issue of water fluoridation, of the 6 legislative bills in favor of salt fluoridation, only one was drafted by a health professional da health, and only two by legislators from the Southeast region. There were more bills by legislators from the Central and Northeast. Those with training in health exhibited positions in defense of some method of systemic fluoridation. The analysis allowed interpreting the historical process of developing the response to the caries problem and the different strategies employed in this process.

Resumen: El objetivo de este trabajo fue analizar los procesos legislativos sobre políticas de fluoración en Brasil, de 1963 a 2019. Se utilizó el marco referencial teórico de Pierre Bourdieu. Se realizó una investigación documental sobre los procesos legislativos que abordan el tema de la fluoración en Brasil, como medida de salud pública, y las discusiones que se produjeron en el Congreso Nacional. Las fuentes de investigación para la construcción del artículo fueron los sitios electrónicos oficiales de la Cámara de los Diputados y del Senado Federal para consultar las acciones legislativas relacionadas con la fluoración en Brasil. De 1963 a 2001 y en 2017 se constató una disputa entre los métodos de fluoración de las aguas de abastecimiento, agua mineral y fluoración de la sal. Mientras tanto, permeaba la comprensión de la importancia y beneficios a cerca de la utilización del flúor sistémico. De 2003 a 2013, los proyectos contestaban la utilización del flúor sistémico, proponiendo su utilización solamente como medio tópico. En los años 1960, 1970 y en 2017 las acciones legislativas presentaban más aproximación al campo científico y fueron propuestos por parlamentarios de la oposición. A diferencia del tema de la fluoración de las aguas, de las 6 acciones legislativas favorables a la fluoración de la sal, solamente una provenía de un profesional de la salud, y solamente dos de legisladores del eje sudeste. Hubo una mayor participación en proyectos de legisladores del Centro-oeste y del Nordeste. Aquellos con formación en salud presentaron toma de posición en defensa de algún método de fluoración sistémica. Este análisis posibilita interpretar el proceso histórico de construcción, en respuesta al problema planteado, y sus distintas estrategias de combate al mismo.

The international response of primary health care to COVID-19: document analysis in selected countries / A resposta internacional da atenção primária em saúde à COVID-19: uma análise documental em países selecionados / La respuesta internacional de la atención primaria en salud a la COVID-19: análisis de documentación en países seleccionados

This study examines the primary health care (PHC) organization in response to the COVID-19 epidemic. This is a descriptive study based on the document analysis of the countries' responses to the coronavirus pandemic with emphasis on PHC. In various countries, there have been different organizations and impacts of strategies since they have conducted actions according to the local characteristics of disease transmission, demography, public health services organization, and health system's capacity and financing, especially in the PHC area. A significant change during the pandemic has been the increase in telephone and video consultations incorporating health information technology. An efficient PHC, guided by essential actions, achieves more suitable results. Also, each country's cumulative capacity or experience makes the difference facing the emerging demands on different health systems.

O estudo examina a organização da atenção primária em saúde (APS) na resposta à epidemia da COVID-19. É um estudo descritivo com base em análise documental das respostas nacionais à pandemia do novo coronavírus, com ênfase na APS. Em distintos países, houve diferentes formas de organização e impactos das estratégias, uma vez que realizaram ações de acordo com as características locais da transmissão da doença, demografia, organização dos serviços de saúde pública e capacidade e financiamento do sistema de saúde, principalmente na APS. Uma mudança significativa durante a pandemia tem sido o aumento nas consultas telefônicas e por videoconferência, incorporando a tecnologia de informação em saúde. Uma APS eficiente, orientada por ações essenciais, alcança resultados mais adequados. Além disso, a capacidade acumulada ou experiência de cada país faz a diferença ao enfrentar as demandas emergentes sobre diferentes sistemas de saúde.

Este estudio examina la organización de la atención primaria en salud (APS), como respuesta a la epidemia de COVID-19. Es un estudio descriptivo basado en el análisis documental de las respuestas de países a la pandemia de coronavirus con énfasis en la APS. En varios países, ha habido diferentes organizaciones e impactos de estrategias, puesto que han llevado a cabo acciones según las características locales de transmisión de la enfermedad, demografía, organización de los servicios públicos de salud, y capacidad del sistema de salud, así como financiación, especialmente en la APS. Un cambio significativo durante la pandemia ha sido el incremento de las consultas por teléfono y vídeo, incorporando tecnología para la información en salud. Una APS eficiente, guiado por acciones básicas, consigue resultados más adecuados. Asimismo, la capacidad acumulativa de cada país o la experiencia es lo que marca la diferencia, enfrentándose a las demandas que surgen en diferentes sistemas de salud.