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.

Public Dental Service Access Policies for People with Autism Spectrum Disorder (ASD) in Salvador, Bahia, Brazil: A Pre-Evaluation Study.

This study sought to carry out a systematic and preliminary evaluation of the policies on access to public dental services for people with ASD in a Brazilian city. The study, conducted between November/2019 and February/2020, was developed through document analysis, the design of the theoretical logical model of the policies, and seven semi-structured interviews with key informants. The sample was intentionally selected. We also considered the answers to 108 questionnaires from a pilot study on the access of people with ASD to dental services applied to caregivers, dentists, and non-dental professionals. No refusals were recorded. The availability study showed that the policies' objectives were not being achieved in terms of care network organization: there were no institutional flows, personal contacts were used between professionals to guarantee access to secondary attention, there was no specific training for the dentists about ASD, and the oral health care network was unknown to non-dentist professionals and caregivers. Most people with ASD have visited the dentist at least once in their lives, but a large percentage of those within this study did not do so in the last year. This study identified difficulties in implementing policies and suggested possible strategies for overcoming them as dimensions and subdimensions for evaluation.

Oral health-care practices and dental assistance management strategies for people with autism spectrum disorder: An integrative literature review.

ABSTRACT: Autism spectrum disorder requires a careful approach from professionals and a favorable clinical environment for dental care and assistance. This article aims To perform a literature review about oral health among people with autism spectrum disorder and dental management strategies for this group. An integrative literature review was carried out in three databases, associating the descriptors: (autism or autism spectrum disorder) with (oral health or oral diseases) and (dental care or dental services). After identification and screening steps, 32 articles were included in the study. The most prevalent subjects were oral health conditions, parents' understanding and practical attitudes about oral health, treatment and management strategies, and the use of technology. The principal barriers to dental care were the scarcity of specialized professionals, unpreparedness in the referral system, poor accessibility of the clinics, and lack of specific care protocols. The world literature on the subject is scarce, and there is still a need for investment and scientific production due to the incidence of autism in the world population and the maintenance of difficulties and barriers in offering quality health care to this group.

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.

Strabismus and Health Related Quality of Life in a pediatric Portuguese population.

Introduction: Strabismus is a common condition among children, and its psychosocial impact has been demonstrated in recent years. The interest in a more comprehensive approach was enhanced by the recognition of health as a four-dimensional concept, arising the term Health-related Quality of Life. Therefore, we aim to evaluate the influence of strabismus in Health-Related Quality of Life of a Portuguese pediatric population. Material and Methods: Case-control prospective transversal study enrolling children between 5 and 12 years old. All had a complete orthoptic and ophthalmological evaluation, followed by an interview with a legal representative to answer the Pediatric Quality-of-Life Inventory 4.0, proxy-version. Results: Seventy-one children were included, 35 in the control group (CG) and 36 in the strabismus group (SG). In the SG, 30 (83.3%) patients had esotropia, 20 (55.6%) had more than 10 prismatic diopters and 26 (72.2%) were already surgically treated. Overall, SG was not statistically different from the CG, showing only mild inferior performance (p > .05). Furthermore, children with exotropia, higher deviations, none or gross stereoacuity and treatment-naïve, scored worse, especially in emotional, social, educational and psychosocial scores although not statistically significant (p > .05). Conclusion: This is the first prospective study addressing HRQoL and strabismus in a pediatric Portuguese population. It would be relevant to further address this issue in order to delineate more effective and global treatment strategies, not only considering ophthalmological goals but also the well-being of both children and guardians.

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

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.

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.

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.

Corneal Epithelial Thickness Changes After Topical Treatment of Dry Eye Disease in Primary Sjögren Syndrome.

Purpose: To evaluate the changes on epithelial thickness before and after topical treatment in primary Sjögren syndrome-associated dry eye disease (SS-DED). Methods: This was a prospective study that included referred women with SS-DED and healthy age-matched controls. Corneal epithelial thickness was evaluated using high-definition anterior segment optical coherence tomography (Cirrus 5000 HD-OCT) in the baseline first consultation, and four weeks after treatment with preservative free 1mg/1mL sodium hyaluronate. Schirmer test 1 (ST1), tear break-up time (TBUT), tear meniscus height (TMH), SICCA Ocular Surface Score (SICCA OSS) and Ocular Surface Disease Index (OSDI) were evaluated. Statistical significance was defined as p-value <0.05. Results: The study included 40 eyes, 20 with SS-DED and 20 controls. At baseline, SS-DED patients had lower ST1 (11.1 ± 2.2mm vs 14.1 ± 3.1mm, p<0.01), faster TBUT (9.1 ± 1.8s vs 13.2 ± 1.1s, p<0.01) and lower TMH (211.2 ± 68.4 µm vs 217.2 ± 60.1µm; p<0.01) than the control group, whereas SICCA OSS and OSDI were higher (p<0.01). The superior epithelium was thinner in SS-DED group (41.1 ± 3.2 µm vs 43.1± 2.3 µm, p<0.01). After treatment, ST1, TBUT, TMH, SICCA OSS, and OSDI improved (p<0.01), and superior epithelium thickened (p<0.01) in the SS-DED group. Conclusion: Treatment with sodium hyaluronate improved ST1, TBUT, TMH, SICCA-OSS, and OSDI score. Superior epithelium tends to be thinner in SS-DED but becomes thicker with treatment. Our results seem to illustrate the morphological changes in the corneal epithelium in DED, which could be further recognized as a clinical biomarker of SS-DED.

The social construction of the PrEP1519 study: conditions of possibility for advances in HIV/AIDS prevention.

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.

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.

Corneal Epithelium Asymmetry in Children With Atopy: The Effect of Hand Dominance.

Purpose: To evaluate the effect of eye rubbing on the epithelial thickness profile in tomographically normal corneas by AS-OCT and to compare right and left eyes in right-handed children. Methods: Thirty right-handed boys (mean age 11.2 years) with ocular allergy and history of eye rubbing were evaluated using Scheimpflug (Pentacam HR, Oculus Wetzlar, Germany) and anterior segment optical coherence tomography. Epithelial thickness (ET) and full corneal thickness (CT) parameters were compared between right and left eyes with a non-parametric Mann-Whitney test. A p-value lower than 0.05 was considered for statistical significance. Results: No eyes had topometric nor tomographic criteria for keratoconus. The min-max ET was lower in right eyes (-2.8 µm vs -3.5; p = 0.02). The difference between inferior and superior (I-S) octants was lower in right eyes (1.1 µm vs 1.9 µm; p = 0.03) as a result of inferotemporal thinning. The highest ET difference was registered between nasal and temporal octants and was more pronounced in the right eyes (2 µm vs 3.1 µm; p < 0.001). Conclusion: AS-OCT analyses reveal different epithelial thickness patterns between the eyes in young atopic patients, likely eye rubbers. Inferior and temporal epithelial thickness seem to be more affected by thinning in the eye on the side of the dominant hand.

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.

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.

Impact of Graves Disease on Ocular Surface and Corneal Epithelial Thickness in Patients With and Without Graves Orbitopathy.

PURPOSE: Our aim was to assess ocular surface and tear film stability and corneal epithelial thickness (CET) in patients with Graves disease (GD) with and without Graves orbitopathy (GO). METHODS: This study included healthy age-matched controls and patients with GD. Symptoms (Ocular Surface Disease Index questionnaire) and signs (schirmer test and tear breakup time test) of dry eye disease were determined, according to the International Dry Eye Workshop II criteria of DED. CET map was also assessed. RESULTS: Twenty-four eyes were included in the control group, with a mean age of 41.00 ± 13.65 years, and 34 in the GD group, 18 with GO and 16 without GO, with a mean age of 44.44 ± 13.95 and 45.75 ± 10.59 years, respectively. All patients with GO had inactive disease (mean clinical activity score: 1.33 ± 0.69). Patients with GD had higher proportion of clinical diagnosis of dry eye disease (GO vs. GD without GO vs. controls: 77.77% vs. 75.00% vs. 4.17%), with higher Ocular Surface Disease Index (GO vs. GD without GO vs. controls: 15.44 vs. 15.06 vs. 9.88) and lower tear breakup time test (GO vs. GD without GO vs. controls: 6.33 s vs. 7.25 s vs. 11.63 s). Superior CET was lower in patients with GD (P < 0.05). No differences were found between patients with and without GO (P > 0.05). CONCLUSIONS: GD negatively influenced ocular surface and CET, with a higher level of eye dryness and corneal thinning regardless of GO status, suggesting that subclinical chronic inflammation may play a role in the pathogenesis of tear film and ocular surface stability.

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.