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In the landscape of cancer treatments, the efficacy of coadjuvant molecules remains a focus of attention for clinical research with the aim of reducing toxicity and achieving better outcomes. Most of the pathogenetic processes causing tumour development, neoplastic progression, ageing, and increased toxicity involve inflammation. Inflammatory mechanisms can progress through a variety of molecular patterns. As is well known, the ageing process is determined by pathological pathways very similar and often parallel to those that cause cancer development. Among these complex mechanisms, inflammation is currently much studied and is often referred to in the geriatric field as 'inflammaging'. In this context, treatments active in the management of inflammatory mechanisms could play a role as adjuvants to standard therapies. Among these emerging molecules, Silibinin has demonstrated its anti-inflammatory properties in different neoplastic types, also in combination with chemotherapeutic agents. Moreover, this molecule could represent a breakthrough in the management of age-related processes. Thus, Silibinin could be a valuable adjuvant to reduce drug-related toxicity and increase therapeutic potential. For this reason, the main aim of this review is to collect and analyse data presented in the literature on the use of Silibinin, to better understand the mechanisms of the functioning of this molecule and its possible therapeutic role.
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Neoplasias , Silibina , Silimarina , Silibina/uso terapêutico , Silibina/farmacologia , Humanos , Silimarina/uso terapêutico , Silimarina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
PURPOSE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their use is associated with immune-related adverse events (irAEs). Estimating the prevalence and patient impact of these irAEs in the real-world data setting is critical for characterizing the benefit/risk profile of ICI therapies beyond the clinical trial population. Diagnosis codes, such as International Classification of Diseases codes, do not comprehensively illustrate a patient's care journey and offer no insight into drug-irAE causality. This study aims to capture the relationship between ICIs and irAEs more accurately by using augmented curation (AC), a natural language processing-based innovation, on unstructured data in electronic health records. METHODS: In a cohort of 9,290 patients treated with ICIs at Mayo Clinic from 2005 to 2021, we compared the prevalence of irAEs using diagnosis codes and AC models, which classify drug-irAE pairs in clinical notes with implied textual causality. Four illustrative irAEs with high patient impact-myocarditis, encephalitis, pneumonitis, and severe cutaneous adverse reactions, abbreviated as MEPS-were analyzed using corticosteroid administration and ICI discontinuation as proxies of severity. RESULTS: For MEPS, only 70% (n = 118) of patients found by AC were also identified by diagnosis codes. Using AC models, patients with MEPS received corticosteroids for their respective irAE 82% of the time and permanently discontinued the ICI because of the irAE 35.9% (n = 115) of the time. CONCLUSION: Overall, AC models enabled more accurate identification and assessment of patient impact of ICI-induced irAEs not found using diagnosis codes, demonstrating a novel and more efficient strategy to assess real-world clinical outcomes in patients treated with ICIs.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Registros Eletrônicos de Saúde , Inibidores de Checkpoint Imunológico , Processamento de Linguagem Natural , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Feminino , Masculino , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Neoplasias/tratamento farmacológico , Pessoa de Meia-Idade , IdosoRESUMO
This paper addresses indoor localization using an anchor-based system based on Bluetooth Low Energy (BLE) 5.0 technology, adopting the Received Signal Strength Indicator (RSSI) for the distance estimation. Different solutions have been proposed in the scientific literature to improve the performance of this localization technology, but a detailed performance comparison of these solutions is still missing. The aim of this work is to make an experimental analysis combining different solutions for the performance improvement of BLE-based indoor localization, identifying the most effective one. The considered solutions involve different RSSI signals' conditioning, the use of anchor-tag distance estimation techniques, as well as approaches for estimating the unknown tag position. An experimental campaign was executed in a complex indoor environment, characterized by the continuous presence in the movement of working staff and numerous obstacles. The exploitation of multichannel transmission using RSSI signal aggregation techniques showed the greater performance improvement of the localization system, reducing the positioning error (from 1.5 m to about 1 m). The other examined solutions have shown a lesser impact in the performance improvement with a decrease or an increase in the positioning errors, depending on the considered combination of the adopted solutions.
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Everyday tasks use sensors to monitor and provide information about processes in different scenarios, such as monitoring devices in manufacturing or homes. Sensors need to communicate, with or without wires, while providing secure information. Power can be derived from various energy sources, such as batteries, electrical power grids, and energy harvesting. Energy harvesting is a promising way to provide a sustainable and renewable source to power sensors by scavenging and converting energy from ambient energy sources. However, low energy is harvested through these methods. Therefore, it is becoming a challenge to design and deploy wireless sensor networks while ensuring the sensors have enough power to perform their tasks and communicate with each other through careful management and optimization, matching energy supply with demand. For this reason, data cryptography and authentication are needed to protect sensor communication. This paper studies how energy harvested with microbial fuel cells can be employed in algorithms used in data protection during sensor communication.
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Fontes de Energia Bioelétrica , Eletricidade , Fontes Geradoras de Energia , Redes de Comunicação de Computadores , AlgoritmosRESUMO
Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 < 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy. Two-hundred and twenty-one patients were included. Median age was 79 (range 56−92) years, M/F 165(74.6%)/56(25.4%), ECOG performance status (PS) 0/1/ ≥ 2 23(10.9%)/94(42.5%)/103(46.6%), with a median of two serious comorbidities. A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. Clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), poor PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of oral metronomic vinorelbine (MetV 78.6%), gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%) and other (O 3.2%). Median progression-free survival (PFS) and overall survival (OS) of single agent treatments ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. All grade toxicities did not differ among single agents, while grade 3−4 toxicities were less frequent with MetV. Up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 < 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (>70 years), comorbidities and poor PS. An oral treatment was frequently proposed with MetV being the most frequent choice according to its safety profile.
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The shop floor or factory floor is the area inside a factory where manufacturing production is executed. The digitalisation of this area has been increasing in the last few years, introducing the Digital Twin (DT) and the Industry 4.0 concepts. A DT is the digital representation of a real object or an entire system. A DT includes a high diversity of components from different vendors that need to interact with each other efficiently. In most cases, the development of standards and protocols does not consider the need to operate with other standards and protocols, causing interoperability issues. Transducers (sensors and actuators) use the communication layer to exchange information with digital contra parts, and for this reason, the communication layer is one of the most relevant aspects of development. This paper covers DT development, going from the physical to the visualisation layer. The reference architecture models, standards, and protocols focus on interoperability to reach a syntactic level of communication between the IEEE 1451 and the IEC 61499 standards. A semantic communication layer connects transducer devices to the digital representation, achieving a semantic level of interoperability. This communication layer adds semantics to the communication process, allowing the development of an interoperable DT based on the IEEE 1451 standards. The DT presented reaches the syntactic and semantic levels of interoperability, allowing the monitoring and visualisation of a prototype system.
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SemânticaRESUMO
Industrial Internet of Things focuses on the manufacturing process and connects with other associated concepts such as Industry 4.0, Cyber-Physical Systems, and Cyber-Physical Production Systems. Because of the complexity of those components, it is necessary to define reference architectures models to manage Industry 4.0 and the Industrial Internet of Things. The reference architecture models aim to solve the interoperability problem enabling the syntactical and semantic levels of interoperability. A reference architecture model provides a bottom/top view of an industrial process, from the physical transducers at the physical layer to the business layer. The physical layer provides access to a twin representation of a physical thing in the digital world, extending the functionalities in the manufacturing process. This paper studies the syntactic interoperability between the IEEE 1451 and IEC 61499 in an industrial environment. The IEEE 1451 family of standards has the essential characteristics to support the information exchange between smart transducers (sensors and actuators), building the digital elements and meeting the Industry 4.0 requirements. The IEC 61499 standard enables industrial control and automation. These two standards combined at the syntactic level solve an interoperability problem. The IEC 61499 also provides data to the framework layer, supplying all the parameters defined for the communication layer specified by a reference architecture model. This paper combines the IEEE 1451 with the IEC 61499, enabling data exchange in a reference architecture model proposed for Industry 4.0. Network performance at the communication level of a reference architecture model in a local network and an external network is evaluated for the proposed application. The IEEE 1451 standard implementation and adoption to acquire data and communicate it inside an industrial process allowed the IEC 61499 standard to control an industrial process. The IEEE 1451 standard is implemented in a MSP430 low power microcontroller. A Raspberry Pi running FORTE and 4diac in the USA and Portugal were used to test a local network in Portugal and an external network in USA. Data related to network performance was obtained with Wireshark and processed with MATLAB. Tests using the Message Queuing Transport Telemetry Transport and Hypertext Transport Protocols verified the performance of these protocols, supported by the IEEE 1451 and IEC 61499 standards, showing that communication inside an Industry 4.0 environment is possible. MQTT protocol is faster, has a small packet size, and consumes less bandwidth. The HTTP protocol uses more bandwidth but is more reliable for real-time communication, essential for Industry 4.0.
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Surgical resection of the insula (insulectomy) is a procedure used for brain lesions and for refractory epilepsy. It has a difficult surgical access and the need of a wide anatomical knowledge and preoperative planning. There are two types of surgical approaches aiming the exposure of the insular cortex: transsylvian and transcortical. The importance of insulectomies is the efficacy in providing a remarkable decrease in seizures. The objective of the present article is to document the results of a series of 10 patients submitted to insulectomies for refractory epilepsies and compare them with the results of other studies reported in the literature, as well as to describe the main nuances of the surgical approaches and their associated risks. In the new case series, all patients corresponded to preoperative Engel classification IV for; after a mean 2-year follow-up period, they corresponded to Engel classification II. A subtotal resection was performed in six patients, and the remaining four underwent a partial resection, most of them leading to temporary complications. The literature review endorsed the good outcomes of the casuistry. A critical analysis of the presented data reiterates the opinion of several authors that insulectomies are beneficial and safe for the patients. A broad anatomical knowledge of the insular region, preoperative planning (limits of resections), and the use of modern microsurgical techniques must be considered as basic principles by neurosurgeons for the prevention of perioperative morbidities. Insulectomies are safe and effective, although they result in temporary postoperative complications, and provide highly satisfactory results in terms of seizure control.
A ressecção cirúrgica da ínsula (insulectomia) é um procedimento utilizado para lesões cerebrais e epilepsia refratária. A ínsula possui um acesso cirúrgico difícil com necessidade de um amplo conhecimento anatômico com planejamento pré-operatório. Existem dois tipos de abordagens cirúrgicas que visam a exposição do córtex insular: transsilvianas e transcorticais. A importância das insulectomias é a eficácia em proporcionar uma diminuição das convulsões. O objetivo do presente artigo é documentar os resultados de uma série de 10 pacientes submetidos a insulectomias para epilepsia refratária e compará-los com os resultados de outros estudos relatados na literatura, além de descrever as principais nuances das abordagens cirúrgicas e os seus riscos associados. Na série de casos, todos os pacientes se enquadravam na classificação pré-operatória de Engel IV e, após um período médio de seguimento de 2 anos, eles se enquadravam na classificação de Engel II. Seis pacientes foram submetidos a uma ressecção subtotal e os quatro restantes a uma ressecção parcial, implicando, majoritariamente, em complicações temporárias. A revisão da literatura endossou os bons resultados da casuística. A análise crítica dos dados apresentados reitera a opinião de vários autores de que as insulectomias são benéficas e seguras para os pacientes. O amplo conhecimento anatômico da região insular, o planejamento pré-operatório (limites das ressecções) e a utilização de técnicas microcirúrgicas modernas devem ser considerados princípios básicos para a prevenção de morbidades perioperatórias. As insulectomias são seguras e eficazes conquanto resultem em complicações pós-operatórias temporárias e proporcionem resultados altamente satisfatórios no que diz respeito ao controle das convulsões.
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ABSTRACT Background: self-limited epilepsy with centrotemporal spikes, previously considered benign focal childhood epilepsy with centrotemporal spikes show clinical signs of involvement of Rolandic areas, mainly lower area, which may affect the planning and execution of motor sequences. Objective: This study aimed to evaluated oral praxis in children with self-limited epilepsy with centrotemporal spikes and compare to the age-matched control group. Methods: This was a descriptive study with 74 children with self-limited epilepsy with centrotemporal spikes, with the classical forms according to International League Against Epilepsy, and between 4 and 15 years of age, selected from the child neurology outpatient clinic of the Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, and 239 age-matched and educational level-matched (convenience sampling) control children. All children were submitted to the battery of oral volitional movements, which consisted of 44 tests for oral movement (tongue, lip, cheek, jaw, and palate) and 34 phonemes and consonant cluster tasks, with simple and sequenced oral movements. Results: The mean age and standard deviation (SD) of children with epilepsy was 9.08 years (SD 2.55) and of controls 9.61 years (SD 3.12). The results showed significant differences between the groups with a poorer performance of children with epilepsy compared to children without epilepsy in simple and particularly in sequenced movements. Conclusion: These findings can be attributed to the genetically determined immaturity of cortical structures related to motor planning in children with self-limited epilepsy with centrotemporal spikes.
RESUMO Antecedentes: Epilepsia autolimitada com descarga centrotemporal, previamente designada por epilepsia benigna focal infantil com espículas centrotemporais, mostra sinais clínicos de envolvimento de áreas rolândicas, principalmente área inferior, que podem afetar o planejamento e a execução de sequências motoras. Objetivo: Este estudo visou avaliar a práxis oral em crianças com epilepsia autolimitada com espículas centrotemporais e comparar com o grupo de controle de mesma idade e grau de escolaridade. Métodos: Tratou-se de um estudo descritivo, com 74 crianças com epilepsia autolimitada com espículas centrotemporais selecionadas no ambulatório de neurologia infantil do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, e 239 crianças do grupo controle da mesma faixa etária e grau de escolaridade. Todas as crianças foram submetidas à bateria de tarefas de movimento oral volitivo, que inclui movimentos orais simples e sequenciados. Resultados: A idade média das crianças com epilepsia era de 9,08 anos (desvio padrão - DP 2,55) e dos controles 9,61 anos (DP 3,12). Os resultados mostraram diferenças significativas entre os grupos, com desempenho mais fraco das crianças com epilepsia em comparação ao das crianças saudáveis, em movimentos simples e particularmente em movimentos sequenciados. Conclusão: Esses resultados podem ser atribuídos à imaturidade geneticamente determinada das estruturas corticais relacionadas com o planejamento motor em crianças com epilepsia autolimitada com espículas centrotemporais.
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Humanos , Criança , Apraxias , Epilepsia Rolândica , Brasil , Grupos Controle , EletroencefalografiaRESUMO
BACKGROUND: self-limited epilepsy with centrotemporal spikes, previously considered benign focal childhood epilepsy with centrotemporal spikes show clinical signs of involvement of Rolandic areas, mainly lower area, which may affect the planning and execution of motor sequences. OBJECTIVE: This study aimed to evaluated oral praxis in children with self-limited epilepsy with centrotemporal spikes and compare to the age-matched control group. METHODS: This was a descriptive study with 74 children with self-limited epilepsy with centrotemporal spikes, with the classical forms according to International League Against Epilepsy, and between 4 and 15 years of age, selected from the child neurology outpatient clinic of the Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, and 239 age-matched and educational level-matched (convenience sampling) control children. All children were submitted to the battery of oral volitional movements, which consisted of 44 tests for oral movement (tongue, lip, cheek, jaw, and palate) and 34 phonemes and consonant cluster tasks, with simple and sequenced oral movements. RESULTS: The mean age and standard deviation (SD) of children with epilepsy was 9.08 years (SD 2.55) and of controls 9.61 years (SD 3.12). The results showed significant differences between the groups with a poorer performance of children with epilepsy compared to children without epilepsy in simple and particularly in sequenced movements. CONCLUSION: These findings can be attributed to the genetically determined immaturity of cortical structures related to motor planning in children with self-limited epilepsy with centrotemporal spikes.
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Apraxias , Epilepsia Rolândica , Brasil , Criança , Grupos Controle , Eletroencefalografia , HumanosRESUMO
Cordotomy consists in the discontinuation of the lateral spinothalamic tract (LST) in the anterolateral quadrant of the spinal cord, which aims to reduce the transference of nociceptive information in the dorsal horn of the gray matter of the spinal cord to the somatosensory cortex. The main indication is for patients with terminal cancer that have a low life expectancy. It improves the quality of life by relieving pain. The results are promising and the pain relief rate varies between 69 and 100%. Generally speaking, the complications are mostly temporary and not remarkable.
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Tratos Espinotalâmicos/cirurgia , Vértebras Cervicais/patologia , Cordotomia/efeitos adversos , Dor do Câncer/cirurgia , Estudos Transversais , Cordotomia/métodos , Dor do Câncer/complicaçõesRESUMO
Objective: This study assessed the oxygen consumption [VO2 mL/(kg·min)], liking, and relative reinforcing (motivating) value (RRV) of a moderately physiologically challenging exergame [Nintendo Wii-Sports Boxing (Boxing)] versus a minimally challenging exergame [Nintendo Wii Lego Star Wars (Lego)]. Materials and Methods: VO2 and liking were recorded in children(N = 28, 7.8 ± 1.3 years old) during three 10-minute conditions: recumbent resting (Resting), and playing Wii Boxing or Wii Lego. Resting was completed first, and the order of exergames was randomized. Next, children performed an operant button pressing task using a progressive fixed ratio to assess the RRV of the two videogame conditions. Children worked to earn up to 11 minutes for Boxing, Lego, or a combination of the two. The output maximum (Omax) performed to earn access to each game was the measure of RRV. Results: There was a significant (P ≤ 0.03 for all conditions) step-wise increase in VO2 from Resting [4.3 ± 1.2 mL/(kg·min)] to Lego [5.3 ± 0.5 mL/(kg·min)] and from Lego to Boxing [11.7 ± 4.2 mL/(kg·min)]. Liking was significantly greater for Boxing (P = 0.003) and Lego (P < 0.0001, 7.1 ± 2.9 cm; 7.1 ± 2.7 cm, respectively) versus Resting (4.6 ± 3.8 cm), with no significant difference between Boxing and Lego (P = 0.358). Lastly, Omax was significantly (P = 0.021) greater for Lego (257.7 ± 390.6 presses) than for Boxing (51.7 ± 131.0 presses). Conclusion: Oxygen consumption during Wii Boxing was significantly greater than during Wii Lego. Despite this greater physiological challenge, liking was similar for both Lego and Boxing. However, children were more motivated to play Lego than Boxing.
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Terapia por Exercício/normas , Jogos de Vídeo/normas , Índice de Massa Corporal , Criança , Terapia por Exercício/métodos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Atividade Motora/fisiologia , Consumo de Oxigênio/fisiologia , Jogos de Vídeo/tendênciasRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are routinely used in advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, their use is associated with gastrointestinal and cutaneous toxicities, including acneiform eruptions, pruritus, xerosis, nail and hair changes. Aside from reducing patients' quality of life, such cutaneous reactions have a considerable impact on the oncologic treatment given that dose reduction or even drug discontinuation may be necessary, especially for the severe forms. OBJECTIVES: To assess the incidence, impact on treatment and management of EGFR inhibitor-related cutaneous reactions in patients with NSCLC. METHODS: We conducted a prospective observational study on 87 consecutive patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors from January to December 2019. Patients who developed mucocutaneous reactions were evaluated and treated by both oncologists and dermatologists, and underwent dermatologic follow-up until resolution of the cutaneous reaction. Demographic and clinical data were collected for each patient, and the severity of the cutaneous reaction was graded using the Common Terminology Criteria for Adverse Events. RESULTS: Seventy-one patients (81.6%) developed cutaneous reactions. The number of cutaneous reactions per patient was 1 in 37%, 2 in 41% and 3 or more in 22%. The most common cutaneous reactions included acneiform eruptions (56.3%), xerosis ± asteatotic eczema (48.3%), nail changes (39.1%), mucositis (29.9%), pruritus (24.1%) and hair changes (12.6%). Afatinib was associated with a higher rate of nail changes and mucositis (p < 0.01 and p < 0.005, respectively) compared to other agents, while no patient-related predictive factors were identified. Dose reduction was performed in 18% of patients. Multidisciplinary management involving dermatologists allowed to resume the drug in all patients who had discontinued it due to the cutaneous reactions. CONCLUSIONS: A multidisciplinary approach to EGFR inhibitor-related cutaneous reactions is advantageous and can reduce the need to discontinue oncologic treatment.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Toxidermias/epidemiologia , Receptores ErbB/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Acrilamidas/efeitos adversos , Idoso , Compostos de Anilina/efeitos adversos , Toxidermias/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Quinazolinas/efeitos adversosRESUMO
Resumo O presente estudo objetivou a busca de evidências científicas publicadas em estudos analíticos que versam sobre fatores de postergação da aposentadoria de trabalhadores idosos. Foi realizada uma revisão integrativa da literatura com busca de artigos originais nas bases da Biblioteca Virtual de Saúde e SciELO no período de janeiro/2009 a março/2018. Foram selecionados 12 artigos após consenso de revisores independentes gerando duas categorias: Literatura Nacional e Literatura Internacional. Tal escolha foi porque o fenômeno do envelhecimento populacional acarreta impactos sociais e econômicos diferentes entre as nações desenvolvidas e naquelas em desenvolvimento, como o Brasil. Na análise dos resultados encontramos que a decisão de aposentadoria dos idosos envolve uma variedade de fatores pessoais, organizacionais e outros (legislativos, culturais, sociopolíticos e tecnológicos). Em conclusão constatamos a escassez de estudos na temática com amostras exclusivasde idosos em ambas as categorias, assim como a maior ou menor relevância de determinado fator dependerá do contexto de vida de cada trabalhador. Além do mais, como a decisão de aposentadoria é um processo dinâmico, existe carência de estudos longitudinais que necessitam ser supridos com pesquisas mais robustas nacionais da população idosa.
Abstract This study aimed to search for scientific evidence published in analytical studies which address elderly workers' retirement postponement factors. An integrative literature review was performed searching for papers in Virtual Health Library (BVS) and SciELO databases from January 2009 to March 2018. Twelve papers were selected following consensus by independent reviewers, generating two categories: National Literature and International Literature. We chose this subject because the phenomenon of population aging entails different social and economic impacts between developed and developing nations, such as Brazil. In the analysis of the results, we found that elderly retirement decision involves a variety of personal, organizational and other factors (legislative, cultural, socio-political, technological). In conclusion, we note scarcity of studies on the subject, with exclusive samples of older adults in both categories, as well as that the greater or lesser relevance of a given factor will depend on the life context of each worker. Moreover, since retirement decision is a dynamic process, there is a shortage of longitudinal studies that need to be met with more robust national surveys of the elderly population.
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Humanos , Idoso , Aposentadoria , Envelhecimento , BrasilRESUMO
This study aimed to search for scientific evidence published in analytical studies which address elderly workers' retirement postponement factors. An integrative literature review was performed searching for papers in Virtual Health Library (BVS) and SciELO databases from January 2009 to March 2018. Twelve papers were selected following consensus by independent reviewers, generating two categories: National Literature and International Literature. We chose this subject because the phenomenon of population aging entails different social and economic impacts between developed and developing nations, such as Brazil. In the analysis of the results, we found that elderly retirement decision involves a variety of personal, organizational and other factors (legislative, cultural, socio-political, technological). In conclusion, we note scarcity of studies on the subject, with exclusive samples of older adults in both categories, as well as that the greater or lesser relevance of a given factor will depend on the life context of each worker. Moreover, since retirement decision is a dynamic process, there is a shortage of longitudinal studies that need to be met with more robust national surveys of the elderly population.
O presente estudo objetivou a busca de evidências científicas publicadas em estudos analíticos que versam sobre fatores de postergação da aposentadoria de trabalhadores idosos. Foi realizada uma revisão integrativa da literatura com busca de artigos originais nas bases da Biblioteca Virtual de Saúde e SciELO no período de janeiro/2009 a março/2018. Foram selecionados 12 artigos após consenso de revisores independentes gerando duas categorias: Literatura Nacional e Literatura Internacional. Tal escolha foi porque o fenômeno do envelhecimento populacional acarreta impactos sociais e econômicos diferentes entre as nações desenvolvidas e naquelas em desenvolvimento, como o Brasil. Na análise dos resultados encontramos que a decisão de aposentadoria dos idosos envolve uma variedade de fatores pessoais, organizacionais e outros (legislativos, culturais, sociopolíticos e tecnológicos). Em conclusão constatamos a escassez de estudos na temática com amostras exclusivasde idosos em ambas as categorias, assim como a maior ou menor relevância de determinado fator dependerá do contexto de vida de cada trabalhador. Além do mais, como a decisão de aposentadoria é um processo dinâmico, existe carência de estudos longitudinais que necessitam ser supridos com pesquisas mais robustas nacionais da população idosa.
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Envelhecimento , Aposentadoria , Idoso , Brasil , HumanosRESUMO
BackgroundNutritional derangements are common hallmarks of non-small-cell lung cancer (NSCLC). Nevertheless, their early detection is overlooked in clinical routine. This study aimed to evaluate nutritional status and its correlation with outcome in NSCLC patients.MethodsData regarding NSCLC patients undergoing nutritional evaluation were prospectively collected (May 2016-October 2018). Nutritional risk was assessed by Nutritional Risk Screening 2002 (NRS-2002). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography and changes were evaluated using Wilcoxon signed-rank test. Clinico-pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan-Meier curves were compared with log-rank test.ResultsThirty-eight patients were included. The majority (65.8%) of them were at nutritional risk (NRS-2002 ≥3). At multivariate analysis for patients with advanced disease, age (HR 2.44, p=0.05), performance status (HR 2.48, p=0.043) and NRS-2002 (HR 1.74, p=0.001) were significant independent predictors for PFS and weight loss (HR 1.07, p=0.008) for OS. Patients with baseline NRS-2002 <3 had significantly longer 1-year PFS (85.7% vs 19.4%, p=0.02) and higher ORR (66.7% vs 21.4%) than those with NRS-2002 ≥3. An explorative evaluation demonstrated that NRS-2002 score significantly decreased after nutritional intervention (p=0.001) for 3 months.ConclusionBaseline nutritional risk represents a prognostic factor in NSCLC. Nutritional counselling should be applied as a fundamental tool to improve nutritional risk in a short period, ameliorating patients' outcome.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment. MATERIALS AND METHODS: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy. Patients were randomized 1:1 to receive maintenance lanreotide 120 mg subcutaneously every 28 days, up to 1 year or progression versus observation. Randomization was stratified according to stage (limited/extended, LD/ED). The primary end-point was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. RESULTS: Seventy-one patients were randomly assigned (39 to lanreotide, 32 to observation) in 9 Italian institutions. Median PFS was 3.6 (95% CI 3.2-3.9) with lanreotide versus 2.3 months (95% CI 1.7-2.9) with observation (HR 1.51, 95% CI 0.90-2.50; P = 0.11). Stage was an independent predictor for PFS (HR 3.14, 95% CI 1.77-5.57; P < 0.0001). Median PFS was 7.0 (95% CI <1-13.5) with lanreotide versus 3.8 months (95% CI <1-8.6) with observation in LD (P = 0.21), and 3.0 (95% CI 2.2-3.8) versus 2.2 (95% 1.7-2.7) in ED (P = 0.19). Median OS was 9.5 (95% CI 4.8-14.3) with lanreotide versus 4.7 months (95% CI <1-16.6) with observation (P = 0.47). Treatment-related adverse events occurred in 28% of patients with lanreotide (grade 3 in two patients). CONCLUSION: Although survival outcomes were not significantly prolonged with lanreotide as a maintenance in SCLC expressing somatostatin receptors after response to standard treatment, lanreotide showed a slight PFS benefit in LD SCLC deserving further investigations.
Assuntos
Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Peptídeos Cíclicos/uso terapêutico , Receptores de Somatostatina/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Somatostatina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Somatostatina/administração & dosagem , Somatostatina/efeitos adversos , Somatostatina/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice. METHODS: MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous EGFR-mutant NSCLC. We reported treatment outcome in terms of median time to treatment failure (mTTF) and assessed the impact of each agent on the expense of the regional health system, comparing it with a prediction based on the pivotal trials. RESULTS: An EGFR mutation test was performed in 447 enrolled patients, of whom 124 had EGFR mutation and who received gefitinib (n = 69, 55%), erlotinib (n = 33, 27%), or afatinib (n = 22, 18%) as first-line treatment. Because erlotinib was administered within a clinical trial to 15 patients, final analysis was limited to 109 patients. mTTF was 15.3 months, regardless of the type of tyrosine kinase inhibitor (TKI) used. In the MOST study, the budget impact analysis showed a total expense of 3,238,602.17, whereas the cost estimation according to median progression-free survival from pivotal phase III trials was 1,813,557.88. CONCLUSION: Good regional adherence and compliance to the diagnostic-therapeutic pathway defined for patients with nonsquamous NSCLC was shown. mTTF did not significantly differ among the three targeted TKIs. Our budget impact analysis suggests the potential application of real-world data in the process of drug price negotiation. IMPLICATIONS FOR PRACTICE: The MOST study is a real-world data collection reporting a multicenter adherence and compliance to diagnostic-therapeutic pathways defined for patients with epidermal growth factor receptor-mutant non-small cell lung cancer. This represents an essential element of evidence-based medicine, providing information on patients and situations that may be challenging to assess using only data from randomized controlled trials, e.g., turn-around time of diagnostic tests, treatment compliance and persistence, guideline adherence, challenging-to-treat populations, drug safety, comparative effectiveness, and cost effectiveness. This study may be of interest to various stakeholders (patients, clinicians, and payers), providing a meaningful picture of the value of a given therapy in routine clinical practice.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Procedimentos Clínicos/estatística & dados numéricos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Afatinib/economia , Afatinib/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/genética , Análise Custo-Benefício , Procedimentos Clínicos/normas , Análise Mutacional de DNA/normas , Análise Mutacional de DNA/estatística & dados numéricos , Progressão da Doença , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib/economia , Cloridrato de Erlotinib/uso terapêutico , Feminino , Seguimentos , Gefitinibe/economia , Gefitinibe/uso terapêutico , Fidelidade a Diretrizes/normas , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/genética , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Mutação , Guias de Prática Clínica como Assunto , Intervalo Livre de Progressão , Estudos Prospectivos , Inibidores de Proteínas Quinases/economia , Fatores de Tempo , Falha de TratamentoRESUMO
OBJECTIVES: Brain metastases are common among patients with non-squamous non-small-cell lung cancer (NSCLC) and result in a poor prognosis. Consequently, such patients are often excluded from clinical trials. In Italy an expanded access program (EAP) was used to evaluate nivolumab efficacy and safety in this subpopulation outside a clinical trial. MATERIALS AND METHODS: In this EAP, nivolumab was available for patients with non-squamous NSCLC in progression after at least one systemic treatment for stage IIIB/IV disease. Nivolumab 3 mg/kg was administered intravenously every 2 weeks. Patients with brain metastases could be included if they were asymptomatic, neurologically stable and either off corticosteroids or on a stable or decreasing dose of ≤10 mg/day prednisone. RESULTS: 409 out of 1588 patients included had asymptomatic or controlled brain metastases. A median of 7 doses (range 1-45) were delivered. Median follow-up was 6.1 months (range 0.1-21.9). The disease control rate was 39%: 4 patients had a complete response, 64 a partial response and 96 showed stable disease. At baseline, 118 patients were on corticosteroids and 74 were undergoing concomitant radiotherapy. The median overall survival in this subpopulation was 8.6 months (95% CI: 6.4-10.8). 337 discontinued treatment for various reasons, 23 (7%) of whom due to adverse events, in line with that observed in the overall population and in previous studies. CONCLUSIONS: Our results confirm that nivolumab is active in non-squamous NSCLC patients with brain metastases, despite their poor prognosis. Its safety profile is also concordant with results in the EAP overall population and in patients with other malignancies.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Imunoterapia/métodos , Neoplasias Pulmonares/epidemiologia , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Progressão da Doença , Feminino , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES:: Never-smokers may be a distinct subgroup among patients with advanced non-small cell lung cancer, appearing to benefit less from immunotherapy than smokers. We report results from never-smokers enrolled in the Italian cohort of the nivolumab expanded access program in pre-treated patients with advanced squamous non-small cell lung cancer. MATERIALS AND METHODS:: Nivolumab (3 mg/kg every 2 weeks for ≤24 months) was available on physician request. Efficacy data included objective tumor response, date of progression, and survival information. Safety was monitored. RESULTS:: Overall, 371 patients received at least one dose of nivolumab, including 31 never-smokers (8%). Objective response rate, disease-control rate, and median overall survival were 23%, 45%, and 12.1 months (95% confidence interval: 3.7-20.4), respectively, in never-smokers, and 18%, 47%, and 7.9 months (95% confidence interval: 6.2-9.6), respectively, in the overall expanded access program population. Any-grade and grade 3-4 treatment-related adverse events were reported in 12 (39%) and 3 (10%) never-smokers, respectively, and in 109 (29%) and 21 (6%) patients, respectively, in the overall expanded access program population. Grade 3-4 treatment-related adverse events in non-smokers were increased transaminases (n = 2; 6%) and diarrhea (n = 1; 3%). Treatment-related adverse events led to treatment discontinuation in 4 non-smokers (17%) and in 26 patients (9%) overall. CONCLUSION:: Pre-treated never-smokers with advanced squamous non-small cell lung cancer in this Italian expanded access program demonstrated efficacy and safety that were consistent with those in the overall expanded access program population and clinical trials. These results suggest that a proportion of never-smoker patients with squamous non-small cell lung cancer may be responsive to immunotherapy. Other factors, such as the tumor mutational load and the status of programmed death-ligand 1, anaplastic lymphoma kinase, and epidermal growth factor receptor, might play a potential key role.