A Structural In Silico Analysis of the Immunogenicity of L-Asparaginase from Penicillium cerradense.

L-asparaginase is an essential drug used to treat acute lymphoid leukemia (ALL), a cancer of high prevalence in children. Several adverse reactions associated with L-asparaginase have been observed, mainly caused by immunogenicity and allergenicity. Some strategies have been adopted, such as searching for new microorganisms that produce the enzyme and applying protein engineering. Therefore, this work aimed to elucidate the molecular structure and predict the immunogenic profile of L-asparaginase from Penicillium cerradense, recently revealed as a new fungus of the genus Penicillium and producer of the enzyme, as a motivation to search for alternatives to bacterial L-asparaginase. In the evolutionary relationship, L-asparaginase from P. cerradense closely matches Aspergillus species. Using in silico tools, we characterized the enzyme as a protein fragment of 378 amino acids (39 kDa), including a signal peptide containing 17 amino acids, and the isoelectric point at 5.13. The oligomeric state was predicted to be a homotetramer. Also, this L-asparaginase presented a similar immunogenicity response (T- and B-cell epitopes) compared to Escherichia coli and Dickeya chrysanthemi enzymes. These results suggest a potentially useful L-asparaginase, with insights that can drive strategies to improve enzyme production.

European value-based healthcare benchmarking: moving from theory to practice.

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.

Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study. / Papel Incremental da Classificação da New York Heart Association e dos Índices do Teste de Exercício Cardiopulmonar para Prognóstico na Insuficiência Cardíaca: um Estudo de Coorte.

BACKGROUND: Central Illustration : Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study LVEF: left ventricular ejection fraction; HR: hazard ratio; CI: confidence interval; NYHA: New York Heart Association; VO 2: oxygen consumption. BACKGROUND: The accuracy of the New York Heart Association (NYHA) classification to assess prognosis may be limited compared with objective cardiopulmonary exercise test (CPET) parameters in heart failure (HF). OBJECTIVE: To investigate the prognostic value of the NYHA classification in addition to Weber class. METHODS: Adult outpatients with HF undergoing CPET in a Brazilian tertiary care center were included. The physician-assigned NYHA class and the CPET-derived Weber class were stratified into "favorable" (NYHA I or II; Weber A or B) or "adverse" (NYHA III or IV; Weber C or D). Patients with one favorable class and one adverse class were defined as "discordant." The primary endpoint was time to all-cause mortality. A 2-sided p value < 0.05 was considered statistically significant. RESULTS: A total of 834 patients were included. Median age was 57 years; 42% (351) were female, and median left ventricular ejection fraction was 32%. Among patients with concordant NYHA and Weber classes, those with adverse NYHA and Weber classes had significantly higher all-cause mortality compared to those with favorable classes (hazard ratio [HR]: 5.65; 95% confidence interval [CI]: 3.38 to 9.42). Among patients with discordant classes, there was no significant difference in all-cause mortality (HR: 1.38; 95% CI: 0.82 to 2.34). In the multivariable model, increments in NYHA class (HR: 1.55 per class increase; 95% CI: 1.26 to 1.92) and reductions in peak VO 2 (HR: 1.47 per 3 ml/kg/min decrease; 95% CI: 1.28 to 1.70) significantly predicted mortality. CONCLUSIONS: Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information for patients with HF.

Ovarian Real-World International Consortium (ORWIC): A multicentre, real-world analysis of epithelial ovarian cancer treatment and outcomes.

Introduction: Much drug development and published analysis for epithelial ovarian cancer (EOC) focuses on early-line treatment. Full sequences of treatment from diagnosis to death and the impact of later lines of therapy are rarely studied. We describe the establishment of an international network of cancer centers configured to compare real-world treatment pathways in UK, Portugal, Germany, South Korea, France and Romania (the Ovarian Real-World International Consortium; ORWIC). Methods: 3344 patients diagnosed with EOC (2012-2018) were analysed using a common data model and hub and spoke programming approach applied to existing electronic medical records. Consistent definition of line of therapy between sites and an efficient approach to analysis within the limitations of local information governance was achieved. Results: Median age of participants was 53-67 years old and 5-29% were ECOG >1. Between 62% and 84% of patients were diagnosed with late-stage disease (FIGO III-IV). Sites treating younger and fitter patients had higher rates of debulking surgery for those diagnosed at late stage than sites with older, more frail patients. At least 21% of patients treated with systemic anti-cancer therapy (SACT) had recurrent disease following second-line therapy (2L); up to 11 lines of SACT treatment were recorded for some patients. Platinum-based SACT was consistently used across sites at 1L, but choices at 2L varied, with hormone therapies commonly used in the UK and Portugal. The use (and type) of maintenance therapy following 1L also varied. Beyond 2L, there was little consensus between sites on treatment choice: trial compounds and unspecified combinations of other agents were common. Discussion: Specific treatment sequences are reported up to 4L and the establishment of this network facilitates future analysis of comparative outcomes per line of treatment with the aim of optimizing available options for patients with recurrent EOC. In particular, this real-world network can be used to assess the growing use of PARP inhibitors. The real-world optimization of advanced line treatment will be especially important for patients not usually eligible for involvement with clinical trials. The resources to enable this analysis to be implemented elsewhere are supplied and the network will seek to grow in coverage of further sites.

Functional assessment based on cardiopulmonary exercise testing in mild heart failure: A multicentre study.

AIMS: In this multicentre study, we compared cardio-pulmonary exercise test (CPET) parameters between heart failure (HF) patients classified as New York Heart Association (NYHA) class I and II to assess NYHA performance and prognostic role in mild HF. METHODS AND RESULTS: We included consecutive HF patients in NYHA class I or II who underwent CPET in three Brazilian centres. We analysed the overlap between kernel density estimations for the per cent-predicted peak oxygen consumption (VO2 ), minute ventilation/carbon dioxide production (VE/VCO2 ) slope, and oxygen uptake efficiency slope (OUES) by NYHA class. Area under the receiver-operating characteristic curve (AUC) was used to assess the capacity of per cent-predicted peak VO2 to discriminate between NYHA class I and II. For prognostication, time to all-cause death was used to produce Kaplan-Meier estimates. Of 688 patients included in this study, 42% were classified as NYHA I and 58% as NYHA II, 55% were men, and mean age was 56 years. Median global per cent-predicted peak VO2 was 66.8% (IQR 56-80), VE/VCO2 slope was 36.9 (31.6-43.3), and mean OUES was 1.51 (±0.59). Kernel density overlap between NYHA class I and II was 86% for per cent-predicted peak VO2 , 89% for VE/VCO2 slope, and 84% for OUES. Receiving-operating curve analysis showed a significant, albeit limited performance of per cent-predicted peak VO2 alone to discriminate between NYHA class I vs. II (AUC 0.55, 95% CI 0.51-0.59, P = 0.005). Model accuracy for probability of being classified as NYHA class I (vs. NYHA class II) across the spectrum of the per cent-predicted peak VO2 was limited, with an absolute probability increment of 13% when per cent-predicted peak VO2 increased from 50% to 100%. Overall mortality in NYHA class I and II was not significantly different (P = 0.41), whereas NYHA class III patients displayed a distinctively higher death rate (P < 0.001). CONCLUSIONS: Patients with chronic HF classified as NYHA I overlapped substantially with those classified as NYHA II in objective physiological measures and prognosis. NYHA classification may represent a poor discriminator of cardiopulmonary capacity in patients with mild HF.

Pertuzumab in Combination with Trastuzumab and Docetaxel in the Neoadjuvant Treatment for HER2-Positive Breast Cancer.

Introduction: This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods: Two consecutive retrospective cohorts (n = 94, 2012-2015 and 2015-2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012-2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015-2017 cohort was treated with the same protocol plus pertuzumab. Results: The 2012-2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015-2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion: Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

Direct healthcare cost of hospital admissions for chronic non-communicable diseases sensitive to primary care in the elderly. / Custo direto de internações hospitalares por doenças crônicas não transmissíveis sensíveis à atenção primária em idosos.

Aging has imposed changes in the epidemiological profile and an increase in the prevalence of chronic non-communicable diseases (CNCDs). The aim was to estimate the direct cost related to hospital admissions of elderly people affected by CNCDs (hypertension, heart failure and diabetes mellitus) sensitive to primary care, in a medium-sized hospital, in the period 2015-2019. Secondly, we investigated whether clinical and demographic factors explain the costs and length of stay. The medical records of 165 elderly people were analyzed. We found a predominance of women with a mean age of 76.9 years. The most frequent cause of hospitalization was heart failure (62%), and the average length of stay was 9.5 days, and 16% of hospitalizations corresponded to rehospitalizations. Of these, 81% were caused by complications from the previous hospitalization. The estimated total cost was R$ 3 million. Male patients had a longer hospital stay compared to female patients. Hypertension and the total number of procedures were significant predictors of cost and length of stay. We found that in 5 years, the costs of hospital admissions for conditions sensitive to primary care in the elderly are considerable, indicating the relevance of investments in primary care.

O envelhecimento tem imposto mudanças epidemiológicas e aumento na prevalência de doenças crônicas não-transmissíveis (DCNT). O objetivo foi estimar o custo direto relacionado às internações hospitalares de idosos acometidos por DCNT (hipertensão arterial, insuficiência cardíaca e diabetes mellitus) sensíveis à atenção primária, em hospital de médio porte, no período de 2015-2019. Secundariamente, investigamos se fatores clínicos e demográficos explicam o custo e tempo de permanência. Foram analisados prontuários de 165 idosos. Verificamos predominância de mulheres com média de idade de 76,9 anos. A causa de internação mais frequente foi insuficiência cardíaca (62%) e o tempo médio de permanência foi de 9,5 dias, e 16% das internações corresponderam a idosos reinternados. Dessas, 81% foram causadas por complicações da internação anterior. O custo total estimado foi de R$ 3 milhões. Pacientes do sexo masculino ficaram mais tempo internados, comparado ao sexo feminino. Hipertensão e o total de exames realizados foram preditores significantes do custo e tempo de permanência. Verificamos que em 5 anos, os custos com internações hospitalares por condições sensíveis à atenção primária em idosos são consideráveis, indicando a relevância de investimentos na atenção primária.

Custo direto de internações hospitalares por doenças crônicas não transmissíveis sensíveis à atenção primária em idosos / Direct healthcare cost of hospital admissions for chronic non-communicable diseases sensitive to primary care in the elderly

Resumo O envelhecimento tem imposto mudanças epidemiológicas e aumento na prevalência de doenças crônicas não-transmissíveis (DCNT). O objetivo foi estimar o custo direto relacionado às internações hospitalares de idosos acometidos por DCNT (hipertensão arterial, insuficiência cardíaca e diabetes mellitus) sensíveis à atenção primária, em hospital de médio porte, no período de 2015-2019. Secundariamente, investigamos se fatores clínicos e demográficos explicam o custo e tempo de permanência. Foram analisados prontuários de 165 idosos. Verificamos predominância de mulheres com média de idade de 76,9 anos. A causa de internação mais frequente foi insuficiência cardíaca (62%) e o tempo médio de permanência foi de 9,5 dias, e 16% das internações corresponderam a idosos reinternados. Dessas, 81% foram causadas por complicações da internação anterior. O custo total estimado foi de R$ 3 milhões. Pacientes do sexo masculino ficaram mais tempo internados, comparado ao sexo feminino. Hipertensão e o total de exames realizados foram preditores significantes do custo e tempo de permanência. Verificamos que em 5 anos, os custos com internações hospitalares por condições sensíveis à atenção primária em idosos são consideráveis, indicando a relevância de investimentos na atenção primária.

Abstract Aging has imposed changes in the epidemiological profile and an increase in the prevalence of chronic non-communicable diseases (CNCDs). The aim was to estimate the direct cost related to hospital admissions of elderly people affected by CNCDs (hypertension, heart failure and diabetes mellitus) sensitive to primary care, in a medium-sized hospital, in the period 2015-2019. Secondly, we investigated whether clinical and demographic factors explain the costs and length of stay. The medical records of 165 elderly people were analyzed. We found a predominance of women with a mean age of 76.9 years. The most frequent cause of hospitalization was heart failure (62%), and the average length of stay was 9.5 days, and 16% of hospitalizations corresponded to rehospitalizations. Of these, 81% were caused by complications from the previous hospitalization. The estimated total cost was R$ 3 million. Male patients had a longer hospital stay compared to female patients. Hypertension and the total number of procedures were significant predictors of cost and length of stay. We found that in 5 years, the costs of hospital admissions for conditions sensitive to primary care in the elderly are considerable, indicating the relevance of investments in primary care.

Deviations from a typical development of the cerebellum in youth are associated with psychopathology, executive functions and educational outcomes.

BACKGROUND: Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. METHODS: Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. RESULTS: Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. CONCLUSIONS: Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

Papel Incremental da Classificação da New York Heart Association e dos Índices do Teste de Exercício Cardiopulmonar para Prognóstico na Insuficiência Cardíaca: um Estudo de Coorte / Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study

Resumo Fundamento A precisão da classificação da New York Heart Association (NYHA) para avaliar o prognóstico pode ser limitada em comparação com os parâmetros objetivos do teste de exercício cardiopulmonar (TECP) na insuficiência cardíaca (IC). Objetivo Investigar o valor prognóstico da classificação da NYHA e da classe Weber. Métodos Foram incluídos pacientes ambulatoriais adultos com IC submetidos a TECP em um centro terciário brasileiro. A classe NYHA atribuída pelo médico e a classe Weber derivada do TECP foram estratificadas como "favorável" (NYHA I ou II com Weber A ou B) ou "adversa" (NYHA III ou IV com Weber C ou D). Pacientes com uma classe favorável e uma classe adversa foram definidos como "discordantes". O desfecho primário foi o tempo para mortalidade por todas as causas. Um valor de p bilateral < 0,05 foi considerado estatisticamente significativo. Resultados Foram incluídos 834 pacientes. A mediana de idade foi de 57 anos; 42% (351) eram do sexo feminino e a mediana da fração de ejeção do ventrículo esquerdo foi de 32%. Entre os pacientes com classes NYHA e Weber concordantes, aqueles com classes NYHA e Weber adversas tiveram mortalidade por todas as causas significativamente maior em comparação com aqueles com classes favoráveis ( hazard ratio [HR]: 5,65; intervalo de confiança de 95%: 3,38 a 9,42). Entre os pacientes com classes discordantes, não houve diferença significativa na mortalidade por todas as causas (HR: 1,38; intervalo de confiança de 95%: 0,82 a 2,34). No modelo multivariado, incrementos na classe NYHA (HR: 1,55 por aumento na classe; intervalo de confiança de 95%: 1,26 a 1,92) e reduções no VO 2 pico (HR: 1,47 por diminuição de 3 ml/kg/min; intervalo de confiança de 95%: 1,28 a 1,70) previu significativamente a mortalidade. Conclusões A classe NYHA atribuída pelo médico e as medidas objetivas do TECP fornecem informações prognósticas complementares para pacientes com IC.

Abstract Background The accuracy of the New York Heart Association (NYHA) classification to assess prognosis may be limited compared with objective cardiopulmonary exercise test (CPET) parameters in heart failure (HF). Objective To investigate the prognostic value of the NYHA classification in addition to Weber class. Methods Adult outpatients with HF undergoing CPET in a Brazilian tertiary care center were included. The physician-assigned NYHA class and the CPET-derived Weber class were stratified into "favorable" (NYHA I or II; Weber A or B) or "adverse" (NYHA III or IV; Weber C or D). Patients with one favorable class and one adverse class were defined as "discordant." The primary endpoint was time to all-cause mortality. A 2-sided p value < 0.05 was considered statistically significant. Results A total of 834 patients were included. Median age was 57 years; 42% (351) were female, and median left ventricular ejection fraction was 32%. Among patients with concordant NYHA and Weber classes, those with adverse NYHA and Weber classes had significantly higher all-cause mortality compared to those with favorable classes (hazard ratio [HR]: 5.65; 95% confidence interval [CI]: 3.38 to 9.42). Among patients with discordant classes, there was no significant difference in all-cause mortality (HR: 1.38; 95% CI: 0.82 to 2.34). In the multivariable model, increments in NYHA class (HR: 1.55 per class increase; 95% CI: 1.26 to 1.92) and reductions in peak VO 2 (HR: 1.47 per 3 ml/kg/min decrease; 95% CI: 1.28 to 1.70) significantly predicted mortality. Conclusions Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information for patients with HF.

Macrophages: key players in erythrocyte turnover

ABSTRACT The development of red blood cells (RBCs), or erythropoiesis, occurs in specialized niches in the bone marrow, called erythroblastic islands, composed of a central macrophage surrounded by erythroblasts at different stages of differentiation. Upon anemia or hypoxemia, erythropoiesis extends to extramedullary sites, mainly spleen and liver, a process known as stress erythropoiesis, leading to the expansion of erythroid progenitors, iron recruitment and increased production of reticulocytes and mature RBCs. Macrophages are key cells in both homeostatic and stress erythropoiesis, providing conditions for erythroid cells to survive, proliferate and differentiate. During RBCs aging and injury, macrophages play a fundamental role again, performing the clearance of these cells and recycling iron for new erythroblasts in development. Thus, macrophages are crucial components of the RBCs turnover and in this review, we aimed to cover the main known mechanisms involved in the process of birth and death of RBCs, highlighting the importance of macrophage functions in the whole RBC lifecycle.

Macrophages: key players in erythrocyte turnover.

The development of red blood cells (RBCs), or erythropoiesis, occurs in specialized niches in the bone marrow, called erythroblastic islands, composed of a central macrophage surrounded by erythroblasts at different stages of differentiation. Upon anemia or hypoxemia, erythropoiesis extends to extramedullary sites, mainly spleen and liver, a process known as stress erythropoiesis, leading to the expansion of erythroid progenitors, iron recruitment and increased production of reticulocytes and mature RBCs. Macrophages are key cells in both homeostatic and stress erythropoiesis, providing conditions for erythroid cells to survive, proliferate and differentiate. During RBCs aging and injury, macrophages play a fundamental role again, performing the clearance of these cells and recycling iron for new erythroblasts in development. Thus, macrophages are crucial components of the RBCs turnover and in this review, we aimed to cover the main known mechanisms involved in the process of birth and death of RBCs, highlighting the importance of macrophage functions in the whole RBC lifecycle.

Atitudes, conhecimento e interesse dos futuros profissionais em relação à geriatria: um estudo transversal / Attitudes, knowledge, and interest of future professionals towards geriatrics: a cross-sectional study / Actitudes, conocimientos e interés de los futuros profesionales hacia la geriatría: un estudio transversal

OBJETIVO: este estudo teve como objetivo analisar as atitudes, conhecimentos e interesse dos estudantes de saúde em relação à geriatria e gerontologia e avaliar suas associações. MÉTODO: participaram do estudo 225 estudantes do último ano dos cursos de Enfermagem, Medicina, Fonoaudiologia, Farmácia e Educação Física. Os questionários incluíram um formulário de características demográficas, a Escala de Diferencial Semântico de Envelhecimento e Questionário Palmore - Fatos sobre o envelhecimento. Foram utilizados modelos de regressão múltipla. RESULTADOS: a atitude em relação aos idosos foi negativa (50,67%) e associada ao menor interesse. O nível de conhecimento foi melhor entre os estudantes de Enfermagem, Medicina e estudantes mais velhos. O aumento do conhecimento se relacionou com a atitude e, no total, 71,43% apresentavam interesse em geriatria. O interesse esteve fortemente associado ao gênero feminino. CONCLUSÃO: os estudantes apresentaram um alto nível de conhecimento, interesse em geriatria e uma atitude negativa em relação aos cuidados geriátricos. Ações focadas na capacitação em geriatria devem ser implementadas.

OBJECTIVE: this study aimed to examine health students' attitudes, knowledge, and interest towards geriatrics and gerontology and evaluate associations. METHOD: a total of 225 students in the final year of Nursing, Medicine, Speech therapy, Pharmacy, and Physical education participated. The questionnaires included a characterization form, the Aging Semantic Differential Scale, and the Palmore Fact on Aging Quiz. Multiple regression models were used. RESULTS: the attitude towards older people was negative (50.67%) and associated with less interest. The level of knowledge was better among Nursing, Medicine, and older students. Increased knowledge was related to attitude and, in total, 71.43% were interested in geriatrics. Interest was strongly associated with female gender. CONCLUSION: students showed a high level of knowledge, interest in geriatrics, and a negative attitude towards geriatric care. Actions focused on geriatric training should be implemented.

OBJETIVO: este estudio tuvo como objetivo examinar las actitudes, los conocimientos y el interés de los estudiantes de salud hacia la geriatría y la gerontología y evaluar las asociaciones. MÉTODO: participaron un total de 225 estudiantes de los últimos años de cursos de Enfermería, Medicina, Fonoaudiología, Farmacia y Educación Física. Los cuestionarios incluían un formulario de caracterización, la Escala de Diferencial Semántico de Envejecimiento y el Cuestionario de Hechos sobre el Envejecimiento de Palmore. Se utilizaron modelos de regresión múltiple. RESULTADOS: la actitud hacia las personas mayores fue negativa (50,67%) y asociada a un menor interés. El nivel de conocimiento fue mejor entre los estudiantes de Enfermería, Medicina y de edad mayor. El aumento de conocimientos estuvo relacionado con la actitud, en total, el 71,43% estaba interesado en la geriatría. El interés estuvo fuertemente asociado con el género femenino. CONCLUSIÓN: los estudiantes mostraron un alto nivel de conocimiento, interés por la geriatría y una actitud negativa hacia la atención geriátrica. Deben implementarse acciones enfocadas a la formación geriátrica.

Recognition of Facial Expressions of Emotion and Depressive Symptoms among Caregivers with Different Levels of Empathy.

OBJECTIVES: To assess differences in the recognition of facial expressions of emotion among caregivers of older people with different levels of empathy. METHODS: A cross-sectional study was conducted with 158 caregivers of older adults who provided care in family residences or nursing homes. The caregivers were divided into three groups based on the score of the multidimensional Interpersonal Reactivity Index: "lower empathy", "intermediate empathy", and "higher empathy". Data collection involved the administration of a sociodemographic questionnaire, the Emotion Recognition Test, and the Patient Health Questionnaire. RESULTS: No significant differences were found among the groups in terms of sociodemographic variables. Regarding clinical characteristics, the "higher empathy" group had more depressive symptoms than the other groups (p = .001). Moreover, the "higher empathy" group exhibited greater accuracy at recognizing the expression of sadness than the "lower empathy" group (p = .033). The recognition of sadness remained significant in the analysis of variance adjusted for depressive symptoms (p < .05). CONCLUSIONS: Caregivers with higher levels of empathy showed greater accuracy at recognizing sadness emotion compared to caregivers with lower levels of empathy. Additionally, caregivers with greater empathy have more depressive symptoms. CLINICAL IMPLICATIONS: The recognition of facial expressions of sadness may give caregivers a skill to infer possible needs in older care recipients. However, a higher level of empathy may exert a negative psychological impact on caregivers of older people, which could have repercussions regarding the quality of care provided.

Depression and empathy in health professionals who work in the long-term care institutions for older adults.

Empathy is an important factor to guarantee the quality of care provided in the long-term care institutions (LTCIs) for older adults, and depression is a factor that affects the health of the professional and, consequently, the care. Thus, it is important that studies are conducted on the relationship of these variables in this context. OBJECTIVE: The aim of this study is to verify the relationship between empathy and depressive symptoms among health professionals working in the LTCIs. METHODS: A cross-sectional study was carried out at LTCIs in the state of São Paulo, Brazil. The final sample was constituted by 101 health professionals (i.e., caregivers and nursing technicians) with direct participation in the care of institutionalized older adults. The instruments were used as follows: the Interpersonal Reactivity Index (IRI) to assess empathy and the Patient Health Questionnaire-9 (PHQ-9) for the diagnosis of depression. For the analyses, the patients were divided into groups with and without depression, according to the score of the PHQ-9. RESULTS: The prevalence of depression among health professionals was 19.8%. Significant statistical differences were found between the groups for the total score of the IRI (p=0.029), for the emotional domain (p=0.023), and for the personal distress (p=0.009). CONCLUSIONS: The findings indicate that the presence of depression among health professionals at LTCIs is related to the higher levels of empathy, especially in the emotional domain. Thus, future studies that contribute to understanding how care must be provided with empathy, but without harming the health of the professional, should be carried out.

A empatia é um importante fator na garantia da qualidade do cuidado prestado em Instituições de Longa Permanência para Idosos (ILPIs), e a depressão é um fator que prejudica a saúde do profissional e, consequentemente, esse cuidado. Dessa forma, é importante que se realizem estudos sobre a relação dessas variáveis nesse contexto. OBJETIVO: Verificar a relação entre empatia e sintomas depressivos em profissionais de saúde de ILPIs. MÉTODOS: Estudo transversal, realizado em ILPIs no estado de São Paulo. A amostra final foi composta por 101 profissionais da saúde (cuidadores e técnicos de enfermagem), que participavam diretamente do cuidado de idosos institucionalizados. Os instrumentos utilizados foram: a Escala Multidimensional de Reatividade Interpessoal (EMRI) para avaliar empatia e o Patient Health Questionnaire-9 (PHQ-9) para o diagnóstico de depressão. Para as análises, os participantes foram divididos em grupos com e sem depressão, de acordo com a pontuação do PHQ-9. RESULTADOS: A prevalência de depressão entre os profissionais de saúde foi de 19,8%. Foram encontradas diferenças estatísticas significativas entre os grupos para a pontuação total do EMRI (p=0,029), para o domínio emocional (p=0,023) e angústia pessoal (p=0,009). CONCLUSÕES: Nossos achados apontam que a presença de depressão entre os profissionais de saúde de ILPIs está relacionada a maiores os níveis de empatia, principalmente no domínio emocional. Assim, pesquisas futuras que contribuam para entender como deve se dar o cuidado prestado com empatia, porém sem prejudicar a saúde do profissional, devem ser realizadas.

The addition of neoadjuvant pertuzumab for the treatment of HER2+ breast cancer: a cost estimate with real-world data.

BACKGROUND: Breast cancer (BC) is largely prevalent worldwide. HER2-positive BC account for roughly 20-25% of all BC cases and has an overall survival lower than other BC. Innovation on BC therapeutics is a constant, but novel therapies have higher costs. Therefore, cost-effectiveness research is essential to provide healthcare decision-makers with solid foundations for a resource allocation. This study aims to estimate the average direct medical costs/patient and cost-effectiveness of adding pertuzumab in neoadjuvant treatment (NeoT) for HER2-positive breast cancer (BC). METHODS: Two retrospective real-world consecutive cohorts of ≥18yo female patients diagnosed with HER2-positive BC treated with NeoT at the Breast Clinic of IPO-Porto were studied. The AC-DH regimen (2012-2015) comprised 8 cycles of neoadjuvant therapy (4 cycles of doxorubicin + cyclosphosphamide followed by 4 cycles ofdocetaxel + trastuzumab), while the AC-DHP regimen (2015-2017) included also pertuzumab as NeoT. NeoT was followed by surgery and adjuvant trastuzumab. Micro-costing technique and a bottom-up approach was used comprising all medical direct costs from the hospital perspective. Unit costs were obtained from government official prices or from IPO-Porto costing system. Costs were adjusted to 2017 and are expressed in euros. Multivariable logistic regression models were used for effectiveness assessment, while generalized linear models with gamma distribution were used for costs. ICER was calculated using the pathological complete response (pCR) as the preferential measure of effectiveness. Sensitivity analysis was also performed. RESULTS: AC-DHP (n = 40) and AC-DH (n = 54) cohorts had heterogenous patient profiles (median age 43y/53y; 67.5%/59.3% positive HR; 60.0%/27.8% operable; 25.0%/24.1% inflammatory, respectively). The AC-DHP average total cost/patient was 56,375€, with pertuzumab accounting for 13,978€ (24.79%) and increasing in 15,982€ the average cost/patient (p < 0.001). Clinical staging and hormone receptors (HR) were significantly associated with pCR. ICER was 1.370€ per percentage point of pCR. CONCLUSIONS: ICER was more favourable in stage III HR negative BC patients compared to other patient profiles. Innovative treatments access is critical to deliver high-quality healthcare, but sustainability must be considered. These results suggest the importance of establishing a cost-effectiveness profile of Pertuzumab in NeoT for HER2-positive BC.

Depression and empathy in health professionals who work in the long-term care institutions for older adults / Depressão e empatia em profissionais de saúde de Instituições de Longa Permanência para Idosos

ABSTRACT Empathy is an important factor to guarantee the quality of care provided in the long-term care institutions (LTCIs) for older adults, and depression is a factor that affects the health of the professional and, consequently, the care. Thus, it is important that studies are conducted on the relationship of these variables in this context. Objective: The aim of this study is to verify the relationship between empathy and depressive symptoms among health professionals working in the LTCIs. Methods: A cross-sectional study was carried out at LTCIs in the state of São Paulo, Brazil. The final sample was constituted by 101 health professionals (i.e., caregivers and nursing technicians) with direct participation in the care of institutionalized older adults. The instruments were used as follows: the Interpersonal Reactivity Index (IRI) to assess empathy and the Patient Health Questionnaire-9 (PHQ-9) for the diagnosis of depression. For the analyses, the patients were divided into groups with and without depression, according to the score of the PHQ-9. Results: The prevalence of depression among health professionals was 19.8%. Significant statistical differences were found between the groups for the total score of the IRI (p=0.029), for the emotional domain (p=0.023), and for the personal distress (p=0.009). Conclusions: The findings indicate that the presence of depression among health professionals at LTCIs is related to the higher levels of empathy, especially in the emotional domain. Thus, future studies that contribute to understanding how care must be provided with empathy, but without harming the health of the professional, should be carried out.

RESUMO A empatia é um importante fator na garantia da qualidade do cuidado prestado em Instituições de Longa Permanência para Idosos (ILPIs), e a depressão é um fator que prejudica a saúde do profissional e, consequentemente, esse cuidado. Dessa forma, é importante que se realizem estudos sobre a relação dessas variáveis nesse contexto. Objetivo: Verificar a relação entre empatia e sintomas depressivos em profissionais de saúde de ILPIs. Métodos: Estudo transversal, realizado em ILPIs no estado de São Paulo. A amostra final foi composta por 101 profissionais da saúde (cuidadores e técnicos de enfermagem), que participavam diretamente do cuidado de idosos institucionalizados. Os instrumentos utilizados foram: a Escala Multidimensional de Reatividade Interpessoal (EMRI) para avaliar empatia e o Patient Health Questionnaire-9 (PHQ-9) para o diagnóstico de depressão. Para as análises, os participantes foram divididos em grupos com e sem depressão, de acordo com a pontuação do PHQ-9. Resultados: A prevalência de depressão entre os profissionais de saúde foi de 19,8%. Foram encontradas diferenças estatísticas significativas entre os grupos para a pontuação total do EMRI (p=0,029), para o domínio emocional (p=0,023) e angústia pessoal (p=0,009). Conclusões: Nossos achados apontam que a presença de depressão entre os profissionais de saúde de ILPIs está relacionada a maiores os níveis de empatia, principalmente no domínio emocional. Assim, pesquisas futuras que contribuam para entender como deve se dar o cuidado prestado com empatia, porém sem prejudicar a saúde do profissional, devem ser realizadas.

Small cell lung cancer treatment and survival in Portugal: A retrospective analysis from the I-O Optimise initiative.

OBJECTIVE: We aim to describe treatment patterns and overall survival (OS) among a Portuguese cohort of patients with small cell lung cancer (SCLC). METHODS: This study utilised a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with SCLC at IPO-Porto between January 2012 and June 2017, with follow-up to December 2017, were included. Patients were stratified into subgroups with limited disease (LD) or extensive disease (ED). Treatment analyses were performed from 2015 onwards. RESULTS: Overall, 227 patients diagnosed with SCLC (37 LD; 190 ED) were analysed. Median OS (interquartile range [IQR]) was 15.0 months (3.8-39.3) for LD-SCLC and 5.0 months (1.7-10.3) for ED-SCLC. Among 19 patients diagnosed with LD-SCLC from 2015 onwards, 12 (63.2%) received initial treatment with systemic anticancer therapy (SACT) ± radiotherapy; 6 (31.6%) received best supportive care (BSC). Among 89 patients with ED-SCLC, 57 (68.5%) received SACT ± palliative radiotherapy; 28 (31.5%) received BSC. For patients receiving platinum doublet chemotherapy (±radiotherapy), median OS (IQR) was not reached for LD-SCLC and 5.4 months (2.3-10.9) for ED-SCLC. CONCLUSION: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for patients diagnosed with SCLC, particularly those with ED, and highlights a need for more effective therapies.

Treatment and outcomes for early non-small-cell lung cancer: a retrospective analysis of a Portuguese hospital database.

AIM: This observational study evaluated treatment patterns and survival for patients with stage I-IIIA non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: Adults newly diagnosed with NSCLC in 2012-2016 at IPO-Porto hospital were included. Treatment data were available for patients diagnosed in 2015-2016. RESULTS: 495 patients were included (median age: 67 years). The most common treatments were surgery alone or with another therapy (stage I: 66%) and systemic anticancer therapy plus radiotherapy (stage II: 54%; stage IIIA: 59%). One-year OS (95% CI) for patients with stage I, II and IIIA NSCLC (diagnosed 2012-2016) were 92% (88-96), 71% (62-82) and 69% (63-75), respectively; one-year OS (95% CI) for treated patients with stage I-II or stage IIIA NSCLC (diagnosed 2015-2016) were 89% (81-97) and 86% (75-98) for non-squamous cell and 76% (60-95) and 49% (34-70) for squamous cell NSCLC. CONCLUSION: Treatment advances are strongly needed for stage I-IIIA NSCLC, especially for patients with squamous cell histology.

Comparing the cost of non-metastatic breast cancer care in a low-income vs a high-income country: A plea for an optimal allocation of health resources in Sub-Saharan Africa.

Breast cancer incidence is rising in low-income countries, but there is limited information regarding health resource allocation for its care. We assessed the cost of care during the first three years after diagnosis in a low-income country (Mozambique; n = 162 women) and compared it with a high-income country (Portugal, n = 703 women). Local currency prices were converted to 2019 international dollars (Int$). In Mozambique, the median cost was lower than in Portugal (2888 vs 18,533 Int$, respectively) and did not vary across stage or tumor subtype. These findings may help improving resource allocation for breast cancer care in Sub-Saharan Africa, despite reflecting an underfunding of treatment in this setting.