Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors).

BACKGROUND: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. METHODS: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. RESULTS: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. CONCLUSIONS: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors)

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

A Bayesian approach for the zero-inflated cure model: an application in a Brazilian invasive cervical cancer database.

This paper aims to discuss the Bayesian estimation approach for the zero-inflated cure class of models, which extends the standard cure model by accommodating zero-inflated data in the survival analysis context. A comprehensive simulation study is carried out to assess the performance of the estimation procedure. A new estimation methodology is illustrated using a real dataset related to women diagnosed with invasive cervical cancer in Brazil.

Impact of a dental care intervention on the hospital mortality of critically ill patients admitted to intensive care units: A quasi-experimental study.

BACKGROUND: We aimed to evaluate the impact of providing dental care to critically ill patients on their risk of death and ventilator-associated pneumonia (VAP). METHODS: A quasi-experimental study was conducted in 2 intensive care units (ICU) from 2016 to 2019. The intervention consisted of implementing routine dental care, focusing on oral hygiene and periodontal treatment, at least 3 times a week, for patients admitted to the study units. In the pre-intervention period, routine oral hygiene was provided by the ICU nursing staff. The primary and secondary study outcomes were mortality, evaluated at the end of the ICU stay, and VAP incidence density, respectively. Data were analyzed using the ARIMA (autoregressive integrated moving average) time series model in R software. RESULTS: During the intervention period, 5,147 dental procedures were performed among 355 patients. The time series showed that ICU mortality was 36.11%, 32.71%, and 32.30% within the 3 years before the intervention, and 28.71% during the intervention period (P = .015). VAP incidence density did not significantly change during the study period (P = .716). CONCLUSION: A dental care intervention focused on oral hygiene and periodontal treatment regularly provided by dentists to critically ill patients may decrease their risk of dying in the ICU. Randomized clinical trials should be performed to confirm these findings. TRIAL REGISTRATION: WHO-affiliated Brazilian Clinical Trials Registry. RBR-4jmz36. Registered 7 October 2018, before first patient enrollment.

Effects of a mindfulness-based intervention on the functional status and mindfulness of primary health care professionals: a before and after study

Abstract Background Contextual factors involving the physical and social environment, as well as personal factors, are closely related to functional status, and they can have positive or negative influences on the health conditions or status of an individual in society. Objectives The objective is to evaluate the effect of a mindfulness-based intervention program on functional status and mindfulness levels in primary health care (PHC) professionals in Ribeirão Preto, Brazil. Methods This is a quasi-experimental study, with 26 PHC professionals, using quantitative methods and an analytical before and after approach of an 8-week mindfulness program. Results There were significant differences in mindfulness facets after the intervention: Observe (p = 0.002); Describe - positive formulation (p = 0.01); Acting with awareness - automatic pilot (p = 0.01) and distraction (p = 0.05); Nonreactivity (p = 0.0005); Nonjudgement (p = 0.01); and in total mindfulness scores (p = 0.0000018). Regarding functional status, significant differences were found: change in health (p = 0.01), overall health (p = 0.007), quality of life (p = 0.04) and feelings (p = 0.01). Discussion The results in improving the functional status and mindfulness of PHC professionals show that mindfulness practices can improve the worker's quality of life and health.

Is it necessary to have a dentist within an intensive care unit team? Report of a randomised clinical trial.

OBJECTIVE: To evaluate the effectiveness of dental treatment in improving oral health in critical patients. METHODS: This randomised clinical trial was conducted in a general intensive care unit (ICU) at a tertiary care public facility from 1 January 2011 to 8 August 2013. Data from 254 adult patients staying in the ICU for 48 hours or more were analysed. The experimental group (n = 127) had access to dental treatment provided by a dentist four to five times a week, in addition to routine oral hygiene, whereas the control group (n = 127) had access only to routine oral hygiene, including topical application of chlorhexidine, provided by the ICU nursing staff. The baseline oral health status of the enrolled patients was poor and included edentulism, caries, gingivitis, periodontitis and residual roots. Dental treatment consisted of toothbrushing, tongue scraping, removal of calculus, scaling and root planing, caries restoration and tooth extraction. RESULTS: The Oral Hygiene Index Simplified (OHI-S) and Gingival Index (GI) scores decreased in the experimental group but did not change significantly in the control group during the ICU stay. Dental treatment prevented most of the episodes of respiratory tract infections, as previously reported. No severe adverse events from the dental treatment were observed. CONCLUSION: From an interprofessional perspective, our results support the idea of including dentists in the ICU team to improve oral health in critical patients and effectively prevent respiratory tract infections, in addition to the improvement achievable by applying chlorhexidine alone.

On the comparison of risk of death according to different stages of breast cancer via the long-term exponentiated Weibull hazard model.

Long-term survivor models have been extensively used for modelling time-to-event data with a significant proportion of patients who do not experience poor outcome. In this paper, we propose a new long-term survivor hazard model, which accommodates comprehensive families of cure rate models as particular cases, including modified Weibull, exponentiated Weibull, Weibull, exponential and Rayleigh distribution, among others. The maximum likelihood estimation procedure is presented. A simulation study evaluates bias and mean square error of the considered estimation procedure as well as the coverage probabilities of the parameters asymptotic and bootstrap confidence intervals. A real Brazilian dataset on breast cancer illustrates the methodology. From the practical point of view, under our modelling, we provide a parameter that works as a metric to quantify and compare the risk between different stages of the disease. We emphasize that, we developed an online platform for oncologists to calculate the probability of survival of patients diagnosed with breast cancer according to the stage of the disease in real time.

Reproducibility for Heart Rate Variability Analysis during 6-Min Walk Test in Patients with Heart Failure and Agreement between Devices.

Heart rate variability (HRV) analysis is a useful method to assess abnormal functioning in the autonomic nervous system and to predict cardiac events in patients with heart failure (HF). HRV measurements with heart rate monitors have been validated with an electrocardiograph in healthy subjects but not in patients with HF. We explored the reproducibility of HRV in two consecutive six-minute walk tests (6MW), 60-minute apart, using a heart rate monitor (PolarS810i) and a portable electrocardiograph (called Holter) in 50 HF patients (mean age 59 years, NYHA II, left ventricular ejection fraction ~35%). The reproducibility for each device was analysed using a paired t-test or the Wilcoxon signed-rank test. Additionally, we assessed the agreement between the two devices based on the HRV indices at rest, during the 6MW and during recovery using concordance correlation coefficients (CCC), 95% confidence intervals and Bland-Altman plots. The test-retest for the HRV analyses was reproducible using Holter and PolarS810i at rest but not during recovery. In the second 6MW, patients showed significant increases in rMSSD and walking distance. The PolarS810i measurements had remarkably high concordance correlation [0.86

Reproducibility for heart rate variability analysis during 6-Min walk test in patients with heart failure and agreement between devices

Heart rate variability (HRV) analysis is a useful method to assess abnormal functioning in the autonomic nervous system and to predict cardiac events in patients with heart failure (HF). HRV measurements with heart rate monitors have been validated with an electrocardiograph in healthy subjects but not in patients with HF. We explored the reproducibility of HRV in two consecutive six-minute walk tests (6MW), 60-minute apart, using a heart rate monitor (PolarS810i) and a portable electrocardiograph (called Holter) in 50 HF patients (mean age 59 years, NYHA II, left ventricular ejection fraction ~35%). The reproducibility for each device was analysed using a paired t-test or the Wilcoxon signed-rank test. Additionally, we assessed the agreement between the two devices based on the HRV indices at rest, during the 6MW and during recovery using concordance correlation coefficients (CCC), 95% confidence intervals and Bland-Altman plots. The test-retest for the HRV analyses was reproducible using Holter and PolarS810i at rest but not during recovery. In the second 6MW, patients showed significant increases in rMSSD and walking distance. The PolarS810i measurements had remarkably high concordance correlation [0.86

[Validation of Body Image Relationship Scale for women with breast cancer]. / Validação do Body Image Relationship Scale para mulheres com câncer de mama.

PURPOSE: To validate the instrument Body Image Relationship Scale (BIRS) for Brazilian women with breast cancer. METHODS: The instrument was administered by trained interviewers to 139 women who used the Brazilian Unified Health System (SUS). All of them had been submitted to cancer treatments between 2006 and 2010. The instrument was validated considering internal consistency and reliability. In order to compare the techniques, the same factorial analysis as used in the original paper was carried out. RESULTS: The Spearman-Brown correlation value was 0.8, indicating high internal reliability. The Cronbach's alpha found was 0.9, indicating a high level of internal consistency. Factorial analysis showed that four items had low factorial load and no discriminatory power, and another five items were relocated to other factors. When the instrument was applied, it showed variability to that of the original instrument. CONCLUSION: The Brazilian version of the Body Image Relationship Scale (BIRS), named Escala de Relacionamento e Imagem Corporal (ERIC), showed evidence of adequate reliability and internal consistency, making this instrument suitable to be recommended for application to Brazilian women with breast cancer, despite some limitations.

Validação do Body Image Relationship Scale para mulheres com câncer de mama / Validation of Body Image Relationship Scale for women with breast cancer

ResumoOBJETIVOValidar o instrumento Body Image Relationship Scale (BIRS) em mulheres brasileiras acometidas pelo câncer de mamaMÉTODOSO instrumento foi aplicado por entrevistadoras treinadas em 139 usuárias do Sistema Único de Saúde que foram submetidas aos tratamentos do câncer entre 2006 e 2010. O instrumento foi aferido considerando-se a consistência interna e a confiabilidade. Para efeito de comparação as técnicas de análise fatorial utilizadas no artigo original foram aplicadasRESULTADOSO valor de correlação Spearman-Brown foi 0,8, o que indica alto nível de confiabilidade, e o alfa de Cronbach encontrado foi 0,9, indicando alto nível de consistência interna. A análise fatorial mostrou que quatro questões não tinham poder discriminatório e carga fatorial baixa e outras cinco foram realocadas em outros domínios. Dessa forma, foi aplicada e mostrou variabilidade semelhante ao instrumento originalCONCLUSÃOA versão brasileira do BIRS, renomeada como Escala de Relacionamento e Imagem Corporal (ERIC), apresentou evidências de adequada confiabilidade e consistência interna, o que torna esse instrumento recomendável para aplicação em mulheres brasileiras com câncer de mama, apesar de alguns poucos limites.

AbstractPURPOSETo validate the instrument Body Image Relationship Scale (BIRS) for Brazilian women with breast cancerMETHODSThe instrument was administered by trained interviewers to 139 women who used the Brazilian Unified Health System (SUS). All of them had been submitted to cancer treatments between 2006 and 2010. The instrument was validated considering internal consistency and reliability. In order to compare the techniques, the same factorial analysis as used in the original paper was carried outRESULTSThe Spearman-Brown correlation value was 0.8, indicating high internal reliability. The Cronbach's alpha found was 0.9, indicating a high level of internal consistency. Factorial analysis showed that four items had low factorial load and no discriminatory power, and another five items were relocated to other factors. When the instrument was applied, it showed variability to that of the original instrumentCONCLUSIONThe Brazilian version of the Body Image Relationship Scale (BIRS), namedEscala de Relacionamento e Imagem Corporal (ERIC), showed evidence of adequate reliability and internal consistency, making this instrument suitable to be recommended for application to Brazilian women with breast cancer, despite some limitations.

[Reproductive and sexual history of women treated of breast cancer]. / História reprodutiva e sexual de mulheres tratadas de câncer de mama.

PURPOSE: To understand the reproductive and sexual life of women treated for breast cancer. METHODS: A total of 139 women with a diagnosis made at least 6 months ago were interviewed after being randomly selected in a rehabilitation service. The interviews were carried out between 2006 and 2010. The inclusion criteria were: to have used a rehabilitation service between 2006 and 2010, to be a Unified Health System user, to have been a patient at a regional hospital and to be resident in the area of DRS XIII-Ribeirão Preto, state of São Paulo. The interviewees were visited at home where a face to face questionnaire regarding sociodemographic features and questions about the disease and reproductive and sexual life was administered. For the last one, the Female Sexual Function Index instrument was used. Data were analyzed statistically by the χ² test, Fisher exact test, Student's t test, multivariate analysis by logistic regression, factorial analysis and the Cronbach's alpha. RESULTS: Most patients had between 2 to 3 children and 80% used some contraceptive. About half of them had had sexual intercourse in the last month, 45.3% had interrupted sexual intercourse during treatment and 25.9% did not. There were reports of decreasing sexual activity, although half of the interviewees had re-started sexual life during the first six months after treatment. About half presented sexual dissatisfaction. An active sexual life is associated with being younger than 40 years of age and to have a partner. No association was found between active sexual life and diagnosis and types of treatment. CONCLUSION: Sexual activity of women treated for breast cancer is not associated with the treatments, but with age and with the opportunity of having sex.

História reprodutiva e sexual de mulheres tratadas de câncer de mama / Reproductive and sexual history of women treated of breast cancer

OBJETIVO: Compreender a vida sexual e reprodutiva de mulheres tratadas de câncer de mama. MÉTODOS: Foram entrevistadas 139 mulheres com diagnóstico há pelo menos seis meses, selecionadas aleatoriamente em um serviço de reabilitação. As entrevistas foram feitas entre 2006 e 2010. Todas eram usuárias do SUS, pacientes de um hospital regional e moradoras da região DRS XIII-Ribeirão Preto, Estado de São Paulo. As entrevistadas foram visitadas em seu domicílio onde foi aplicado um questionário face a face que abordava questões relativas às características sociodemográficas, da doença e da vida reprodutiva e sexual, para esta última aplicou-se o instrumento Índice de Função Sexual Feminina (IFSF). A análise estatística incluiu o teste do χ², o teste exato de Fisher e o teste t de Student, análise multivariada por regressão logística e análise fatorial e alfa de Cronbach. RESULTADOS: A maioria teve entre 2 e 3 filhos e 80% utilizaram algum método anticoncepcional. Cerca de metade das mulheres tiveram relação sexual no último mês, 45,3% interromperam as relações sexuais durante o tratamento e 25,9% não interromperam. Houve relato de diminuição da frequência sexual, embora metade das entrevistadas tenha retomado a vida sexual nos primeiros seis meses após o tratamento. Pouco mais de metade apresentou insatisfação sexual. Encontrou-se vida sexual ativa associada à idade menor que 40 anos e a ter parceiro. Não foi encontrada associação entre vida sexual ativa e ao diagnóstico e tipos de tratamento. CONCLUSÃO: A atividade sexual de mulheres tratadas para câncer de mama não está associada aos tratamentos, mas à idade e à oportunidade de ter sexo.

PURPOSE: To understand the reproductive and sexual life of women treated for breast cancer. METHODS: A total of 139 women with a diagnosis made at least 6 months ago were interviewed after being randomly selected in a rehabilitation service. The interviews were carried out between 2006 and 2010. The inclusion criteria were: to have used a rehabilitation service between 2006 and 2010, to be a Unified Health System user, to have been a patient at a regional hospital and to be resident in the area of DRS XIII-Ribeirão Preto, state of São Paulo. The interviewees were visited at home where a face to face questionnaire regarding sociodemographic features and questions about the disease and reproductive and sexual life was administered. For the last one, the Female Sexual Function Index instrument was used. Data were analyzed statistically by the χ² test, Fisher exact test, Student's t test, multivariate analysis by logistic regression, factorial analysis and the Cronbach's alpha. RESULTS: Most patients had between 2 to 3 children and 80% used some contraceptive. About half of them had had sexual intercourse in the last month, 45.3% had interrupted sexual intercourse during treatment and 25.9% did not. There were reports of decreasing sexual activity, although half of the interviewees had re-started sexual life during the first six months after treatment. About half presented sexual dissatisfaction. An active sexual life is associated with being younger than 40 years of age and to have a partner. No association was found between active sexual life and diagnosis and types of treatment. CONCLUSION: Sexual activity of women treated for breast cancer is not associated with the treatments, but with age and with the opportunity of having sex.

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma.

BACKGROUND: KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes. METHODS: Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status. RESULTS: KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients. CONCLUSION: The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.