O impacto da COVID-19 na população idosa com doença pulmonar crônica não transmissível / The impact of COVID-19 on the elderly population with non-communicable chronic lung disease

Introdução: Envelhecer resulta em transformações biológicas que afetam os indivíduos de maneira heterogênea. A maioria dos sistemas orgânicos experimenta redução em suas funções motoras e cognitivas, interferindo na capacidade de adaptação frente a agentes estressores. Na pneumonia pelo SARS-CoV2, evidenciaram-se implicações da função pulmonar em idosos com doenças pulmonares crônicas. Objetivo: Investigar as evidências científicas sobre implicações clínicas da COVID-19 em indivíduos idosos com doença pulmonar crônica não transmissível. Métodos: revisão integrativa realizada em novembro de 2020 nas bases de dados CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase, Scopus, Medline/Pubmed (via National Library of Medicine) e Web of Science, utilizando-se os descritores "COVID-19", "SARS-CoV2 infection", "aged", "chronic pulmonar obstructive disease", "non-communicable diseases" e operadores booleanos AND e OR. Foram incluídos textos científicos originais, a exemplo de artigos disponibilizados na íntegra, sobre a COVID-19 em idosos com Doenças Respiratórias Crônicas Não Transmissíveis. Resultados: Idosos com comorbidades estão propensos a complicações durante a infecção por COVID-19, com altas taxas de mortalidade e alterações tomográficas atípicas. Conclusão: A forma grave da COVID-19 e a elevada mortalidade em idosos podem ser atribuídas à alta comorbidade, prevalência de demência e síndromes geriátricas. (AU)

Safety and preliminary immunogenicity of JNJ-64041809, a live-attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer.

BACKGROUND: The safety and immunogenicity of JNJ-64041809 (JNJ-809), a live-attenuated, double-deleted Listeria monocytogenes (LADD Lm)-based immunotherapy targeting 4 relevant prostate cancer antigens, was evaluated in a phase 1 study in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Men with progressive mCRPC who had received ≥2 prior approved therapies were enrolled. Primary study objectives were to determine the recommended phase 2 dose (RP2D) and to evaluate the safety and immunogenicity of JNJ-809. RESULTS: A total of 26 patients received JNJ-809 (1 × 108 CFU (n = 6); 1 × 109 CFU (n = 20)). No dose-limiting toxicities were reported, and 1 × 109 CFU was selected as the RP2D. The most common adverse events (AEs) reported were chills (92%), pyrexia (81%), and fatigue (62%). The most frequent grade ≥3 AEs were lymphopenia (27%) and hypertension (23%). Serious AEs were reported in 27% of patients including 1 patient with grade 3 intestinal obstruction. JNJ-809 transiently induced peripheral cytokines, including interferon-γ, interleukin-10, and tumor necrosis factor-α. Of the 7 patients evaluable for T cell responses at the 1 × 109 CFU dose, evidence of post-treatment antigenic responses were observed in 6 to the Listeria antigen listeriolysin O and in 5 to ≥1 of the 4 encoded tumor antigens. Best overall response was stable disease in 13/25 response-evaluable patients. The study was terminated early as data collected were considered sufficient to evaluate safety and immunogenicity. CONCLUSIONS: JNJ-809 has manageable safety consistent with other LADD Lm-based therapies. Limited antigen-specific immune responses were observed, which did not translate into objective clinical responses.

Alta hospitalar qualificada e orientações multidisciplinares aos pacientes idosos com COVID-19: revisão integrativa / Hospital discharge and multidisciplinary guidelines for elderly patients with COVID-19: integrative review

Resumo Objetivo buscar as evidências científicas disponíveis sobre orientações multidisciplinares ofertadas por profissionais da saúde aos pacientes idosos diagnosticados com a COVID-19 após a alta hospitalar. Método revisão integrativa da literatura realizada por meio das bases de dados/biblioteca virtual selecionadas para o desenvolvimento da pesquisa: Lilacs, MEDLINE/Pubmed, Scopus e CINAHL (EBSCO). Para a realização da busca foram utilizadas combinações com os seguintes Descritores em Ciência da Saúde (DeCS) e Medical Subject Headings (Mesh): Idoso (Aged); COVID-19; Cuidados Posteriores (Aftercare) e Alta do Paciente (Patient Discharge) combinados por meio dos operadores booleanos "AND" e "OR". Resultados foram identificadas referências entre janeiro de 2019 a janeiro de 2022 e recuperados quatro artigos para inclusão e análise desta pesquisa. As publicações selecionadas abordaram a temática da continuidade do cuidado com a perspectiva de intervenção em reabilitação à saúde e gerenciamento de sintomas e/ou supervisão da recuperação funcional da pessoa idosa, sendo tais orientações realizadas por equipe interprofissional. Conclusão evidenciou-se a escassez de publicações sobre a temática de orientações fornecidas pela equipe de assistência à saúde às pessoas idosas na perspectiva da alta hospitalar, bem como a importância e necessidade de futuras produções científicas em torno do impacto funcional decorrentes da COVID-19 nesta população, desde o momento da admissão hospitalar até o pós-alta no retorno para casa, subsidiada por ações estratégicas ou protocolos institucionais que viabilizem informações educativas para a preparação de uma alta hospitalar pautada no autocuidado, valorização do bem-estar e qualidade de vida das pessoas idosas.

Abstract Objective to search for available scientific evidence on multidisciplinary guidelines offered by health professionals to older patients diagnosed with COVID-19 after hospital discharge. Method an integrative literature review was carried out on the databases/virtual library selected: Lilacs, MEDLINE/Pubmed, Scopus and CINAHL (EBSCO). The search strategy involved use of combinations with the following Health Science Descriptors (DeCS) and Medical Subject Headings (Mesh): Elderly (Aged); Covid-19; Aftercare and Patient Discharge combined using Boolean operators "AND" and "OR". Results relevant articles published between January 2019 and January 2022 were identified, of which four were retrieved for inclusion and analysis. The selected studies addressed the theme of continuity of care with the perspective of intervention in health rehabilitation and symptom management and/or supervision of the functional recovery of older patients, with guidelines devised by an interprofessional team. Conclusion the study revealed the scarcity of publications on the topic of guidance provided by health care teams to older patients from the perspective of hospital discharge. The study also served to highlight the importance and need for future scientific output addressing the functional impact of COVID-19 on this population, from hospital admission to post-discharge at home, supported by strategic actions or institutional protocols that disseminate educational information preparing patients for hospital discharge and promoting self-care, well-being and quality of life of older people.

Perfil epidemiológico dos usuários atendidos em centro de atenção psicossocial, álcool e drogas, em uma capital do nordeste brasileiro / Epidemiological profile of users served in Psychosocial Care Center, alcohol and drugs, in a capital of northeast Brazil / Perfil epidemiológico de usuarios servidos en Centro de Atención Psicosocial, alcohol y drogas, en uma capital del noreste de Brasil

Introdução:O uso de álcool e drogas é um problema crescente no Brasil e no mundo. Conhecer a epidemiologia dessa população nos serviços de atendimento aos usuários de substâncias psicoativas é um imperativo para melhor trata-los.Objetivo:descrever o perfil epidemiológico dos usuários de um Centro de Atenção Psicossocial Álcool e Drogas no Nordeste do Brasil. Metodologia:estudo descritivo, transversal, quantitativo. Por meio de planilha eletrônica, foram analisados os 281 prontuários de todas as pessoas maiores de 18 anos que utilizavam o serviço. Foi empregado o teste de qui-quadrado considerando o fator de p significativo menor ou igual a 0,05. O estudo foi aprovado eticamente.Resultados:homens, média de 42,06 anos, com nível fundamental de escolaridade e casados, formavam a maior parte da amostra. Foram estatisticamente relevantes: o maior consumo de álcool nos homens (p=0,03); maior escolaridade nos usuários de cocaína (p=0,013); maior tabagismo nos menos escolarizados (p=0,017); prole como proteção ao uso de cocaína (p=0,0006) e cannabis (p=0,0004); não ter filhos com menos uso de álcool (p=0,0015); uso precoce de cannabis (p=0,0002) e álcool (p=0,0065). Conclusões:perfis epidemiológicos em centros especializados podem nortear políticas públicas, na perspectiva de cuidado aos usuários de drogas (AU).

Introduction:The use of alcohol and drugs is a growing problem in Brazil and worldwide. Knowing the epidemiology of this population in services for users of psychoactive substances is an imperative to better treat them. Objective:to describe the epidemiological profile of users of a Psychosocial Care CenterAlcohol and Drugsin Northeastern Brazil. Methodology:descriptive, cross-sectional, quantitative study. Through an electronic spreadsheet, 281 medical records of people over 18 years of age who used the service were analyzed. The chi-square test was used considering the significant p factor less than or equal to 0.05. The study was ethically approved. Results:men, mean of 42.06 years, with basic education level and married, formed the majority of the sample. They were statistically relevant: the highest alcohol consumption in men (p = 0.03); higher education among cocaine users (p = 0.013); greater smoking in the less educated (p = 0.017); offspring as protection against the use of cocaine (p = 0.0006) and cannabis(p = 0.0004); not having children with less alcohol use (p = 0.0015); early use of cannabis (p = 0.0002) and alcohol (p = 0.0065). Conclusions:public policies expanding access to treatment for drug users are important solutions to this problem (AU).

Introducción: El uso de alcohol y drogas es un problema creciente en Brasil y en todo el mundo. Conocer la epidemiología de esta población en los servicios para usuarios de sustancias psicoactivas es un imperativo para tratarlos mejor.Objetivo: describir el perfil epidemiológico de los usuarios de un Centro de Atención PsicosocialAlcohol y Drogas en el noreste de Brasil.Metodología: estudio descriptivo, transversal, cuantitativo. Utilizando una hoja de cálculo electrónica, se analizaron los 281 registros de todas las personas mayores de 18 años que utilizaron el servicio. La prueba de chi-cuadrado se utilizó considerando el factor p significativo menor o igual a 0.05. El estudio fue aprobado éticamente.Resultados: hombres, promedio de 42.06 años, con nivel de educación básica y casados, formaron la mayoría de la muestra. Eran estadísticamente relevantes: el mayor consumo de alcohol en hombres (p = 0.03); educación superior entreusuarios de cocaína (p = 0.013); mayor tabaquismo en los menos educados (p = 0.017); descendencia como protección contra el uso de cocaína (p = 0,0006) y cannabis (p = 0,0004); no tener hijos con menos consumo de alcohol (p = 0.0015); uso temprano de cannabis (p = 0.0002) y alcohol (p = 0.0065).Conclusiones: los perfiles epidemiológicos en centros especializados pueden guiar las políticas públicas, desde la perspectiva de la atención a los consumidores de drogas (AU).

Evidências científicas sobre hérnia de disco na pessoa idosa / Scientific evidence on disk hernia in elderly person / Evidencia científica sobre el disco hernia en persona mayor

Objetivo: identificar as produções científicas sobre hérnia de disco na pessoa idosa. Método: protocolo de scoping review segundo o método do Joanna Briggs Institute com artigos das bases de dados CINAHL, Scopus, Cochrane, Web of Science, MEDLINE e ScienceDirect. Analisaram-se 10 artigos cujos critérios de inclusão foram investigações primárias e/ou secundárias, qualitativas e quantitativas escritos em inglês, português e espanhol, formando 3 categorias temáticas. O recorte do estudo foi delimitado a partir da observação na prática profissional dos pesquisadores sobre o aumento de casos de idosos com hérnia de disco. Resultados: a cirurgia representa constante indicação médica para o tratamento da hérnia de disco. Conclusão:a lombalgia decorrente da hérnia de disco é uma frequente causa de incapacidade nos adultos e idosos com protocolos cirúrgicos constantes, principalmente quando há compressão neural. No entanto, estudos mostram a possibilidade de regressão quando os pacientes são submetidos aos tratamentos conservadores

Objective: to identify scientific productions about herniated discs in the elderly. Method: scoping review protocol according to the Joanna Briggs Institute method with articles from the CINAHL, Scopus, Cochrane, Web of Science, MEDLINE and ScienceDirect databases. Were analyzed 10 articles whose inclusion criteria were primary and / or secondary, qualitative and quantitative investigations written in English, Portuguese and Spanish, forming 3 thematic categories. The study was delimited based on the observation in the professional practice of researchers about the increase in cases of elderly people with herniated discs. Results:surgery is a constant medical indication for the treatment of herniated discs. Conclusion: low back pain due to herniated discs is a frequent cause of disability in adults and the elderly with constant surgical protocols, especially when there is neural compression. However, studies show the possibility of regression when patients are submitted to conservative treatments

Objetivo: identificar producciones científicas sobre hernias discales en ancianos. Método: protocolo de revisión del alcance según el método del Instituto Joanna Briggs con artículos de las bases de datos CINAHL, Scopus, Cochrane, Web of Science, MEDLINE y ScienceDirect. Se analizaron 10 artículos cuyos criterios de inclusión fueron investigaciones primarias y / o secundarias, cualitativas y cuantitativas escritas en inglés, portugués y español, formando 3 categorías temáticas. El estudio se delimitó en función de la observación en la práctica profesional de los investigadores sobre el aumento de casos de personas mayores con discos herniados. Resultados: la cirugía representa una indicación médica constante para el tratamiento de discos herniados. Conclusión:el dolor lumbar debido a discos herniados es una causa frecuente de discapacidad en adultos y ancianos con protocolos quirúrgicos constantes, especialmente cuando hay compresión neural. Sin embargo, los estudios muestran la posibilidad de regresión cuando los pacientes son sometidos a tratamientos conservadores

A drug-drug interaction study of ibrutinib with moderate/strong CYP3A inhibitors in patients with B-cell malignancies.

This was an open-label, multicenter, phase-1 study to evaluate the drug interaction between steady-state ibrutinib and moderate (erythromycin) and strong (voriconazole) CYP3A inhibitors in patients with B-cell malignancies and to confirm dosing recommendations. During cycle 1, patients received oral ibrutinib 560 mg qd alone (Days 1-4 and 14-18), and ibrutinib 140 mg (Days 5-13; 19-27) plus erythromycin 500 mg tid (Days 5-11) and voriconazole 200 mg bid (Days 19-25). Twenty-six patients (median [range] age: 64.5 [50-88] years) were enrolled. Geometric mean ratio (90% confidence intervals) after co-administration of ibrutinib 140 mg with erythromycin and voriconazole was 74.7 (53.97-103.51) and 143.3 (107.77-190.42), respectively, versus ibrutinib 560 mg alone. The most common (≥20%) adverse events were diarrhea (27%) and neutropenia (23%). The results demonstrate that ibrutinib 140 mg with voriconazole or erythromycin provides exposure within the clinical range for patients with B-cell malignancies.

A phase I trial to determine the safety, pharmacokinetics, and pharmacodynamics of intercalated BMS-690514 with paclitaxel/carboplatin (PC) in advanced or metastatic solid malignancies.

PURPOSE: A phase I dose escalation study was performed to determine the maximum tolerated dose (MTD) of intercalated dosing of BMS-690514, a reversible oral panHER/VEGF receptor inhibitor, combined with paclitaxel/carboplatin (PC) in advanced solid tumors. Secondary endpoints included safety, pharmacokinetics (PK), exploratory pharmacodynamics (PD), and preliminary efficacy. EXPERIMENTAL DESIGN: Patients received fixed doses of P (200 mg/m(2)) and C (AUC 6 mg/mL min) q21 days with intercalated BMS-690514 (Days 4-19) starting at 100 mg/day and increasing by 50 mg/day using a 3 + 3 dose escalation design until the MTD was reached. Twenty additional patients were enrolled in the expansion cohort at the recommended phase II dose (RP2D). RESULTS: The MTD was reached at 150 mg/day. DLTs included grade 3 thrombosis at 100 mg (1 patient) and grade 3 diarrhea at 150 mg (1 patient) and 200 mg (2 patients). Serious adverse events (AEs) occurring in 20/37 patients included neutropenia (n = 5), diarrhea (n = 4), pulmonary embolism (n = 3), and simultaneous dehydration, acute renal failure, and febrile neutropenia (n = 2). BMS-690514-related AEs included diarrhea (97 %), acneiform rash (60 %), fatigue (43 %), nausea (30 %), and anorexia (30 %). There were no treatment-related deaths. Sequential intermittent administration of PC did not affect the PK of BMS-690514. Of the 32 patients evaluable for efficacy, there were 12 partial responses including five patients with non-small-cell lung cancer and 12 patients with stable disease. CONCLUSIONS: The MTD of intercalated BMS-609514 combined with PC was 150 mg/day. This approach was tolerable with manageable toxicities and antitumor activity in a variety of solid tumor types.

Metabolism, excretion, and pharmacokinetics of oral brivanib in patients with advanced or metastatic solid tumors.

The goal of this study was to evaluate the pharmacokinetics, mass balance, metabolism, routes and extent of elimination, and safety of a single oral dose of (14)C-labeled brivanib alaninate and the safety and tolerability of brivanib after multiple doses in patients with advanced or metastatic solid tumors. This was a two-part, single-center, open-label, single oral-dose (part A) followed by multiple-dose (part B) study in patients with advanced or metastatic solid tumors. In part A, patients received a single dose of [(14)C]brivanib alaninate and in part B patients received 800 mg of nonradiolabeled brivanib alaninate every day. Four patients (two white, two black: two with non-small-cell lung cancer, one with ovarian cancer, and one with renal cell carcinoma) were treated in both parts. The median time to reach the maximal plasma concentration of brivanib was 1 h, geometric mean maximal plasma concentration was 6146 ng/ml, mean terminal half-life was 13.8 h, and geometric mean apparent oral clearance was 14.7 l/h. After a single oral dose of [(14)C]brivanib alaninate, 12.2 and 81.5% of administered radioactivity was recovered in urine and feces, respectively. Brivanib alaninate was completely converted to the active moiety, brivanib, and the predominant route of elimination was fecal. Renal excretion of unchanged brivanib was minimal. Brivanib was well tolerated; fatigue was the most frequent adverse event occurring in all patients and the most frequent treatment-related adverse event in three (75%). The best clinical response in one patient was stable disease; the other three had progressive disease. Brivanib alaninate was rapidly absorbed and extensively metabolized after a single 800-mg oral dose; the majority of drug-related radioactivity was excreted in feces.