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BACKGROUND: Antiretroviral therapy has transformed HIV from a progressive and often fatal infection to a chronic disease. Currently, people living with HIV (PLHIV) have near-normal life expectancy; however, they face accelerated ageing and a rise in non-AIDS-defining HIV-associated conditions. Comorbidities increase the number of prescribed drugs and, therefore, the risk of polypharmacy and prescribing potentially inappropriate medications (PIMs). Still, there are no specific tools to identify PIMs in older PLHIV, which opens a pathway to investigate the particularities in the prescription of medication in this population. METHODS: We conducted a scoping review in 5 electronic databases for studies reporting the use of tools to identify PIMs in older PLHIV. No language or date restrictions were applied. To complete the search, abstracts published in the most relevant HIV Conferences and Events in their editions from 2010 to 2022 were screened. RESULTS: Of 50,193 records returned (13,701 of the databases and 36,492 of the Congresses), 39 studies met the inclusion criteria. Most studies were single-centre and conducted in Europe. Twenty-eight studies were cross-sectional, and most researchers used explicit criteria, mainly Beers and STOPP-START criteria, to identify PIMs. CONCLUSIONS: Potentially inappropriate prescribing is frequent among older PLHIV. Explicit conventional tools to identify PIMs in older populations may need to be adapted to tackle the needs of PLHIV. Implicit tools may be more valid, although their use is more time-consuming, and standardization is complex.
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Infecções por HIV , Prescrição Inadequada , Humanos , Idoso , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Polimedicação , Europa (Continente) , PrescriçõesRESUMO
OBJECTIVE: HIV Clinical Guidelines have positioned integrase inhibitors recently as first-line treatment. However, two of these drugs have also been associated with adverse side effects on the central nervous system, especially with sleep disturbances. The objective was to analyse the influence of bictegravir and dolutegravir on the sleep quality in HIV patients. METHODS: An observational, cross-sectional study was carried out between December 2020 and January 2021 in HIV patients attended in a pharmacy care clinic. Demographic and adherence variables were collected. Sleep quality was measured using the Pittsburgh questionnaire or PSQI. We classified patients into two groups: patients with bictegravir or dolutegravir in their treatment (study group) and the rest (control group). The influence of the variables collected on the PSQI result was analysed using the Chi-Square test for categorical variables and the student t-test or Mann-Whitney U test for continuous variables. RESULTS: One hundred and nineteen patients were included. 64% in the study group and 67% in the control group suffered from sleep disorders according to the PSQI questionnaire (p=0.788). Neither were statistical differences found when the different components of sleep were analysed between the two groups. CONCLUSIONS: A high percentage of patients, regardless of whether their treatment includes bictegravir or dolutegravir, have problems with their sleep quality. We didn't find a correlation between sleep quality and treatment with bictegravir or dolutegravir compared to the other treatments.
OBJETIVO: Los inhibidores de la integrasa se han posicionado recientemente en todas las Guías Clínicas de VIH como tratamiento antirretroviral de primera línea para el VIH. Sin embargo, dos de estos fármacos se han asociado también a efectos adversos a nivel del sistema nervioso central, concretamente con alteraciones del sueño. El objetivo del trabajo fue analizar la influencia de bictegravir y dolutegravir en la calidad del sueño en personas que viven con VIH (PVIH). METODOS: Se realizó un estudio observacional y transversal entre los meses de diciembre de 2020 y enero de 2021 en las PVIH de las consultas de atención farmacéutica del hospital. Se recogieron variables demográficas y de adherencia. La calidad del sueño se midió mediante el Cuestionario de Pittsburgh o PSQI. Las PVIH se clasificaron en 2 grupos: el grupo estudio, constituido por participantes con bictegravir o dolutegravir en su tratamiento, y el grupo control, integrado por el resto de PVIH. Se analizó la influencia de las variables recogidas sobre el resultado del PSQI mediante la prueba de chi cuadrado/odds ratio para variables categóricas y el de t de Student o U de Mann Whitney para variables continuas. RESULTADOS: Se incluyeron 119 PVIH, de las cuales un 64% en el grupo estudio y un 67% en el grupo control sufrían trastornos del sueño según el PSQI (p=0,788). Tampoco hubo diferencias estadísticamente significativas cuando se compararon los diferentes componentes del sueño entre los dos grupos. CONCLUSIONES: Un elevado porcentaje de PVIH, independientemente de si el TAR incluye bictegravir o dolutegravir, tienen problemas relacionados con la calidad del sueño. No se encuentra correlación entre la calidad del sueño y el tratamiento con bictegravir o dolutegravir comparado con el resto de tratamientos.
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Infecções por HIV , Transtornos do Sono-Vigília , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Tenofovir/efeitos adversos , Emtricitabina/efeitos adversos , Adenina/uso terapêutico , Estudos Transversais , Espanha , Piridonas/efeitos adversos , Transtornos do Sono-Vigília/induzido quimicamente , Transtornos do Sono-Vigília/epidemiologiaRESUMO
INTRODUCTION: Bronchiectasis is typically treated with inhaled antibiotics in clinical practice. However, there is a striking lack of standardised procedures for the preparation of noncommercial solutions. We used biochemical parameters to analyse the safety and tolerability of inhaled antibiotics in patients with bronchiectasis, and determined potential associations between the inhaled antibiotics used and adherence to the medications and quality of life. METHODS: We conducted a literature review, biochemical testing, and a pilot study of patients admitted to our hospital with noncystic fibrosis bronchiectasis. The MEDLINE database was searched for studies involving inhaled antibiotics to treat bronchiectasis. We analysed the pH, osmolality, and sodium and chloride ion concentrations of the antibiotics used. The pilot study included patients receiving inhaled antibiotic treatment. Demographic data, adherence, and quality of life were recorded and assessed. We determined potential associations between the study variables. RESULTS: The literature review identified 429 articles: 106 included precise instructions for diluting antibiotics, and 18 reported data on the biochemical parameters analysed. Laboratory results showed that some antibiotic dilutions were outside the range of tolerability, especially those involving dry powders for intravenous infusion, which must be diluted for their inhalation. Adherence was good in more than 80% of the patients, and higher in men and older patients. Men reported better quality of life. No associations were found between the antibiotics used and the other variables. CONCLUSION: Regarding the biochemical parameters analysed, there is a lack of information on the tolerability and biochemical safety of noncommercial dilutions of inhaled antibiotics used to treat bronchiectasis.
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Antibacterianos , Bronquiectasia , Administração por Inalação , Bronquiectasia/tratamento farmacológico , Humanos , Masculino , Projetos Piloto , Qualidade de VidaRESUMO
Background: A global outbreak of the human monkeypox virus (HMPXV), first identified in May 2022, was declared a health emergency of international concern on 23 July 2022. Before the global outbreak, monkeypox cases were mostly confined to central and west African countries, where this virus is prevalent. Close contact, mainly sexual contact, is supposed to be the main route of transmission, and it is remarkable that the incidence is higher in men who have sexual relationships with other men. Case summary: A 40-year-old Caucasian man arrived at the emergency department complaining of oppressive epigastric pain extending to the chest after a diagnosis of pharyngitis, which was suspected to be caused by the human monkeypox virus. Based on the clinical symptoms, physical examination, serum cardiac biomarkers, and electrocardiographic findings, he was diagnosed with myopericarditis. The real-time PCR for human monkeypox in skin lesions, urine, plasma, and the oropharyngeal swab was positive. The peak of troponin I was 20.6 ng/ml, and the electrocardiogram showed an upward concavity in the ST segment in diffuse leads, which was in agreement with the previous diagnosis. The presence of edema, subepicardial, and myocardial late gadolinium enhancement, and increased values on T1 mapping in the cardiac MRI were in agreement with the diagnosis of myopericarditis. Antiviral treatment with tecovirimat was started with excellent tolerability. After 6 days, the patient recovered and was discharged. Discussion: To our knowledge, this is one of the first reported cases of myopericarditis due to human monkeypox infection, which was confirmed by a cardiac MRI following modified Lake Louise criteria. The short span between the onset of the mucocutaneous symptoms and the myocardial damage suggests a pathogenic association. Furthermore, the active viral replication in plasma samples and the negative results on real-time PCR for other viruses support this clinical association.
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BACKGROUND: SARS-CoV-2 has caused a high mortality in institutionalised individuals. There are very few studies on the involvement and the real impact of COVID-19 in nursing homes. This study analysed factors related to morbidity and mortality of COVID-19 in institutionalised elderly people. METHODS: This cohort study included 842 individuals from 12 nursing homes in Sant Cugat del Vallès (Spain) from 15 March to 15 May 2020. We evaluated individual factors (demographic, dependence, clinical, and therapeutic) and those related to the nursing homes (size and staff) associated with infection and mortality by SARS-CoV-2. Infection was diagnosed by molecular biology test. RESULTS: Of the 842 residents included in the analysis, 784 underwent a Polymerase Chain Reaction (PCR) test; 74.2% were women, the mean age was 87.1 years, and 11.1% died. The PCR test was positive in 44%. A total of 33.4% of the residents presented symptoms compatible with COVID-19 and of these, 80.9% were PCR-positive for SARS-CoV-2. Infection by SARS-CoV-2 among residents was associated with the rate of staff infected in the homes. Mortality by SARS-CoV-2 was related to male sex and a greater grade of dependence measured with the Barthel index. CONCLUSIONS: SARS-Cov-2 infection in institutionalised people is associated with the infection rate in nursing home workers and mortality by SARS-Cov-2 with sex and greater dependency according to the Barthel index. Adequate management of nursing home staff and special attention to measures of infection control, especially of individuals with greater dependence, are keys for successful management of future pandemic situations.
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COVID-19 , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Morbidade , Fatores de Risco , SARS-CoV-2RESUMO
Introducción: Es indiscutible la importancia de la investigación científica y los beneficios que ofrece no solo para el investigador sino para todo un país. A pesar de esto, Latinoamérica incluyendo Panamá, está muy por debajo en producción científica a nivel mundial. Nuestro personal de salud es el primero en ser llamado a esta cultura de investigación. ¿Por qué no está ocurriendo? Si conocemos el problema podremos ser capaces de establecer posibles soluciones. Objetivo: determinar el interés, participación y limitantes que presentan los médicos residentes de las especialidades clínicas del Complejo Hospitalario Dr. Arnulfo Arias Madrid (CHDrAAM) para realizar investigación científica durante el mes de julio 2020. Metodología: descriptivo de corte transversal. Los datos se obtendrán mediante un formulario con 21 preguntas en línea usando la herramienta Google Forms. Las preguntas de esta encuesta fueron previamente validadas. Se usará el programa Epi Info para su análisis. Resultados: de los participantes un 71.4% están entre los 29 a 32 años y predomina el sexo femenino. Más de dos tercios refiere interés en realizar investigación científica y un 25% no sabe cómo realizarla. A pesar de que muchos han estado involucrados en realización de trabajos de investigación, solo 26.7% lo ha llevado a la publicación. Las principales limitantes son: falta de tiempo, no contar con mentores y no saber cómo realizarlas. Conclusiones: Si existe interés en realizar investigación científica por parte de los médicos residentes, sin embargo, impresiona que tengan que escoger entre su carga laboral y la investigación. (provisto por Infomedic International)
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OBJECTIVES: To analyze the seriousness of medication reconciliation errors (MREs) in the treatment of older patients admitted to an emergency department's acute geriatric unit. To identify and describe discrepancies, including the drug groups involved, and to explore risk factors. MATERIAL AND METHODS: Prospective, observational 6-month study. A pharmacist recorded medications in each patient's history and compared the patient's usual treatment to the regimen prescribed in the emergency department; discrepancies were flagged for evaluation as possible MREs. A geriatric medicine specialist evaluated MRE seriousness. RESULTS: Three hundred twenty-eight discrepancies were detected (93.8% of the total of 351 patients); 151 patients (43.02%) had at least 1 MRE. Three hundred MREs were identified, 248 (82.7%) reached the patient, and 27 (9%) caused reversible injury. No errors led to prolonged injury or death. CONCLUSION: MREs were common but not serious, and the injuries caused were reversible.
OBJETIVO: Analizar la gravedad de los errores de conciliación (EC) producidos en el servicio de urgencias (SU) en pacientes que ingresan en una unidad de agudos de geriatría. Cuantificar y describir las discrepancias y los EC. Analizar los grupos farmacológicos y los factores de riesgo. METODO: Estudio observacional prospectivo. Un farmacéutico realizó la historia farmacoterapéutica y comparó el tratamiento habitual con el prescrito en el SU, identificó discrepancias y posibles EC y un geriatra evaluó su gravedad. RESULTADOS: Se incluyeron 351 pacientes, de los que 328 (93,8%) presentaron discrepancias, 151 pacientes (43,02%) presentaron al menos 1 EC. Se observaron 300 EC de los que 248 (82,7%) alcanzaron al paciente, y 27 EC (9%) produjeron daño reversible. No hubo ningún error que causase daño prolongado o mortal. CONCLUSIONES: Los EC fueron frecuentes pero de escasa gravedad, y los daños que ocasionaron fueron reversibles.
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Serviço Hospitalar de Emergência , Erros de Medicação , Reconciliação de Medicamentos , Idoso , Hospitalização , Humanos , Estudos ProspectivosRESUMO
Introduction: Satisfaction and knowledge among patients with HIV after switching from tenofovir to tenofovir/alafenamide remain unexplored. Given that both parameters are associated with better health outcomes it is relevant to measure them in patients during routine clinical practice. Objective: To evaluate the degree of knowledge and satisfaction in patients who had their antiretroviral regimen switched from rilpivirine (RPV)/emtricitabine (FTC)/TDF to RPV/FTC/TAF. Materials and methods: We conducted a prospective study in a third-level hospital between September, 2018, and November, 2018. We included patients who had previously been treated with RPV/FTC/TDF and collected their RPV/FTC/TAF treatment in the second visit. A 5-point Likert-type agreement/disagreement scale was used to assess satisfaction and knowledge regarding the medication switch. Results: We included 116 patients in the study of whom 75% were satisfied and 64% had a high-level of knowledge. Young patients were less satisfied with the way in which the change was explained (p=0.0487). Concerning the new medication, the patients were better informed about its renal (85% of them) and bone benefits (82%) than about its adverse effects on the lipid profile (40%). Conclusions: The patients were generally satisfied with the change in medication and well nformed about the dosage and advantages of TAF over TDF, but less well informed about the possible adverse effects of TAF.
Introducción. La satisfacción y el conocimiento del cambio de tenofovir por tenofovir-alafenamida en pacientes con HIV no se han estudiado aún. Estos dos parámetros se relacionan con mejores resultados en salud y, por lo tanto, es importante medirlos durante la práctica clínica habitual. Objetivo. Evaluar el grado de conocimiento y satisfacción de los pacientes positivos para HIV ante el cambio de tratamiento antirretroviral con rilpivirina, emtricitabina y tenofovir (RPV-FTC-TDF) por rilpivirina, emtricitabina y tenofovir-alafenamida (RPV-FTC-TAF). Materiales y métodos. Se llevó a cabo un estudio prospectivo en un hospital de tercer nivel entre los meses de septiembre y noviembre de 2018. Se incluyeron pacientes previamente tratados con RPV-FTC-TDF que acudían por segunda vez a consulta para recibir el tratamiento con RPV-FTC-TAF. La satisfacción y el grado de conocimiento se analizaron mediante nueve preguntas, usando una escala de tipo Likert de 5 puntos para evaluar el grado de acuerdo. Resultados. Se incluyeron 116 pacientes en el estudio. El 75 % de ellos se mostró satisfecho con el cambio y se consideró que el 64 % conocía lo que implicaba. Los pacientes jóvenes se mostraron menos satisfechos con el modo en que se les explicó el cambio (p=0,0487). Los pacientes estaban mejor informados sobre las ventajas renales (85 % de conocimiento) y óseas (82 %) de la nueva medicación, que sobre sus inconvenientes para el perfil lipídico (40 %). Conclusiones. En general, los pacientes se mostraron satisfechos con el cambio de medicación y conocían la posología del medicamento y las ventajas de la tenofovir-alafenamida frente al tenofovir, pero no sus posibles efectos adversos.
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Adenina/análogos & derivados , Antivirais/uso terapêutico , Substituição de Medicamentos , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Satisfação do Paciente , Rilpivirina/uso terapêutico , Tenofovir/uso terapêutico , Adenina/uso terapêutico , Adulto , Alanina , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Introducción. La satisfacción y el conocimiento del cambio de tenofovir por tenofovir- alafenamida en pacientes con HIV no se han estudiado aún. Estos dos parámetros se relacionan con mejores resultados en salud y, por lo tanto, es importante medirlos durante la práctica clínica habitual. Objetivo. Evaluar el grado de conocimiento y satisfacción de los pacientes positivos para HIV ante el cambio de tratamiento antirretroviral con rilpivirina, emtricitabina y tenofovir (RPV-FTC-TDF) por rilpivirina, emtricitabina y tenofovir-alafenamida (RPV-FTC-TAF). Materiales y métodos. Se llevó a cabo un estudio prospectivo en un hospital de tercer nivel entre los meses de septiembre y noviembre de 2018. Se incluyeron pacientes previamente tratados con RPV-FTC-TDF que acudían por segunda vez a consulta para recibir el tratamiento con RPV-FTC-TAF. La satisfacción y el grado de conocimiento se analizaron mediante nueve preguntas, usando una escala de tipo Likert de 5 puntos para evaluar el grado de acuerdo. Resultados. Se incluyeron 116 pacientes en el estudio. El 75 % de ellos se mostró satisfecho con el cambio y se consideró que el 64 % conocía lo que implicaba. Los pacientes jóvenes se mostraron menos satisfechos con el modo en que se les explicó el cambio (p=0,0487). Los pacientes estaban mejor informados sobre las ventajas renales (85 % de conocimiento) y óseas (82 %) de la nueva medicación, que sobre sus inconvenientes para el perfil lipídico (40 %). Conclusiones. En general, los pacientes se mostraron satisfechos con el cambio de medicación y conocían la posología del medicamento y las ventajas de la tenofovir- alafenamida frente al tenofovir, pero no sus posibles efectos adversos.
Introduction: Satisfaction and knowledge among patients with HIV after switching from tenofovir to tenofovir/alafenamide remain unexplored. Given that both parameters are associated with better health outcomes it is relevant to measure them in patients during routine clinical practice. Objective: To evaluate the degree of knowledge and satisfaction in patients who had their antiretroviral regimen switched from rilpivirine (RPV)/emtricitabine (FTC)/TDF to RPV/FTC/TAF. Materials and methods: We conducted a prospective study in a third-level hospital between September, 2018, and November, 2018. We included patients who had previously been treated with RPV/FTC/TDF and collected their RPV/FTC/TAF treatment in the second visit. A 5-point Likert-type agreement/disagreement scale was used to assess satisfaction and knowledge regarding the medication switch. Results: We included 116 patients in the study of whom 75% were satisfied and 64% had a high-level of knowledge. Young patients were less satisfied with the way in which the change was explained (p=0.0487). Concerning the new medication, the patients were better informed about its renal (85% of them) and bone benefits (82%) than about its adverse effects on the lipid profile (40%). Conclusions: The patients were generally satisfied with the change in medication and well informed about the dosage and advantages of TAF over TDF, but less well informed about the possible adverse effects of TAF.
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HIV , Satisfação do Paciente , Conhecimento do Paciente sobre a Medicação , Farmacêuticos , Rilpivirina , TenofovirRESUMO
INTRODUCTION: The prescription of antiretroviral treatment (ART) that contains pharmacokinetic enhancers such as ritonavir and cobicistat is frequent. The objective of this stdy was to analyze the potential interactions of ART that include these molecules in their formulation with the patient's home medication, as well as the clinical management of those potentially serious. METHODS: Prospective study conducted in the pharmacy care clinic of a third level hospital between January and December of 2018. Those HIV+patients with an ART containing cobicistat or ritonavir were included in the study. Potential interactions between ART and concomitant medication were analysed in three databases (Micromedex®, Drugs.com and Liverpool), the interventions carried out were detailed, and adverse drug reactions analysed. RESULTS: 968 patients were included with a total of 2,148 prescriptions (274 different medications). A total of 86 interventions were performed regarding potential interactions in patients. The most frequent were substitutions of corticoid treatments, treatment suspensions and closer monitoring of treatments. A total of possible adverse drug reactions were analysed. The degree of agreement in the severity classification of the interactions for cobicistat and ritonavir was good among the three databases. It was remarkable Micromedex® as the most complete because it has more registered medications. CONCLUSION: The interactions between ART with pharmacokinetic enhancers in its composition and concomitant medication is frequent and requires a significant variety of interventions. The check of interactions in different databases is recommended since they can cause adverse drug reactions.
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Cobicistat/farmacologia , Infecções por HIV , Ritonavir/farmacologia , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Cobicistat/efeitos adversos , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacologia , Humanos , Estudos Prospectivos , Ritonavir/efeitos adversosRESUMO
COVID-19 Community acquired pneumonía is a recent and frequent cause of admission in European intensive care units. Currently, there are many open questions regarding the management and prognostic factors of these patients. Among them, its association with acute renal failure in patients on mechanical ventilation. Analysis of acute renal failure in COVID-19 patients on mechanical ventilation. Prognosis and factors related to its development. Retrospective observational study carried out in the intensive care unit of a University Hospital during the COVID-19 pandemic. We analysed patients admitted to the ICU with the diagnosis of Respiratory Failure due to Pneumonia COVID-19 between 6/3/2020 and 21/4/2020. Demographic data (age, sex), APACHE II, comorbidities, analytical data (ferritin, total bilirubin), length of stay, treatments administered (mechanical ventilation, muscle relaxant, vasoactive drugs, prone) and its association to acute renal failure were analysed. 67 patients received complete treatment in our hospital. Length of stay (days) 14.1 ± 10, average age 60 years, APACHE II 14.3 ± 5.2, 67.2% males. Maximum creatinine mean value (mg/dl) 1.48 ± 1.26, Maximum ferritin mean value (ng/ml) 2,310 ± 3,322, Maximum total bilirubin mean value (mg/dl) 2 ± 2.2. 100% of the patients required mechanical ventilation. 65.7% prone positioning, 74.6% neuromuscular blockers and 98.5% required vasoactive drugs. Establishing renal failure as creatinine values greater than 1.2 mg/dl. Patients with maximum creatinine above 1.2 mg/dl presented average values of bilirubin and ferritin higher than those with values under 1.2 mg/dl (P < 0.05). The presence of renal failure was also statistically significantly associated with sex (male), presence of dyslipidaemia, and mortality. In our sample, we have associated acute renal failure with higher ferritin valúes. Likewise, we have observed higher creatinine valúes in the group of non-survivors, those with dyslipidaemia and men, with statistical signification.
La neumonía adquirida en la comunidad COVID-19 es una causa reciente y frecuente de ingreso en las unidades de cuidados intensivos europeos. Actualmente, hay muchas preguntas abiertas con respecto al manejo y los factores pronósticos de estos pacientes. Entre ellos, su asociación con insuficiencia renal aguda en pacientes en ventilación mecánica. Análisis de insuficiencia renal aguda en pacientes con COVID-19 en ventilación mecánica. Pronóstico y factores relacionados con su desarrollo. Estudio observacional retrospectivo realizado en la unidad de cuidados intensivos de un Hospital Universitario durante la pandemia de COVID-19. Analizamos los pacientes ingresados en UCI con el diagnóstico de insuficiencia respiratoria por neumonía COVID-19 entre el 3/6/2020 y el 21/4/2020. Se analizaron datos demográficos (edad, sexo), APACHE II, comorbilidades, datos analíticos (ferritina, bilirrubina total), tiempo de estancia, tratamientos administrados (ventilación mecánica, relajante muscular, fármacos vasoactivos, prono) y su asociación con insuficiencia renal aguda. 67 pacientes recibieron tratamiento completo en nuestro hospital. Duración de la estancia (días) 14,1 ± 10, edad media 60 años, APACHE II 14,3 ± 5,2, 67,2% varones. Valor medio máximo de creatinina (mg/dl) 1,48 ± 1,26, valor medio máximo de ferritina (ng/ml) 2.310 ± 3.322, valor medio máximo de bilirrubina total (mg/dl) 2 ± 2,2. El 100% de los pacientes requirió ventilación mecánica. El 65,7% en decúbito prono, el 74,6% bloqueantes neuromusculares y el 98,5% requirieron fármacos vasoactivos. Estableciendo la insuficiencia renal como valores de creatinina superiores a 1,2 mg/dl, los pacientes con creatinina máxima superior a 1,2 mg/dl presentaron valores medios de bilirrubina y ferritina superiores a aquellos con valores menores a 1,2 mg/dl, de forma estadísticamente significativa. La presencia de fallo renal, también se asoció de forma estadísticamente significativa al sexo hombre, la presencia de dislipidemia como antecedente personal de interés y a la mortalidad. En nuestra muestra hemos asociado la insuficiencia renal aguda con valores más elevados de ferritina. Asimismo, hemos observado mayores valores de creatinina en el grupo de no supervivientes, los que presentan dislipidemia y los hombres, con significación estadística.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Respiração Artificial/efeitos adversos , Injúria Renal Aguda/mortalidade , COVID-19/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Creatinina/análise , Dislipidemias , Injúria Renal Aguda/diagnóstico , Ferritinas/análise , Hospitais Universitários , Unidades de Terapia IntensivaRESUMO
Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study. Serum levels of vascular endothelial growth factor-A165, soluble vascular endothelial growth factor receptor 1, and hepatocyte growth factor were assessed by enzyme-linked immunosorbent assay method basally and every 3 cycles (at the time of computed tomography evaluation) in a preplanned translational study in the first-line BECOX trial in metastatic colorectal cancer patients treated with CAPOX plus bevacizumab. Response was evaluated by routine contrast-enhanced computed tomography by RECIST 1.1 by investigator assessment and by three blinded independent radiologists. Ratios between soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A and hepatocyte growth factor/vascular endothelial growth factor-A were established and variations through time were related to RECIST 1.1 by investigator assessment and independent radiologist. The BECOX trial included 68 patients, and 27 patients were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by investigator assessment and 56 by independent radiologist. We found that a 3.22-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by investigator assessment and a 3.06-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by independent radiologist from previous determination were associated with responses compared with 1.38-fold increase by investigator assessment and 1.59 by independent radiologist in non-responders (p = 0.0009 and p = 0.03, respectively). Responders had a 3.36-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A from previous determination by investigator assessment and 3.66-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A by independent radiologist compared with 1.43-fold increase by investigator assessment and 1.53 by independent radiologist for non-responders (p = 0.002 and 0.003, respectively). In conclusion, a decrease in vascular endothelial growth factor-A and an increase in soluble vascular endothelial growth factor receptor 1 during chemotherapy and bevacizumab exposure can contribute to both chemotherapy (due to c-MET/b-catenin activation) and bevacizumab (due to low vascular endothelial growth factor requirements) resistance. Because hepatocyte growth factor levels decrease also during acquired resistance, alternative strategies to hepatocyte growth factor-ligand inhibition should be investigated.
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Neoplasias Colorretais/tratamento farmacológico , Fator de Crescimento de Hepatócito/sangue , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/sangue , Neovascularização Patológica/patologia , Compostos Organoplatínicos/administração & dosagem , OxaliplatinaRESUMO
INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Síndrome Mão-Pé/epidemiologia , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Síndrome Mão-Pé/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
The low- and high-temperature phases (alpha and beta, respectively) of solid nitric acid dihydrate (NAD) are studied in depth by DFT methods. Each phase contains two types of complex structures (H(3)O(+)) x (H(2)O), designated A and B, with different hydrogen-bonding (HB) characteristics. The theoretical study reveals that type A complexes are weakly bound and could be described as (H(3)O)(+) and H(2)O aggregates, with decoupled vibrational modes, whereas in type B structures the proton is situated close to the centre of the O...O bond and induces strong vibrational coupling. The proton-transfer mode is predicted at quite different wavenumbers in each complex, which provides an important differentiating spectral feature, together with splitting of some bands in beta-NAD. Theoretical spectra are estimated by using two GGA parameterizations, namely, PBE and BLYP. The potential-energy surface for each type of HB in NAD is also studied, as is the spectral influence of displacement of the shared H atom along the O-O bond. The results are compared to literature infrared spectra recorded by different techniques, namely, transmission and reflection-absorption, with both normal and tilted incident radiation. This work provides a thorough assignment of the observed spectra, and predictions for some spectra not yet available. The usefulness of high-level theoretical calculations as performed herein to discriminate between two phases of a solid crystal is thus evidenced.
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The solid phases of methanol were investigated using IR spectroscopy and numerical calculations with the SIESTA method. Improved spectra are reported of amorphous methanol at 90 K, and in particular of the alpha and beta phases at 130 and 165 K, respectively, with assignments of bands not previously measured. The main features of the spectra of each phase are discussed and compared. A study of spectral changes with temperature leads to the conclusion that the metastable phase previously reported might be a mixture of the two known stable phases. Such a mixture could explain all spectral features observed in this investigation. The theoretical calculations provide reasonable agreement with the experimental data for most of the parameters, but predict H-bondings stronger than those observed. Differences between the spectra of the alpha and beta phases are predicted with similar characteristics to the experimental results.
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Ice mixtures of CO2 and H2O are studied using Fourier transform reflection-absorption infrared (RAIR) spectroscopy. Mixtures are prepared by sequential deposition or co-deposition of the two components from the gas phase onto an Al plate kept at 87 K inside a low-pressure chamber. Two CO2 structures are found in most experiments: a crystalline form similar to pure CO2, which evaporates when warming at 105 K, and a noncrystalline species which remains embedded in amorphous water ice after warming. Significant spectral variations are found depending on the deposition method and the thickness of the solid. Features characteristic of the RAIR technique appear in the spectral regions of the normal modes of the bending and asymmetric stretching CO2 vibrations. Simulations using Fresnel theory and Mie scattering are carried out with acceptable agreement with the experimental spectra of solids of variable thickness, from approximately 1 microm to the limit of nanoparticles. Theoretical calculations of a pure CO2 crystal are performed. The relaxed geometry of the solid and its vibrational spectrum are determined and compared to the experimental results.
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Studies with the gemcitabine/vinorelbine (GV) or the gemcitabine/docetaxel (GD) combinations have shown similar efficacy and less toxicity compared to platinum-based chemotherapies, in patients with advanced non-small-cell lung cancer (NSCLC). The present trial was designed to test the efficacy and safety of both, GV and GD, combinations. Chemotherapy-naïve patients (n=39)