RESUMEN
Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs.
Asunto(s)
Ensayos Clínicos Controlados Aleatorios como Asunto/veterinaria , Animales , Exactitud de los Datos , Interpretación Estadística de Datos , Determinación de Punto Final/veterinaria , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Medición de Riesgo , Resultado del Tratamiento , Medicina Veterinaria/métodosRESUMEN
BACKGROUND: Pleural effusion is a common cause of dyspnea in cats. N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement, using a first-generation quantitative ELISA, in plasma and pleural fluid differentiates cardiac from noncardiac causes of pleural effusion. HYPOTHESIS/OBJECTIVES: To determine whether NT-proBNP measurements using second-generation quantitative ELISA and point-of-care (POC) tests in plasma and pleural fluid distinguish cardiac from noncardiac pleural effusions and how results compare to the first-generation ELISA. ANIMALS: Thirty-eight cats (US cohort) and 40 cats (UK cohort) presenting with cardiogenic or noncardiogenic pleural effusion. METHODS: Prospective cohort study. Twenty-one and 17 cats in the US cohort, and 22 and 18 cats in the UK cohort were classified as having cardiac or noncardiac pleural effusion, respectively. NT-proBNP concentrations in paired plasma and pleural fluid samples were measured using second-generation ELISA and POC assays. RESULTS: The second-generation ELISA differentiated cardiac from noncardiac pleural effusion with good diagnostic accuracy (plasma: sensitivity, 95.2%, specificity, 82.4%; pleural fluid: sensitivity, 100%, specificity, 76.5%). NT-proBNP concentrations were greater in pleural fluid (719 pmol/L (134-1500)) than plasma (678 pmol/L (61-1500), P = 0.003), resulting in different cut-off values depending on the sample type. The POC test had good sensitivity (95.2%) and specificity (87.5%) when using plasma samples. In pleural fluid samples, the POC test had good sensitivity (100%) but low specificity (64.7%). Diagnostic accuracy was similar between first- and second-generation ELISA assays. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of NT-proBNP using a quantitative ELISA in plasma and pleural fluid or POC test in plasma, but not pleural fluid, distinguishes cardiac from noncardiac causes of pleural effusion in cats.
Asunto(s)
Enfermedades de los Gatos/diagnóstico , Cardiopatías/veterinaria , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Derrame Pleural/veterinaria , Sistemas de Atención de Punto , Animales , Líquidos Corporales/química , Gatos , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Exudados y Transudados/química , Femenino , Cardiopatías/complicaciones , Cardiopatías/diagnóstico , Masculino , Péptido Natriurético Encefálico/química , Fragmentos de Péptidos/química , Derrame Pleural/diagnóstico , Derrame Pleural/etiología , Sensibilidad y EspecificidadRESUMEN
In 2005, southwestern Amazonia experienced the effects of an intense drought that affected life and biodiversity. Several major tributaries as well as parts of the main river itself contained only a fraction of their normal volumes of water, and lakes were drying up. The consequences for local people, animals and the forest itself are impossible to estimate now, but they are likely to be serious. The analyses indicate that the drought was manifested as weak peak river season during autumn to winter as a consequence of a weak summertime season in southwestern Amazonia; the winter season was also accompanied by rainfall that sometimes reached 25% of the climatic value, being anomalously warm and dry and helping in the propagation of fires. Analyses of climatic and hydrological records in Amazonia suggest a broad consensus that the 2005 drought was linked not to El Niño as with most previous droughts in the Amazon, but to warming sea surface temperatures in the tropical North Atlantic Ocean.
Asunto(s)
Desastres , Ecosistema , Árboles , Clima Tropical , Conservación de los Recursos Energéticos , Incendios , Factores de TiempoRESUMEN
Established cell lines have long been used for in vitro studies of tumor biology, enabling investigators to control growth conditions and to draw important conclusions about the oncogenic microenvironment. However, gene expression behavior in cultured cells may not always reflect the actual in vivo scenario, and analysis derived from such experiments should take into consideration the existing differences between the two environments. We used suppression subtractive hybridization to study transcriptional changes elicited after oncogene transformation and cell line establishment. We found that transcriptional changes elicited in cultured cell lines are in fact representative of late events, and they do not occur early after oncogene transfection or activation. We also determined that a fraction of the transcriptional changes is oncogene specific, whereas other changes are shared between two or more different oncogenes.