I. The role of research ethics committees in observational studies: epidemiological registries, case reports, interviews, and retrospective studies

Abstract It is often unclear to the clinical investigator whether observational studies should be submitted to a research ethics committee (REC), mostly because, in general, no active or additional interventions are performed. Moreover, obtaining an informed consent under these circumstances may be challenging, either because these are very large epidemiological registries, or the subject may no longer be alive, is too ill to consent, or is impossible to contact after being discharged. Although observational studies do not involve interventions, they entail ethical concerns, including threats such as breaches in confidentiality and autonomy, and respect for basic rights of the research subjects according to the good clinical practices. In this context, in addition to their main function as evaluators from an ethical, methodological, and regulatory point of view, the RECs serve as mediators between the research subjects, looking after their basic rights, and the investigator or institution, safeguarding them from both legal and unethical perils that the investigation could engage, by ensuring that all procedures are performed following the international standards of care for research. The aim of this manuscript is to provide information on each type of study and its risks, along with actions to prevent such risks, and the function of RECs in each type of study.

Actualidades terapéuticas en el tratamiento de linfoma no Hodgkin / Current therapeutic advances in the treatment of non-Hodgkin lymphoma

El linfoma es un cáncer de las células linfoides originado en los tejidos linfoides. El tipo no Hodgkin (LNH) representa 90% de los casos. En México, el linfoma no Hodgkin constituye el tercer cáncer más común en el sexo masculino y el sexto en el femenino. El tratamiento del linfoma ha tenido un avance muy significativo en la última década, pasando a ser una neoplasia con alta probabilidad de curación. Actualmente se dispone de rituximab, un anticuerpo monoclonal dirigido contra el antígeno CD20 expresado en las células malignas B maduras, que induce la destrucción de las células del linfoma no Hodgkin tipo B a través de citotoxicidad mediada por complemento, apoptosis y sensibilización al efecto tóxico de la quimioterapia. Rituximab ha revolucionado los resultados del tratamiento al poder ofrecer a los pacientes con linfomas agresivos una mayor posibilidad de curación, y en los linfomas indolentes aumenta el periodo sin enfermedad. El tratamiento estándar actual en pacientes con linfoma no Hodgkin agresivo es rituximab-CHOP (inmunoquimioterapia). La adición de rituximab al tratamiento del linfoma no Hodgkin tiene ventajas fármaco-económicas, demostradas en estudios de costo-utilidad y costo-efectividad.

Lymphoma is a lymphoid cell cancer that originates in lymphoid tissues. Non Hodgkin (NHL) type represents 90% of cases. In Mexico, NHL constitutes the third most common cancer in males and the sixth among females. NHL treatment has achieved significant advances in the last decade and NHL is currently becoming a disease with a high probability of cure. Rituximab has become an alternative for the treatment of NHL. Rituximab is a monoclonal antibody that targets the CD20 antigen expressed in the mature malignant B cells. It induces NHL B cells destruction by complement-mediated citotoxicity, apoptosis and sensitization to the toxic effect of chemotherapy. Rituximab has revolutionized treatment results by offering patients with aggressive NHL a higher possibility of cure and in the case of the intractable forms of NHL it increases the disease free period. The standard treatment for a patient with NHL is rituximab-CHOP (immunotherapy). In addition, rituximab has pharmacoeconomic advantages as shown in various cost-utility and cost-effectiveness studies.

Bradicardia asociada al uso de talidomida en pacientes con enfermedades hematológicas: experiencia en una sola institución / Thalidomide-associated bradycardia in patients with hematologic diseases: A single institution experience

Thalidomide, an immunomodulatory and antiangio genie agent, is useful in the treatment of some hematologic and oncologic diseases. Up to 6.8% of thalidomide-treated patients present bradycardia. Herein the incidence of thalidomide-associated bradycardia in patients with hematologic diseases treated in a single institution is reported. In a 34-month period, 33 patients with different hematologic diseases (multiple myeloma [MM], 20; myelodysplastic syndrome, eight; Waldenstróm macroglobulinemia, two; non-Hodgkin's lymphoma, two; malignant histiocytosis, one) were treated with thalidomide. Of them, five (15.1%) had bradycardia, all with MM. Bradycardia was detected with a daily thalidomide dose ranging from 100 to 300 mg and the time patients received thalidomide before cardiac event went from one to 18 months. In all affected cases the electrocardiogram showed sinus bradycardia with cardiac frequency between 32 to 48 beats per minute. Time to normal cardiac beat recovery ranged from 12 to 21 days after thalidomide discontinuation. There were no fatalities due to thalidomide-associated bradycardia. It is concluded that: a) thalidomide-associated bradycardia was detected only in patients with MM, b) herein the incidence of bradycardia was higher as compared with other series, and c) in patients with MM thalidomide therapy must be prescribed with caution particularly in those with cardiovascular diseases of any etiology.

La talidomida, agente inmunomodulador y antiangiogénico, es útil en el tratamiento de enfermedades hematologicas y oncológicas. Los efectos adversos asociados al uso de talidomida son múltiples e incluyen bradicardia sinusal que se presenta hasta en 6.8% de los casos. En el presente estudio se informa la frecuencia de bradicardia asociada al uso de talidomida en pacientes con enfermedades hematologicas atendidos en una sola institución. En un lapso de 34 meses se encontró que 33 pacientes con diversos padecimientos hematológicos (mieloma múltiple [MM], 20; síndrome mielodisplásico, ocho; macroglobulinemia de Waldenstróm, dos; linfoma no Hodgkin, dos; histiocitosis maligna, uno) recibieron tratamiento con talidomida. De ellos, cinco (15.1%) presentaron bradicardia, todos con MM. La dosis de talidomida al momento de la bradicardia fue de entre 100 a 300 mg por día y el tiempo que recibieron el fármaco antes del evento osciló entre uno y 18 meses. El electrocardiograma mostró bradicardia sinusal en todos los casos con frecuencia cardiaca (FC) de entre 32 a 48 latidos por minuto. Suspendida la talidomida la FC se normalizó en todos los enfermos en un tiempo que osciló entre 12 a 21 días. Ninguno de los pacientes falleció por esta complicación. Se concluye que: a) la bradicardia asociada a talidomida se identificó sólo en pacientes con MM, b) la frecuencia de bradicardia en nuestra serie fue superior a la informada en otras y c) en MM el tratamiento con talidomida debe prescribirse con precaución en aquellos pacientes con algún padecimiento cardiovascular de cualquier etiología.