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Aging of the immune system, or immunosenescence, alters the viral immune response in the elderly, especially when frailty exists. Research findings have demonstrated an imbalance in pro- and anti-inflammatory mechanisms, reduced production and diversification of T lymphocytes, and an alteration in immunovigilance and antibody synthesis. In this context, nutrition has a role in combating sarcopenia and frailty. Some food components that contribute to immune-competence are protein, vitamin D, n-3 fatty acids, antioxidant vitamins (vitamins C and E), zinc, selenium and iron. In times of a pandemic, nutritional recommendations for immune-competence in the elderly should be based on clinical studies. In this article, immunosenescence and its relationship to nutrition are addressed, including interventions studied in the context of the COVID-19 pandemic.

Introduction: The use of psychotropic drugs in children and adolescents is widespread but associated with suboptimal treatment effects. Therapeutic drug monitoring (TDM) can improve safety of psychotropic drugs in children and adolescents but is not routinely performed. A major reason is that the relationship between drug concentrations and effects is not well known. Areas covered: This systematic review evaluated studies assessing the relationship between psychotropic drug concentrations and clinical outcomes in children and adolescents, including antipsychotics, psychostimulants, alpha-agonists, antidepressants, and mood-stabilizers. PRISMA guidelines were used and a quality assessment of the retrieved studies was performed. Sixty-seven eligible studies involving 24 psychotropic drugs were identified from 9,298 records. The findings were generally heterogeneous and the majority of all retrieved studies were not of sufficient quality. For 11 psychotropic drugs, a relationship between drug concentrations and side-effects and/or effectiveness was evidenced in reasonably reported and executed studies, but these findings were barely replicated. Expert opinion: In order to better support routine TDM in child- and adolescent psychiatry, future work must improve in aspects of study design, execution and reporting to demonstrate drug concentration-effect relationships. The quality criteria proposed in this work can guide future TDM research. Systematic review protocol and registration PROSPERO CRD42018084159.

Postoperative pain management contributes to reducing postoperative morbidity and unscheduled readmission. Compared to other opioids that manage postoperative pain like morphine, few randomized trials have tested the efficacy of intraoperatively administered methadone to provide evidence for its regular use or be included in clinical guidelines.We conducted a randomized clinical trial comparing the use of intraoperative methadone to assess its impact on postoperative pain. Eighty-six patients undergoing elective laparoscopic cholecystectomy were allocated to receive either methadone (0.08 mg/kg) or morphine (0.08 mg/kg).Individuals who received methadone required less rescue morphine in the Post Anesthesia Care Unit for postoperative pain than those who received morphine (p = 0.0078). The patients from the methadone group reported less pain at 5 and 15 minutes and 12 and 24 hours following Post Anesthesia Care Unit discharge, exhibiting fewer episodes of nausea. Time to eye-opening was equivalent between the two groups.Intraoperative use of methadone resulted in better management of postoperative pain, supporting its use as part of a multimodal pain management strategy for laparoscopic cholecystectomy under remifentanil-based anesthesia.El manejo del dolor postoperatorio contribuye a reducir la morbilidad postoperatoria y los reingresos no programados. Pocos ensayos clínicos aleatorizados han evaluado la eficacia de la administración intraoperatoria de metadona en comparación con otros opioides como morfina, para el tratamiento del dolor postoperatorio, como para proporcionar evidencia de su uso regular o incluirse en guías clínicas.Realizamos un ensayo clínico aleatorizado comparando el uso de metadona intraoperatoria para evaluar su impacto sobre el dolor postoperatorio. Ochenta y seis pacientes sometidos a colecistectomía laparoscópica electiva fueron asignados para recibir metadona (0,08 mg/kg) o morfina (0,08 mg/kg).El grupo de pacientes que recibió metadona requirió menos morfina de rescate en la unidad de cuidados post-anestésicos para el manejo del dolor posoperatorio, en comparación con el grupo morfina (p = 0,0078). Los pacientes del grupo metadona reportaron menos dolor a los 5 y 15 minutos, y a las 12 y 24 horas postoperatorias, además de presentar menos episodios de náuseas. El tiempo de despertar entre ambos grupos fue equivalente.El uso intraoperatorio de metadona es superior a morfina en el manejo del dolor postoperatorio, apoyando su uso como parte de la estrategia de manejo multimodal del dolor para colecistectomía laparoscópica bajo anestesia total endovenosa con remifentanilo.

Introduction Chile has an incipient policy regarding humanized birth practices. Obstetric violence is becoming an issue in the public discussion, as brought up by women. Despite this advancement, no initiatives were observed to overcome the conflict. Questions arise from the different points of view of the main stakeholders involved. These questions help identify strategies contributing to the development of health policies that consider influencing actors. Objectives To identify stakeholders' perceptions of humanized care in childbirth and obstetric violence. Methods We conducted a scoping review that included articles and analysis of texts reflecting the scientific communities' point of view. We included statements from governmental, social, professional, and political actors as expressed in institutional websites. Moreover, we performed a qualitative inductive, thematic content analysis. Results We included seventy documents. The scientific community is visualized as aligned with ministerial recommendations for personalized childbirth. Several researchers analyze the difficulties for its improvement due to the historical, socio-cultural, and economic construction of the predominantly biomedical model for birthing. Convergence is observed among the scientific community and other stakeholders in recognition of humanized birth benefits and the need to overcome institutional obstacles within the health sector. However, the progress of the proposed change is slow, and health professionals' resistance to address women's complaints towards obstetric violence and claim of quality care is observed. This discussion finds its reflection in a parliamentary discussion. Conclusions The stakeholders' analysis reflects areas of conflict and consensus, as well as the diverse interacting dimensions that hinder the advance of humanized care in childbirth. This broad analysis strategy contributes to identifying critical aspects to be addressed in the development of integral and effective health policies.

Background Attentional deficit hyperactivity disorder (ADHD) in adults is associated with borderline personality characteristics or cluster B (emotional instability), but in certain populations, such as medical students, it might be associated with cluster C traits (perfectionism, dependency, anxiety). This may be compensatory to ADHD. Aim To analyze the association between ADHD and cluster C personality traits in medical students. Material and methods Biodemographic characteristics, the presence of ADHD and personality traits according to clusters A, B and C were evaluated in medical students. These characteristics were compared between students with unlikely diagnosis of ADHD (Group 1) and likely or very likely diagnosis of ADHD (Group 2). Results We included 336 participants (44% women). A likely or very likely diagnosis of ADHD was present in 64% (Group 2). Concerning personality traits, 45% exhibited traits of cluster A, 57% of cluster B, and 67% of cluster C. Compared to their counterparts of Group 1, participants in Group 2 were more likely to have a history of psychiatric/psychological care, previous diagnosis of ADHD and traits of cluster B (37 and 68% respectively) and C (55 and 74% respectively). The odds ratio of having A, B or C traits when a likely or very likely ADHD was present, were 1.29 95% confidence interval (CI) [0.8-2.07], 3.79 95% CI [2.3-6.22] and 2.4 95% CI [1.46-3.96], respectively. Conclusions Cluster C personality traits were frequent among medical students and were significantly associated with ADHD.

International audience; Post-transplantation lymphoproliferative disorder (PTLD) is a severe complication in organ transplant recipients. The use of T lymphocyte-depleting antibodies (TLDAb), especially rabbit TLDAb, contributes to PTLD, and the V158F polymorphism of Fc gamma receptor IIIA (FcγRIIIA) also named CD16A could affect the concentration–effect relationship of TLDAb. We therefore investigated the association of this polymorphism with PTLD in kidney transplant recipients. We characterized the V158F polymorphism in two case–control cohorts (discovery, n = 196; validation, n = 222). Then, we evaluated the binding of rabbit IgG to human FcγRIIIA-158V and FcγRIIIA-158F. The V158F polymorphism was not linked to PTLD in the overall cohorts, but risk of PTLD was increased in VV homozygous recipients receiving TLDAb compared with F carriers in both cohorts, especially in recipients receiving TLDAb without muromonab (discovery HR = 2.22 [1.03–4.76], P = 0.043, validation HR = 1.75 [1.01–3.13], P = 0.049). In vitro, we found that the binding of rabbit IgG to human NK-cell FcγRIIIA was increased when cells expressed the 158-V versus the 158-F allotype. While the 158-V allotype of human FcγRIIIA binds rabbit immunoglobulin-G with higher affinity, the risk of PTLD was increased in homozygous VV kidney transplant recipients receiving polyclonal TLDAb.

Case-control studies have been essential to the field of epidemiology and in public health research. In this design, data analysis is carried out from the outcome to the exposure, that is, retrospectively, as the association between exposure and outcome is studied between people who present a condition (cases) and those who do not (controls). They are thus very useful for studying infrequent conditions, or for those that involve a long latency period. There are different case selection methodologies, but the central aspect is the selection of controls. Data collection can be retrospective (obtained from clinical records) or prospective (applying data collection instruments to participants). Depending on the objective of the study, different types of case-control studies are available; however, all present a particular vulnerability to information bias and confounding, which can be controlled at the level of design and in the statistical analysis. This review addresses general theoretical concepts concerning case-control studies, including their historical development, methods for selecting participants, types of case-control studies, association measures, potential biases, as well as their advantages and disadvantages. Finally, concepts about the relevance on this study design are discussed, with a view to aid comprehension for undergraduate and graduate students of the health sciences. This is the third of a methodological series of articles on general concepts in biostatistics and clinical epidemiology developed by the Chair of Scientific Research Methodology at the School of Medicine, University of Valparaíso, Chile.Los estudios de casos y controles han sido esenciales en el desarrollo de la epidemiología y de la salud pública. En este diseño, el análisis de los datos se realiza desde el desenlace hacia la exposición, es decir, retrospectivamente, ya que se estudia la asociación entre factores de exposición y un desenlace conocido entre personas que ya presentan una condición (casos) y quienes no la presentan (controles). Por lo tanto, son muy útiles en condiciones infrecuentes o que requieren una larga latencia para ocurrir. Existen distintas metodologías de selección de casos, pero el aspecto central es la adecuada selección de controles. La recolección de los datos puede ser retrospectiva (desde de registros clínicos) o prospectiva (mediante la aplicación de instrumentos de recolección de datos a los participantes). En función del objetivo del estudio, se dispone de distintos tipos de estudios de casos y controles, pero todos presentan una vulnerabilidad particular al sesgo de información y de confusión, los que pueden controlarse a nivel del diseño y del análisis estadístico. En este artículo se abordan conceptos teóricos generales sobre los estudios de casos y controles, considerando aspectos históricos, metodología de selección de participantes, tipos estudios de casos y controles, medidas de asociación, potenciales sesgos, ventajas y desventajas. Finalmente, se discuten algunos conceptos de relevancia sobre este diseño para los estudiantes de pre y posgrado de ciencias de la salud. Esta revisión es la tercera entrega de una serie metodológica sobre conceptos generales en bioestadística y epidemiología clínica desarrollada por la Cátedra de Metodología de la Investigación Científica de la Escuela de Medicina de la Universidad de Valparaíso, Chile.

Systematic literature reviews are one of the main methodologies used to substantiate the health properties of foods and food constituents purported to affect human physiology. This tool is based on scientific evidence obtained from correctly performed randomized controlled trials. Systematic reviews make it possible to conclude whether there is a causal relationship between food consumed and health effects observed, thus supporting the use of the term “functional foods.” We present and analyze the prinicpal characteristics of, and ways by which, systematic reviews can contribute to the regulatory approval of health claims directed to consumers.Las revisiones sistemáticas de literatura constituyen una de las principales metodologías utilizadas en la validación de las propiedades saludables de los alimentos, o factores alimentarios, que afectan la fisiología humana. Esta herramienta, basada en la evidencia obtenida a través de ensayos clínicos aleatorizados realizados con un diseño experimental adecuado, permite concluir si existe una relación causal entre el producto consumido y un efecto beneficioso para la salud, principio que sustenta el calificativo de los alimentos como “funcionales”. Se presentan y analizan las características y la forma en la que las revisiones sistemáticas pueden contribuir a que las agencias regulatorias aprueben un mensaje saludable (health claim), dirigido al consumidor.

In experimental studies, researchers apply an intervention to a group of study participants and analyze the effects over a future or prospective timeline. The prospective nature of these types of studies allows for the determination of causal relationships, but the interventions they are based on require rigorous bioethical evaluation, approval from an ethics committee, and registration of the study protocol prior to implementation. Experimental research includes clinical and preclinical testing of a novel intervention or therapy at different phases of development. The main objective of clinical trials is to evaluate an interventions efficacy and safety. Conventional clinical trials are blinded, randomized, and controlled, meaning that participants are randomly assigned to either the study intervention group or a comparator (a control group exposed to a placebo intervention or another non-placebo or active interventionor not exposed to any intervention) to reduce selection and confounding biases, and researchers are also unaware of the type of intervention being applied. Intention-to-treat analysis (inclusion of all originally randomized subjects) should be done to avoid the effects of attrition (dropout) and crossover (variance in the exposure or treatment over time). A quasi-experimental design and external controls may also be used. Metrics used to measure the magnitude of effects include relative risk, absolute and relative risk reductions, and numbers needed to treat and harm. Confounding factors are controlled by randomization. Other types of bias to consider are selection, performance, detection, and reporting. This review is the fifth of a methodological series on general concepts in biostatistics and clinical epidemiology developed by the Chair of Scientific Research Methodology at the School of Medicine, University of Valparaíso, Chile. It describes general theoretical concepts related to randomized clinical trials and other experimental studies in humans, including fundamental elements, historical development, bioethical issues, structure, design, association measures, biases, and reporting guidelines. Factors that should be considered in the execution and evaluation of a clinical trial are also covered.En los estudios experimentales, el investigador aplica una intervención sobre los participantes, por lo que su eje temporal es prospectivo. Estas características permiten probar relaciones causales, pero implican una rigurosa evaluación bioética y una inscripción previa del protocolo de estudio. Entre las investigaciones experimentales se encuentran los estudios preclínicos y diversos ensayos con objetivos distintos según la fase de desarrollo en que se encuentre. Entre ellos se incluyen los ensayos clínicos, cuyo objetivo principal es evaluar la eficacia y la seguridad de alguna intervención o terapia. El diseño convencional de ensayo clínico es aleatorizado controlado enmascarado, donde se asigna aleatoriamente a los participantes a una intervención y a sus comparadores (otra intervención, placebo o nada); lo que permite controlar el sesgo de selección y el de confusión. Asimismo, los participantes y los investigadores no conocen la intervención que fue asignada. El análisis de sus resultados debe considerar a todos los sujetos originalmente aleatorizados, lo que se conoce como análisis por intención de tratar. Otros tipos de estudios experimentales incluyen los estudios cuasiexperimentales y los estudios experimentales con controles externos. Las medidas de magnitud del efecto utilizadas son el riesgo relativo, las reducciones absolutas y relativas de riesgo y los números necesarios a tratar y dañar. Si bien los factores de confusión son controlados por el proceso de aleatorización, otros sesgos que hay que considerar son los de selección, desarrollo, detección, desgaste y reporte. En este artículo, se abordan los conceptos teóricos generales sobre los estudios experimentales en seres humanos, fundamentalmente sobre los ensayos clínicos aleatorizados, considerando sus elementos fundamentales, desarrollo histórico, aspectos bioéticos, construcción, variantes en el diseño, medidas de asociación, sesgos y pautas de reporte. Finalmente, se sintetizan algunas consideraciones que siempre hay que tener en mente durante la ejecución y la evaluación de un ensayo clínico. Esta revisión es la quinta entrega de una serie metodológica sobre conceptos generales en bioestadística y epidemiologia clínica desarrollada por la Cátedra de Metodología de la Investigación Científica de la Escuela de Medicina de la Universidad de Valparaíso, Chile.

Patients of the Short-stay Child and Adolescent Unit of the Del Salvador Psychiatric Hospital (Valparaíso, Chile) exhibit different clinical and social characteristics compared to literature reports of other national centers, although published data are scarce.To describe the operation of the Unit, the socio-familial and clinical characteristics of its patients and analyze factors associated with their clinical evolution.We performed a cross-sectional study to describe the patients hospitalized over a three-year period. Variables were registered in an anonymized database. Clinical evolution was evaluated over the year following hospital discharge.The Unit's model of care can be described as involving biomedical, psychodynamic, and ecological components. We included 98 patients, of which 70.4% were male, and the average age was 11.5 ± 2.3 years. 82.6% were of low socioeconomic status, and 35.7% did not attend school; 98.9% presented family dysfunction, and 91.8% of parents had a history of psychopathology. The most frequent reason for admission was the risk of harm to self or others. The most frequent discharge diagnoses were behavioral, depressive, and personality development disorders. The average length of stay was 41.8 ± 31.1 days. The most commonly used pharmacological agents were antipsychotics and mood stabilizers. Regarding clinical evolution in the first year post-discharge, 47% were evaluated as positive, 27% regular, and 26% unsatisfactory. The factor associated with an unsatisfactory clinical course was having had in-patient antidepressants. Re-admission during the first year post-discharge was associated with comorbid substance use disorder. Treatment noncompliance was associated with a history of behavioral disorder at hospital discharge and having parents with a history of suicide or consummated suicide.The patient profile is one of low socioeconomic status, severe psychopathology, maladaptive behavior, family dysfunction, and parental psychopathology. Substance use disorder is also associated with readmission.La Unidad de Corta Estadía Infanto-juvenil del Hospital Psiquiátrico del Salvador (Valparaíso, Chile) y sus pacientes poseen características clínicas y sociales diferentes a las reportadas por la escasa literatura nacional al respecto.Describir el funcionamiento la unidad, las características sociofamiliares y clínicas de sus pacientes y analizar los factores asociados a su evolución clínica.Estudio transversal que describió el universo de pacientes hospitalizados durante tres años. Las variables se recogieron desde una base de datos anonimizada. Se evaluó la evolución clínica dentro del año posterior al egreso hospitalario.El modelo de atención de la unidad presenta los componentes biomédico, psicodinámico y ecológico. Se analizaron 98 pacientes, 70,4% hombres, con edad promedio de 11,5 ± 2,3 años. Un 82,6% perteneció al nivel socioeconómico bajo y 35,7% estaba desescolarizado; 98,9% presentó disfunción familiar y 91,8% de los padres portaba alguna psicopatología. Los motivos de ingreso más frecuente fueron riesgo de hetero y autoagresión. Los diagnósticos de egreso más frecuente fueron trastornos de conducta, depresivos y del desarrollo de la personalidad. El tiempo de estadía promedio fue de 41,8 ± 31,1 días. Los fármacos más utilizados fueron antipsicóticos y estabilizadores del ánimo. Un 47% tuvo una buena evolución clínica, 27% regular y 26% insatisfactoria. El único factor que se asoció a esta última fue haber tenido prescrito un antidepresivo durante la hospitalización. El factor que consistentemente se vinculó al reingreso a lo largo de un año, fue el haber presentado trastorno por consumo de sustancias. El abandono a tratamiento se relacionó con haber presentado un trastorno de conducta al egreso hospitalario y a tener padres con antecedente de suicidio o suicidio consumado.El perfil de pacientes de esta unidad corresponde a pacientes de nivel socioeconómico bajo, psicopatología severa, conducta desadaptativa, disfunción familiar y frecuente psicopatología parental. El trastorno por consumo de sustancias es un factor significativamente asociado al reingreso hospitalario.

Medicines are an economic good and a fundamental component of public and private spending and health decision-making. Assurance of their quality, efficiency and safety is essential. However, the variety of products on the Chilean market, including innovative and generic productsthe latter accounted for by many products that are certified as bioequivalent while others are notresults in a potentially confusing scenario for consumers and health providers. In this review, we intend to shed light on the concepts of bioequivalency (applicable to compounds of small molecular size) and biosimilarity (applicable to biological compounds of greater molecular complexity). In both cases, how the active substance interacts with the host organism must be demonstrated by studies carried out for this purpose. A direct application of the concept of bioequivalence is interchangeability, defined as the possibility of using a product of the same active principle, as long as the pharmaceutical form and dosage scheme are the same. Regulations related to bioequivalence and biosimilarity must not only guarantee safety and efficacy when products are interchanged, but also facilitate cost savings and access to medicines. Likewise, the implementation of evidence-based guidelines that standardize concepts of interchangeability should be encouraged, as this could lead to a more educated usage and a reduction in the information asymmetry between patients (users) and the industry. The importance of interchangeability of medicines is particularly relevant in two governmental health initiatives in Chile: the Explicit Health Guarantees Plan (GES) and the Financial Protection for Diagnoses and Treatments of High Cost, known as the Ricarte Soto Act. Nonetheless, it is not possible to guarantee that all alternative products to an innovative drug on the Chilean market are bioequivalent. The synthesis of knowledge available on this subject may impact and contribute to decision-making by stakeholders. It could also help to develop better health policies regarding bioequivalent and biosimilar pharmaceutical products in our country.

Phacoeresis is the procedure through which the lens is surgically removed to treat cataracts. A corneal endothelial loss is a recognized sequel. Although several factors associated with this harm have been described, the surgeon’s prior experience has been scarcely evaluated.To assess the association between the surgeon’s experience and other variables associated with a corneal endothelial cell loss in the context of phacoeresis.Clinical records of 198 patients undergoing cataract operations were prospectively reviewed. The experience of the surgeon and other variables were recorded, including cumulative dissipated energy, viscoelastic type, the use of trypan blue, amount of fluidics, ultrasound time, combined phacoemulsification energy, and pre- and postoperative corneal endothelial cell counts.No differences were observed in the postoperative corneal endothelial cell count between surgeons with more or less than five years of experience. Nevertheless, ophthalmologists with more than five years’ experience used less trypan blue, but more cumulative dissipated energy in each procedure, while less experienced ophthalmologists used less fluidics.Although there were differences in the surgical management regarding the surgeons’ experience in factors known to influence corneal endothelial cell loss, no differences in endothelial cell loss were observed as an outcome.La facoéresis es el procedimiento en que se extrae quirúrgicamente el cristalino para tratar las cataratas. La pérdida endotelial corneal es una complicación reconocida. Si bien se han descrito diversos factores asociados a este daño, la experiencia del cirujano ha sido poco explorada.Evaluar la asociación entre la experiencia del cirujano y otras variables asociadas a la pérdida celular endotelial en el contexto de la facoéresis.Se analizaron registros clínicos de 198 cirugías de cataratas, evaluando el efecto de la experiencia del cirujano y otras variables asociadas: energía disipada acumulada, tipo de viscoelástico empleado, uso de azul tripán, cantidad de fluídica, tiempo de ultrasonido, energía de facoemulsificación combinada y recuento celular endotelial pre y postoperatorio.No se observaron diferencias en el conteo postoperatorio de células endoteliales. Los oftalmólogos con más de cinco años de experiencia presentaron menor uso de azul tripán pero mayor cantidad de energía disipada acumulada en cada procedimiento, mientras que los oftalmólogos con menor experiencia utilizaron mayor cantidad de fluídica.Aunque hubo diferencias en el manejo de algunos factores influyentes sobre la pérdida endotelial cornal según la experiencia de los oftalmólogos, no se hallaron diferencias en relación a dicha pérdida como resultado final.

Therapeutic drug monitoring (TDM) is a clinical science centered around the quantification of drug concentrations in body fluids. To be considered candidates for TDM drugs must possess certain characteristics, including a narrow therapeutic index; in other words, to avoid toxicity at clinical doses. The relationship between dose and systemic concentration is particularly poor and unpredictable in special populations liable to different or dynamically changing pharmacokinetics. Antimicrobial use in the critical care setting has received special attention, where adequate concentrations for efficacy are especially pertinent. This chapter reviews recent evidence for TDM of established candidate drugs, aminoglycosides and vancomycin, and emerging evidence for beta-lactams, fluoroquinolones, linezolid, colistin and daptomycin, in the critically ill patient. The use of dose adaptation software for dose adjustment is discussed.

Observational studies evaluate variables of interest in a sample or a population, without intervening in them. They can be descriptive if they focus on the description of variables, or analytical when comparison between groups is made to establish associations through statistical inference. Cross-sectional studies and ecologicalalso called correlationalstudies are two observational methodological designs. Cross-sectional studies collect the data of the exposure variable and the outcome at the same time, to describe characteristics of the sample or to study associations. Ecological studies describe and analyze correlations among different variables, and the unit of analysis is aggregated data from multiple individuals. In both types of studies, associations of interest for biomedical research can be established, but no causal relationships should be inferred. This is the second of a methodological series of articles on general concepts in biostatistics and clinical epidemiology developed by the Chair of Scientific Research Methodology at the School of Medicine, University of Valparaíso, Chile. In this review, we address general theoretical concepts about cross-sectional and ecological studies, including applications, measures of association, advantages, disadvantages, and reporting guidelines. Finally, we discuss some concepts about observational designs relevant to undergraduate and graduate students of health sciences.Los estudios observacionales analizan las variables de interés en la muestra o en la población, sin intervenir en ellas. Pueden ser meramente descriptivos si se focalizan en la descripción de las variables, o analíticos, en el caso de presentar grupos de comparación para establecer asociaciones mediante la inferencia estadística. Los estudios transversales y los estudios ecológicos, también llamados correlacionales, son dos diseños metodológicos observacionales. Los estudios transversales recogen los datos de la variable exposición y desenlace en un mismo momento, para describir sus características y eventualmente estudiar asociaciones. Los estudios ecológicos describen y analizan las correlaciones entre distintas variables, pero su unidad de análisis corresponde a datos agregados de múltiples individuos. En ambos casos no puede inferirse una relación causal, pero sí pueden establecerse asociaciones de gran interés para la investigación biomédica. Esta revisión es la segunda entrega de una serie metodológica sobre conceptos generales en bioestadística y epidemiología clínica desarrollada por la Cátedra de Metodología de la Investigación Científica de la Escuela de Medicina de la Universidad de Valparaíso, Chile. En este artículo se abordan conceptos teóricos generales sobre estudios transversales y estudios ecológicos, considerando sus aplicaciones, medidas de asociación, ventajas, desventajas y reporte. Finalmente, se discuten algunos conceptos de relevancia sobre diseños observacionales para los estudiantes de pre y posgrado de ciencias de la salud.

Interindividual variability in immunosuppressive drug responses might be partly explained by genetic variants in proteins involved in the immune response or associated with IS pharmacodynamics. On a general basis, the pharmacogenetics of drug target proteins is less known and understood than that of proteins involved in drug disposition pathways. The aim of this review is to facilitate research related to the pharmacodynamics of the main immunosuppressive drugs used in solid organ transplantation. We elaborated a quality of evidence grading system based on a literature review and identified ‘highly recommended’, ‘recommended’ or ‘potential’ candidates for further research. It is likely that a number of additional rare variants might further explain drug response phenotypes in transplantation, and particularly the most severe ones. The advent of next-generation sequencing will help to identify those variants.

Voriconazole (VCZ) use is limited by its narrow therapeutic range and significant interpatient variability in exposure. This study aimed to assess (i) the impact of CYP2C19 genotype on VCZ exposure and (ii) the doses required to achieve the therapeutic range in adult patients with invasive fungal infections (IFIs). Therapeutic drug monitoring (TDM) of VCZ, based on trough concentration measurement, and CYP2C19 genotyping were used to guide VCZ dosing in Caucasian patients with IFIs. The two common polymorphisms in Caucasians (CYP2C19*2 and *17), associated with decreased or increased CYP2C19 activity, respectively, were correlated with the daily VCZ dose, pharmacokinetic parameters and concentration-to-dose ratio. In total, 111 trough concentration measurements from 35 genotyped patients were analysed using linear mixed-effect models. The mean VCZ doses required to achieve target concentrations were significantly higher in CYP2C19*17 carriers compared with CYP2C19*1/*1 individuals (P

International audience; Post-transplant lymphoproliferative disorders (PTLDs) represent a serious complication in solid organ transplantation and are the first cause of cancer related mortality in this population. Pre-transplant Epstein Barr Virus seronegativity and receipt of T cell depleting agents for induction or severe/refractory rejection are known risk factors, but they primarily impact early occurring disease. On the other hand, late occurring disease, which has typically not correlated with the above or other specific risk factors, has recently been shown to be associated with older recipient age and prolonged receipt of calcineurin inhibitors. Furthermore, recent data has contributed to and, in some instances shed light on, previous debate concerning the role of viruses other than EBV and the level of HLA mismatches as risk factors for PTLD. Gene association studies focusing on key cytokines and their receptors have identified several polymorphisms that may prove useful to identify patients at risk, with distinction for early and late occurring disease. Determining the influence of individual maintenance immunosuppressive agents on lymphomagenesis has been limited by the complexity of the multi-drug regimens used and absence of measures of drug exposure and time-dependent covariates in multivariable analyses. Biomarkers that measure the extent of immunosupression may have a role in avoiding PTLD, and other post-transplant complications.