Search

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.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of cannabis‐based medicines, compared to placebo or an alternative treatment strategy, for preventing nausea and vomiting during the postoperative period among adults undergoing elective surgery.

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.

Purpose: Antibiotics are commonly used during pregnancy. However, physiological changes during pregnancy can affect the pharmacokinetics of drugs, including antibiotics, used during this period. Pharmacokinetic evaluations have shed light on how antibiotics are affected during pregnancy and have influenced dosing recommendations in this context. Methods: A narrative review was conducted and included reports providing data reflecting drug distribution and exposure in the context of pregnancy. Results: Pharmacokinetic parameters of antibiotics in pregnancy and transplacental passage of antibiotics are comprehensively presented. Conclusions: Knowledge about the impact on pharmacokinetics and fetal exposure is especially helpful for complicated or severe infections, including intra-amniotic infection and sepsis in pregnancy, where both mother and fetus are at risk. Further studies are warranted to consolidate the role of therapeutic drug monitoring in complicated or severe infections in pregnant patients.

Background: The importance of foods or food constituents in mental health is increasingly recognized, and “nutritional psychiatry” is a growing discipline. Objective: This narrative review aims to present work supporting associations between food or food constituents and mental health, specifically depressive disorders. Methods: The data presented is derived from preclinical and clinical work, including in vitro and in vivo assays, as well as observational studies and randomized clinical trials of dietary interventions. The focus of the review is the mediation of inflammatory processes and oxidative stress by dietary constituents that are an integral part of a healthy diet, such as the Mediterranean diet and similar. Results and Discussion: We present evidence for the role of the diet in prevention and management of depressive disorders, beyond the effect of individual nutrients. The findings indicate that among the dietary components with higher degree of evidence to influence depressive disorders are long chain n-3 polyunsaturated fatty acids (EPA and DHA), and various dietary bioactive compounds, especially plant-derived secondary metabolites represented by polyphenols such as flavonoids and resveratrol. Conclusion: Diet exerts an important role on mental health, and evidence indicates that some dietary constituents contribute to the prevention of depressive disorders.

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.

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.

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.To analyze the association between ADHD and cluster C personality traits in medical students.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).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.Cluster C personality traits were frequent among medical students and were significantly associated with ADHD.

Resumen Introducción: Las infecciones por levaduras del género Cryptococcus afectan principalmente a pacientes con déficit de la inmunidad mediada por células. Han sido escasos los estudios de sensibilidad realizados para este género en Chile. Objetivos: Determinar la sensibilidad in vitro de Cryptococcus sp a antifúngicos de uso habitual y evaluar la concordancia esencial entre sensibilidad determinada por microdilución en caldo y por difusión en agar con tiras comerciales. Materiales y Método: Estudio descriptivo de 21 cepas aisladas desde liquido céfalo-raquídeo y sangre. Las CIM50 y CIM90 para fluconazol, voriconazol y anfotericina B se determinaron por microdilución en caldo (Sensititre Yeast One®) y por difusión en agar con tiras comerciales (MIC Test Strips). Resultados: Todas las cepas correspondieron a C. neoformans. Los rangos de CIM50 y CIM90 para cada antifúngico estudiado fueron amplios por ambos métodos. La concordancia esencial entre microdilución y difusión en agar con tiras comerciales fue de 24, 62 y 29% para fluconazol, voriconazol y anfotericina B, respectivamente. Conclusiones: La prueba de Sensititre Yeast One® y la de difusión en agar con tiras comerciales, MIC Test Strips, tienen una pobre concordancia esencial para fluconazol y anfotericina B.

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.

Cryptococcus yeast infections primarily affect immunocompromised patients. There have been few susceptibility studies conducted for this genus in Chile.To determine the in vitro susceptibility to commonly used antifungals and evaluate the concordance between susceptibility determined by microdilution in broth and commercially available strips.Descriptive study of 21 Cryptococcus strains, isolated from cerebrospinal fluid and blood. The MIC50 and MIC90 for fluconazole, voriconazole and amphotericin B was determined by broth microdilution (Sensititre Yeast One®) and by commercial drug sensitivity strips (MIC Test Strips).All strains corresponded to C. neoformans. The ranges of MIC50 and MIC90 for each antifungal studied were wide by both methods. The essential agreement between Sensititre Yeast One test and strips was 24, 62 and 29% for fluconazole, voriconazole and amphotericin B, respectively.The Sensititre Yeast One test and MIC Test Strips exhibited poor essential concordance, especially for fluconazole and amphotericin B.

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.

Aging is a physiological process accompanied by cognitive decline, principally in memory and executive functions. Alterations in the connectivity of the default mode network (DMN) have been found to participate in cognitive decline, as well as in several neurocognitive disorders. The DMN has antisynchronic activity with attentional networks (task-positive networks (TPN)), which are critical to executive function and memory. Findings pointing to the regulation of the DMN via activation of TPN suggest that it can be used as a strategy for neuroprotection. Meditation is a noninvasive and nonpharmacological technique proven to increase meta-awareness, a cognitive ability which involves the control of both networks. In this review, we discuss the possibility of facilitating healthy aging through the regulation of networks through meditation. We propose that by practicing specific types of meditation, cognitive decline could be slowed, promoting a healthy lifestyle, which may enhance the quality of life for the elderly.

Aim: To investigate the potential influence of variants in genes involved in the calcineurin pathway on the efficacy and toxicity of calcineurin inhibitors in renal transplantation. Materials & methods: Twenty-three polymorphisms in thirteen genes were tested in 381 renal transplant recipients receiving ciclosporin (n = 221) or tacrolimus (n = 160) and mycophenolate mofetil. Data were collected prospectively over the first year post-transplantation. Results: Multivariate survival analyses revealed no genetic associations with biopsy proven acute graft rejection and serious infections. Donor–recipient Cytomegalovirus mismatch was the only variable associated with serious infection. Conclusion: This large exploratory study casts doubts on the potential interest of genetic biomarkers related to CNI pharmacodynamics but associations with other phenotypes in transplantation deserve further studies.

The modulation of the immune system following solid organ transplantation has made considerable progress with new immunosuppressive regimens and has considerably improved rejections rates. The improvement in long-term allograft survival is, however, modest. A complex network of cytokines, chemokines, adhesion, activation and co-stimulatory molecules are the frontline contributors to allograft rejection, which in turn determines the evolution of graft function and its long-term survival. Polymorphisms in these genes influence protein levels and presumably their signaling effects. In this review, we present a relevant panel of candidate genes related to the immune system in the context of solid organ transplantation; we discuss the most convincing reports of genetic associations with outcomes in renal transplantation and highlight the most promising loci among the vast body of literature.

The placenta is a transitory organ, located between the mother and the foetus, which supports intrauterine life. This organ has nutritional, endocrine and immunologic functions to support foetal development. Several factors are related to the correct functioning of the placenta including foetal and maternal blood flow, appropriate nutrients, expression and function of receptors and transporters, and the morphology of the placenta itself. Placental morphology is crucial for understanding the pathophysiology of the organ as represents the physical structure where nutrient exchange occurs. In pathologies of pregnancy such as diabetes mellitus in humans and animal models, several changes in the placental morphology occur, related mainly with placental size, hypervascularization, higher branching capillaries of the villi and increased glycogen deposits among others. Gestational diabetes mellitus is associated with modifications in the structure of the human placenta including changes in the surface area and volume, as well as histological changes including an increased volume of intervillous space and terminal villi, syncytiotrophoblast number, fibrinoid areas, and glycogen deposits. These modifications may result in functional changes in this organ thus limiting the wellbeing of the developing foetus. This review gives an overview of recurrent morphological changes at macroscopic and histological levels seen in the placenta from gestational diabetes in humans and animal models. This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.

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.

We tested the influence of four polymorphisms and gene duplication in CYP2D6 on in vivo enzyme activity in a Chilean mestizo population in order to identify the most relevant genetic profiles that account for observed phenotypes in this ethnic group. CYP2D6 *2 (2850C>T), *3 (2549A>del), *4 (1846G>A), *17 (1023C>T) and gene duplication were determined by PCR-RFLP or PCRL in a group of 321 healthy volunteers. Individuals with different variant alleles were phenotyped by determining debrisoquine 4-hydroxylase activity as a metabolic ratio (MR) using a validated HPLC assay. Minor allele frequencies were 0.41, 0.01, 0.12 and 0.00 for CYP2D6 *2, *3, *4 and *17 variants, respectively, and the duplication frequency was 0.003. Genotype analysis correlated with phenotypes in 18 of 23 subjects (78.3%). 11 subjects were extensive metabolizers (EM), 8 were intermediate metabolizers (IM), 2 were poor metabolizers (PM) and 2 were ultra-rapid metabolizers (UM) which is fairly coincident with expected phenotypes metabolic ratios ranged from 0.11 to 126.41. The influence of CYP2D6 *3 was particularly notable, although only heterozygote carriers were present in our population. Individuals homozygous for *4 were always PM. As expected, the only subject with gene duplication was UM. In conclusion, there was a clear effect of genotype on observed CYP2D6 activity. Classification of EM, PM and UM through genotyping was useful to characterize CYP2D6 phenotype in the Chilean mestizo population.

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.

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.