Implementing a pharmacogenomic-driven algorithm to guide antiplatelet therapy among Caribbean Hispanics: a non-randomised clinical trial.

OBJECTIVES: To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months. DESIGN: An open-label, multicentre, non-randomised clinical trial. SETTING: Eight secondary and tertiary care hospitals (public and private) in Puerto Rico. PARTICIPANTS: 300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases. INTERVENTIONS: Patients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3-5 days after PCI. Adherence medication score was also measured. PRIMARY AND SECONDARY OUTCOMES: The occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. RESULTS: The genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p< 0.0001). CONCLUSIONS: The potential benefit of implementing our PGx-CDS algorithm to significantly reduce the incidence rate of MACCEs in post-PCI Caribbean Hispanic patients on clopidogrel was observed exclusively among high-risk patients, with apparently no evident effect in other patient groups. TRIAL REGISTRATION NUMBER: NCT03419325.

Temperature Differences Between Controlled Primary Hypothyroidism and Healthy Patients: An Exploratory Study.

Introduction: Hypothyroidism is conventionally treated with replacement therapy through levothyroxine (LT4). Despite the improvement in symptoms, cold intolerance persists in some patients. The present study aims to determine whether there is a difference in temperature perception and skin temperature between patients with primary controlled hypothyroidism (PCH) and a group of healthy controls matched for body mass index and age. Secondarily we aimed to determine difference in quality of life. Methodology: Skin temperature measurements were performed in both groups, both in the central and peripheral regions of the body. In addition, subjects were asked about their perception of temperature in a temperature-controlled room; anthropometric measurements were taken, their quality of life was assessed using the ThyPRO-39, and a thyroid hormone profile was performed. Results: Eleven patients in the PCH group and 30 patients in the control group were studied. It was found that the group with PCH presented a significantly lower palmar temperature than the control group [mean (SD) of 32.05 (1.79) vs 33.10 (1.30) oC, P = .046]. A mediation model showed a direct effect. Temperature perception was equal between groups. The median (interquartile range) of ThyPRO was 8 (5.2) points in the control group vs 21.8 (13.5) in the group of controlled hypothyroidism, P < .001. Discussion: These results suggest that, despite LT4 treatment, patients continue to present abnormalities in thermogenesis-related thermogenesis, and this may be due to a lack of hormonal adaptation to environmental changes and physiological demands, leading to lower body temperatures and increased sensitivity to cold.

Guiding Clinical Prescription of Topical Extemporaneous Formulations of Sodium Cromoglycate Based on Pharmaceutical Performance.

Cromoglycate (SCG) is widely used for allergy processes, and inflammatory states acting as a mast cell membrane stabilizer that inhibits the histamine and mediator release. Currently, SCG topical extemporaneous compounding formulations are prepared in hospitals and community pharmacies, as no industrial fabricated medicines are available in Spain. The stability of these formulations is unknown. Additionally, there are no clear guidelines on which concentration and vehicle are more suitable to enhance permeation across the skin. In this work, the stability of commonly prescribed topical SCG formulations in clinical practice was evaluated. Different vehicles commonly employed by pharmacists daily for formulating topical SCG were investigated (Eucerinum, Acofar Creamgel, and Beeler's base) at different concentrations, ranging from 0.2 to 2%. The stability of topical extemporaneous compounded SCG formulations can be extended for up to three months at room temperature (25 °C). Creamgel 2% formulations significantly improved the topical permeation of SCG across the skin, being 4.5-fold higher than formulations prepared with Beeler's base. The reason attributed to this performance can be related to the lower droplet size formed upon dilution in aqueous media combined with a lower viscosity, which facilitates its application and extensibility on the skin. The higher the SCG concentration in Creamgel formulations, the higher the permeability across both synthetic membranes and pig skin (p-value < 0.05). These preliminary results can be used as a guide to prompt a rational prescription of topical SCG formulations.

Implementing a Pharmacogenomic-driven Algorithm to Guide Antiplatelet Therapy among Caribbean Hispanics: A non-randomized prospective cohort study.

Background: After percutaneous coronary intervention (PCI), clopidogrel resistant patients are at an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs). We aimed to assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the occurrence of these ischemic events and improves outcomes among Caribbean Hispanic patients from Puerto Rico, who are underrepresented in clinical pharmacogenomic (PGx)-guided implementation studies. Methods: Individual platelet function testing (PRU) measures, CYP2C19*2 and PON1 rs662 genotypes, clinical and demographic data from 8 medical facilities were included. Patients were separated into standard of care (SoC) and genotype-guided groups (150 each). Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Alternative therapy with ticagrelor was recommended for patients with a high risk score ≥2. Statistical associations between patient time free of MACCEs and predictor variables (i.e., treatment groups, risk scores) were tested in this population using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. Results: Median age of participants is 67 years; BMI: 27.8; 48% women; 14% smokers; 59% with type-2 diabetes mellitus (T2DM). Among patients with high-risk scores who were free from MACCE events 6 months after coronary stenting, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in terms of reducing the incidence rate of atherothrombotic events. Conclusions: The clinical utility of our PGx-driven CDS algorithm to reduce the incidence rate of MACCEs among post-PCI Caribbean Hispanic patients on clopidogrel was externally demonstrated. Clinical Trial Registration Unique Identifier: NCT03419325.

El abordaje de la depresión en el ámbito del trabajo: recomendaciones clave / Management of depression in the work setting: key recommendations

La depresión en el ámbito del trabajo representa una de las primeras causas de pérdida de productividad, absentismo laboral, incremento de accidentes laborales, utilización de los servicios de salud y jubilación anticipada. Los costes totales atribuibles a la depresión constituyen más del 1% del PIB, por lo que su correcto abordaje repercutirá no solo en el bienestar emocional de los trabajadores sino también en la productividad de las empresas y la sostenibilidad del Sistema Nacional de Salud. La depresión no solo es un problema estrictamente sanitario, sino que hay que enmarcarlo en un contexto mucho más amplio vinculado al bienestar social. El presente documento es el resultado de un proceso de consulta y reuniones entre un grupo multidisciplinar de expertos y ofrece una serie de recomendaciones sobre la definición, detección y opciones de tratamiento de la depresión, con especial interés en el ámbito del trabajo. Entre otras medidas, se propone promover programas que permitan concienciar y ayudar a los empleados y empleadores a reconocer y manejar la depresión en los lugares de trabajo, así como mejorar las políticas y la legislación que les protegen. Esta estrategia multidimensional y efectiva, basada en un acercamiento holístico al problema, debe situar la depresión como un problema clave en las empresas, cuyo abordaje debe ser un objetivo estratégico prioritario (AU)

Depression in the work setting is one of the leading causes of lost productivity, absenteeism, increased accidents, use of health services, and early retirement. As the total costs attributable to depression are more than 1% of GDP, the correct approach will impact not only on the emotional welfare of workers but also on business productivity and sustainability of the National Health System. Depression is not just a health problem, but should be framed it in a much broader context linked to social welfare. This document is the result of a process of consultation and meetings between a multidisciplinary group of experts, and offers a series of recommendations on the definition, detection and treatment options of depression, with special interest in the occupational setting. Among other measures, it intends to promote programs that should raise awareness and help employees and employers to recognise and manage depression in the workplace, and to improve policies and legislation that protect them. This multidimensional and effective strategy, based on a holistic approach to the problem, places depression as a key problem in companies, for which the approach should be a priority strategic objective (AU)