Application of machine learning to predict reduction in total PANSS score and enrich enrollment in schizophrenia clinical trials

Clinical trial efficiency, defined as facilitating patient enrollment, and reducing the time to reach safety and efficacy decision points, is a critical driving factor for making improvements in therapeutic development. The present work evaluated a machine learning (ML) approach to improve phase II or proof-of-concept trials designed to address unmet medical needs in treating schizophrenia. Diagnostic data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial were used to develop a binary classification ML model predicting individual patient response as either "improvement," defined as greater than 20% reduction in total Positive and Negative Syndrome Scale (PANSS) score, or "no improvement," defined as an inadequate treatment response (<20% reduction in total PANSS). A random forest algorithm performed best relative to other tree-based approaches in model ability to classify patients after 6 months of treatment. Although model ability to identify true positives, a measure of model sensitivity, was poor (<0.2), its specificity, true negative rate, was high (0.948). A second model, adapted from the first, was subsequently applied as a proof-of-concept for the ML approach to supplement trial enrollment by identifying patients not expected to improve based on their baseline diagnostic scores. In three virtual trials applying this screening approach, the percentage of patients predicted to improve ranged from 46% to 48%, consistently approximately double the CATIE response rate of 22%. These results show the promising application of ML to improve clinical trial efficiency and, as such, ML models merit further consideration and development

Relationship between functional capacity and psychosocial profile among community-dwelling elderly-people. A gender based study

Objetivos: Describir la relación que la capacidad funcional tiene sobre la calidad de vida relacionada con la salud en personas mayores no institucionalizadas. Métodos: Se utilizó un diseño de corte transversal-observacional en el que se incluyeron 43 sujetos (19 hombres y 24 mujeres). Se analizó la capacidad funcional (T6MW, TUG, CST y PM) y variables psicosociales de calidad de vida (SF-36). Se establecieron diferencias en función del nivel de capacidad funcional de cada una de las pruebas, así como las relaciones entre cada una de las variables. Resultados. Se observó que aquellos sujetos que alcanzaban mayores niveles en las pruebas de capacidad funcional, reportaban mayores puntuaciones en las diferentes dimensiones del SF36. Conclusión y Discusión. Los resultados que presentamos en nuestro estudio sugieren que mayores niveles en la capacidad funcional pueden mejorar la CVRS de personas mayores no institucionalizadas.Objective: to elucidate the relationship between functional capacity and Health-related quality of life among community-dwelling elderly people. Methods: A cross-sectional design was used with 43 subjects (19 males and 24 females). Functional capacity (T6MW, TUG, CST y PM) and Health-related Quality of Life (SF-36) were assessed. Differences based on functional capacity were analyzed. The relationships between the variables of the study were also tested. Results: Those participants reporting better functional capacity values also depicted better scores on SF-36 (p<0.05). Conclusion and Discussion: Results from this study suggests that greater levels of functional capacity could enhance the health-related quality of life among community-dwelling elderly people.Sin financiaciónNo data 201

Immunosenescence and CoQ10

The decline of the immune system associated to aging is becoming a global issue nowadays due to the increase of lifespan. Immunosenescence is the deteriorated adaptative capacity of the immune system leading to increase in morbidity and mortality in elderly population. Aging has been related to a progressive affectation of mitochondria such as increase of mtDNA mutation, deregulation of electron transport chain, increase in ROS production and reduction in ATP production. Immunosenescence has been associated with aging associated mitochondrial dysfunction linked to chronic inflammation that induce higher oxidative stress levels and mitochondrial damage deteriorating the already compromised immune system. CoQ10 administration could be considered a beneficial strategy in order to reduce the progression of age-related diseases. Highlighting the important role of CoQ10 on mitochondrial function it has been proposed that this unique antioxidant soluble lipid could be helpful in the management of immunosenescence. High levels of CoQ10 have been related with a delay of immunosenescence attributable to a reduction in DNA damage. Other prolongevity factors, such as caloric restriction and exercise, have been considered for their potential effect in delaying aging effect and immunosenescence mainly affecting mitochondrial physiology and biogenesis and antioxidant activity

Extramitochondrial coenzyme Q10 in aging

Organisms maintain a complex relationship between the production of oxidative radicals and endogenous antioxidant levels and antioxidant enzymatic activities. Apart of its bioenergetics role in mitochondria, CoQ10 is also present in the rest of cell membranes and in plasma lipoproteins. In these structures, CoQ10 plays a key antioxidant role, preventing lipidic oxidative damage and regulating enzymatic and regulatory activities. Many years ago, two essential CoQ10-dependent dehydrogenases were characterized, cytochrome b5 reductase and NQO1. These enzymes are able to maintain a redox cycle of CoQ10 in membrane, preventing oxidative damage and maintaining other antioxidant systems depending on ascorbic acid and α-tocopherol. Recently, other CoQ10-dependent enzymes such as a mitochondrial dehydrogenase (FSP1) and a dehydrogenase associated with the outer leaf of the plasma membrane have increased the importance of CoQ10 in the prevention of oxidative damage and the regulation of apoptosis. The role of these enzymes in aging remains to be clearly determined but CR, a known prolongevity procedure, increases the activity of CoQ10-dependent dehydrogenases and prevents oxidative damage associated with aging. Then, maintenance of the activity of these extramitochondrial CoQ10-dependent activities seems to be important for aging and longevity.This work was supported by grants from the Instituto de Salud Carlos III