Nueva metodología de evaluación del Holter basada en los sistemas dinámicos y la geometría fractal: confirmación de su aplicabilidad a nivel clínico

Introducción: La teoría de sistemas dinámicos establece medidas cuantitativas de evolución de los sistemas mediante la construcción de atractores. Medidas de ocupación espacial de atractores cardiacos en el espacio fractal de Box Counting diferenciaron normalidad y enfermedad crónica de enfermedad aguda. Objetivo: Aplicar la metodología desarrollada para evaluar matemáticamente el estado cardiaco de Holter con diferentes patologías, confirmando la aplicabilidad de esta metodología para la detección de dinámicas agudas mediante medidas de concordancia estadística respecto al Gold Standard. Metodología: Se analizaron 170 Holter, incluyendo normales, crónicos y en estado agudo. Se construyeron simulaciones de la totalidad de la dinámica basada en número de latidos y frecuencia mínima y máxima cada hora durante 21 horas, para construir atractores en el espacio de fases. Se calculó la dimensión fractal de los atractores evaluando su ocupación espacial en el espacio de Box Counting, estableciendo cuáles corresponden a normalidad y enfermedad aguda de acuerdo con resultados matemáticos previos. Se comparó el diagnóstico matemático con el diagnóstico convencional del Holter, tomado como Gold Standard, estableciendo valores de sensibilidad, especificidad y coeficiente Kappa. Resultados: La dimensión fractal no logró evidenciar diferencias cuantitativas mientras que la metodología detectó en todos los casos dinámicas normales y en estado agudo independientemente de la patología, logrando valores de sensibilidad, especificidad, valor predictivo positivo y negativo de 100%, y coeficiente Kappa de 1. Conclusiones: Se confirmó la capacidad de la metodología físico-matemática para detectar dinámicas agudas independientemente de la patología asociada, confirmando una auto-organización acausal de la dinámica del sistema cuya evaluación permite establecer medidas de aplicabilidad clínica.  Introduction: Dynamic systems theory provides quantitative measures of evolution of systems by building attractors. Spatial occupation measures of cardiac attractors in fractal Box Counting space differentiated normality and chronic disease from acute illness. Objective: To apply the developed methodology to evaluate mathematically the cardiac status of Holter with different pathologies, confirming the applicability of this methodology for the detection of acute dynamic by statistical measures of agreement regarding the Gold Standard. Methodology: 170 Holter, including normal, chronic and in acute states were evaluated. Simulations were constructed the entire dynamic based on the number of beats and the minimum and maximum frequencies every hour for 21 hours, to build attractors in the phase space. The fractal dimension of attractors is calculated, evaluating the spatial occupation in the Box Counting space, establishing which corresponds to normal setting and acute disease in accordance with previous mathematical results. Mathematical diagnosis was compared with conventional diagnostic Holter, taken as the Gold Standard, setting sensitivity, specificity, positive and negative predictive value and Kappa coefficient. Results: The fractal dimension failed to show quantitative differences while the methodology detected in all cases normal dynamics and acute state independently of the disease, achieving sensitivity, specificity, positive and negative predictive value of 100% and a Kappa 1. Conclusions: the ability of the physical-mathematical methodology to detect acute dynamic regardless of the associated pathology was confirmed, as well as an acausal self-organization of the system dynamics, which allows for assessment of clinical applicability measures

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Azimuthal separation in nearly back-to-back jet topologies in inclusive 2-and 3-jet events in pp collisions at root s=13TeV

A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Delta phi(12), is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 35.9 fb(-1) are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with themeasurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 degrees <Delta phi(12) <180 degrees. The 2- and 3-jet measurements are not simultaneously described by any of models.Peer reviewe

An Unusual Case of Multiple Tendinous Xanthomas Involving the Extremities and the Ears

Tendinous and subcutaneous xanthomas are nodular deposits of lipid-filled macrophages, which commonly form on the Achilles tendon, hands, feet, elbows, and knees. These nodules are frequently associated with familial hyperlipidemia, a group of diseases involving impaired cholesterol metabolism, and the accelerated development of atherosclerotic plaques. Since xanthomas may precede the diagnosis of hyperlipidemia, early identification can lead to preventative treatment that reduces the risk and morbidity of cardiovascular disease, including myocardial infarction. This case report presents a 43-year-old African-American male with multiple xanthomas involving the Achilles tendon, soles, hands, knees, elbows, and is associated with the unusual involvement of the ear

Prediction of Vigilant Attention and Cognitive Performance Using Self-Reported Alertness, Circadian Phase, Hours since Awakening, and Accumulated Sleep Loss

Sleep restriction causes impaired cognitive performance that can result in adverse consequences in many occupational settings. Individuals may rely on self-perceived alertness to decide if they are able to adequately perform a task. It is therefore important to determine the relationship between an individual’s self-assessed alertness and their objective performance, and how this relationship depends on circadian phase, hours since awakening, and cumulative lost hours of sleep. Healthy young adults (aged 18–34) completed an inpatient schedule that included forced desynchrony of sleep/wake and circadian rhythms with twelve 42.85-hour “days” and either a 1:2 (n = 8) or 1:3.3 (n = 9) ratio of sleep-opportunity:enforced-wakefulness. We investigated whether subjective alertness (visual analog scale), circadian phase (melatonin), hours since awakening, and cumulative sleep loss could predict objective performance on the Psychomotor Vigilance Task (PVT), an Addition/Calculation Test (ADD) and the Digit Symbol Substitution Test (DSST). Mathematical models that allowed nonlinear interactions between explanatory variables were evaluated using the Akaike Information Criterion (AIC). Subjective alertness was the single best predictor of PVT, ADD, and DSST performance. Subjective alertness alone, however, was not an accurate predictor of PVT performance. The best AIC scores for PVT and DSST were achieved when all explanatory variables were included in the model. The best AIC score for ADD was achieved with circadian phase and subjective alertness variables. We conclude that subjective alertness alone is a weak predictor of objective vigilant or cognitive performance. Predictions can, however, be improved by knowing an individual’s circadian phase, current wake duration, and cumulative sleep loss

The relationship between <i>PVT standard deviation</i> and <i>PVT mean</i>.

<p>Data are shown for Chronic Sleep Restriction (CSR) and Control conditions. Data from both conditions demonstrate a robust relationship between the standard deviation and mean of the Psychomotor Vigilance Task (PVT). Logarithms of each variables are plotted to the wide ranges that the data span. Each data point represents one 10-min session. The same polynomial fit is shown to data in both plots with 95% confidence intervals indicated by dashed lines.</p

<i>PVT mean</i> vs. Subjective <i>Alertness</i>.

<p>Data are shown for Chronic Sleep Restriction (CSR) and Control conditions. Individual data points represent Subjective <i>Alertness</i> and mean Psychomotor Vigilance Task (PVT) responses from the same individual, paired by close timing in the same testing session. A single logistic function is fit to all data (solid line), with 95% confidence intervals of the best-fit line indicated by dashed lines.</p