Nueva metodología de evaluación del Holter basada en los sistemas dinámicos y la geometría fractal: confirmación de su aplicabilidad a nivel clínico / New methodology in Holter evaluation based on dynamics systems and fractal geometry: confirmation of its applicability at clinical level

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.

Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial.

Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks.

[Hemihypertrophy and scoliosis revealing a Chiari 1 malformation with syringomyelia]. / Hémi-hypertrophie et scoliose révélatrices d'une malformation de Chiari de type 1 avec syringomyélie.

We report the case of a 9-year-old boy with progressive thoracic scoliosis and crossed hemihypertrophy who was discovered with a Chiari 1 malformation and syringomyelia. These disorders are connected by complex physiopathological mechanisms; their association deserves attention. This observation reviews the importance of the clinical examination, particularly the neurological exam, in childhood scoliosis. The features suggesting a neurogenic background of spine deformation should be sought. Scoliosis with hemihypertrophy can be the sign of an underlying neurological abnormality.

Social and environmental factors and life expectancy, infant mortality, and maternal mortality rates: results of a cross-national comparison.

Using data from United Nations sources we conducted an international comparison study of infant and maternal mortality rates and life expectancy at birth. We examined these three dependent variables in relation to a range of independent variables including dietary factors, medical resource availability, gross national product (GNP/capita), literacy rates, growth in the labor force, and provision of sanitation facilities and safe water. Based on exploratory stepwise regression models, we fitted a series of general linear models for each of the three dependent variables. For the models with the highest explanatory ability, the percent of households without sanitation facilities showed the strongest association with all three dependent variables: life expectancy at birth (R2 = 0.83, B = -0.088, P = 0.0007); infant mortality rate (R2 = 0.87, B = +0.611, P < 0.0001); and maternal mortality rate (R2 = 0.54, B = +8.297, P = 0.002). Additional significant predictors of life expectancy at birth and infant mortality rate included the quantity of animal products consumed, the percent of households without safe water, excess calories consumed as fat, and the total literacy level. Maternal mortality rate was significantly associated with total energy consumption and excess energy consumed as fat. Using residuals from the general linear models we chose three outlying countries: Costa Rica, Sri Lanka and Egypt, on which to do case studies. These country case studies are discussed briefly in regard to characteristics that could account for their differing statistical relationships.

Presentation of growth velocities of rural Haitian children using smoothing spline techniques.

The examination of monthly (or quarterly) increments in weight or length is important for assessing the nutritional and health status of children. Growth velocities are widely thought to be more important than actual weight or length measurements per se. However, there are no standards by which clinicians, researchers, or parents can gauge a child's growth. This paper describes a method for computing growth velocities (monthly increments) for physical growth measurements with substantial measurement error and irregular spacing over time. These features are characteristic of data collected in the field where conditions are less than ideal. The technique of smoothing by splines provides a powerful tool to deal with the variability and irregularity of the measurements. The technique consists of approximating the observed data by a smooth curve as a clinician might have drawn on the child's growth chart. Spline functions are particularly appropriate to describe bio-physical processes such as growth, for which no model can be postulated a priori. This paper describes how the technique was used for the analysis of a large data base collected on pre-school aged children in rural Haiti. The sex-specific length and weight velocities derived from the spline-smoothed data are presented as reference data for researchers and others interested in longitudinal growth of children in the Third World.

Comparison of Haitian children in a nutrition intervention programme with children in the Haitian national nutrition survey.

PIP: Weight-for-height and height-for-age data were compared for preschool-age Haitian children enrolled in a community health and nutrition intervention program and children measured in the Haiti national nutrition survey of 1978. Cross-sections of the longitudinal data of the intervention program corresponding to the season when the national survey was conducted (May-September) were chosen for the 3 years of available program data (1969-71). Significantly less stunting was found in children in the 1970 and 1971 intervention group than in the children covered by the national survey. Tests of trend also showed that the height (or length) status of the children in the intervention program improved from 1969-71. Wasting, or low weight status, was in general not significantly different in any of the comparisons. Nevertheless, the data were more favorable to children in the intervention groups, even in 1970, a year of food shortages. The results of the comparison are consistent with a positive program effect. (author's)^ieng