Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology. METHODS: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.

A Maximum Likelihood Ensemble Filter Via A Modified Cholesky Decomposition For Non-Gaussian Data Assimilation.

This paper proposes an efficient and practical implementation of the Maximum Likelihood Ensemble Filter via a Modified Cholesky decomposition (MLEF-MC). The method works as follows: via an ensemble of model realizations, a well-conditioned and full-rank square-root approximation of the background error covariance matrix is obtained. This square-root approximation serves as a control space onto which analysis increments can be computed. These are calculated via Line-Search (LS) optimization. We theoretically prove the convergence of the MLEF-MC. Experimental simulations were performed using an Atmospheric General Circulation Model (AT-GCM) and a highly nonlinear observation operator. The results reveal that the proposed method can obtain posterior error estimates within reasonable accuracies in terms of ℓ - 2 error norms. Furthermore, our analysis estimates are similar to those of the MLEF with large ensemble sizes and full observational networks.

Teasing and disordered eating behaviors in Spanish adolescents.

The purpose of this study is to investigate the associations between peer teasing and body dissatisfaction (BD), emotional symptoms, drive for thinness (DT), and abnormal eating behaviors, as well as to analyze the mediating role of gender and body mass index (BMI) in such disorders. We screened 57,997 school children between 13 and 16 years of age. Scores in weight-related teasing and competency-related teasing were higher among girls, as well as overweight or obese individuals. Weight-teasing correlated more strongly with abnormal eating attitudes and behaviors, whereas competency-teasing correlated with emotional symptoms. Multiple linear regression analysis showed that weight-teasing is significantly and independently associated with BD, especially in boys. Multivariate analysis revealed a significant association between weight-teasing and abnormal eating in girls, although its predictive value was very low (Exp(B) = 1.009). Mediation analysis and Path analysis showed the mediating role of DT in this association. Interventions on teasing do not seem to be a priority in eating disorder prevention programs.

Children's eating attitudes test: validation in a sample of Spanish schoolchildren.

OBJECTIVE: To validate the Spanish version of the Children's Eating Attitudes Test (ChEAT). METHOD: The factor structure and other psychometric characteristics of the questionnaire were examined using the answers of 38,554 schoolchildren. Diagnostic efficiency was based on a standardized clinical interview of 968 schoolchildren who had previously completed the questionnaire. RESULTS: Five factors ("preoccupation with thinness," "dieting," "social pressure to eat," "purging," and "preoccupation with food and oral control") explained 46% of the variance. Cronbach's α was .858 for the total scale. The area under the receiver operating characteristic curve was .851. Sensitivity (SE) was 27% and specificity (SP) 96% for a cut-off of 20. A more appropriate cut-off was 15, where SE and SP were 62% and 90% respectively, and the positive and negative predictive values 27 and 98%. DISCUSSION: The ChEAT psychometric characteristics are adequate. The questionnaire is valid. A cut-off point of 15 is recommended for adolescents.

On the mathematical modelling and data assimilation for air pollution assessment in the Tropical Andes.

Air pollution assessment in the Tropical Andes requires a multidisciplinary approach. This can be supported from the understanding of the underlying biological dynamics and atmospheric behavior, to the mathematical approach for the proper use of all available information. This review paper touches on several aspects in which mathematical models can help to solve challenging problems regarding air pollution in reviewing the state-of-the-art at the global level and assessing the corresponding state of development as applied to the Tropical Andes. We address the complexities and challenges that modelling atmospheric dynamics in a mega-diverse region with abrupt topography entails. Understanding the relevance of monitoring and facing the problems of data scarcity, we call attention to the usefulness of data assimilation for uncertainty reduction, and how these techniques could help tackle the scarcity of regional monitoring networks to accelerate the implementation and development of modelling systems for air quality in the Tropical Andes. Finally, we suggest a cyberphysical framework for decision-making processes based on the data assimilation of chemical transport models, the forecast of scenarios, and their use in regulation and policy making.

A Simple Monte Carlo Framework to Assess Suicide Risk in Adolescents: A Study at a High School in Colombia.

It is very common to perform statistical tests to obtain insights about populations based on samples. For instance, in the context of psychology, when a set of instruments are applied to individuals, psychologists typically look for an explanation of particular psychological constructs (variables), such as personality, intelligence, or emotional functioning. It is common to cross statistical information from the results of different psychological tests to measure certain variables or to confirm prior beliefs. Here, we estimate the Joint Probability Density Function of suicide-related vulnerability and protective factors to assess suicide risk in adolescents. A Markov Chain Monte Carlo Method is employed to move away from the typical Gaussian assumption on data. This allows us to estimate probabilities of the development of suicidal ideation based on samples (which form a Markov chain). We employ our proposed statistical method at a high school in Colombia. The results reveal that adolescents can develop suicidal ideation as a consequence of the following factors, together with their corresponding probabilities: poor school performance 52%, low academic expectations 27%, school integration problems 68%, risky eating behaviors (binge-purge) 42%, risky eating behaviors (compensatory measurements) 21%, risky eating habits (restriction) 22%, and low family functionality 16%.

Teasing as a risk factor for abnormal eating behaviours: A prospective study in an adolescent population. / Burlas como factor de riesgo para conductas alimentarias anómalas: estudio prospectivo en una población adolescente.

INTRODUCTION: There are discrepancies in the literature about the role of teasing in the onset of eating pathology. This article aims to establish the influence of teasing in abnormal eating behaviors and attitudes in the adolescent population. MATERIAL AND METHODS: This is a two-year prospective study conducted in 7,167 adolescents between 13 and 15 years of age. In a first assessment, teasing about weight and teasing about abilities were measured by means of the POTS.questionnaire. Its association with eating psychopathology after two years was analyzed controlling nutritional status (BMI), body dissatisfaction, drive to thinness, perfectionism (EDI), emotional symptoms and hyperactivity (SDQ) which had also been measured in the first assessment. The analysis was carried out independently for both genders. RESULTS: The multivariant analysis found no significant or independent effect of teasing about weight or teasing about abilities in the onset of later eating psychopathology. The obtained models were similar for both genders although in girls, but not in boys, controlling BMI was enough to make any effect of teasing disappear. CONCLUSIONS: Teasing about weight or abilities has no direct effect, neither in boys nor in girls of 13 to 15 years old, in the development of eating psychopathology.

Anesthetic management of a patient with 3-methylcrotonyl-CoA carboxylase deficiency.

Patients with inborn errors of metabolism require special considerations in perioperative care. In the following case report, we describe the successful management of a patient with 3-methylcrotonyl-CoA carboxylase deficiency, a deficit that causes a secondary carnitine deficiency and impaired beta oxidation. Patients may have significant underlying cardiomyopathy, and are at risk for metabolic decompensation, acidosis, and hypoglycemia during periods of stress.

Is the physician's behavior in dyslipidemia diagnosis in accordance with guidelines? Cross-sectional ESCARVAL study.

BACKGROUND: Clinical inertia has been defined as mistakes by the physician in starting or intensifying treatment when indicated. Inertia, therefore, can affect other stages in the healthcare process, like diagnosis. The diagnosis of dyslipidemia requires ≥2 high lipid values, but inappropriate behavior in the diagnosis of dyslipidemia has only previously been analyzed using just total cholesterol (TC). OBJECTIVES: To determine clinical inertia in the dyslipidemia diagnosis using both TC and high-density lipoprotein cholesterol (HDL-c) and its associated factors. DESIGN: Cross-sectional. SETTING: All health center visits in the second half of 2010 in the Valencian Community (Spain). PATIENTS: 11,386 nondyslipidemic individuals aged ≥20 years with ≥2 lipid determinations. MEASUREMENT VARIABLES: Gender, atrial fibrillation, hypertension, diabetes, cardiovascular disease, age, and ESCARVAL training course. Lipid groups: normal (TC<5.17 mmol/L and normal HDL-c [≥1.03 mmol/L in men and ≥1.29 mmol/L in women], TC inertia (TC≥5.17 mmol/L and normal HDL-c), HDL-c inertia (TC<5.17 mmol/L and low HDL-c), and combined inertia (TC≥5.17 mmol/L and low HDL-c). RESULTS: TC inertia: 38.0% (95% CI: 37.2-38.9%); HDL-c inertia: 17.7% (95% CI: 17.0-18.4%); and combined inertia: 9.6% (95% CI: 9.1-10.2%). The profile associated with TC inertia was: female, no cardiovascular risk factors, no cardiovascular disease, middle or advanced age; for HDL-c inertia: female, cardiovascular risk factors and cardiovascular disease; and for combined inertia: female, hypertension and middle age. LIMITATIONS: Cross-sectional study, under-reporting, no analysis of some cardiovascular risk factors or other lipid parameters. CONCLUSIONS: A more proactive attitude should be adopted, focusing on the full diagnosis of dyslipidemia in clinical practice. Special emphasis should be placed on patients with low HDL-c levels and an increased cardiovascular risk.

Diabetes gestacional, hipotiroidismo y concentración urinaria de yodo en embarazadas. Yodurias en escolares en Paraguay: Exceso de yodo en la sal y riesgo de hiper e hipotiroidismo / Gestational diabetes, hypothyroidism and iodine urinary concentration in pregnant women. Urinary iodine in schoolage children in Paraguay: Iodine excess in salt and hyper and hypothyroidism risk

The main inclicator of iodine nutritional status of salt for human con-sumption is the urinary concentration of iodine, which is useful in monitoring universal levels in salt. Paraguay has suffered deficiency in salt with highprevalence of goiter in thepopulation reaching48.6%. In 2000, results of the ThyroidMobileproject in Latin America showed a goiter prevalence of 17% but 79.6% of the consumed iodized salt was adequate in paraguayan households (more than 15 ppm of iodine). The average values of iodine urinary concentration in 4487 scholars was 437 µg/L, 30% of the average value was between the ideal of 100 to 199 µg/L and 46.1% were above 300 mg/L, with risk of excess iodine. Urinary concentration of iodine during pregnancy was measure for the first time in Paraguay in 200 women; the average was 484 µg/L but diabetes and hypothyroidism during pregnancy was observe in 50% of them. Objective: Determine iodine concentration in urine of the school population in 17 departments of the country and measure the levels of iodine in urine in 200 pregnant women from 15-37 years of age and their levels of glycaemia, and thyroid TSH. Methods: During the years, 2006 and 2007 were evaluated 4487 school randomized, in a probabilistic sample, 3198 in rural areas and 1,289 in urban areas; casual urine samples was collected to determine iodine content. The urinary concentration of iodine in two hundredpregnant women, concentration of iodine in salt, and levels of glycaemia and TSH were also included in the present study All candidates agreed with the informed consent under the ethics rules. Results: These data showed by comparing the levels of iodine in urine concentration in more than adequate and excessive level but this last was markedly elevated (93.8%). The median level greater than 300 µg/L was observed in 100% of the 4,487 urine samples, while the median urinary iodine levels of300-500 µg/L was 91.3% and above 500 was 9.7%. These levels showed the risk of developing thyroid autoimmune diseases. In 200 pregnancy women the average of urine concentration of iodine was 498 pcg/L, subclinical and clinical hypothyroidism and gestational diabetes was 50% of both. Conclu-sion: To obtain normal median urinary iodine levels is necessary to decrease the amount of iodine in salt. The main recommendation is to insist on adequate monitoring of iodized salt consumption. Also continue surveillance and monitoring in sentinel sites reporting the importance of adequate iodine intake of the population especially in pregnant women that also need to be warm about the diabetes during pregnancy but also a regimen is necessary to keep them within the normal levels of glycemia. The subclinical hypothyroidism has been also studied in the same patients.

El principal indicador del impacto de la yodación de la sal de consumo humano es la concentración urinaria de yodo la cual es útil en el monitoreo de la sal. En la encuesta del año 1988 realizada en el Paraguay, se alcanzó una prevalencia de bocio de 48,6% en la población escolar con un déficit de yodo en la sal, pero el año 2000 en el estudio del proyecto de Tiroides Móvil, se redujo por el método ecográfico a 17%. Ese mismo año la mediana de los niveles urinarios en niños escolares de 6-12 años fue 258 µg/L, considerando que 30% se encontraba entre el valor ideal de 100 a 199 µg/L y 46,1% sobre 300 µg/L, implicando un riesgo de exceso de yodo en dicha población con las posibles consecuencias de aparición tanto de hipo como de hipertiroidismo. El 93% presentó exceso de yodo en la sal y la mediana urinaria fue 437 ug/ mL. Un grupo de embarazadas han sido estudiadas en el Hospital San Pablo por primera vez en el Paraguay para la determinación de la yoduria, yodo en sal, diabetes gestacional, hipotiroidismo en el embarazo y sus valores antropométricos resultando un hipotiroidismo subclínico del 50% y diabetes gestacional del 50%. Objetivo: Determinar las yodurias en la población escolar de 6-12 años pre púber de ambos sexos en 17 departamentos del país y en una submuestra en embarazadas y también niveles de glicemia en el embarazo en un hospital de Asunción. Sujetos y Métodos: En el periodo del 2006-2007 fueron evaluados 4.487 escolares randomizados, en una muestra probabilística, 3.198 en el área rural y 1.289 en el área urbana con muestras en orina casual. El año 2015, doscientas embarazadas fueron estudiadas con muestras de glicemia en ayunas y 2 horas post prandial, dosaje de TSH, yodo en sal de 100 gramos de la sal de consumo en sus hogares y de orina para ver la concentración de yodo en sal y urinaria de yodo. Todos los candidatos fueron estudiados bajo consentimiento autorizado y de acuerdo a normas éticas. Resultados: Al comparar los niveles de yodo en orina en el nivel más que adecuado y el excesivo de la yoduria se vió que éste último nivel estaba marcadamente elevado (93.8%), que la mediana de los niveles mayores a 300 ug/L era del 100% del total de las 4.487 muestras de orina, mientras que la mediana de los niveles de yoduria entre 300-500 µg/L fue de 91,3% y por encima de 500 fue 9.7% lo cual implicó el riesgo de desarrollar enfermedades tiroideas autoinmunes. Las embarazadas presentaron una mediana urinaria de yodo 484 µg/L, diabetes gestacional e hipotiroidismo subclínico en 50%. Conclusión: Para normalizar los niveles de yoduria, es necesario disminuir la cantidad de yodo en la sal. La recomendación es insistir en el monitoreo de la adecuada yodación de las sales de consumo familiar y continuar con la vigilancia y el monitoreo constante en sitios centinelas divulgando la importancia de la adecuada ingesta de yodo a la población. Un régimen dietético a las embarazadas es necesario implementar en el primer trimestre del embarazo.

Comorbidity between obesity and attention deficit/hyperactivity disorder: population study with 13-15-year-olds.

OBJECTIVE: This study analyzes whether obese children have a higher risk of attention deficit/hyperactivity "characteristics" (AD/HD) than do children with other nutritional states. METHOD: This study included 35,403 participants from 486 community schools. They completed the AD/HD scale of the Strengths and Difficulties Questionnaire (SDQ) and were weighed and measured. 2879 of the participants were obese and 78 were morbidly obese (BMI>40). RESULTS: A discrete, nonsignificant, increment was found in the AD/HD characteristics of male participants with morbid obesity, as compared with the other nutritional states. Among morbidly obese females, the prevalence of AD/HD characteristics was slightly superior, although not significantly, to that found in participants with normal weight, overweight or obese (BMI<40). CONCLUSION: Among nonclinical populations with a communitarian origin, previous findings reporting high rates of AD/HD in obese children are not replicated. This increment in the prevalence of AD/HD among hospitalized obese children could be the result of selection bias.

Alteraciones de los valores normales de yoduria en los niños de la escuela Juan de Salazar de la ciudad de Limpio / Alterations of normal values of ioduria in children of school Juan de Salazar of Limpio city

Introducción: Los valores alterados de yodo, ya sean inferiores o superiores al rango normal producen alteraciones en la función tiroidea. Con el presente trabajo, se determinó la yoduria en niños de 5 a 13 años de la escuela Juan de Salazar de la Ciudad de Limpio en el primer semestre del 2010. Diseño: Es un estudio observacional, descriptivo, de corte transverso, retrospectivo. Muestreo probabilístico. Resultados: La muestra estudiada estaba constituida por 83 niños, de los cuales 30 arrojaron valores de yoduria alterados. De los alterados, el 46.66% correspondió al sexo femenino y el restante, 53.33%, correspondió al sexo masculino. La edad promedio fue de 8.60 con extremos de 5 y 13 años. Al rango etario de 8 a10 años le corresponde el 53.33% del total de niños con valores alterados. Entre los niños con valores de yoduria superiores a los normales, 9 fueron del sexo masculino (47.36%), y 10 fueron del sexo femenino (52.63%). Entre los niños con valores de yoduria inferiores a los normales, 7 fueron del sexo masculino (63.63%), y 4 fueron del sexo femenino (36.36%).