Treatment with natalizumab during pregnancy in multiple sclerosis: The experience of implementing a clinical practice protocol (NAP-30).

BACKGROUND: Pregnancy planning in women with highly active multiple sclerosis (HAMS) who need a high-efficacy disease-modifying therapy (heDMT) currently requires a careful risk-benefit evaluation. This includes minimizing fetal drug toxicity and preventing MS reactivation. We describe our experience with natalizumab in women with HAMS and unplanned pregnancy by implementing a clinical practice protocol (NAP-30) designed to maintain the effectiveness of natalizumab during pregnancy, reduce fetal exposure and prevent complications. METHODS: This was an observational retrospective study including women with HAMS on active treatment with natalizumab who became unexpectedly pregnant in the period 2018-2021 and continued this treatment during pregnancy according to the NAP-30 protocol. MS clinical and radiological variables were analyzed before and during pregnancy and in the postpartum period, along with maternal and fetal toxicity during pregnancy and safety findings in newborns. We also describe the NAP-30 protocol, which includes the use of a bridging dose to adjust and maintain natalizumab infusions every 6 weeks during pregnancy up to week 30 and scheduled delivery at week 40. RESULTS: Six women (one in her first gestation) with a median age of 31.5 years at the onset of pregnancy (min-max: 24-37 years) were included. All were negative for anti-John Cunningham virus (JCV) antibodies and were on treatment with intravenous natalizumab 300 mg every 4 weeks. At the time of conception, three patients had received 12, 17 and 53 infusions of natalizumab, respectively, while for the remaining three patients natalizumab was their first DMT (two patients had received 6 infusions and one patient had received 3 infusions of natalizumab). All six patients received 6 doses of natalizumab during pregnancy according to the NAP-30 protocol. After delivery, all six patients restarted natalizumab every 4 weeks (median: 3 days; range: 2-4 days). No patients had relapses during pregnancy or at 6 months postpartum, nor did they develop any general health or laboratory abnormalities. The MRI scan performed at 4-6 months postpartum showed no new T2 lesions or gadolinium-enhancing lesions. No miscarriages or threatened miscarriages were reported. One of the patients underwent elective preterm delivery at week 35 after mild-to-moderate anemia was detected by fetal Doppler scan. The newborn had low birth weight (2080 g) and mild anemia, which resolved within two months with oral iron supplementation. The other infants were born with normal birth weight and showed no blood count abnormalities. After a median follow-up of 10 months, all six babies showed normal development with no complications detected. CONCLUSIONS: Based on our experience, the implementation of the NAP-30 protocol in women with HAMS and unplanned pregnancy undergoing treatment with natalizumab allows the continuation of natalizumab during pregnancy, with a very favorable clinical and radiological effectiveness and maternal-fetal safety profile during pregnancy and postpartum. Both in pregnancy with HAMS and in general, and particularly for successful implementation of the NAP-30 protocol, obstetric support and monitoring is essential for adequate pregnancy management.

The Influence of Flower Head Order and Gibberellic Acid Treatment on the Hydroxycinnamic Acid and Luteolin Derivatives Content in Globe Artichoke Cultivars.

Flower head orders and the use of GA3 (gibberellic acid) treatment could be two influencing factors determining the bioactive compound levels in artichoke, but little to no information is available about their effects. In this study, we have therefore evaluated the influence of these factors on the hydroxycinnamic acid and luteolin derivative levels in three categories of artichoke: Seed-propagated open-pollinated cultivars; vegetatively propagated cultivars; and seed-propagated hybrids. The hydroxycinnamic acids and luteolin derivatives were quantified by RP-HPLC-DAD. The average flower head weight was the lowest in tertiary heads and GA3-treated artichokes, followed by secondary and main heads. Moreover, the hydroxycinnamic acid and luteolin derivatives levels were significantly higher in tertiary heads than in secondary or main heads. In addition, the GA3 treatment significantly reduced the hydroxycinnamic acid content and, in contrast, improved luteolin derivatives levels. These effects depended on the flower head order and cultivar. Knowledge of the effects of flower head order and GA3 treatment is therefore key in order to achieve the greatest health-benefits from artichoke consumption.

Teaching Facilitation of Family Participation in Educational Institutions.

The participation of families in schools where their children study is a recurring research topic. This field tends to address the perception of parents or teaching staff. This work is novel in that it considers what teachers, and not families, do to facilitate this participation. The purpose of this work has been to contrast a theoretical model with a multidimensional questionnaire designed to obtain information on the assistance provided by teachers to improve parental involvement in schools. It will allow us to lay the foundations for the content necessary for the initial and permanent training of teachers. Then, an initial questionnaire was created and, after being subjected to expert judgment, it was applied to 225 Spanish teachers, using a quantitative and a non-experimental methodology. After calculating the exploratory and confirmatory factor analysis and applying the structural equation model, a questionnaire (QFIS-TP) was obtained that had satisfactory construct validity and reliability.

Prevention of rebound effect after natalizumab withdrawal in multiple sclerosis. Study of two high-dose methylprednisolone schedules.

BACKGROUND: Natalizumab (NTZ) is a disease-modifying treatment (DMT) in multiple sclerosis (MS) whose discontinuation can produce a "rebound effect", consisting of severe clinical deterioration and/or evidence of disease reactivation on magnetic resonance imaging (MRI). OBJECTIVE: To analyze the efficacy of two treatment schedules with intravenous methylprednisolone (IVMP) administered during the washout period of natalizumab (i.e., before starting another DMT) in preventing the rebound phenomenon. METHODS: Five-year retrospective study of NTZ withdrawals after at least 24 uninterrupted doses. Two IVMP schedules were tested. In schedule 1 (3-month washout), 1, 2, and 3 g of IVMP were administered on the first, second, and third month respectively. In schedule 2 (2-month washout), 1 and 2 g of IVMP were administered on the first and second month respectively. A new DMT was started 10 days after the end of each schedule. Rebound was defined as at least one clinical relapse plus rebound activity on MRI (>5 gadolinium-enhanced lesions and a number of new/T2-enhanced and/or gadolinium-enhanced lesions greater than before initiation of NTZ) during washout or at 6 months after new DMT initiation (6M-DMT). Clinical and MRI evaluations were performed at 3, 6, 12, and 24 months after initiation of the new DMT. RESULTS: Fifty patients (68% women) were included, with a mean (SD) age of 37.76 (10.88) years and pre-NTZ annualized relapse rate (ARR) of 1.78 (1.04). During NTZ therapy, mean Expanded Disability Status Scale (EDSS) score was 3.7 (1.73) and ARR was 0.23 (0.39). The ARR (mean of both schedules) was 0.1 (0.71) during washout and 0.32 (0.84) at 6M-DMT. Rebound was observed in 10% of cases (n = 5), with no significant clinical or radiological differences (p>0.05) between the two IVMP schedules. Rebound was observed in younger patients and was associated with new MRI lesions and higher ARR at 3M-DMT and 6M-DMT respectively, with no difference in EDSS after 2 years of follow-up. Neither the ARR before NTZ initiation nor the choice of new DMT after NTZ discontinuation was associated with development of rebound effect. CONCLUSIONS: Both IVMP schedules were well tolerated during NTZ washout and rebound was observed in only 10% of cases. In our experience, administration of IVMP during NTZ washout could reduce the possibility of a rebound effect.

Decision-making for the treatment of climacteric symptoms using the Menopause Rating Scale.

OBJECTIVE: The Menopause Rating Scale (MRS) is one of the most frequently used instruments to evaluate menopausal symptoms; however, no cut-off score is given that would indicate the need for treatment. Our goal was to determine such a cut-off score on the MRS, using as a standard a woman's own perception of her need for treatment in relation to the severity of her symptoms. MATERIAL AND METHODS: The sample comprised 427 healthy women aged 40-59 years who were not taking hormonal treatment. Based on the concept of quality of life, we considered that the patient required treatment if she herself believed that she required it, on the basis of the severity of at least one of her menopausal symptoms. To obtain an optimal MRS cut-off score associated with the need for treatment, an ROC curve analysis was performed. RESULTS: The symptoms rated "very severe" on the MRS (i.e. that most require treatment) were physical and mental exhaustion (95.8% of women) and muscle and joint discomfort (95.1%). In total, 378 women (88.5%) considered that their symptoms required treatment. The ROC curve analysis determined that the optimal cut-off score on the MRS to indicate the need for treatment would be 14 (area under the curve 0.86, p < 0.0001). This score achieved 76.5% sensitivity and 83.6% specificity. With this cut-off score, 97.1% of the women who considered that they required treatment for at least one of their symptoms would be treated. There was concordance of more than 90% between this cut-off score and a score of 4 (i.e. a rating of "very severe") for any of the symptoms on the scale. CONCLUSIONS: An MRS score ≥14 indicates the need for treatment for climacteric symptoms. In clinical practice, a score of 4 for any of the MRS items could be taken to indicate the need for treatment.

Manejo terapéutico de la sintomatología climatérica

La menopausia ha sido definida por la Sociedad Internacional de Menopausia como el cese permanente de la menstruación en la mujer, suceso determinado por la disminución de la producción hormonal. Trae consigo, por una parte, una sintomatología que interfiere en la calidad de vida de la mujer, la cual incluye síntomas vasomotores, psíquicos, atrofia urogenital; y, por otra, cambios metabólicos que implican aumento del riesgo de enfermedades crónicas como las enfermedades cardiovasculares y la osteoporosis. Con el progresivo aumento de la esperanza de vida, los grupos de mayor edad comienzan a ser parte importante de la población mundial. Por lo tanto, el manejo clínico de la posmenopausia pasa a ser un problema relevante de salud pública. Tiene como objetivo mejorar la calidad de vida y disminuir el riesgo de enfermedades crónicas. Para medir la existencia de síntomas y signos asociados a la menopausia se puede utilizar la Menopause Rating Scale (MRS), escala que permite evaluar la intensidad de la sintomatología. Se debe valorar además el riesgo cardiovascular y de osteoporosis. El tratamiento incluye mejorar los estilos de vida, el uso de terapia hormonal y de terapias para las comorbilidades. Estas orientaciones tienen como objetivo ser una ayuda para el médico al momento de evaluar a una mujer en este periodo de la vida. Se han basado principalmente en las 'Orientaciones Técnicas para la atención integral de la mujer en edad de climaterio en el nivel primario de red de salud' del Programa de Salud de la Mujer, Ministerio de Salud, Chile. Sin embargo, son solo orientaciones; cada decisión terapéutica debe ser siempre individualizada acorde a las características particulares de cada paciente.

Menopause has been defined by the International Menopause Society as the permanent cessation of menstruation in women, an event determined by the decrease in hormonal production. On one hand, the associated symptomatology interferes with the quality of life of the woman, and includes vasomotor and psychic symptoms and urogenital atrophy; on the other hand, metabolic changes that imply an increase in the risk of chronic diseases such as cardiovascular disease and osteoporosis. With the progressive increase in life expectancy, the older groups begin to be an important part of the world population. Therefore, the clinical management of the postmenopause becomes a relevant public health problem. Its objective is to improve the quality of life and reduce the risk of chronic diseases. The Menopause Rating Scale (MRS) is a scale to assess the existence and intensity of symptoms. Cardiovascular risk and osteoporosis should also be assessed. Treatment includes improving lifestyle, the use of hormonal therapy and therapies for comorbidities. These guidelines are intended to be an aid to the physician when evaluating a woman in this period of life. They have been based mainly on the "Technical Guidelines for the comprehensive care of women of climacteric age at the primary level of the health network" of the Women's Health Program, Ministry of Health, Chile. However, they are only orientations. Every therapeutic decision should be individualized according to the particular characteristics of each patient.

Clinical and radiological control of highly active relapsing-remitting multiple sclerosis with first-line natalizumab.

A 33-year-old man with gait instability, weakness of the left lower extremity, decreased visual acuity in the left eye, and urgency and urine incontinence was diagnosed of relapsing-remitting multiple sclerosis. He was treated with natalizumab (300 mg intravenously every 4 weeks) as first-line therapy, which reached at 6 months a favorable clinical evolution and dramatic radiological improvement (T2-weighted lesion load decreased by 50% and no gadolinium-enhancing T1 lesions) sustained over the course of 8 years. This clinical case shows the efficacy of natalizumab in a real-world setting and, particularly, the sustained effect of this drug in the long term as demonstrated by persistent radiological improvement. Natalizumab can be considered as the treatment of choice in relapsing-remitting multiple sclerosis forms presenting with two relapses and gadolinium-enhancing (Gd+) lesions.

Bilateral ethmoidal dural arteriovenous fistula: unexpected surgical diagnosis.

Dural arteriovenous fistulae (DAVFs) are infrequent lesions, the most common locations of which are the cavernous, sigmoid and transverse sinuses. The cribiform plate is one of the less frequent sites for DAVFs, where they entail a high hemorrhage risk. Feeding arteries for ethmoidal DAVFs can be uni- or bilateral. However, the draining fistulous system has classically been described as unilateral. The authors report the second case in literature of bilateral ethmoidal DAVF, which is defined as that with bilateral draining veins. The present case was diagnosed only after surgical exploration of both cribiform plates. No preoperative radiological test could detect the presence of a bilateral venous draining system from the ethmoidal DAVF. Possible reasons for that lack of presurgical diagnosis are discussed. Bilateral surgical exploration of the anterior cranial fossa is recommended when dealing with ethmoidal DAVFs, even when they seem to be unilateral on preoperative studies.

[Internal structure and standardised scores of the Torrance Test of Creative Thinking]. / Estructura interna y baremación del Test de Pensamiento Creativo de Torrance.

The present work sets out to study the internal structure of the Torrance Test of Creative Thinking (TTCT) and to establish standardised scores that will enable the test to be used in both a diagnostic and educational context. 649 students (319 girls and 330 boys), aged 5 to 12 years from various schools in Murcia and Alicante (SE Spain), took part in the study. The findings suggest that the psychometric characteristics of TTCT are satisfactory, and its internal structure can be attributed to three factors that are responsible for a high percentage of the variance (73.8%). The standardised score tables, which are provided for first time in this context, will be useful in the evaluation of creativity and the identification of students with high intellectual abilities.

Estructura interna y baremación del Test de Pensamiento Creativo de Torrance / Internal structure and standardised scores of the Torrance Test of Creative Thinking

Con el presente trabajo se pretende, por una parte, estudiar la estructura interna del TTCT (Torrance Thinking Creative TTCT), y, por otra, establecer los baremos con el fin de poder utilizar el test en el diagnóstico y ambientes educativos. En el trabajo han participado 649 alumnos (319 niñas y 330 niños) cuyas edades oscilan entre 5 y 12 años de edad, pertenecientes a diferentes colegios de Murcia y Alicante. Los datos apuntan a que el TTCT reúne las características psicométricas exigibles a este tipo de pruebas y su estructura interna responde a tres factores que explican un elevado porcentaje de varianza (73,8%). Los baremos que se ofrecen, por primera vez, en nuestro contexto educativo serán de gran utilidad para la evaluación de la creatividad y la detección de alumnos con altas habilidades intelectuales

The present work sets out to study the internal structure of the Torrance Test of Creative Thinking (TTCT) and to establish standardised scores that will enable the test to be used in both a diagnostic and educational context. 649 students (319 girls and 330 boys), aged 5 to 12 years from various schools in Murcia and Alicante (SE Spain), took part in the study. The findings suggest that the psychometric characteristics of TTCT are satisfactory, and its internal structure can be attributed to three factors that are responsible for a high percentage of the variance (73.8%). The standardised score tables, which are provided for first time in this context, will be useful in the evaluation of creativity and the identification of students with high intellectual abilities