Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences / Interacciones recogidas en la ficha técnica de Paxlovid, clasificadas según los riesgos, grupos farmacológicos y consecuencias

Paxlovid (nirmatrelvir plus ritonavir) is a new oral antiviraltherapeutic for the treatment of COVID-19. Nirmatrelvir is aninhibitor of SARS-CoV-2 main protease, while ritonavir is usedas a CYP3A inhibitor in low doses to slow the metabolism ofnirmatrelvir, thus enhancing their therapeutic effect. The isoenzyme CYP3A4 is responsible for at least part of the oxidativemetabolism of approximately 60% of available medicationsand ritonavir is therefore a significant source of drug interactions. We describe here the drugs that are contraindicatedor should be used with or without precautions when Paxlovid(nirmaltrevir plus ritonavir) should be administered accordingto each fact sheet in force at the Spanish Agency for Medicines and Health Products (AU)

Paxlovid (nirmatrelvir más ritonavir) es un nuevo tratamiento antivírico oral para la COVID-19. Nirmatrelvir es un inhibidor de la principal proteasa del SARS-CoV-2, mientras queritonavir es usado como un inhibidor de la CYP3A a baja dosispara reducir el metabolismo de nirmatrelvir, potenciando asísu efecto terapéutico. La isoenzima CYP3A4 es responsable deal menos una parte del metabolismo oxidativo de aproximadamente el 60% de los medicamentos disponibles, por lo que elritonavir es una fuente importante de interacciones farmacológicas. Describimos los fármacos cuyo uso está contraindicado o deben utilizarse con precauciones o sin ella cuando debeadministrase Paxlovid (nirmaltrevir más ritonavir), de acuerdocon cada ficha técnica vigente en la Agencia Española de Medicamentos y Productos Sanitarios (AU)

Robust midgap states in band-inverted junctions under electric and magnetic fields.

Several IV-VI semiconductor compounds made of heavy atoms, such as Pb1-x Sn x Te, may undergo band-inversion at the L point of the Brillouin zone upon variation of their chemical composition. This inversion gives rise to topologically distinct phases, characterized by a change in a topological invariant. In the framework of the k·p theory, band-inversion can be viewed as a change of sign of the fundamental gap. A two-band model within the envelope-function approximation predicts the appearance of midgap interface states with Dirac cone dispersions in band-inverted junctions, namely, when the gap changes sign along the growth direction. We present a thorough study of these interface electron states in the presence of crossed electric and magnetic fields, the electric field being applied along the growth direction of a band-inverted junction. We show that the Dirac cone is robust and persists even if the fields are strong. In addition, we point out that Landau levels of electron states lying in the semiconductor bands can be tailored by the electric field. Tunable devices are thus likely to be realizable, exploiting the properties studied herein.

Influência da estabilização segmentar core na dor e funcionalidade da coluna lombar / Influence of segmental core stabilization in pain and spinal lumbar functionality

Atualmente a dor lombar descreve-se como uma dor limitante que resulta em incapacidade funcional. Dentre as técnicas de intervenção terapêutica, destaca-se o fortalecimento segmentar do core. O objetivo do presente trabalho é analisar o efeito do fortalecimento do core na dor e na função da coluna lombar. Trata-se de um estudo clínico de intervenção, desenvolvido nas Clínicas Integradas Guairacá, com 12 indivíduos, de ambos os sexos, com média de idade de 49,2 ± 6,6 anos, que apresentaram dor lombar inespecífica. Foram incluídos no estudo indivíduos que conseguissem realizar os exercícios de estabilização segmentar do core. Para quantificar a dor da coluna lombar, utilizou-se a Escala Visual Analógica da Dor (EVAD) e para avaliação da função lombar foi aplicado o Índice Funcional de Oswestry (IFO). Para a análise estatística, utilizou-se o software BioEstat 5.3. Para testar a normalidade dos dados, foi utilizado o teste de d'Agostino e para testar a significância dos resultados, utilizou-se o teste T-Student, com significância de p ? 0,05. Na comparação pré e pós-intervenção dos valores do IFO, observou-se uma redução estatisticamente significante p = 0,0012. Na comparação pré e pós-intervenção dos valores EVAD observou-se uma redução estatisticamente significante p = 0,0001. Contudo, o presente trabalho demonstra que a aplicação dos exercícios de estabilização lombar core apresenta-se efetiva na melhora da dor e da função lombar. (AU)

Currently low back pain is described as a limit pain that results in functional disability. Among the techniques of therapeutic therapy, the segmental strengthening of the "core" is highlighted. The aim of the present study is to analyze the effect of core strengthening on pain and lumbar spine function. The present study is a clinical intervention study, developed in the Guairacá Integrated Clinics, with 12 individuals, of the both sexes, mean age 49.2 ± 6.6 years, with nonspecific low back pain. There are also included in the study individuals that were able to perform segmental stabilization exercises of the core. To quantify the pain of the lumbar spine, the Visual Analog Pain Scale (VAS) was used to quantify the pain of lumbar spine, and for evaluation of the lumbar function was applied the Oswestry Functional Index (OFI). For statistical analysis we used the software BioEstat 5.3. To test the normality of data was used the D'Agostino Test, and to test the significance of the results the Student's T-test was applied, with significance of p ? 0.05. By comparing the test before and after intervention of OFI values, a statistically significant reduction was observed (p = 0.0012). Before and after intervention of VAS values, a statistically significant reduction was observed (p = 0.0001). However, the present study shows that the lumbar stabilization exercises core are effective in the improvement of pain and lumbar function. (AU)

The relationship between homocysteine and genes of folate-related enzymes in migraine patients.

BACKGROUND: It has been suggested that homocysteine (Hcy) and the 5'-10'-methylenetetrahydrofolate reductase (MTHFR) C677T variant are implicated in the pathogenesis of migraine. Homocysteine has the potential to damage endothelium and accelerate atherosclerosis. Genetic factors such as the MTHFR C677T polymorphism, and other polymorphisms in folate-related genes associated with high homocysteine levels, may contribute to increasing this vascular risk. RESULTS: We recruited 427 migraine patients (199 without aura [MO]; 228 with aura [MA]), and 310 controls in a neurologic clinic. Hcy levels and 6 polymorphisms corresponding to 6 folate-related genes, including the MTHFR C677T variant, were determined in all migraine participants and in a subset of 155 controls. We found higher sex-adjusted Hcy levels in MA (mean: 11.02 microM) than MO patients (9.86 microM; P = .005 for the difference). Hcy levels higher than 12.0 microM doubled the risk for MA (OR = 2.145; 95% confidence intervals [CI] = 1.3-3.4; P = .001), and those higher than 15.0 microM incurred a 6-fold increase (OR = 5.95; 95% CI = 2.1-20.0, P < .001). The number of MTHFR 677T alleles was the best genetic predictor of Hcy levels (r(2) = 0.06; P = 6.2e-6; corrected for genetic variants analyzed) and this effect remained significant after correction for other confounding factors. Using multi-dimensionality reduction approaches, we observed significant epigenetic interaction among some of the folate-related genetic variants to predict higher Hcy levels, and also among higher Hcy levels and folate-related genetic variants to predict the end-diagnosis of MA only among migraineurs. In controls, Hcy levels and the number of MTHFR 677T alleles were found to be intermediate between those observed in MA and MO patients. CONCLUSION: Our results suggest that MA patients have higher Hcy levels. We also observed complex epigenetic interaction among folate-related enzymes, sex, and Hcy levels predicting MA phenotype. Nevertheless, genetic factors explained only a minor proportion of the variance for both Hcy plasma levels and for predicting MA phenotype. Determination of MTHFR C677T polymorphisms and Hcy levels may be useful to identify patients with a high risk of suffering from MA.

CT protocol for acute stroke: tips and tricks for general radiologists.

Acute stroke services have been installed in most hospitals in the industrialized world, and dealing with hyperacute stroke has become one of the most frequently performed tasks of the on-call radiologist. Imaging plays a key role in current guidelines for thrombolysis, and knowledge of classic early ischemic signs or depiction of hemorrhage at nonenhanced computed tomography (CT) is necessary (although not sufficient) for a satisfactory imaging study. A modern CT examination must also include perfusion CT and CT angiography. Perfusion CT delineates the ischemic tissue (penumbra) by showing increased mean transit time with decreased cerebral blood flow (CBF) and normal or increased cerebral blood volume (CBV), whereas infarcted tissue manifests with markedly decreased CBF and decreased CBV. CT angiography can depict the occlusion site, help grade collateral blood flow, and help characterize carotid atherosclerotic disease. A complete CT study (nonenhanced CT, perfusion CT, and CT angiography) may be performed and analyzed rapidly and easily by general radiologists using a simple standardized protocol and may even facilitate diagnosis by less experienced radiologists in affected patients.

Unusual MRI findings in a patient with history of frontal fracture and skin infestation by fly larvae, as a possible sign of intracerebral myiasis.

We report a case of an 11-year-old columbian immigrant with mild non-specific cephalalgia. He had a previous history of frontal fracture and skin infestation caused by Dermatobia hominis larvae. MRI performed revealed multiple subependymal and intraventricular lesions with concentric blooming artifacts and moderate hydrocephalus. Based on his previous history, intracerebral myiasis diagnosis was suggested. His mother denied any kind of diagnostic surgery or treatment. To the best of our knowledge, this is the first MRI report of a possible intracerebral myiasis, an exceedingly rare entity.

Genetic association study and meta-analysis of the HTR2C Cys23Ser polymorphism and migraine.

The objectives of this study were to determine if the HTR2C Cys23Ser polymorphism is associated with migraine in a case-control study, and to perform a meta-analysis with present and previous available studies. The HTR2C gene is located at the Xq24-q28 chromosomal band. This band was linked to migraine with aura (MA) in two Australian families. Using the HTR2C Cys23Ser allelic variant, this gene has been ruled out as a migraine gene in 3 out of 4 studies. Only the Japanese study reported a higher risk for MA (OR=6.11; 95% CI=1.70-21.97, p trend<0.01). We performed a case-control study with 335 migraine subjects and 335 sex- and age-matched controls, and a meta-analysis pooling the results of the available data from MA subsets of patients. In the association study we found no significant differences among migraine and MA patients for this polymorphism. In the meta-analysis, under the fixed-effect model, the Ser allele did not confer higher risk for suffering MA (pooled OR=1.1; 99% CI=0.8-1.5, p=0.499). Our study did not confirm the HTR2C Cys23Ser polymorphism as a risk factor for migraine and MA.

Association of migraine and ESR1 G325C polymorphism.

Migraine is a genetically complex disorder in which sexual hormones influence the phenotype. ESR1 G594A polymorphism has been associated with migraine in Australians. We performed a case-control study with G594A and G325C polymorphisms to determine whether ESR1 is associated with migraine in our population. An association between G594A and migraine could not be demonstrated here. By contrast, we observed that the C325 allele conferred a 1.6 (95% confidence interval=1.1-2.4) higher risk for suffering from migraine in women than the G allele. Women carrying the C352C genotype were over 3 times more likely to suffer from migraine than those carrying the G325G genotype. Therefore, we conclude that ESR1 G325C polymorphism is associated with migraine in our population.

Drogas y sexualidad: grandes enemigos / Drugs and sexuality: two big enemies

Partiendo de la conjetura del adolescente que habitualmente piensa que el uso de las drogas constituye una estimulación para la sexualidad, cuando en realidad ocurre lo contrario, se decidió hacer una revisión bibliográfica con el objetivo de describir los efectos de las drogas en la sexualidad, ampliando el conocimiento sobre este tema. Se encontró que los principales efectos de las drogas en la sexualidad femenina constituyen la alteración del ciclo menstrual, y por tanto, trastornos en la ovulación, la disminución del deseo sexual, la anorgasmia, la disminución de la lubricación vaginal, el bloqueo de la respuesta sexual, la disfunción sexual y la infertilidad. En el caso del sexo masculino se identificó como principales efectos de las drogas: la disminución de las hormonas masculinas (testosterona), la disminución en la producción de espermatozoides, la disfunción eréctil, la disminución del deseo sexual, la impotencia, la infertilidad, el aumento del tamaño de la próstata (en el caso del uso de esteroides), el retraso en la eyaculación y la disfunción sexual

Drogas y sexualidad: grandes enemigos / Drugs and sexuality: two big enemies

Partiendo de la conjetura del adolescente que habitualmente piensa que el uso de las drogas constituye una estimulación para la sexualidad, cuando en realidad ocurre lo contrario, se decidió hacer una revisión bibliográfica con el objetivo de describir los efectos de las drogas en la sexualidad, ampliando el conocimiento sobre este tema. Se encontró que los principales efectos de las drogas en la sexualidad femenina constituyen la alteración del ciclo menstrual, y por tanto, trastornos en la ovulación, la disminución del deseo sexual, la anorgasmia, la disminución de la lubricación vaginal, el bloqueo de la respuesta sexual, la disfunción sexual y la infertilidad. En el caso del sexo masculino se identificó como principales efectos de las drogas: la disminución de las hormonas masculinas (testosterona), la disminución en la producción de espermatozoides, la disfunción eréctil, la disminución del deseo sexual, la impotencia, la infertilidad, el aumento del tamaño de la próstata (en el caso del uso de esteroides), el retraso en la eyaculación y la disfunción sexual(AU)

Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms modulate the risk for migraine conferred by the MTHFR T677 allele.

There is growing evidence that folate metabolism is involved in migraine pathophysiology, mainly in migraine with aura. Even though folate metabolism is regulated by a number of enzymes, only two functional polymorphisms have been tested in association studies with migraine. Here, we have explored the possible role in migraine of other folate-metabolizing enzymes which are in close interdependency with 5',10'-methylenetetrahydrofolate reductase analyzing functional polymorphisms of these enzymes in a case-control study. Individually, thymidylate synthase (TS), methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthase (MTHFD1), or methionine synthase (MS) polymorphisms did not modify the general risk for suffering migraine. Nevertheless, we observed a strong interaction between TS and MTHFR mutated genotypes, which increased over 8-fold the risk for experiencing aura among migraineurs; MTHFD1 and MTHFR mutated genotypes also increased together the risk for migraine in general (OR = 3.08; 95% CI = 1.3-7.4). We conclude that the pathogenetic role of the MTHFR T677 allele in migraine is modulated by functional polymorphisms of TS and MTHFD1.

Pseudomigraine with lymphocytic pleocytosis.

Pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis is a self-limited syndrome of unknown origin characterized by headache accompanied by transient neurologic symptoms and cerebrospinal fluid lymphocytosis. Patients with this condition are between 15 and 40 years of age. The syndrome is more frequent in men. The clinical picture encompasses one to 12 episodes of changing variable neurologic deficits accompanied by moderate to severe headache and occasional fever. These headaches are described as predominantly throbbing and bilateral with a variable duration (mean, 19 hours). The average duration of the transient neurologic deficit is 5 hours. Sensory (78% episodes), aphasic (66%), and motor (56%) disturbances are the most common. Migraine-like visual symptoms are relatively rare (18% episodes). Patients are asymptomatic between episodes and after the symptomatic period (duration > 3 months). Lymphocytic pleocytosis (10 to 760 cells mm(3)) and increased cerebrospinal fluid protein are found with negative bacteriologic, viral, fungal, and immunologic studies. Brain computed tomography and magnetic resonance imaging are normal, but an electroencephalogram frequently shows focal slowing over the symptomatic brain area. Single photon emission computed tomography reveals transient focal areas of decreased uptake consistent with the clinical symptoms. It is possible that pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis could result from an activation of the immune system secondary to a recent viral infection, which would produce antibodies against neuronal or vascular antigens. This autoimmune attack may induce an aseptic leptomeningeal vasculitis, accounting for the headache and the transient symptoms likely through a spreading depression-like mechanism.