Optimization of resources by drug management: A multicentred web-administered study on the use of ipilimumab in Italy.

OBJECTIVE: In a scenario of new expensive cancer therapies entering the market, strategies of optimisation and cost containment are crucial in oncology care. Better management of drug waste and centralization of drug preparation can be effective strategies to achieve these goals. The aim of this work is to describe the economic management of a high cost anticancer drug (ipilimumab) in some Italian reference centres. METHODS: This was an observational, multicentred study in which economical and clinical data of 21 cancer centres (418 patients) were collected during the enrollment period from February 2013 to August 2014. The follow-up period ended in July 2015. RESULTS: Participants purchased 10.7% more vials of ipilimumab than necessary for compounding. The results were variable among centres, and only five centres had a deviation lower than 5% between the drug purchased and the drug prescribed. Hospitals applying the drug day reached a statistically significant residual of drug effectively used compared to the amount prescribed (P = 0.018). Consequently, the price for treating a model patient was significantly lower in those hospitals (median spare of 7456 euro per patient). CONCLUSIONS: This study demonstrated that the careful management of drug waste and the application of drug-day, through a proper selection of vial and the ability to use the leftover drug, can generate economic savings. However, tailoring the drug stock to clinical need is still an open issue which deserves further analysis.

Malignant brain tumors in patients with glutaric aciduria type I.

Three young patients with glutaric aciduria type I (age 6-23 years) of different ethnic origins, treated for their metabolic disease since early childhood, presented with malignant central nervous system tumors. We recommend continuing clinical follow-up, including monitoring of neurological manifestations and neuroradiological findings, in all patients with glutaric aciduria type I beyond early childhood, especially if adherence to diet is poor or the treatment was not started neonatally.

Lung cancer risk assessment due to traffic-generated particles exposure in urban street canyons: A numerical modelling approach.

Combustion-generated nanoparticles are responsible for negative health effects due to their ability to penetrate in the lungs, carrying toxic compounds with them. In urban areas, the coexistence of nanoparticle sources and particular street-building configurations can lead to very high particle exposure levels. In the present paper, an innovative approach for the evaluation of lung cancer incidence in street canyon due to exposure to traffic-generated particles was proposed. To this end, the literature-available values of particulate matter, PAHs and heavy metals emitted from different kind of vehicles were used to calculate the Excess Lifetime Cancer Risk (ELCR) at the tailpipe. The estimated ELCR was then used as input data in a numerical CFD (Computational Fluid Dynamics) model that solves the mass, momentum, turbulence and species transport equations, in order to evaluate the cancer risk in every point of interest inside the street canyon. Thus, the influence of wind speed and street canyon geometry (H/W, height of building, H and width of the street, W) on the ELCR at street level was evaluated by means of a CFD simulation. It was found that the ELCR calculated on the leeward and windward sides of the street canyon at a breathable height of 1.5 m, for people exposed 15 min per day for 20 years, is equal to 1.5 × 10-5 and 4.8 × 10-6, respectively, for wind speed of 1 m/s and H/W equal to 1. The ELCR at street level results higher on the leeward side for aspect ratios equal to 1 and 3, while for aspect ratio equal to 2 it is higher on the windward side. In addition, the simulations showed that with the increasing of wind speed the ELCR becomes lower everywhere in the street canyon, due to the increased in dispersion.

[Indications of the surgical treatment of epilepsy]. / Indicaciones del tratamiento quirúrgico de la epilepsia.

INTRODUCTION: The surgery of epilepsy is expanding considerably all over the world. It is becoming a standard treatment in patients who are resistant to conventional medical treatment. DEVELOPMENT: In this article we explain the methodology used by the authors and suggest concepts regarding the epileptogenous area. We also explain the procedures used in neuroimaging and neurophysiology studies. CONCLUSIONS: Good methodology, such as that used by the authors, results in up to 65% of the patients in whom amygdalo-hippocampectomy is done becoming completely seizure-free. Amygdalo-campectomy is the most specific indication in mesolimbic temporal epilepsy, which is also the main indication for the surgery of epilepsy.

Indicaciones del tratamiento quirúrgico de la epilepsia / Indications for the surgical treatment of epilepsy

Introducción. La cirugía de la epilepsia está adquiriendo un desarrollo extraordinario en todo el mundo y se va incorporando como una terapia estándar en aquellos pacientes refractarios al tratamiento médico convencional. Desarrollo. En este artículo se explica la metodología utilizada y seguida por los autores y se sugiere una conceptualización del área epileptógena; se explica asimismo el procedimiento a seguir en los estudios de neuroimagen y neurofisiológico. Conclusiones. Una buena metodología como la seguida por los autores consigue, en el caso de la amígdalo-hipocampectomía selectiva, que hasta un 65 por ciento de los pacientes queden totalmente libres de crisis. La amígdalo-hipocampectomía es la indicación más específica para la epilepsia temporal mesolímbica que, a su vez, es la primera indicación de cirugía de epilepsia (AU)

Parvalbumin and calbindin-D28k immunocytochemistry in human neocortical epileptic foci.

Serial sections of cortical resection of 30 patients suffering from drug-resistant epilepsy were processed for parvalbumin and calbindin-D28k immunocytochemistry to determine local circuit neuron populations. Our findings indicate that there is not a simple mechanism to explain neocortical epileptic foci. On the basis of the present results it can be suggested that: (1) reduced percentage of local circuit neurons in the vicinity of neoplasms may account for a decreased intracortical inhibition. (2) Abnormal morphology and distribution of local circuit neurons may result in abnormal cortical inhibition in patients with focal cortical dysplasia, and, probably, in other focal migrational disorders, including neuronal nests in the white matter. (3) Increased percentages of immunoreactive local circuit neurons and fibers in focal neocortical necrosis (cavernous angiomas), diffuse hypoxic encephalopathy, and hippocampus in patients with temporal lobe epilepsy due to mesial sclerosis, may play a role in epilepsy. These neurons can be activated by reduced excitatory inputs, or they may establish abnormal synaptic contacts with other inhibitory neurons. (4) Lack of consistent morphologic abnormalities in the neocortex of patients with temporal lobe epilepsy, and in patients with cryptogenetic frontal lobe epilepsy, suggests that electrically abnormal neocortical foci in these cases are probably epiphenomena.

What is needed for resective epilepsy surgery from a neurosurgical point of view?

Invasive versus non-invasive epileptogenic zone definition was analyzed in a series of 89 patients operated on for drug-resistant epilepsy. In the group of 69 cortical resections, 26% needed invasive recordings, 13.5% when foreign-tissue lesions had been detected by MRI and 32% when were absent. In this last group temporal resections had invasive EEG recordings in 23.5% versus 54.5% when the epileptogenic zone was extratemporal. In a group of 43 temporal resections with more than one year follow-up MRI has detected some abnormality in 84%. Excluding focal lesions, MRI detected hippocampal/temporal lobe atrophy in 66% of the cases in agreement with other noninvasive tests and in 4% contralateral to the epileptogenic zone located by subdural strips. The outcome analysis showed that 85% of the patients with MRI-EEG agreement were seizure free in contrast to only 43% when MRI was non-lateralizing. Future studies has to be oriented to better understand the epileptic process of patients without MRI abnormalities.

[Anesthesia in surgery for epilepsy]. / Anestesia en la cirugía de la epilepsia.

OBJECTIVES: To evaluate the efficacy of general anesthesia during epileptic surgery. MATERIAL AND METHODS: A retrospective study of 64 patients who received general anesthesia during epileptic surgery. In the preoperative period, anticonvulsive medication was adjusted in accordance with plasma levels and withdrawn entirely 8 hours before surgery. After premedication with droperidol and fentanyl, a balanced anesthetic technique was applied, based on pentothal, pancuronium (or vecuronium), fentanyl, N2O and isoflurane. Continuous monitoring of ECG, arterial blood pressure, pulse oximetry, ET CO2 and neuromuscular function. Isoflurane was stopped for 10 min after the opening of the duramadre so that ECoG could be recorded and methohexital or propofol was given in some cases in order to activate the epileptogenic focus. Muscular relaxation was restored intraoperatively following the study of somatosensory evoked potentials. Immediate and later complications related to anesthesia or surgery were recorded. RESULTS: The surgical procedure performed in most cases was temporal or frontal resection, with a mean duration for anesthesia of 377 +/- 50 min and for surgery of 318 +/- 50 min. Only one patient received local anesthesia and no hemodynamic changes were observed. Perioperative complications were cerebral edema (4 cases), arrhythmia (2 cases) and bronchospasm (1 case). Postoperative complications were as follows: 3 of 9 patients undergoing callosotomy required mechanical ventilation for 24 hours, 4 patients experienced language alterations, 3 wounds were infected, 2 cases of hemiplegia were observed, 1 status epilepticus occurred after administration of propofol and there was 1 case of respiratory distress. Anticonvulsive medication was given parenterally after surgery. CONCLUSIONS: General anesthesia is a safe and effective method for epileptic surgery, with local anesthesia providing additional sedation for isolated cases. Appropriate treatment requires an understanding of the pharmacokinetics and pharmacodynamics of the drugs used, as well as knowledge of the condition and the anticonvulsive medications used.

Abnormal local-circuit neurons in epilepsia partialis continua associated with focal cortical dysplasia.

A limited cortical resection including the rolandic fissure and the pre- and postcentral cortical regions was carried out in a patient suffering from epilepsia partialis continua resistant to antiepileptic drugs. The histological examination revealed several foci of very large neurons distributed with no laminar organization in the depth of the rolandic fissure and in the crown of the primary motor and primary somatosensory areas; these lesions were consistent with focal cortical dysplasia. In addition, decreased numbers of neurons, astrocytosis and proliferation of capillaries, compatible with chronic tissue necrosis, were found in the inferior regions of the banks of the rolandic fissure. Subpopulations of local-circuit neurons were examined with parvalbumin, calbindin D-28k and somatostatin immunocytochemistry. Focal areas of cortical dysplasia contained abnormal immunoreactive neurons. Huge parvalbumin-immunoreactive cells were distributed at random and resembled axo-axonic (chandelier) and basket neurons. Abnormal calbindin D-28k-immunoreactive cells were reminiscent of double-bouquet neurons and multipolar cells. Very large somatostatin-immunoreactive cells were seldom observed in the dysplastic foci. On the other hand, areas of tissue necrosis displayed massive reduction of immunoreactive cells and fibers. Abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons observed here for the first time in focal cortical dysplasia may have a pivotal role in the appearance and prolongation of electrical discharges and continuous motor signs in human focal epilepsy.

[Machado-Joseph disease in a family of Spanish origin]. / Maladie de Machado-Joseph dans une famille d'origine espagnole.

The clinical observations in five patients, of a family of catalan origin (NE of Spain), affected with Machado-Joseph disease are reported. The pedigree showed the presence of 22 members affected (15 men, 7 women) over six generations. The symptoms and signs were variable among the patients and also variable in a same patient during the course of the disease. However, the main neurological alterations were ataxia, akinesia, distal amyotrophy, progressive external ophthalmoplegia, facial and lingual fasciculations and bulging eyes. The neuropathological examination performed in one patient disclosed degeneration of the posterior and spinocerebellar tracts in the spinal cord, marked nerve cell loss in Clarke's column and anterior horns and axonal degeneration of the peripheral nerves, in addition to nerve cell loss in the nuclei of the III, IV and VII cranial nerves and neuronal depletion in the substantia nigra. No other structures, including the striate complex and dentate nucleus, were significantly affected.

Versive seizures of probable occipital origin in a case of posttraumatic epilepsy.

Oculoclonic versive elemental partial seizures developed in a 38-year-old male, who has suffered from a grave traumatism by impaling. Posttraumatic epileptic symptoms could be related to anatomical lesions at the exit orifice in the right occipitoparietal region.