COMPREHENSIBILITY OF THE PACKAGE LEAFLETS OF ALL MEDICINAL PRODUCTS FOR HUMAN USE: A QUESTIONNAIRE SURVEY ABOUT THE USE OF SYMBOLS AND PICTOGRAMS

Directive 92/27EEC establishes that the package leaflet is a document, which must be included in the package of medicinal products for human use in EU countries. This informative leaflet is directed at the users and it must give full and comprehensible information. The Law suggests the use of symbols but it does not give advice about the subjects to be represented. In order to evaluate the attitude of patients towards package leaflets provided with symbols, we planned a survey interviewing 1004 patients in pharmacies. The data suggest that Italian patients usually read the package leaflet but they neither understand it easily nor find the needed information readily. Most respondents (74.3%) considered the use of symbols helpful in finding the needed information. We proposed five symbols for each heading (therapeutic indications, side effects, paediatric use, contraindications, use in pregnancy) and asked to select which symbol could be used. In the case of 'side effects', 'paediatric use', 'use in pregnancy' and 'dose', most of the respondents chose the same symbol. In the case of 'therapeutic indications' and 'contraindications' there was no uniformity in the answers. The choice depends greatly on education, age and employment of respondents.     

Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbances: evidence for anti‐N‐methyl‐d‐aspartate receptor encephalitis

Aim We report four cases of acquired severe encephalopathy with massive hyperkinesia, marked neurological and cognitive regression, sleep disturbance, prolonged mutism, and a remarkably delayed recovery (time to full recovery between 5 and 18mo) with an overall good outcome, and its association with anti‐N‐methyl‐d ‐aspartate (anti‐NMDA) receptor antibodies. Method We reviewed the four cases retrospectively and we also reviewed the literature. Results Anti‐NMDA receptor antibodies (without ovarian teratoma detected so far) were found in the two children tested in this study. Interpretation The clinical features are similar to those first reported in 1992 by Sebire et al., 1 and rarely recognized since. Sleep disturbance was not emphasized as part of the disorder, but appears to be an important feature, whereas coma is less certain and difficult to evaluate in this setting. The combination of symptoms, evolution (mainly seizures at onset), severity, paucity of abnormal laboratory findings, very slow recovery, and difficult management justify its recognition as a specific entity. The neuropathological substrate may be anatomically close to that involved in encephalitis lethargica, in which the same target functions (sleep and movement) are affected but in reverse, with hypersomnolence and bradykinesia. This syndrome closely resembles anti‐NMDA receptor encephalitis, which has been reported in adults and is often paraneoplastic.     

Pacemaker Interference with Screening Mammography

In female pacemaker recipients undergoing screening mammography, the impact of a pulse generator placed in the pectoral region has yet to be reviewed. We evaluated mammograms from 74 female pacemaker patients aged 40 years and older. The pulse generator obscured a portion of the mammogram in 7 patients (12%). During pacemaker implantation in women, the potential for the pulse generator to interfere with screening mammography should be considered. Baseline mammography should be obtained or reviewed; in high risk patients a nonconventional location for the pulse generator may be appropriate.     

Automatic Management of Left Ventricular Stimulation: Hints for Technologic Improvement

Background: We used a cardiac resynchronization therapy defibrillator device with an algorithm for automatic verification of left ventricular (LV) stimulation to understand LV threshold variability, such as to provide hints to program the algorithm features. We also evaluated the algorithm performance over long term, and tested a stimulation setting to achieve 99% effective stimulation while maximizing device longevity. Methods: The LV output was programmed as threshold + 0.5 V; the upper limit of LV output adjustment was 6 V at programmed pulse width. The algorithm is insensitive to the strength of the pacing pulse, thus pulse width was conveniently programmed to minimize the use of voltage multipliers in all the patients. Follow‐ups occurred at 1 month, then every 3 months, for clinical assessment and manual threshold verification. The efficacy of this programming at long term was also evaluated by Holter validation of LV stimulation. Results: Twenty patients were followed for 14 ± 5 months (6–21). LV threshold showed no changes in 97% of consecutive days, whereas a 0.5‐V and 1‐V increase occurred, respectively, in 2.3% and 0.6%. Maximum variability of LV threshold was ≤0.5 V during 90% of the follow‐up period. Our programming of LV output provided 99–100% effective stimulation in 18 of 20 patients, and 90% efficacy in two patients because of missed threshold measurements. A 25% increase of device longevity can be expected by this programming. Conclusions: LV threshold variability is truly modest. Daily update of LV threshold should be improved to ensure 100% LV stimulation by a threshold + 0.5 V safety margin. Device longevity is maximized when LV stimulation occurs below battery voltage.     

Structural and spatial organisation of brain parenchymal vessels in the lizard, Podarcis sicula: a light, transmission and scanning electron microscopy study

The structure and 3-dimensional pattern of the intraparenchymal microvessels in the brain of the lizard, Podarcis sicula , were studied by a combination of light and transmission electron microscopy as well as scanning electron microscopy of vascular corrosion casts. The angioarchitecture pattern consists of narrow hairpin-shaped microvascular loops of different length originating from the meningeal surface. In each loop, descending and ascending vessels are closely apposed to one another throughout their length and are connected by a narrow U-shaped terminal loop at their tips. The 2 limbs of the vessel pairs show a slightly different diameter but lack other structural differences. While some paired vessels give rise to a secondary hairpin-shaped loop with 2 possible branching patterns, there are no anastomotic intraparenchymal connections with analogous neighbouring structures. The cerebral vascular pattern of Podarcis sicula resembles that found in a few representatives of other vertebrate classes. All cerebral vessels structurally appear to be capillaries. Also the observations carried out on semithin and thin sections strongly support the capillary loop model in the Podarcis brain vasculature and, in accordance with studies carried out on various vertebrates, the general submicroscopic features of the brain capillary wall suggest the presence of an endothelial type blood-brain barrier.