Children’s views on unlicensed/off-label paediatric prescribing and paediatric clinical trials.

Objectives: To explore the views and perspectives of children on the unlicensed/off-label use of medicines in children and on the participation of children in clinical trials. Methods: Focus-group discussions, involving school children, were carried out in a range of primary and secondary schools in Northern Ireland. A purposeful sample was chosen to facilitate representation of various socioeconomic groupings. Results: A total of 123 pupils, aged from 10 to 16 years, from six schools, participated in 16 focus groups. In general, pupils viewed the unlicensed/off-label use of medicines in children as unsafe and unethical and felt it is necessary to test medicines in children to improve the availability of licensed products. The majority felt that older children should be told, and that parents should be told, about the unlicensed/off-label use of medicines in children, yet they recognised some implications of this, such as potential medication non-adherence. Conclusions: This is the first study to explore the views of healthy children on unlicensed medicine use in children. Children were able to recognise potential risks associated with the unlicensed use of medicines and felt it is necessary to test and license more medicines in children. Practice implications Health care professionals should consider the views of children in decisions that affect their health.

The cardiac responses of the scallop Pecten maximus (L.) to respiratory stress

Heart activity of Pecten maximus (L.) has been recorded during various forms of experimentally induced respiratory stress. There was considerable variation in the responses of individual scallops but bradycardia generally occurred in response to all forms of respiratory stress, with the rate of fall in heart rate dependent upon the severity of hypoxia. When oxygen tension declined slowly in a closed respirometer there was regulation of both heart rate and oxygen consumption. The critical tension, Pc, for oxygen consumption lay between 70 and 80 mm Hg, and corresponded with a slight regulatory upswing of the heart rate, whereas the Pc for heart rate was much lower at 20–30 mm Hg. Sudden transfer to deoxygenated water for 3 h resulted in very rapid bradycardia and there was a rapid recovery and initial overshoot of the normal rate on return to well-oxygenated sea water. Aerial exposure for 3 h produced more gradual bradycardia followed by gradual recovery on return to sea water. The results of this work are compared in some detail with previous work on other species of bivalve from different geographical areas and habitats, and the mechanisms controlling cardiac and respiratory regulation are discussed. It is concluded that there are few clear-cut general differences between littoral and sublittoral species in their behavioural and physiological adaptations to hypoxia; the main distinguishing feature of littoral-adapted species is their ability to control air-gaping. Changes in heart activity generally indicate variations in metabolic rate, the speed at which the metabolic rate may be altered reflecting the degree of adaptation to the littoral environment.

Development and validation of a dried blood spot LC-MS/MS assay to quantify ranitidine in paediatric samples.

A novel approach has been developed to determine ranitidine in paediatric samples using dried blood spots (DBS) on Guthrie cards (Whatman 903). A selective and sensitive HPLC-MS/MS assay has been developed and validated using small volumes of blood (30µl). A 6mm disc was punched from each DBS and extracted with methanolic solution of the internal standard (IS) nizatidine. This was further subjected to solid phase extraction (SPE), followed by reversed phase HPLC separation, using a XBridge™ C18 column and mobile phase 10mM ammonium acetate/methanol (98:2 v/v) with a flow rate of 0.3mL/min. This was combined with multiple reaction monitoring (MRM) mass detection using electrospray ionisation (ESI). The calibration curve for ranitidine was found linear over the range 10-500ng/mL (r=0.996). The limit of quantification (LOQ) of the method was validated at 10ng/mL. Accuracy and precision values for within and between days were

AM1- receptor dependent protection by intermedin of human vascular and cardiac non-vascular cells from ischaemia-reperfusion injury

Intermedin (IMD) protects rodent heart and vasculature from oxidative stress and ischaemia. Less is known about distribution of IMD and its receptors and the potential for similar protection in man. Expression of IMD and receptor components were studied in human aortic endothelium cells (HAECs), smooth muscle cells (HASMCs), cardiac microvascular endothelium cells (HMVECs) and fibroblasts (v-HCFs). Receptor subtype involvement in protection by IMD against injury by hydrogen peroxide (H2O2, 1 mmol l?¹) and simulated ischaemia and reperfusion were investigated using receptor component-specific siRNAs. IMD and CRLR, RAMP1, RAMP2 and RAMP3 were expressed in all cell types.When cells were treated with 1 nmol l?¹ IMD during exposure to 1 mmol l?¹ H2O2 for 4 h, viability was greater vs. H2O2 alone (P<0.05 for all cell types). Viabilities under 6 h simulated ischaemia differed (P<0.05) in the absence and presence of 1 nmol l?¹ IMD: HAECs 63% and 85%; HMVECs 51% and 68%; v-HCFs 42% and 96%. IMD 1 nmol l?¹ present throughout ischaemia (3 h) and reperfusion (1 h) attenuated injury (P<0.05): viabilities were 95%, 74% and 82% for HAECs, HMVECs and v-HCFs, respectively, relative to those in the absence of IMD (62%, 35%, 32%, respectively). When IMD 1 nmol l?¹ was present during reperfusion only, protection was still evident (P<0.05, 79%, 55%, 48%, respectively). Cytoskeletal disruption and protein carbonyl formation followed similar patterns. Pre-treatment (4 days) of HAECs with CRLR or RAMP2, but not RAMP1 or RAMP3, siRNAs abolished protection by IMD (1 nmol l?¹) against ischaemia-reperfusion injury. IMD protects human vascular and cardiac non-vascular cells from oxidative stress and ischaemia-reperfusion,predominantly via AM1 receptors.

A virtual surgery in general practice: evaluation of a novel undergraduate virtual patient learning package

Background: A suite of 10 online virtual patients developed using the IVIMEDS ‘Riverside’ authoring tool has been introduced into our undergraduate general practice clerkship. These cases provide a multimedia-rich experience to students. Their interactive nature promotes the development of clinical reasoning skills such as discriminating key clinical features, integrating information from a variety of sources and forming diagnoses and management plans.

Aims: To evaluate the usefulness and usability of a set of online virtual patients in an undergraduate general practice clerkship.
Method: Online questionnaire completed by students after their general practice placement incorporating the System Usability Scale questionnaire.

Results: There was a 57% response rate. Ninety-five per cent of students agreed that the online package was a useful learning tool and ranked virtual patients third out of six learning modalities. Questions and answers and the use of images and videos were all rated highly by students as useful learning methods. The package was perceived to have a high level of usability among respondents.

Conclusion: Feedback from students suggest that this implementation of virtual patients, set in primary care, is user friendly and rated as a valuable adjunct to their learning. The cost of production of such learning resources demands close attention to design.

Voltage-activated currents in cardiac myocytes of the blue mussel, Mytilus edulis

Voltage-sensitive ionic currents were identified and characterised in ventricular myocytes of the bivalve mollusc, Mytilus edulis, using the whole-cell patch-clamp technique. Two outward currents could be distinguished. A potassium A current (I-A) activated at - 30 mV from a holding potential of - 60 mV. This transient current was inactivated by holding the cells at a potential of - 40 mV and was also blocked by applying 4-aminopyridine (3 mM) to the external bath solution. A second current was identified as a delayed rectifier (I-K). This also activated at - 30 mV but exhibited a sustained time course and was still activated at a holding potential of - 40 mV. Both outward currents were reduced in the presence of tetraethylammonium ions (30 mM). A small number of heart cells also showed an inward sodium current (I-Na). This current appeared at potentials more positive than - 50 mV, reached a maximum at - 20 mV, and decreased with further depolarisation. I-Na was inactivated at a holding potential of - 40 mV and was blocked by tetrodotoxin (1 mu M). A second inward current had a sustained time course and was not inactivated by holding the cell at a potential of -40 mV, and was also not abolished by tetrodotoxin. This current peaked at 0 mV, decreasing with further depolarisation. Furthermore, it was enhanced by the addition of barium ions (3 mM) to the bath and was blocked by external cobalt (2 mM) or nifedipine (15 mu M) These findings are consistent with this being an L-type calcium current (I-Ca) The possible physiological roles of these currents in M. edulis heart are discussed. (C) 1999 Elsevier Science Inc. All rights reserved.