Prescribing indicators: what can Canada learn from European countries?

BACKGROUND: Drug therapy can improve patients' quality of life and health outcomes; however, underuse, overuse and inappropriate use of drugs can occur. Systematic examination of potential opportunities for improving prescribing and medication use is needed. OBJECTIVE: To convene a diverse group of stakeholders to learn about and discuss advantages and limitations of data sources, tools and methods related to drug prescribing indicators; foster methods to assess safe, appropriate and cost-effective prescribing; increase awareness of international organizations who develop and apply performance indicators relevant to Canadian researchers, practitioners and decision-makers; and provide opportunities to apply information to the Canadian context. METHODS: Approximately 50 stakeholders (health system decision-makers, senior and junior researchers, healthcare professionals, graduate students) met June 1-2, 2009 in Halifax, Canada. Four foundational presentations on evaluating quality of prescribing were followed by discussion in pre-assigned breakout groups of a prepared case (either antibiotic use or prescribing for seniors), followed by feedback presentations. RESULTS: Many European countries have procedures to develop indicators for prescribing and quality use of medicines. Indicators applied in diverse settings across the European Union use various mechanisms to improve quality, including financial incentives for prescribers. CONCLUSION: Further Canadian approaches to develop a system of Canadian prescribing indicators would enable federal/provincial/territorial and international comparisons, identify practice variations and highlight potential areas for improvement in prescribing, drug use and health outcomes across Canada. A more standardized system would facilitate cross-national research opportunities and enable Canada to examine how European countries use prescribing indicators, both within their country and across the European Union.

Reduction of glial glutamate transporters in the parietal cortex and hippocampus of the EL mouse.

There is extensive experimental evidence indicating a crucial role for glutamate in epileptogenesis and epileptic activity. The glial glutamate transporters GLT1 and GLAST are proposed to account for the majority of extracellular glutamate re-uptake. In the present study, polyclonal antibodies specific to GLT1 and GLAST were generated and characterized, revealing distribution patterns for the two transporters confirming those previously reported. In situ hybridization and immunoblotting were then used to compare levels of these two transporters in the parietal cortex and hippocampus of unstimulated and stimulated EL mice with DDY control mice. Additionally, HPLC determined tissue glutamate concentrations in the same regions of these animals. These experiments revealed reductions in GLT1 mRNA and protein in the parietal cortex of unstimulated and stimulated EL mice compared with DDY controls, accompanied by an increase in tissue glutamate concentration in the stimulated EL mice group. GLT1 mRNA was also reduced in the CA3 hippocampal subfield of both unstimulated and stimulated EL mice. GLAST protein was reduced in the hippocampus of the stimulated EL mice group, while no changes in GLAST mRNA or protein were detected in the parietal cortex of EL mice when compared with DDY controls. The glial glutamate transporter down-regulation reported here may play a role in seizure initiation, spread and maintenance in the EL mouse.

Glial glutamate transporter mRNAs in the genetically absence epilepsy rat from Strasbourg.

Recent studies support a critical role for the glutamatergic system and glutamate transporters in the pathogenesis of epilepsy. The glial glutamate transporters GLT-1 (L-glutamate transporter) and GLAST (L-glutamate/L-aspartate transporter) are known to be responsible for the majority of glutamate reuptake from the synaptic cleft and constitute one mechanism by which extracellular glutamate levels may be controlled. The present study therefore compared GLT-1 and GLAST mRNA levels in the genetically absence epilepsy rat from Strasbourg (GAERS) with those of age-matched non-epileptic controls. The GAERS rat has been proposed as an animal model of inherited human absence epilepsy, displaying recurrent, generalised, non-convulsive seizures that originate from thalamic and cortical structures. In situ hybridisation with 35S-labelled oligonucleotide probes demonstrated substantial and significant increases in GLT-1 mRNA levels in the ventromedial nucleus of the thalamus (VM) and the subthalamic nucleus (STN) of GAERS rats. Increases in GLAST mRNA were found in the primary somatosensory cortex (SS1) and temporal cortex (Te) of GAERS. These data, along with previous studies, suggest that regional imbalances in GABAergic and glutamatergic systems may be associated with the pathogenesis of absence seizures in GAERS.

The interstimulus interval in classical autonomic conditioning of young infants.

Conditioned auditory discrimination and extinction of the skin potential response were attempted in 4-month-old infants using interstimulus intervals of 1500, 3500, 5500, and 7500 msec. Half of the infants in each of the interstimulus interval groups were defined as high magnitude orienters and half were low magnitude orienters. Conditioning was successful with the 5500- and 7500-msec interstimulus intervals, but not with the 1500- and 3500-msec intervals. Analysis of individual subject data indicated that individual subject data indicated that individual differences in conditionability were related to interstimulus interval and orienting response magnitude. Also, those subjects discriminating at the longer intervals tended to be high magnitude orienters. In other words, longer interstimulus intervals interacted with a high magnitude or orienting to facilitate conditioning. The results were taken as evidence that individual differences in the magnitude of the orienting response reflect different individual needs in stimulus information processing time.

Child abuse and neglect: effect on Bayley Scale scores.

Compared to controls, children who were diagnosed as victims of Nonaccidental Trauma or Failure to Thrive had depressed Bayley Scale Mental Index scores, p less than .002 and p less than .0001, respectively. Failure-to-Thrive children also had depressed Bayley Scale Motor Index scores, p less than .0001. Nonaccidental-Trauma children had Mental and Motor Scale range scores, as determined by differences between basal and ceiling items on the Mental and Motor scales, that were a function of measured Mental and Motor Index Scores. Specifically, Nonaccidental-Trauma children with lower Mental Index scores had higher Mental Scale range scores than Nonaccidental-Trauma children with higher Mental Index scores, p less than .003. Control children had Mental Scale range scores that did not differ between the high-low Mental Index score conditions. On the Motor Scale, range scores of Nonaccidental-Trauma children in the high-low Motor Index score conditions did not differ. However, children with higher Motor Index scores had higher Motor Scale range scores than control children with lower Motor Index scores, p less than .02. In addition, the Infant Behavior Record of the Bayley Scales revealed behavior ratings of Nonaccidental-Trauma and Failure-to-Thrive children that differed from Mental and Motor Scale scores on several dimensions. These differences may reflect differential effects of the Nonaccidental-Trauma and Failure-to-Thrive conditions.