Журнал клинических случаев

Pharmacogenetics (PGx) is an emerging science which looks at genetic factors (pharmacogenes) that can influence drug tolerability and efficacy, depending upon variations in the resulting proteins function or structure. Variants of certain pharmacogenes can increase the risk of side effects, affect drug exposure and help predict likelihood of efficacy or inefficacy. The prevalence of such genetic mutations varies by ancestry and is not equally distributed in populations. Commercial PGx assays typically evaluate both pharmacokinetic (PK) and pharmacodynamic (PD) genes. Pharmacokinetic genes, such as those coding for the cytochrome P450 enzyme superfamily, have been shown to affect drug exposure and influence the absorption and metabolism of many drugs used across multiple disease states. Pharmacodynamic genes typically encode for proteins that are more often drug targets, such as receptors. They are more related to drug sensitivity or response without providing any dosing guidance. In general, PK genes are considered more actionable than PD genes. We present a complex case in which multiple genetic variants provided insights into the patients previous care and future management.

A 53-year-old woman with a history of craniotomy and clipping of a left supraclinoid internal carotid artery aneurysm nine years prior and breast cancer in remission presented who was referred to a neurological surgery clinic for evaluation of a suspected brain aneurysm. Further workup with catheter angiography and magnetic resonance imaging (MRI) ultimately revealed a dural-based lesion at the site of the prior craniotomy. The patient underwent surgical resection and pathology confirmed the diagnosis of a low-grade glioma. This case highlights the importance of thorough evaluation and monitoring for patients with a history of intracranial pathology, as meningiomas may develop at the site of prior surgeries.

Background: Incident reporting systems are being implemented throughout the world to record safety incidents in healthcare. The quality of the recording and analysis of reporting systems is important for the development of safety promotion measures.

Methods: To assess the reliability of incident reporting ratings collected in a hospital setting, a three level interrater comparison was undertaken. The routine ratings of the frontline event handlers responsible for evaluating safety incident reports (n=495) were compared with the parallel ratings of two trained patient safety coordinators. The two patient safety coordinators then each separately reviewed about half of the 495 reports, followed by reclassification of a random sample (a random data subset of 60 reports) previously reclassified by the other coordinator during the first reclassification. The following seven patient safety variables were included: Nature of the incident, type of incident, patient impact, treating unit impact, circumstances and contributory factors, immediate actions taken, and risk category. Interrater agreement was tested with kappa, weighted kappa or iota.

Results: For the seven variables examined, event handlers had an average of 1.36 missing answers, patient safety coordinators 0.32. For the first interrater comparison, the average change between the three ordinal scale variables for all variables together was towards more serious in 29% (95% CI: 27%, 32%) and towards less serious in 2% (95% CI: 0%, 5%) of incidents. The net change for the first interrater comparison was 27% (95% CI: 25%, 30%) towards a more serious incident. The average selection of several categories, when allowed, increased from 7% (95%CI: 6%, 8%) to 33% (95% CI: 31%, 35%). For all three paired interrater comparisons, the average interrater agreements were in the range of 0.44 to 0.53 and considered moderate. While patient safety coordinators should in theory represent a ‘golden standard’, the coordinator interrater agreement seen in this study was moderate.

Conclusion: Consensus at national level on how to classify high risk incidents is needed to develop incident reporting reliability. Also, continuous training in common practices; terminology and rating systems should be given more attention. Having a patient safety coordinator reclassify incident reports can improve reporting accuracy and thereby corrective actions and learning.