• We provide the first critical quantitative review of this rapidly developing area of research to serve as a basis for subsequent research and overviews.• We summarize data on population prevalence and functional effects of CYP2C19*17.• We argue on the basis of current evidence that potentially significant clinical effects are unlikely except for drugs with very narrow therapeutic windows. Of studied substrates, only clopidogrel may fall into this category. Even then, only homozygotes of the variant allele are likely to be at significantly increased risk.• The assignment of CYP2C19*17 homozygotes as EM, rather than UM, is adequate as the metabolic ratios of all probe drugs studied so far overlap completely the range of values seen in wild-type homozygotes.• The implications of CYP2C19*17 on the clinical effects of tamoxifen require further study. AIMSCytochrome P450 2C19 metabolizes many important drugs. In 2006, a variant allele (CYP2C19*17) associated with increased activity was discovered, but its likely clinical significance is controversial. Investigators disagree about the phenotype to be assigned to the two CYP2C19*17 genotypes. The aim of this study was to provide a critical summary, helpful to prescribers. METHODSWe searched MEDLINE for papers on the allele from 2006 and then undertook historical searches through the reference lists of papers retrieved. The relevant information was critically assessed and summarized. RESULTSCYP2C19*17 was associated with increased enzymic activity. Substrates studied were omeprazole, pantoprazole, escitalopram, sertraline, voriconazole, tamoxifen and clopidogrel. Most studies used pharmacokinetic variables as outcome measure. For clopidogrel, activated by CYP2C19, pharmacodynamic consequences focused on platelet aggregation. While for most pharmacokinetic parameters of the substrates studied the average value was altered, the range of values showed mostly complete overlap for CYP2C19*1/*17 heterozygotes and wild-type homozygotes. Even for CYP2C19*17 homozygotes, the absolute effect was modest compared with the effect of previously identified loss-of-function alleles. In Helicobacter pylori eradication CYP2C19*2 carriage was associated with an altered eradication rate (odds ratio 4.20, 95% confidence interval 1.23, 16.44) relative to the wild-type, but CYP2C19*17 homozygosity was not. Prevalence of the variant allele was typically <5% in Asians and about four times higher in White and African populations. CONCLUSIONSAssignment of CYP2C19*17 homozygotes as extensive metabolizers rather than ultrarapid metabolizers is adequate. CYP2C19*17 genotyping is unlikely to have clinical utility except for drugs with very narrow therapeutic indices.

Providing the best possible care for the child and family is paramount to health professionals working in paediatric palliative care. However, there is little research which enables practitioners to question their current practice. There are concerns about conducting research on children receiving palliative care at such a sensitive time for the child and his/her family. These concerns must be considered against the growing demand for clear standards and guidelines for practice within health care. According to the Department of Health (DoH) there is no place within the modern healthcare system for the adoption of unproven theories or outdated care (DoH, 1998). While no-one would question the dedication and care being delivered to children and their families by well-trained staff, the lack of research is a cause for concern. A group of students undertaking a degree module in paediatric palliative care identified the lack of literature and research in this area and have undertaken a review of the available literature.

Advances in genomics promise to deliver personalized medicine both for prevention and treatment of disease. Considerable effort is being directed towards translating observed associations between various genetic variants, such as single nucleotide polymorphisms (SNPs), and disease or drug response into clinically useful genetic tests. Unfortunately, because reported associations are usually weak or moderate, tests based on them are generally not accurate enough for use in routine clinical practice, and therefore, ensuring the appropriate use of genetic tests is important. In a recent report, a combination of 5 SNPs was claimed to improve the predictive value of the test for prostate cancer, compared with the individual SNPs. This led the authors to suggest that a 5-SNP-test could be used to predict the risk of prostate cancer. We evaluate the characteristics of the proposed test, comment on it, and summarize the views of others on its potential clinical utility. We hope that this may serve as a case-example for the evaluation of the many new genetic tests being suggested for adoption.

No abstract

The close of the year is here and this offers us a time to reflect on the directions taken in palliative care. The year has been a good one for the journal with the quality of papers always increasing and the editorial team would like to thank all of our readers and authors for their consistent support and offer our best wishes for a safe and festive Christmas break. The introduction of commentaries and other forms of debate in the journal offers us an opportunity to reflect on our work and consider the ways forward for our specialism.