While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.

An ever-expanding annotation of the human genome sequence continues to promise a new era of precision medicine. Advances in knowledge management and the ability to leverage genetic information to make clinically relevant, predictive, diagnostic, and targeted therapeutic choices offer the ability to improve patient outcomes and reduce the overall cost of healthcare. However, numerous barriers have resulted in a modest start to the clinical use of genetics at scale. Examples of successful deployments include oncologic disease treatment with targeted prescribing; however, even in these cases, genome-informed decision-making has yet to achieve standard of care in most major healthcare systems. In the last two decades, advances in genetic testing, therapeutic coverage, and clinical decision support have resulted in early-stage adoption of pharmacogenomics – the use of genetic information to routinely determine the safety and efficacy profile of specific medications for individuals. Here, through their complicated histories, we review the current state of pharmacogenomic testing technologies, the information tools that can unlock clinical utility, and value-driving implementation strategies that represent the future of pharmacogenomics-enabled healthcare decision-making. We conclude with real-world economic and clinical outcomes from a full-scale deployment and ultimately provide insight into potential tipping points for global adoption, including recent lessons from the rapid scale-up of high-volume test delivery during the global SARS-CoV2 epidemic.

Objectives: The aim of this study is to determine the relative value and contribution of searching different sources to identify adverse effects data.

Methods: The process of updating a systematic review and meta-analysis of thiazolidinedione-related fractures in patients with type 2 diabetes mellitus was used as a case study. For each source searched, a record was made for each relevant reference included in the review noting whether it was retrieved with the search strategy used and whether it was available but not retrieved. The sensitivity, precision, and number needed to read from searching each source and from different combinations of sources were also calculated.

Results: There were 58 relevant references which presented sufficient numerical data to be included in a meta-analysis of fractures and bone mineral density. The highest number of relevant references were retrieved from Science Citation Index (SCI) (35), followed by BIOSIS Previews (27) and EMBASE (24). The precision of the searches varied from 0.88% (Scirus) to 41.67% (CENTRAL). With the search strategies used, the minimum combination of sources required to retrieve all the relevant references was; the GlaxoSmithKline (GSK) website, Science Citation Index (SCI), EMBASE, BIOSIS Previews, British Library Direct, Medscape DrugInfo, handsearching and reference checking, AHFS First, and Thomson Reuters Integrity or Conference Papers Index (CPI).

Conclusions: In order to identify all the relevant references for this case study a number of different sources needed to be searched. The minimum combination of sources required to identify all the relevant references did not include MEDLINE

Inappropriate prescribing to the elderly is a serious problem and is one factor contributing to adverse drug reactions in this group. It is well-known that reliance on promotional literature for prescribing information leads to less appropriate prescribing. This study surveyed ads in two major Canadian medical journals which portrayed people who appeared to be over 65 years of age. The elderly were shown in just over 7 per cent of the ads. These ads did not appear to take into account the special drug needs of the elderly. Ads featuring the elderly could lead to inappropriate prescribing because of their pictorial content, their written content or a combination of both. Further research into this area is needed, specifically directed at factors which influence prescribing to the elderly. In the meantime physicians dealing with the elderly should critically analyse the message in drug advertisements and be aware of the risks of using them for therapeutic information.

Adverse drug reactions (ADR) pose significant health-related problems for the older person. Many studies from around the world report a significant incidence of ADR in general and in elderly people in particular, resulting in an increase in drug-related morbidity and mortality. Older people appear to be particularly at risk of experiencing an ADR due to a range of factors, which include polypharmacy, altered drug pharmacokinetic profiles and pharmacodynamic responses, drug interactions and cognitive problems that increase the risk in this patient group. Certain drug classes, such as hypoglycaemic agents and cardiovascular active medicines, have been identified as common causes of ADR. Many studies suggest that the majority of ADR are preventable, so that several different approaches have been tried in an attempt to limit this problem, such as the use of computerized systems to communicate routine issues of patient care, interventions made by pharmacists, spontaneous reporting and continuous education of health care professionals. Whilst all have been shown to reduce drug-related events, identifying individuals at high risk of developing ADR at the point of prescribing by using a risk stratification model could improve the identification and prevention of ADR. This article discusses the clinical impact of ADR in older people and the relative merits of the various approaches tested to date before suggesting areas that require further research.

Background and aim The effects of analgesic drugs on sleep are poorly understood. We investigated short- and medium-term effects of tramadol on sleep structure.

Methods Eight healthy volunteers received a placebo (predrug placebo-night), then, in a randomized, double-blind, cross-over fashion a single oral dose of tramadol 50 mg or 100mg (drug-night), and finally, again a placebo (postdrug placebo-night). Standardized polysomnography (electroencephalogram, electro-oculogram, submental electromyogram) was continuously recorded during placebo- and drug-nights

Results During drug-nights both doses of tramadol significantly increased the duration of stage 2 sleep, and significantly decreased the duration of slow-wave sleep (stage 4). Tramadol 100mg but not 50 mg significantly decreased the duration of paradoxical (rapid eye movement) sleep. In the placebo-night after tramadol 100mg (but not after 50 mg) duration of stage 2 sleep was significantly shorter, and duration of stage 4 sleep was significantly longer compared with the predrug placebo-night. Conclusion In healthy volunteers, a single dose of tramadol 50 mg disturbs sleep in the night of drug application. With 100mg, sleep is disturbed in both the night of drug application and in the subsequent night.