A survey about label enhancement methods for parenteral medication in European hospital pharmacies.

PURPOSE: Unclear labeling has been recognized as an important cause of look-alike medication errors. Little is known about which labeling practices are currently used in European hospitals. The aim of this article is to obtain an overview of the labeling practices for parenteral medications, in relation to national guidelines, in the Netherlands, Germany, and the UK. METHODS: An online survey was conducted using the Qualtrics® software. The survey was distributed to hospital pharmacists in the Netherlands, Germany, and the UK. The results were downloaded from Qualtrics and exported to Microsoft Excel. Data were categorized into groups and analyzed descriptively. RESULTS: In total, 104 responses were received. The response rate was 63% (n = 48) in the Netherlands and 11% (n = 41) for Germany; for the UK, 15 responses were received. In general almost 90% of the respondents followed the National guidelines concerning labeling of pharmacy-prepared parenteral products. The use of label enhancement techniques was relatively low in all countries. On average, the use of "Tall Man" lettering was 19%, the use of color coding was 29%, and the use of a barcode on the label was 27%. CONCLUSION: Label-enhancement methods for parenteral medication in hospital pharmacies do not seem to be widely implemented and acknowledged in European hospitals, but response rates were limited for two countries. Greater standardization in conjunction with research for evidence-based enhancement techniques is needed to guide improvement in labeling practices across Europe.

Medication safety at the interface: evaluating risks associated with discharge prescriptions from mental health hospitals.

WHAT IS KNOWN AND OBJECTIVE: When compared to general hospitals, relatively little is known about the quality and safety of discharge prescriptions from specialist mental health settings. We aimed to investigate the quality and safety of discharge prescriptions written at mental health hospitals. METHODS: This study was undertaken on acute adult and later life inpatient units at three National Health Service (NHS) mental health trusts. Trained pharmacy teams prospectively reviewed all newly written discharge prescriptions over a 6-week period, recording the number of prescribing errors, clerical errors and errors involving lack of communication about medicines stopped during hospital admission. All prescribing errors were reviewed and validated by a multidisciplinary panel. Main outcome measures were the prevalence (95% CI) of prescribing errors, clerical errors and errors involving a lack of details about medicines stopped. Risk factors for prescribing and clerical errors were examined via logistic regression and results presented as odds ratios (OR) with corresponding 95% CI. RESULTS AND DISCUSSION: Of 274 discharge prescriptions, 259 contained a total of 1456 individually prescribed items. One in five [20·8% (95%CI 15·9-25·8%)] eligible discharge prescriptions and one in twenty [5·1% (95%CI 4·0-6·2%)] prescribed or omitted items were affected by at least one prescribing error. One or more clerical errors were found in 71·9% (95%CI 66·5-77·3%) of discharge prescriptions, and more than two-thirds [68·8% (95%CI 56·6-78·8%)] of eligible discharge prescriptions erroneously lacked information on medicines discontinued during hospital admission. Logistic regression analyses revealed that middle-grade [whole discharge prescription level OR 3·28 (3·03-3·56)] and senior [whole discharge OR 1·43 (1·04-1·96)] prescribers as well as electronic discharge prescription pro formas [whole discharge OR 2·43 (2·08-2·83)] were all associated with significantly higher risks of prescribing errors than junior prescribers and handwritten discharges, respectively. Similar findings were reported at the individually prescribed item level. Middle-grade prescribers were also more likely to make both non-psychotropic and psychotropic prescribing errors than their junior colleagues [individual item OR 4·24 (2·14-8·40) and OR 1·70 (1·16-2·48), respectively]. WHAT IS NEW AND CONCLUSION: Discharge prescriptions issued by mental health NHS hospitals are affected by high levels of prescribing, clerical and communication errors. Important targets for intervention have been identified to improve medication safety problems at care transfer.

Estimating the heritability of reporting stressful life events captured by common genetic variants.

BACKGROUND: Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies. Method We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings. RESULTS: A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This 'heritability' was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10-8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R 2 = 0.08 in SLEs (p = 0.03). CONCLUSIONS: These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project.

There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report suggests that both factors interact in predicting response to antidepressants. GENDEP, a prospective part-randomized pharmacogenomics trial, collected longitudinal data on the outcome of 811 patients with major depression undergoing treatment with either an SSRI (escitalopram) or a tricyclic antidepressant (nortriptyline). Life events experienced over 6 months preceding treatment were measured using a List of Threatening Experiences Questionnaire, and several polymorphisms in the serotonin transporter gene (SLC6A4) have been genotyped including the serotonin transporter-linked polymorphic region (5-HTTLPR). Stressful life events were shown to predict a significantly better response to escitalopram but had no effect on response to nortriptyline. Variation in the 5-HTTLPR and another polymorphism in the gene, STin4, significantly modified these effects. Gene-environment interactions including life events may therefore be important not only in the aetiology of depression, but also in predicting response to antidepressant medication.

Extracting a needle from a haystack: reanalysis of whole genome data reveals a readily translatable finding.

There is significant unmet need for more effective treatments for bipolar disorder. The drug discovery process is becoming prohibitively expensive. Hence, biomarker clues to assist or shortcut this process are now widely sought. Using the publicly available data from the whole genome association study conducted by the Wellcome Trust Case Control Consortium, we sought to identify groups of genetic markers (single nucleotide polymorphisms) in which each marker was independently associated with bipolar disorder, with a less stringent threshold than that set by the original investigators (p< or =1 x 10(-4)). We identified a group of markers occurring within the CACNA1C gene (encoding the alpha subunit of the calcium channel Cav1.2). We then ascertained that this locus had been previously associated with the disorder in both a smaller and a whole genome study, and that a number of drugs blocking this channel (including verapamil and diltiazem) had been trialled in the treatment of bipolar disorder. The dihydropyridine-based blockers such as nimodipine that bind specifically to Cav1.2 and are more penetrant to the central nervous system have shown some promising early results; however, further trials are indicated. In addition, migraine is commonly seen in affective disorder, and calcium channel antagonists are successfully used in the treatment of migraine. One such agent, flunarizine, is structurally related to other first-generation derivatives of antihistamines such as antipsychotics. This implies that flunarizine could be useful in the treatment of bipolar disorder, and, furthermore, that other currently licensed drugs should be investigated for antagonism of Cav1.2.

Genome-wide expression and response to exposure-based psychological therapy for anxiety disorders.

Exposure-based psychological treatments for anxiety have high efficacy. However, a substantial proportion of patients do not respond to therapy. Research examining the potential biological underpinnings of therapy response is still in its infancy, and most studies have focussed on candidate genes. To our knowledge, this study represents the first investigation of genome-wide expression profiles with respect to treatment outcome. Participants (n=102) with panic disorder or specific phobia received exposure-based cognitive behavioural therapy. Treatment outcome was defined as percentage reduction from baseline in clinician-rated severity of their primary anxiety diagnosis at post treatment and 6 month follow-up. Gene expression was determined from whole blood samples at three time points using the Illumina HT-12v4 BeadChip microarray. Linear regression models tested the association between treatment outcome and changes in gene expression from pre-treatment to post treatment, and pre-treatment to follow-up. Network analysis was conducted using weighted gene co-expression network analysis, and change in the detected modules from pre-treatment to post treatment and follow-up was tested for association with treatment outcome. No changes in gene expression were significantly associated with treatment outcomes when correcting for multiple testing (q<0.05), although a small number of genes showed a suggestive association with treatment outcome (q<0.5, n=20). Network analysis showed no association between treatment outcome and change in gene expression for any module. We report suggestive evidence for the role of a small number of genes in treatment outcome. Although preliminary, these findings contribute to a growing body of research suggesting that response to psychological therapies may be associated with changes at a biological level.

The gold rush 1925-35.

Although from the time of Koch onwards there had been desultory experiments with a variety of gold preparations in the management of pulmonary tuberculosis, gold as a recognised and accepted treatment did not emerge until 1925. In that year Holger Mollgaard of Copenhagen introduced sanocrysin, a double thiosulphate of gold and sodium, with which he had conducted an extensive series of animal experiments. The results of these were considered to justify its use in clinical practice and two physicians, Secher and Faber, undeterred by its toxicity, reported enthusiastically in its favour. Other Danish physicians followed but, alarmed by violent reactions, modified the dosage, an example followed by British workers. Encouraging results continued to be reported although each series contained a significant proportion of failures, and toxicity remained high. The first properly planned and fully controlled clinical trial took place in the United States and produced a report which was wholly adverse and which sounded the death knell of gold therapy throughout America. Until 1934-35 gold was used extensively in Europe but thereafter there was a sudden and largely universal cessation of interest and within a few years gold, introduced with such éclat and carrying so many high hopes, had vanished from the therapy of tuberculosis even though, at that point, no better alternative was available.

Two forgotten pioneers. James Carson and George Bodington.

James Carson, a Scot, graduated from Edinburgh in 1799. He settled in Liverpool where he became a successful and respected physician and where he also found time to pursue a longstanding interest in physiology and to conduct certain important experiments. He read a series of papers on these experiments and their import before the Literary and Philosophical Society of Liverpool of which the two most important were On the elasticity of the lungs and On lesions of the lungs. In the first he clarified the mechanics of respiration while in the second he suggested that this knowledge might be employed to produce temporary collapse of the lung as a therapeutic measure. Two attempts at a clinical trial were defeated by widespread pleural adhesions but the first recorded attempts at artificial pneumothorax had been made. George Bodington, a Warwickshire man, after serving a surgical apprenticeship studied at St Bartholomew's Hospital and obtained the licence of the Society of Apothecaries in 1825. He later practised near Sutton Coldfield where he was known as an acute observer and a thoughtful and fluent speaker. In 1840 he published an essay on the treatment and cure of pulmonary consumption in which he roundly condemned the current therapy and advocated instead fresh air in abundance, gentle exercise in the open, an adequate and varied diet, and a minimum of medicaments. Violently attacked by the reviewers he became discouraged about tuberculosis and devoted the remainder of his professional life to the care of the mentally ill.

Richard Morton (1637-98) and his Phthisiologia.

Richard Morton was one of the outstanding physicians of the seventeenth century. After graduating BA at Oxford he elected to enter the Church, becoming ultimately Vicar of Kinver in Staffordshire. On the Restoration he found himself unable to comply with the requirements of the Act of Uniformity and was ousted from his Staffordshire living. He disappeared for eight years but reappeared in 1670 when, on the sponsorship of the Prince of Orange, the degree of MD was conferred on him by the University of Oxford. He set up in practice in London and was elected a Fellow of the Royal College of Physicians in 1678. He has left a lasting memorial in the form of his book Phthisiologia which deals with all aspects of phthisis, the word being interpreted in its widest sense to denote any disease associated with wasting. It is not known where Morton obtained his medical education nor is there anything in his writings to indicate where he spent the eight years between 1662 and 1670. It is suggested that he may have been in Holland for part of those years attending the University of Leyden and making the acquaintance of the Prince of Orange whose patronage was to prove so useful at Oxford in 1670.

Laennec: his medical history.

Critical study of the career of Théophile Laënnec, with particular reference to his medical history, gives cause to query the commonly accepted belief that his whole life was a constant battle against pulmonary tuberculosis. He developed respiratory symptoms almost immediately on his arrival in Paris but they were those of bronchial asthma and responded promptly and completely to a change of environment. It was only in the concluding years of his life and when he was worn out by overwork that the symptoms of tuberculosis appeared and thereafter the disease progressed rapidly to its fatal termination.