Patients' understanding of risk associated with medication use: impact of European Commission guidelines and other risk scales

Patients want and need comprehensive and accurate information about their medicines so that they can participate in decisions about their healthcare: In particular, they require information about the likely risks and benefits that are associated with the different treatment options. However, to provide this information in a form that people can readily understand and use is a considerable challenge to healthcare professionals. One recent attempt to standardise the Language of risk has been to produce sets of verbal descriptors that correspond to specific probability ranges, such as those outlined in the European Commission (EC) Pharmaceutical Committee guidelines in 1998 for describing the incidence of adverse effects. This paper provides an overview of a number of studies involving members of the general public, patients, and hospital doctors, that evaluated the utility of the EC guideline descriptors (very common, common, uncommon, rare, very rare). In all studies it was found that people significantly over-estimated the likelihood of adverse effects occurring, given specific verbal descriptors. This in turn resulted in significantly higher ratings of their perceived risks to health and significantly lower ratings of their likelihood of taking the medicine. Such problems of interpretation are not restricted to the EC guideline descriptors. Similar levels of misinterpretation have also been demonstrated with two other recently advocated risk scales (Caiman's verbal descriptor scale and Barclay, Costigan and Davies' lottery scale). In conclusion, the challenge for risk communicators and for future research will be to produce a language of risk that is sufficiently flexible to take into account different perspectives, as well as changing circumstances and contexts of illness and its treatments. In the meantime, we urge the EC and other legislative bodies to stop recommending the use of specific verbal labels or phrases until there is a stronger evidence base to support their use.

Brief behavioural activation for adolescent depression: working with complexity and risk

Given the long-term negative outcomes associated with depression in adolescence, there is a pressing need to develop brief, evidence based treatments that are accessible to more young people experiencing low mood. Behavioural Activation (BA) is an effective treatment for adult depression, however little research has focused on the use of BA with depressed adolescents, particularly with briefer forms of BA. In this article we outline an adaptation of brief Behavioral Activation Treatment of Depression (BATD) designed for adolescents and delivered in eight sessions (Brief BA). This case example illustrates how a structured, brief intervention was useful for a depressed young person with a number of complicating and risk factors.

Aging is associated with positive responding to neutral information but reduced recovery from negative information

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36–84 years). We recorded eye-blink startle magnitudes and corrugator activity during and after the presentation of positive, neutral and negative pictures. The most robust age effect was found in response to neutral stimuli, where increasing age is associated with a decreased corrugator and eyeblink startle response to neutral stimuli. These data suggest that an age-related positivity effect does not essentially alter the response to emotion-laden information, but is reflected in a more positive interpretation of affectively ambiguous information. Furthermore, older women showed reduced corrugator recovery from negative pictures relative to the younger women and men, suggesting that an age-related prioritization of well-being is not necessarily reflected in adaptive regulation of negative affect.

Individual Differences in Amygdala and Ventromedial Prefrontal Cortex Activity are Associated with Evaluation Speed and Psychological Well-being

Using functional magnetic resonance imaging, we examined whether individual differences in amygdala activation in response to negative relative to neutral information are related to differences in the speed with which such information is evaluated, the extent to which such differences are associated with medial prefrontal cortex function, and their relationship with measures of trait anxiety and psychological well-being (PWB). Results indicated that faster judgments of negative relative to neutral information were associated with increased left and right amygdala activation. In the prefrontal cortex, faster judgment time was associated with relative decreased activation in a cluster in the ventral anterior cingulate cortex (ACC, BA 24). Furthermore, people who were slower to evaluate negative versus neutral information reported higher PWB. Importantly, higher PWB was strongly associated with increased activation in the ventral ACC for negative relative to neutral information. Individual differences in trait anxiety did not predict variation in judgment time or in amygdala or ventral ACC activity. These findings suggest that people high in PWB effectively recruit the ventral ACC when confronted with potentially aversive stimuli, manifest reduced activity in subcortical regions such as the amygdala, and appraise such information as less salient as reflected in slower evaluative speed.

Errors associated with the preparation of aseptic products in UK hospital pharmacies: lessons from the national aseptic error reporting scheme

Background Pharmacy aseptic units prepare and supply injectables to minimise risks. The UK National Aseptic Error Reporting Scheme has been collecting data on pharmacy compounding errors, including near-misses, since 2003. Objectives The cumulative reports from January 2004 to December 2007, inclusive, were analysed. Methods The different variables of product types, error types, staff making and detecting errors, stage errors detected, perceived contributory factors, and potential or actual outcomes were presented by cross-tabulation of data. Results A total of 4691 reports were submitted against an estimated 958 532 items made, returning 0.49% as the overall error rate. Most of the errors were detected before reaching patients, with only 24 detected during or after administration. The highest number of reports related to adult cytotoxic preparations (40%) and the most frequently recorded error was a labelling error (34.2%). Errors were mostly detected at first check in assembly area (46.6%). Individual staff error contributed most (78.1%) to overall errors, while errors with paediatric parenteral nutrition appeared to be blamed on low staff levels more than other products were. The majority of errors (68.6%) had no potential patient outcomes attached, while it appeared that paediatric cytotoxic products and paediatric parenteral nutrition were associated with greater levels of perceived patient harm. Conclusions The majority of reports were related to near-misses, and this study highlights scope for examining current arrangements for checking and releasing products, certainly for paediatric cytotoxic and paediatric parenteral nutrition preparations within aseptic units, but in the context of resource and capacity constraints.

Errors associated with preparation of adult and paediatric parenteral nutrition in UK hospital pharmacies

Rationale: In UK hospitals, the preparation of all total parenteral nutrition (TPN) products must be made in the pharmacy as TPNs are categorised as high-risk injectables (NPSA/2007/20). The National Aseptic Error Reporting Scheme has been collecting data on pharmacy compounding errors in the UK since August 2003. This study reports on types of error associated with the preparation of TPNs, including the stage at which these were identified and potential and actual patient outcomes. Methods: Reports of compounding errors for the period 1/2004 - 3/2007 were analysed on an Excel spreadsheet. Results: Of a total of 3691 compounding error reports, 674 (18%) related to TPN products; 548 adult vs. 126 paediatric. A significantly higher proportion of adult TPNs (28% vs. 13% paediatric) were associated with labelling errors and a significantly higher proportion of paediatric TPNs (25% vs. 15% adult) were associated with incorrect transcriptions (Chi-Square Test; p<0.005). Labelling errors were identified equally by pharmacists (42%) and technicians (48%) with technicians detecting mainly at first check and pharmacists at final check. Transcription errors were identified mainly by technicians (65% vs. 27% pharmacist) at first check. Incorrect drug selection (13%) and calculation errors (9%) were associated with adult and paediatric TPN preparations in the same ratio. One paediatric TPN error detected at first check was considered potentially catastrophic; 31 (5%) errors were considered of major and 38 (6%) of moderate potential consequence. Five errors (2 moderate, 1 minor) were identified during or after administration. Conclusions: While recent UK patient safety initiatives are aimed at improving the safety of injectable medicines in clinical areas, the current study highlights safety problems that exist within pharmacy production units. This could be used in the creation of an error management tool for TPN compounding processes within hospital pharmacies.

Nitrogen fertilizer and seed rate effects on Hagberg failing number of hybrid wheats and their parents are associated with alpha-amylase activity, grain cavity size and dormancy

Field experiments were carried out to assess the effects of nitrogen fertilization and seed rate on the Hagberg falling number (HFN) of commercial wheat hybrids and their parents. Applying nitrogen (200 kg N ha(-1)) increased HFN in two successive years. The HFN of the hybrid Hyno Esta was lower than either of its parents (Estica and Audace), particularly when nitrogen was not applied. Treatment effects on HFN were negatively associated with a-amylase activity. Phadebas grain blotting suggested two populations of grains with different types of a-amylase activity: Estica appeared to have a high proportion of grains with low levels of late maturity endosperm a-amylase activity (LMEA); Audace had a few grains showing high levels of germination amylase; and the hybrid, Hyno Esta, combined the sources from both parents to show heterosis for a-amylase activity. Applying nitrogen reduced both apparent LMEA and germination amylase. The effects on LMEA were associated with the size and disruption of the grain cavity, which was greater in Hyno Esta and Estica and in zero-nitrogen treatments. External grain morphology failed to explain much of the variation in LMEA and cavity size, but there was a close negative correlation between cavity size and protein content. Applying nitrogen increased post-harvest dormancy of the grain. Dormancy was greatest in Estica and least in Audace. It is proposed that effects of seed rate, genotype and nitrogen fertilizer on HFN are mediated through factors affecting the size and disruption of the grain cavity and therefore LMEA, and through factors affecting dormancy and therefore germination amylase. (c) 2004 Society of Chemical Industry.

Characterization and origin of infection of Rhizoctonia solani associated with Brassica oleracea crops in the UK

An extensive study was conducted to determine where in the production chain Rhizoctonia solani became associated with UK module-raised Brassica oleracea plants. In total, 2600 plants from 52 crops were sampled directly from propagators and repeat sampled from the field. Additional soil, compost and water samples were collected from propagation nurseries and screened using conventional agar isolation methods. No isolates of R. solani were recovered from any samples collected from propagation nurseries. Furthermore, nucleic acid preparations from samples of soil and compost from propagation nurseries gave negative results when tested for R. solani using real-time PCR. Conversely, R. solani was recovered from 116 of 1300 stem bases collected from field crops. All the data collected suggested R. solani became associated with B. oleracea in the field rather than during propagation. Parsimony and Bayesian phylogenetic studies of ribosomal DNA suggested the majority of further classified isolates belonged to anastomosis groups 2-1 (48/57) and AG-4HGII (8/57), groups known to be pathogenic on Brassica spp. in other countries. Many R. solani isolates were recovered from symptomless plant material and the possibilities for such an association are discussed.

Recovering potential: factors associated with success in engaging challenging students with alternative pre-16 provision

The study focuses on a group of young people for whom conventional school placements had broken down and were attending vocational courses at an FE college while still of compulsory school age. The students had been excluded by, or had failed to attend, their schools or had achieved at very low levels in the academic curriculum. Over half successfully completed the vocational course at college. Many factors conventionally regarded as predictors for poor educational outcomes were not associated with completion and non-completion. For example, students who had been excluded, who had statements of special educational needs and had been involved with the criminal justice system were as likely to complete their courses as other students. However, students who had very poor attendance records at school also tended to drop out of college. The results suggest that the increased flexibility, guidance and elements of work-related learning promised in current 14 - 19 developments may help meet the needs of this group of students.

Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia

Aims/hypothesis Recent evidence suggests that a particular gut microbial community may favour occurrence of the metabolic diseases. Recently, we reported that high-fat (HF) feeding was associated with higher endotoxaemia and lower Bifidobacterium species (spp.) caecal content in mice. We therefore tested whether restoration of the quantity of caecal Bifidobacterium spp. could modulate metabolic endotoxaemia, the inflammatory tone and the development of diabetes. Methods Since bifidobacteria have been reported to reduce intestinal endotoxin levels and improve mucosal barrier function, we specifically increased the gut bifidobacterial content of HF-diet-fed mice through the use of a prebiotic (oligofructose [OFS]). Results Compared with normal chow-fed control mice, HF feeding significantly reduced intestinal Gram-negative and Gram-positive bacteria including levels of bifidobacteria, a dominant member of the intestinal microbiota, which is seen as physiologically positive. As expected, HF-OFS-fed mice had totally restored quantities of bifidobacteria. HF-feeding significantly increased endotoxaemia, which was normalised to control levels in HF-OFS-treated mice. Multiple-correlation analyses showed that endotoxaemia significantly and negatively correlated with Bifidobacterium spp., but no relationship was seen between endotoxaemia and any other bacterial group. Finally, in HF-OFS-treated-mice, Bifidobacterium spp. significantly and positively correlated with improved glucose tolerance, glucose-induced insulin secretion and normalised inflammatory tone (decreased endotoxaemia, plasma and adipose tissue proinflammatory cytokines). Conclusions/interpretation Together, these findings suggest that the gut microbiota contribute towards the pathophysiological regulation of endotoxaemia and set the tone of inflammation for occurrence of diabetes and/or obesity. Thus, it would be useful to develop specific strategies for modifying gut microbiota in favour of bifidobacteria to prevent the deleterious effect of HF-diet-induced metabolic diseases.

Chronic disease risk associated with different dietary saturated fatty acids

This chapter compares the risks of chronic disease, and cardiovascular disease in particular, associated with consumption of different saturated fatty acids. Emphasis is placed on the effects of stearic acid as this has potential to replace trans fatty acids in certain manufactured food products. The chapter first reviews the effects of individual saturated fatty acids on blood lipids, including cholesterol, as these are commonly used as markers of disease risk. It then looks directly at evidence in relation to health outcomes. Finally, recent evidence specifically on the effect of stearic acid relative to other fatty acids, including trans fatty acids, is summarised.

Perceived helplessness is associated with individual differences in the central motor output system

Learned helplessness is a maladaptive response to uncontrollable stress characterized by impaired motor escape responses, reduced motivation and learning deficits. There are important individual differences in the likelihood of becoming helpless following exposure to uncontrollable stress but little is known about the neural mechanisms underlying these individual differences. Here we used structural MRI to measure gray and white matter in individuals with chronic pain, a population at high risk for helplessness due to prolonged exposure to a poorly controlled stressor (pain). Given that self-reported helplessness is predictive of treatment outcomes in chronic pain, understanding such differences might provide valuable clinical insight. We found that the magnitude of self-reported helplessness correlated with cortical thickness in the supplementary motor area (SMA) and midcingulate cortex, regions implicated in cognitive aspects of motor behavior. We then examined the white matter connectivity of these regions and found that fractional anisotropy of connected white matter tracts along the corticospinal tract was associated with helplessness and mediated the relationship between SMA cortical thickness and helplessness. These data provide novel evidence that links individual differences in the motor output pathway with perceived helplessness over a chronic and poorly controlled stressor.

Evidence of increased net ecosystem productivity associated with a longer vegetated season in a deciduous forest in south-central Indiana, USA

Observations of net ecosystem exchange (NEE) of carbon and its biophysical drivers have been collected at the AmeriFlux site in the Morgan-Monroe State Forest (MMSF) in Indiana, USA since 1998. Thus, this is one of the few deciduous forest sites in the world, where a decadal analysis on net ecosystem productivity (NEP) trends is possible. Despite the large interannual variability in NEP, the observations show a significant increase in forest productivity over the past 10 years (by an annual increment of about 10 g C m−2 yr−1). There is evidence that this trend can be explained by longer vegetative seasons, caused by extension of the vegetative activity in the fall. Both phenological and flux observations indicate that the vegetative season extended later in the fall with an increase in length of about 3 days yr−1 for the past 10 years. However, these changes are responsible for only 50% of the total annual gain in forest productivity in the past decade. A negative trend in air and soil temperature during the winter months may explain an equivalent increase in NEP through a decrease in ecosystem respiration.

Prolonged marital stress is associated with short-lived responses to positive stimuli

Marital stress is associated with a higher incidence of psychiatric disorders, in particular major depression. One pathway through which marital stress may impact emotional health is by compromising emotion-responding processes. We examined a longitudinal sample of adults (N = 116; 59 males; 39–84 years) to verify how marital stress predicts reactivity to, and recovery from, emotional provocation. Individuals watched positive, neutral, and negative pictures while an objective measure of affective state, corrugator supercilii muscle activity, was recorded continuously. Our results indicate that marital stress is associated with short-lived responses to positive pictures, indexed by a less persistent decrease in corrugator activity after picture offset. Extending beyond the prior focus on negative emotional processes, these results suggest that social stress may impact health by influencing the time course of responding to positive events.

Atmospheric circulation patterns associated with extreme cold winters in the UK

This study examines the atmospheric circulation patterns and surface features associated with the seven coldest winters in the U.K. since 1870, using the 20th Century Reanalysis. Six of these winters are outside the scope of previous reanalysis datasets; we examine them here for the first time. All winters show a marked lack of the climatological southwesterly flow over the UK, displaying easterly and northeasterly anomalies. Six of the seven winters (all except 1890) were associated with a negative phase of the North Atlantic Oscillation; 1890 was characterised by a blocking anticyclone over and northeast of the UK.