Preventing drug related morbidity: a process for facilitating changes in practice

Aim: To describe how quantitative data obtained from applying a series of indicators for preventable drug related morbidity (PDRM) in the electronic patient record in English general practice can be used to facilitate changes aimed at helping to improve medicines management. Design: A multidisciplinary discussion forum held at each practice facilitated by a clinical researcher. Subjects and setting: Eight English general practices. Outcome measures: Issues discussed at the multidisciplinary discussion forum and ideas generated by practices for tackling these issues. Progress made by practices after 1, 3, and 6 months. Results: A number of clinical issues were raised by the practices and ideas for moving them forward were discussed. The issues that were easiest and most straightforward to deal with (for example, reviewing specific patient groups) were quickly addressed in most instances. Practices were less likely to have taken steps towards addressing issues at a systems level. Conclusions: Data generated from applying PDRM indicators can be used to facilitate practice-wide discussion on medicines management. Different practices place different priority levels on the issues they wish to pursue. Individual practice "ownership'' of these, together with having a central committed figure at the practice, is key to the success of the process.

Causes of preventable drug-related hospital admissions: a qualitative study

Objective: To explore the causes of preventable drug-related admissions (PDRAs) to hospital. Design: Qualitative case studies using semi-structured interviews and medical record review; data analysed using a framework derived from Reason's model of organisational accidents and cascade analysis. Participants: 62 participants, including 18 patients, 8 informal carers, 17 general practitioners, 12 community pharmacists, 3 practice nurses and 4 other members of healthcare staff, involved in events leading up to the patients' hospital admissions. Setting: Nottingham, UK. Results: PDRAs are associated with problems at multiple stages in the medication use process, including prescribing, dispensing, administration, monitoring and help seeking. The main causes of these problems are communication failures ( between patients and healthcare professionals and different groups of healthcare professionals) and knowledge gaps ( about drugs and patients' medical and medication histories). The causes of PDRAs are similar irrespective of whether the hospital admission is associated with a prescribing, monitoring or patient adherence problem. Conclusions: The causes of PDRAs are multifaceted and complex. Technical solutions to PDRAs will need to take account of this complexity and are unlikely to be sufficient on their own. Interventions targeting the human causes of PDRAs are also necessary - for example, improving methods of communication.

A qualitative exploration of the underlying causes of preventable drug-related morbidity in primary care, resulting in hospitalisation

This study has explored the underlying causes of preventable drug-related admissions to hospital, from primary care through semi-structured interviews and review of patients’ medical records. Analysis of the data has revealed that communication failures between different groups of healthcare professionals and between healthcare professionals and patients contribute to preventable drug-related admissions, as do knowledge gaps about medication in both healthcare professionals and patients. In addition, working conditions for community pharmacists severely limit their ability to effectively act as a safety barrier to patients receiving inappropriate medication. Limitations include heavy workloads, lack of access to patients’ clinical information, poor relationships with general practitioners and time restrictions. The results of this study represent an important addition to our understanding of the contribution of human error as an underlying cause of preventable drug-related morbidity, and the factors which contribute to errors occurring in the primary healthcare setting.

A structural basis for the inhibition of collagen-stimulated platelet function by quercetin and structurally related flavonoids

Background and purpose: Molecular mechanisms underlying the links between dietary intake of flavonoids and reduced cardiovascular disease risk are only partially understood. Key events in the pathogenesis of cardiovascular disease, particularly thrombosis, are inhibited by these polyphenolic compounds via mechanisms such as inhibition of platelet activation and associated signal transduction, attenuation of generation of reactive oxygen species, enhancement of nitric oxide production and binding to thromboxane A2 receptors. In vivo, effects of flavonoids are mediated by their metabolites, but the effects and modes of action of these compounds are not well-characterized. A good understanding of flavonoid structure–activity relationships with regard to platelet function is also lacking. Experimental approach: Inhibitory potencies of structurally distinct flavonoids (quercetin, apigenin and catechin) and plasma metabolites (tamarixetin, quercetin-3′-sulphate and quercetin-3-glucuronide) for collagen-stimulated platelet aggregation and 5-hydroxytryptamine secretion were measured in human platelets. Tyrosine phosphorylation of total protein, Syk and PLCγ2 (immunoprecipitation and Western blot analyses), and Fyn kinase activity were also measured in platelets. Internalization of flavonoids and metabolites in a megakaryocytic cell line (MEG-01 cells) was studied by fluorescence confocal microscopy. Key results: The inhibitory mechanisms of these compounds included blocking Fyn kinase activity and the tyrosine phosphorylation of Syk and PLCγ2 following internalization. Principal functional groups attributed to potent inhibition were a planar, C-4 carbonyl substituted and C-3 hydroxylated C ring in addition to a B ring catechol moiety. Conclusions and implications: The structure–activity relationship for flavonoids on platelet function presented here may be exploited to design selective inhibitors of cell signalling.

Supranutritional selenium induces alterations in molecular targets related to energy metabolism in skeletal muscle and visceral adipose tissue of pigs

While selenium (Se) is an essential micronutrient for humans, epidemiological studies have raised concern that supranutritional Se intake may increase the risk to develop Type 2 diabetes mellitus (T2DM). We aimed to determine the impact of Se at a dose and source frequently ingested by humans on markers of insulin sensitivity and signalling. Male pigs were fed either a Se-adequate (0.17 mg Se/kg) or a Se-supranutritional (0.50 mg Se/kg; high-Se) diet. After 16 weeks of intervention, fasting plasma insulin and cholesterol levels were non-significantly increased in the high-Se pigs, whereas fasting glucose concentrations did not differ between the two groups. In skeletal muscle of high-Se pigs, glutathione peroxidase activity was increased, gene expression of forkhead box O1 transcription factor and peroxisomal proliferator-activated receptor- coactivator 1 were increased and gene expression of the glycolytic enzyme pyruvate kinase was decreased. In visceral adipose tissue of high-Se pigs, mRNA levels of sterol regulatory element-binding transcription factor 1 were increased, and the phosphorylation of Akt, AMP-activated kinase and mitogen-activated protein kinases was affected. In conclusion, dietary Se oversupply may affect expression and activity of proteins involved in energy metabolism in major insulin target tissues, though this is probably not sufficient to induce diabetes.

Determination of orientations of aromatic groups in self-assembled peptide fibrils by polarised Raman spectroscopy

In this paper we describe a novel combination of Raman spectroscopy, isotope editing and X-ray scattering as a powerful approach to give detailed structural information on aromatic side chains in peptide fibrils. The orientation of the tyrosine residues in fibrils of the peptide YTIAALLSPYS with respect to the fibril axis has been determined from a combination of polarised Raman spectroscopy and X-ray diffraction measurements. The Raman intensity of selected tyrosine bands collected at different polarisation geometries is related to the values and orientation of the Raman tensor for those specific vibrations. Using published Raman tensor values we solved the relevant expressions for both of the two tyrosine residues present in this peptide. Ring deuteration in one of the two tyrosine side chains allowed for the calculation to be performed individually for both, by virtue of the isotopic shift that eliminates band overlapping. Sample disorder was taken into account by obtaining the distribution of orientations of the samples from X-ray diffraction experiments. The results provide previously unavailable details about the molecular conformation of this peptide, and demonstrate the value of this approach for the study of amyloid fibrils.

Evidence for a genetic interaction in allergy-related responsiveness to vitamin D deficiency

Our study on white European adults was consistent with a previous study on children from largely non-white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white Europeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy-related responsiveness to VDD.

Selecting valuable information to remember: age-related differences and similarities in self-regulated learning

It is often necessary to selectively attend to important information, at the expense of less important information, especially if you know you cannot remember large amounts of information. The present study examined how younger and older adults select valuable information to study, when given unrestricted choices about how to allocate study time. Participants were shown a display of point values ranging from 1–30. Participants could choose which values to study, and the associated word was then shown. Study time, and the choice to restudy words, was under the participant's control during the 2-minute study session. Overall, both age groups selected high value words to study and studied these more than the lower value words. However, older adults allocated a disproportionately greater amount of study time to the higher-value words, and age-differences in recall were reduced or eliminated for the highest value words. In addition, older adults capitalized on recency effects in a strategic manner, by studying high-value items often but also immediately before the test. A multilevel mediation analysis indicated that participants strategically remembered items with higher point value, and older adults showed similar or even stronger strategic process that may help to compensate for poorer memory. These results demonstrate efficient (and different) metacognitive control operations in younger and older adults, which can allow for strategic regulation of study choices and allocation of study time when remembering important information. The findings are interpreted in terms of life span models of agenda-based regulation and discussed in terms of practical applications. (PsycINFO Database Record (c) 2013 APA, all rights reserved)(journal abstract)

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.

I owe you: age-related similarities and differences in associative memory for gains and losses

Older adults often experience associative memory impairments but can sometimes remember important information. The current experiments investigate potential age-related similarities and differences associate memory for gains and losses. Younger and older participants were presented with faces and associated dollar amounts, which indicated how much money the person “owed” the participant, and were later given a cued recall test for the dollar amount. Experiment 1 examined face-dollar amount pairs while Experiment 2 included negative dollar amounts to examine both gains and losses. While younger adults recalled more information relative to older adults, both groups were more accurate in recalling the correct value associated with high value faces compared to lower value faces and remembered gist-information about the values. However, negative values (losses) did not have a strong impact on recall among older adults versus younger adults, illustrating important associative memory differences between younger and older adults.

Paracoccidioidomycosis-related mortality trend, state of Sao Paulo, Brazil: a study using multiple causes of death

Objective. To investigate mortality in which paracoccidioidomycosis appears on any line or part of the death certificate. Method. Mortality data for 1985-2005 were obtained from the multiple cause-of-death database maintained by the Sao Paulo State Data Analysis System (SEADE). Standardized mortality coefficients were calculated for paracoccidioidomycosis as the underlying cause-of-death and as an associated cause-of-death, as well as for the total number of times paracoccidioidomycosis was mentioned on the death certificates. Results. During this 21-year period, there were 1950 deaths related to paracoccidioidomycosis; the disease was the underlying cause-of-death in 1 164 cases (59.69%) and an associated cause-of-death in 786 (40.31%). Between 1985 and 2005 records show a 59.8% decline in the mortality coefficient due to paracoccidioidomycosis as the underlying cause and a 53.0% decline in the mortality as associated cause. The largest number of deaths occurred among men, in the older age groups, and among rural workers, with an upward trend in winter months. The main causes associated with paracoccidioidomycosis as the underlying cause-of-death were pulmonary fibrosis, chronic lower respiratory tract diseases, and pneumonias. Malignant neoplasms and AIDS were the main underlying causes when paracoccidioidomycosis was an associated cause-of-death. The decision tables had to be adapted for the automated processing of causes of death in death certificates where paracoccidioidomycosis was mentioned. Conclusions. Using the multiple cause-of-death method together with the traditional underlying cause-of-death approach provides a new angle on research aimed at broadening our understanding of the natural history of paracoccidioidomycosis.

Fatigue and workability in Brazilian textile companies in different corporate social responsibility score groups

The aim of this study was to evaluate working conditions in the textile industry for different stages of Corporate Social Responsibility (CSR) development, and workers` perception of fatigue and workability. A cross-sectional study was undertaken with 126 workers in the production areas of five Brazilian textile plants. The corporate executive officers and managers of each company provided their personal evaluations of CSR. Companies were divided into 2 groups (higher and lower) of CSR scores. Workers completed questionnaires on fatigue, workability and working conditions. Ergonomic job analysis showed similar results for working conditions, independent of their CSR score. Multivariate analysis models were developed for fatigue and workability, indicating that they are both associated to factors related to working conditions and individual workers` characteristics and life styles. Work organization, (what, how, when, where and for how long the work is done), is also an associated factor for fatigue. This study suggests that workers` opinions should be taken into greater consideration when companies develop their CSR programs, in particular for those relating to working conditions. Relevance to industry: This paper underlines the importance of considering working conditions and workers` opinions of them, work organization and individual workers` characteristics and life styles in order to restore or to maintain workability and to reduce fatigue, independently of how developed a company may be in the field of Corporate Social Responsibility. (C) 2010 Elsevier B.V. All rights reserved.

Chronic colitis associated with HIV infection can be related to intraepithelial infiltration of the colon by CD8+T lymphocytes

Gastrointestinal complications in AIDS patients with diarrhoea are common clinical manifestations, frequently diagnosed by colonoscopy as non-specific colitis. We retrospectively study colon biopsies diagnosed as chronic colitis associated with HIV (CCH). Biopsies were sorted as patients with AIDS (serum CD4 < 200 cell/mm(3)) but without any clear infectious process (n = 12) and patients without HIV infection (n = 24). There are low numbers of CD4+ T lymphocytes in lamina propria of AIDS patients, but CD8+ T populations in this area appear to be similar in all studied groups, regardless of HIV infection or laboratory evidence of a specific agent. We found the clear evidence of CD8+ T cells infiltration in colonic mucosa in HIV patients with microscopic colitis. An imbalance of lymphocyte subpopulations in the colon, both in the lamina propria and epithelium, could result in an intraepithelial CD8 infiltration, involved in the pathogenesis of CCH in AIDS patients.

Exercise reduces inhibitory neuroactivity and protects myenteric neurons from age-related neurodegeneration

The practice of regular exercise is indicated to prevent some motility disturbances in the gastrointestinal tract, such as constipation, during aging. The motility alterations are intimately linked with its innervations. The goal of this study is to determine whether a program of exercise (running on the treadmill), during 6 months, has effects in the myenteric neurons (NADH- and NADPH-diaphorase stained neurons) in the colon of rats during aging. Male Wister rats 6 months (adult) and 12 months (middle-aged) old were divided into 3 different groups: AS (adult sedentary), MS (middle-aged sedentary) and MT (middle-aged submitted to physical activity). The aging did not cause a decline significant (p > 0.05) of the number of NADH-diaphorase stained neurons in sedentary rats (AS vs. MS group). In contrast, a decline of 3 1% was observed to NADPH-diaphorase stained neurons. Thus, animals that underwent physical activity (AS vs. MT group) rescued neurons from degeneration caused by aging (total number, density and profile of neurons did not change with age - NADH-diaphorase method). On the other hand, physical activity augmented the decline of NADPH-diaphorase positive neurons (total number, density and profile of neurons decreased). Collectively, the results show that exercise inhibits age-related decline of myenteric neurons however, exercise augments the decline of neurons with inhibitory activity (nitric oxide) in the colon of the rats. (c) 2008 Elsevier B.V. All rights reserved.

Apolipoprotein E genotype is related to nitric oxide production in platelets

The presence of the, 4 allele of apolipoprotein E (APOE) is considered a risk factor for sporadic Alzheimer`s disease (AD). Our recent data demonstrated that the systemic modulation of oxidative stress in platelets and erythrocytes is disrupted in aging and AD. In this study, the relationship between APOE genotype and oxidative stress markers, both in AD patients and controls, was evaluated. The AD group showed an increase in the content of thiobarbituric acid-reactive substances (TBARS) and in the activities of nitric oxide synthase (NOS) and Na, K-ATPase, when compared to controls. Both groups had a similar cGMP content and superoxide dismutase activity. APOE epsilon 4 allele carriers showed higher NOS activity than non-carriers. These results suggest a possible influence of APOE genotype on nitric oxide (NO) production that might enhance the effects of age-related specific factor(s) associated with neurodegenerative disorders. Copyright (C) 2008 John Wiley & Sons, Ltd.