Evidence based pharmacogenetics study of the use of anti-psychotics in treatment of schizophrenia

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A pharmacy led program to review anti-psychotic prescribing for people with dementia

Background: Anti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics. Methods: This project was conducted within primary care in Medway Primary Care Trust (PCT) in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search. Results: Data were collected from 59 practices. One hundred and sixty-one (15.3%) of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462) vs. 7.3% of people living at home (43/589)] than people living in their own homes (p?anti-psychotics. Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4%) following the pharmacy-led medication review. Conclusions: In total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to people with dementia.

Psychotropic medication use by adults with intellectual disabilities living in community settings

This study examined the variables related to psychotropic medication use among 73 adults with intellectual disabilities living in community residential settings in Ontario, Canada over a one-year period based on staff reports. Despite only 16% percent having a documented psychiatric diagnosis, 84% of these individuals were receiving psychotropic medications, and 74% were receiving two or more psychotropic medications (polypharmacy). Anti-psychotics, anti-anxiety medications, and anti-convulsant medications were the most frequently reported drug classes. While problem behaviour was reported for 60% of the participants, only 33% had a formal behaviour plan. There was a significant relationship between the reported number of problem behaviours and the reported number of prescribed psychotropic medications. Reported medication reviews did not adhere to the Canadian 'Consensus Guidelines for the Primary Care of Adults with Developmental Disabilities' (Sullivan et aI., 2006). Results, based on staff reports, suggested incongruence with recommended best practices, and raised concern about over-reliance on psychotropic medication with these individuals. Keywords: intellectual disabilities, psychotropic medication, problem behaviour

Utilisation de médicaments durant la grossesse et l’allaitement : données d’un centre d’information sur les tératogènes

Les centres d’information sur les tératogènes (CIT) fournissent aux professionnels de la santé ainsi qu’au public de l’information sur les risques et bienfaits associés à l’utilisation des médicaments durant la grossesse et l’allaitement. Le Centre IMAGe (Info-Médicaments en Allaitement et Grossesse) du CHU Sainte-Justine (Centre Hospitalier Universitaire Sainte-Justine) au Québec, est un CIT qui offre depuis 1997 un service téléphonique d’information gratuit aux professionnels de la santé. Deux études ont été réalisées à partir des appels reçus au Centre IMAGe. La première étude a été réalisée sur l’ensemble des appels reçus entre janvier 2004 et avril 2007 au sujet de femmes qui prenaient ou envisageaient prendre un médicament durant la grossesse ou l’allaitement. Les objectifs de cette étude visaient à déterminer les classes de médicaments les plus fréquentes ainsi que les indications d’utilisation et les déterminants d’un appel à leur sujet (caractéristiques maternelles associées). Les antidépresseurs, les anti-inflammatoires, les antibiotiques, les benzodiazépines et les antipsychotiques sont les classes de médicaments qui correspondaient aux plus grands nombres d’appels. Cela porte à croire que pour ces classes de médicaments, il existe chez les professionnels de la santé un besoin d’information en ce qui concerne les risques et bienfaits de leur utilisation durant la grossesse et l’allaitement. La dépression représentait une des trois indications les plus prévalentes chez les femmes qui prenaient ou désiraient prendre des antidépresseurs, des benzodiazépines ou des anti-psychotiques durant la grossesse ou l’allaitement. Le tabagisme était associé à l’utilisation des antidépresseurs et des anti-psychotiques durant la grossesse, ainsi qu’à un appel au sujet des anti-inflammatoires durant l’allaitement. La deuxième étude a été réalisée sur l’ensemble des appels reçus entre janvier 2003 et mars 2008. Cette étude visait à déterminer l’impact des avis émis par Santé Canada concernant les risques de l’exposition aux antidépresseurs durant la grossesse et celui concernant le retrait du rofécoxib, sur le nombre d’appels reçus à IMAGe. L’analyse des séries temporelles du nombre hebdomadaire d’appels reçus a révélé que l’avis de Santé Canada sur les risques de malformations cardiaques associés à l’utilisation de la paroxétine lors du premier trimestre de la grossesse a généré une augmentation statistiquement significative, soudaine et permanente du nombre d’appels reçus à IMAGe au sujet des antidépresseurs. Ces études permettent de mieux comprendre le besoin d’information des professionnels de la santé sur les risques et bienfaits de l’utilisation des médicaments durant la grossesse et l’allaitement.

Medication -related adverse events in older people with dementia:causes and possible solutions

This submission for a PhD by previously published work is based upon six publications in peer reviewed journals, reflecting a 9-year research programme. My research has shown, in a coherent and original way, the difficulty in treating people with dementia with safe and effective medication whilst providing research-founded guidance to develop mechanisms to optimise medication choice and minimise iatrogenic events. A wide range of methods, including systematic reviews, meta-analysis, randomised controlled trials (RCTs), quantitative research and mixed methods were used to generate the data, which supported the exploration of three themes. The first theme, to understand the incidence and causes of medication errors in dementia services, identified that people with dementia may be more susceptible to medication-related iatrogenic disease partly due to inherent disease-related characteristics. One particular area of concern is the use of anti-psychotics to treat the Behavioural and Psychological Symptoms of Dementia (BPSD). The second and third themes, respectively, investigated a novel pharmacological and health services intervention to limit anti-psychotic usage. The second phase found that whilst the glutamate receptor blocker memantine showed some promise, further research was clearly required. The third phase found that anti-psychotic usage in dementia may be higher than official figures suggest and that medication review linking primary and secondary care can limit such usage. My work has been widely cited, reflecting a substantial contribution to the field, in terms of our understanding of the causes of, and possible solutions to limit, medication-related adverse events in people with dementia. More importantly, this work has already informed clinical practice, patients, carers and policy makers by its demonstrable impact on health policy. In particular my research has identified key lines of enquiry for future work and for the development of my own personal research programme to reduce the risk associated with medication in this vulnerable population.

Patterns of psychotropic prescribing and polypharmacy in older hospitalized patients in Ireland: the influence of dementia on prescribing

Neuropsychiatric Symptoms (NPS) are ubiquitous in dementia and are often treated pharmacologically. The objectives of this study were to describe the use of psychotropic, anti-cholinergic, and deliriogenic medications and to identify the prevalence of polypharmacy and psychotropic polypharmacy, among older hospitalized patients in Ireland, with and without dementia. All older patients (≥ 70 years old) that had elective or emergency admissions to six Irish study hospitals were eligible for inclusion in a longitudinal observational study. Of 676 eligible patients, 598 patients were recruited and diagnosed as having dementia, or not, by medical experts. These 598 patients were assessed for delirium, medication use, co-morbidity, functional ability, and nutritional status. We conducted a retrospective cross-sectional analysis of medication data on admission for 583/598 patients with complete medication data, and controlled for age, sex, and co-morbidity. Of 149 patients diagnosed with dementia, only 53 had a previous diagnosis. At hospital admission, 458/583 patients experienced polypharmacy (≥ 5 medications). People with dementia (PwD) were significantly more likely to be prescribed at least one psychotropic medication than patients without dementia (99/147 vs. 182/436; p < 0.001). PwD were also more likely to experience psychotropic polypharmacy (≥ two psychotropics) than those without dementia (54/147 vs. 61/436; p < 0.001). There were no significant differences in the prescribing patterns of anti-cholinergics (23/147 vs. 42/436; p = 0.18) or deliriogenics (79/147 vs. 235/436; p = 0.62). Polypharmacy and psychotropic drug use is highly prevalent in older Irish hospitalized patients, especially in PwD. Hospital admission presents an ideal time for medication reviews in PwD.

Anti-metabolic effects of Galanthus nivalis agglutinin and wheat germ agglutinin on nymphal stages of the common brown leafhopper using a novel artificial diet system

The common brown leafhopper, Orosius orientalis (Matsumura) (Homoptera: Cicadellidae), previously described as Orosius argentatus (Evans), is an important vector of several viruses and phytoplasmas worldwide. In Australia, phytoplasmas vectored by O. orientalis cause a range of economically important diseases, including legume little leaf (Hutton & Grylls, 1956), tomato big bud (Osmelak, 1986), lucerne witches broom (Helson, 1951), potato purple top wilt (Harding & Teakle, 1985), and Australian lucerne yellows (Pilkington et al., 2004). Orosius orientalis also transmits Tobacco yellow dwarf virus (TYDV; genus Mastrevirus, family Geminiviridae) to beans, causing bean summer death disease (Ballantyne, 1968), and to tobacco, causing tobacco yellow dwarf disease (Hill, 1937, 1941). TYDV has only been recorded in Australia to date. Both diseases result in significant production and quality losses (Ballantyne, 1968; Thomas, 1979; Moran & Rodoni, 1999). Although direct damage caused by leafhopper feeding has been observed, it is relatively minor compared to the losses resulting from disease (P Tr E bicki, unpubl.).

Response efficacy : the key to minimizing rejection and maximizing acceptance of emotion-based anti-speeding messages

This study sought to improve understanding of the persuasive process of emotion-based appeals not only in relation to negative, fear-based appeals but also for appeals based upon positive emotions. In particular, the study investigated whether response efficacy, as a cognitive construct, mediated outcome measures of message effectiveness in terms of both acceptance and rejection of negative and positive emotion-based messages. Licensed drivers (N = 406) participated via the completion of an on-line survey. Within the survey, participants received either a negative (fear-based) appeal or one of the two possible positive appeals (pride or humor-based). Overall, the study's findings confirmed the importance of emotional and cognitive components of persuasive health messages and identified response efficacy as a key cognitive construct influencing the effectiveness of not only fear-based messages but also positive emotion-based messages. Interestingly, however, the results suggested that response efficacy's influence on message effectiveness may differ for positive and negative emotion-based appeals such that significant indirect (and mediational) effects were found with both acceptance and rejection of the positive appeals yet only with rejection of the fear-based appeal. As such, the study's findings provide an important extension to extant literature and may inform future advertising message design.

Enhancing road safety for young drivers : how Graduate Driver Licensing initiatives can complement "anti-hooning" legislation

Street racing and associated (hooning) behaviours have attracted increasing concern in recent years. While New Zealand and all Australian jurisdictions have introduced “antihooning” legislation and allocated significant police resources to managing the problem, there is limited evidence of the road safety implications of hooning. However, international and Australian data suggests that drivers charged with a hooning offence tend to be young males who are accompanied by one or more peers, and hooning-related crashes tend to occur at night. In this regard, there is considerable evidence that drivers under the age of 25 are over-represented in crash statistics, and are particularly vulnerable soon after obtaining a Provisional licence, when driving at night, and when carrying peer-aged passengers. The similarity between the nature of hooning offenders, offences and crashes, and road safety risks for young drivers in general, suggests that hooning is an issue that may be viewed as part of the broader young driver problem. Many jurisdictions have recently implemented a range of evidence-based strategies to address young driver road safety, and this paper will present Queensland crash and offence data to highlight the potential benefit of Graduated Driver Licensing initiatives, such as night driving restrictions and peer-aged passenger restrictions, to related road safety issues, including hooning. An understanding of potential flow-on effects is important for evaluations of anti-hooning legislation and Graduated Driver Licensing programs, and may have implications for future law enforcement resource allocation and policy development.

Establishment of a mouse model of colitis and its use to evaluate the anti-inflammatory effects of two ghrelin peptides

Ghrelin is a gut-brain peptide hormone that induces appetite, stimulates the release of growth hormone, and has recently been shown to ameliorate inflammation. Recent studies have suggested that ghrelin may play a potential role in inflammation-related diseases such as inflammatory bowel diseases (IBD). A previous study with ghrelin in the TNBS mouse model of colitis demonstrated that ghrelin treatment decreased the clinical severity of colitis and inflammation and prevented the recurrence of disease. Ghrelin may be acting at the immunological and epithelial level as the ghrelin receptor (GHSR) is expressed by immune cells and intestinal epithelial cells. The current project investigated the effect of ghrelin in a different mouse model of colitis using dextran sodium sulphate (DSS) – a luminal toxin. Two molecular weight forms of DSS were used as they give differing effects (5kDa and 40kDa). Ghrelin treatment significantly improved clinical colitis scores (p=0.012) in the C57BL/6 mouse strain with colitis induced by 2% DSS (5kDa). Treatment with ghrelin suppressed colitis in the proximal colon as indicated by reduced accumulative histopathology scores (p=0.03). Whilst there was a trend toward reduced scores in the mid and distal colon in these mice this did not reach significance. Ghrelin did not affect histopathology scores in the 40kDa model. There was no significant effect on the number of regulatory T cells or TNF-α secretion from cultured lymph node cells from these mice. The discovery of C-terminal ghrelin peptides, for example, obestatin and the peptide derived from exon 4 deleted proghrelin (Δ4 preproghrelin peptide) have raised questions regarding their potential role in biological functions. The current project investigated the effect of Δ4 peptide in the DSS model of colitis however no significant suppression of colitis was observed. In vitro epithelial wound healing assays were also undertaken to determine the effect of ghrelin on intestinal epithelial cell migration. Ghrelin did not significantly improve wound healing in these assays. In conclusion, ghrelin treatment displays a mild anti-inflammatory effect in the 5kDa DSS model. The potential mechanisms behind this effect and the disparity between these results and those published previously will be discussed.

Lyprinol : is it a useful anti-inflammatory agent?

The New Zealand green lipped mussel preparation Lyprinol is available without a prescription from a supermarket, pharmacy or Web. The Food and Drug Administration have recently warned Lyprinol USA about their extravagant anti-inflammatory claims for Lyprinol appearing on the web. These claims are put to thorough review. Lyprinol does have anti-inflammatory mechanisms, and has anti-inflammatory effects in some animal models of inflammation. Lyprinol may have benefits in dogs with arthritis. There are design problems with the clinical trials of Lyprinol in humans as an anti-inflammatory agent in osteoarthritis and rheumatoid arthritis, making it difficult to give a definite answer to how effective Lyprinol is in these conditions, but any benefit is small. Lyprinol also has a small benefit in atopic allergy. As anti-inflammatory agents, there is little to choose between Lyprinol and fish oil. No adverse effects have been reported with Lyprinol. Thus, although it is difficult to conclude whether Lyprinol does much good, it can be concluded that Lyprinol probably does no major harm.

Anti-cancer activity of zoledronic acid in breast cancer

Background: Zoledronic acid is used to prevent the bone loss associated with antioestrogen treatments in subjects with breast cancer. Preclinical studies suggest that zoledronic acid may have anticancer activity in its own right. This anticancer possibility with zoledronic acid has not been investigated extensively in clinical trials. Objectives/methods: This evaluation is of a large clinical trial that investigated the effect of zoledronic acid on cancer outcomes in premenopausal women with breast cancer. Results: The trial showed that after 4 years, 94.0% of subjects who were treated with zoledronic acid were disease-free compared with 90.8% of those not treated with zoledronic acid. Recurrence survival was a secondary end point; this occurred in 94.0% with, and 90.9% without, zoledronic acid treatment. Conclusions: Zoledronic acid does have anticancer activity in premenopausal women with cancer.

CTA1-DD is an effective adjuvant for targeting anti-chlamydial immunity to the murine genital mucosa

Chlamydia trachomatis is a significant human pathogen with potentially severe disease sequelae in the genital tract, including infertility. A successful vaccine will need to effectively target immunity to the genital mucosa. Intranasal immunisation with cholera toxin (CT) can target immunity to the genital tract, but has the potential to cause neurological side effects. CTA1-DD is a non-toxic potent mucosal adjuvant which combines the enzymatic properties of CT, with a B cell targeting moiety. Here, we demonstrate that intranasal immunisation with CTA1-DD and chlamydial Major Outer Membrane Protein (MOMP) results in the induction of neutralising systemic and mucosal antibodies, and reduces the level of chlamydial shedding following intravaginal challenge with Chlamydia muridarum. Thus, CTA1-DD is an effective adjuvant for vaccine development against Chlamydia trachomatis, and possibly also a range of other genital pathogens.