The role of long- and short-term typical dose, concurrent alcohol consumption and executive processes in ecstasy related prospective memory deficits.

Building on previous research demonstrating prospective memory (PM) deficits in ecstasy users the purpose of this thesis was to explore the specific nature of these deficits focussing on establishing dose related effects and exploring possible mediators. Using laboratory-based measures of PM and a detailed background drug use questionnaire, the extent to which the typical dose of ecstasy per session can predict PM performance was examined. In Chapter 7, increased dose of ecstasy per session (typical dose of ecstasy per session in the 12 months prior to the test-session) was associated with poor short-term time-based PM performance. Chapter 8 examined the effects of concurrent alcohol and ecstasy use on PM performance. The use of alcohol and ecstasy together was not associated with additional PM performance deficits. Chapter 10 investigated the role of executive functioning processes in accounting PM deficits in ecstasy users. Verbal word fluency, updating, shifting and inhibition executive functions did not predict PM performance in ecstasy users. Chapter 11 used correlational analyses to investigate the effects of long- and short-term indicators of ecstasy, cannabis and cocaine use on PM performance. Clear relationships were established between long-term indicators of ecstasy and cocaine use and PM performance. Total lifetime ecstasy and cocaine consumption and the long-term average dose of ecstasy and cocaine per session were related to PM performance. For both drugs, increased lifetime consumption and larger doses consumed in a typical session were associated with adverse outcomes on PM tasks. PM impairments in ecstasy users were found in all studies in this thesis. These findings have important implications for those individuals who use ecstasy. Firstly, the use of ecstasy is detrimental to PM performance and therefore can potentially be debilitating to normal everyday functioning. More specifically, those individuals who consume higher doses of ecstasy per session may be more likely to display PM impairments compared to those individuals who consume lower doses. This information should be used to educate ecstasy users as to the possible consequences of its use. Future research should further explore the importance of typical dose of ecstasy per session in relation to cognitive performance in general. In addition to the administration of laboratory-based measures of PM, the use of neuroimaging techniques could be employed. This would allow researchers to potentially identify specific brain regions that may be implicated in PM deficits in those ecstasy users who consume large doses of ecstasy in a representative session

Explicit criteria as clinical tools to minimize inappropriate medication use and its consequences

Polypharmacy and prescribing of potentially inappropriate medications (PIMs) are the key elements of inappropriate medication use (IMU) in older multimorbid people. IMU is associated with a range of negative healthcare consequences including adverse drug events and unplanned hospitalizations. Furthermore, prescribing guidelines are commonly derived from randomized controlled clinical trials which have specifically excluded older adults with multimorbidity. Consequently, indiscriminate application of single disease pharmacotherapy guidelines to older multimorbid patients can lead to increased risk of drug?drug interactions, drug?disease interactions and poor drug adherence. Both polypharmacy and PIMs are highly prevalent in older people and strategies to improve the quality and safety of prescribing, largely through avoidance of IMU, are needed. In the last 30?years, numerous explicit PIM criteria-based tools have been developed to assist physicians with medication management in clinically complex multimorbid older people. Very few of these PIM criteria sets have been tested as an intervention compared with standard pharmaceutical care in well-designed clinical trials. In this review, we describe the most widely used sets of explicit PIM criteria to address inappropriate polypharmacy with particular focus on STOPP/START criteria and FORTA criteria which have been associated with positive patient-related outcomes when used as interventions in recent randomized controlled trials

The structure of triphenylgermanium hydroxide

C18H~6GeO, Mr = 320.9, triclinic, Pi, a = 15.408 (6), b = 19.974 (7), c = 23.264 (11) A, a = 107.78 (4), 13 = 1.03.54 (4), y= 101.51 (3) °, V = 6338 (5)/~3, Z = 16, Dx = 1.34 g cm -3, a(Mo Ka) = 0.71073A, /z = 19.1cm-1, F(000)=2624, T= 293 K, R = 0.055 for 6846 observed reflections. The eight independent molecules in the asymmetric unit form two independent O--H...O hydrogen-bonded tetramers with the O atoms in a flattened tetrahedral arrangement [hydrogen-bond distances in the range 2.609 (11) to 2.657 (11)A]. The Ge atoms are tetrahedrally coordinated with mean Gc O 1.791 (7) and Gc C 1.931 (8) A

Methods to reduce prescribing errors in elderly patients with multimorbidity

The global population of multimorbid older people is growing steadily. Multimorbidity is the principal cause of complex polypharmacy, which in turn is the prime risk factor for inappropriate prescribing and adverse drug reactions and events. Those who prescribe for older frailer multimorbid people are particularly prone to committing prescribing errors of various kinds. The causes of prescribing errors in this patient population are multifaceted and complex, including prescribers’ lack of knowledge of aging physiology, geriatric medicine, and geriatric pharmacotherapy, overprescribing that frequently leads to major polypharmacy, inappropriate prescribing, and inappropriate drug omission. This review examines the various ways of minimizing prescribing errors in multimorbid older people. The role of education in physician prescribers and clinical pharmacists, the use of implicit and explicit prescribing criteria designed to improve medication appropriateness in older people, and the application of information and communication-technology systems to minimize errors are discussed in detail. Although evidence to support any single intervention to prevent prescribing errors in multimorbid elderly people is inconclusive or lacking, published data support focused prescriber education in geriatric pharmacotherapy, routine application of STOPP/START (screening tool of older people’s prescriptions/screening tool to alert to right treatment) criteria for potentially inappropriate prescribing, electronic prescribing, and close liaison between clinical pharmacists and physicians in relation to structured medication review and reconciliation. Carrying out a structured medication review aimed at optimizing pharmacotherapy in this vulnerable patient population presents a major challenge. Another challenge is to design, build, validate, and test by clinical trials suitably versatile and efficient software engines that can reliably and swiftly perform complex medication reviews in older multimorbid people. The European Union-funded SENATOR and OPERAM clinical trials commencing in 2016 will examine the impact of customized software engines in reducing medication-related morbidity, avoidable excess cost, and rehospitalization in older multimorbid people

Roles for NFkappaB, PHD3 and neural activity in the development of the peripheral nervous system

In the developing peripheral nervous system, neuronal survival and axonal growth are regulated to a large extent by neurotrophic factors acting via intracellular signalling cascades that are not fully understood. Here, I describe crucial roles for the nuclear factor-kappa B (NFκB) transcription cascade and the cellular oxygen sensor proline hydroxylase domain 3 (PHD3) in the regulation of axonal growth and neuronal survival during the phase of target field innervation, and I describe a novel role for purinergic signalling in promoting neuronal survival at a later stage of development. Using sensory neurons of the nodose ganglion, I show that distinct NFκB activation mechanisms are responsible for neurite growth promoted by ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Whereas a non-canonical NFκB signalling pathway that requires tyrosine phosphorylation of IkBo. is crucial for CNTF-promoted growth, canonical signalling that requires serine phosphorylation of IicBa contributes to BDNF-promoted growth. Using sympathetic neurons of the superior cervical ganglion of wild type and PHD3-deficient mice, I show that PHD3 exerts a negative regulatory effect on neuronal survival and neurite growth, implicating oxygen sensitive pathways in the regulation of sympathetic neuron development. Despite increased numbers of sympathetic neurons in PHD3-deficient mice there was decreased target innervation density and defective sympathetic function. Finally, in nodose neurons I describe roles for depolarization and purinergic signalling in promoting neuronal survival during a window of development as the neurons begin to lose their dependence on BDNF for survival

A Visual Guide for Communities Working with Academics on Participatory Research Projects

This illustrated guide is for communities interested in participatory research and engagement with academics as part of participatory projects. It has been written by community members, activists and academics who have been involved in research of this kind. It is intended to provide communities with basic explanations of the background to, and motivations for, participatory research, as well as overviews of the processes of research, the implications that communities should consider when deciding whether or not to participate in projects and the key steps participants can take to minimize risks and maximize benefits. What follows should be regarded only as an introduction to the topic and should be read in combination with more detailed work on specific elements of participatory research outlined in the references list below. While there are many other forms of engagement between communities and academics, such as practice placements, site visits and teaching contributions, this guide deals only with participatory research – a process which can stem from, or provide the basis for, other instances of collaboration. It is freely available online on the website of ‘A Cross-Cultural Working Group on “Good Culture” and Precariousness’ (http://wp.lancs.ac.uk/good-culture/a-guide-for-communities-working-withacademics-on-participatory-research-projects/), a participatory project involving community members from Ashington, Northumberland, and Aboriginal groups around Brisbane, Australia. It was during the development of this broader project that the need for an introductory guide emerged. It is hoped that drawing on those experiences, among others, will help community members and academics to find mutually beneficial means of advancing research capable of improving the lives of those participating in it

Prospective memory deficits in illicit polydrug users are associated with the average long term typical dose of ecstasy typically consumed in a single session

Rationale Neuroimaging evidence suggests that ecstasy-related reductions in SERT densities relate more closely to the number of tablets typically consumed per session rather than estimated total lifetime use. In order to better understand the basis of drug related deficits in prospective memory (PM) we explored the association between PM and average long-term typical dose and long-term frequency of use. Method Study 1: Sixty five ecstasy/polydrug users and 85 non-ecstasy users completed an event based, a short-term and a long-term time based PM task. Study 2: Study 1 data were merged with outcomes on the same PM measures from a previous study creating a combined sample of 103 ecstasy/polydrug users, 38 cannabis-only users and 65 nonusers of illicit drugs. Results Study 1: Ecstasy/polydrug users had significant impairments on all PM outcomes compared to non-ecstasy users. Study 2: Ecstasy/polydrug users were impaired in event based PM compared to both other groups and in long-term time based PM compared to non illicit drug users. Both drug using groups did worse on the short-term time based PM task compared to nonusers. Higher long-term average typical dose of ecstasy was associated with poorer performance on the event and short-term time based PM tasks and accounted for unique variance in the two PM measures over and above the variance associated with cannabis and cocaine use. Conclusions The typical ecstasy dose consumed in a single session is an important predictor of PM impairments with higher doses reflecting increasing tolerance giving rise to greater PM impairment