Introducing evidence-based family assessment and therapy in child and youth mental health services: Applying systemic principles to maintain, sustain and build capacity

The purpose of this article is to overview the context of the mental health service in which we work, and family therapy's status prior to and after the impact of changes wrought by the introduction of the National Mental Health Policy. We then explore some key issues that we think contribute to the persistence of the occlusion of family therapy in child psychiatric services; and the strategies that we developed and are continuing to develop to support change, finally, we describe the use of a family assessment instrument that we believe is central to our change strategy.

Ideological Closure : Drug Prevention in a Post-political Society

The aim of this thesis is to critically examine drug prevention as a field of problematizations  – how drug prevention becomes established as a political technology within this field, how it connects to certain modes of governance, how and under which conditions it constitutes it’s problematic, the questions it asks,  it´s implications in terms of political participation and representation, the various bodies of knowledge through which it constitutes the reality upon which it acts, the limits it places on ways of being, questioning, and talking  in the world. The main analyses have been conducted in four separate but interrelated articles. Each article addresses a specific dimension of drug prevention in order to get a grasp of how this field is organized. Article 1 examines the shift that has occurred in the Swedish context during the period 1981–2011 in how drugs have been problematized, what knowledge has grounded the specific modes of problematization and which modes of governance this has enabled. In article 2, the currently dominant scientific discipline in the field of drug prevention – prevention science – is critically examined in terms of how it constructs the “drug problem” and the underlying assumptions it carries in regard to reality and political governance. Article 3 addresses the issue of communities’ democratic participation in drug prevention efforts by analyzing the theoretical foundations of the Communities That Care prevention program. The article seeks to uncover how notions of community empowerment and democratic participation are constructed, and how the “community” is established as a political entity in the program. The fourth and final article critically examines the Swedish Social and Emotional Training (SET) program and the political implications of the relationship the program establishes between the subject and emotions. The argument is made that, within the field of drug prevention, questions of political values and priorities in a problematic way are decoupled from the political field and pose a significant problem in terms of the possibilities to engage in democratic deliberation. Within this field of problematizations it becomes impossible to mobilize a politics against social injustice, poverty and inequality. At the same time, the scientific grounding of this mode of governing the drug “problem” acts to naturalize a specific – highly political – way of engaging with drugs.

Modulating receptor function through RAMPs:can they represent drug targets in themselves?

G protein-coupled receptors (GPCRs) are successfully exploited as drug targets. As our understanding of how distinct GPCR subtypes can be generated expands, so do possibilities for therapeutic intervention via these receptors. Receptor activity-modifying proteins (RAMPs) are excellent examples of proteins that enhance diversity in. GPCR function. They facilitate the creation of binding pockets, controlling the pharmacology of some GPCRs. Moreover, they have the ability to regulate cell-surface trafficking, internalisation and signalling of GPCRs, creating novel opportunities for drug discovery. RAMPs could be directly targeted by drugs, or advantage could be taken of unique RAMP/GPCR interfaces for generating highly selective ligands.

Human amniotic epithelial cells induce localized cell-mediated immune privilege in vitro:implications for pancreatic islet transplantation

Chronic systemic immunosuppression in cell replacement therapy restricts its clinical application. This study sought to explore the potential of cell-based immune modulation as an alternative to immunosuppressive drug therapy in the context of pancreatic islet transplantation. Human amniotic epithelial cells (AEC) possess innate anti-inflammatory and immunosuppressive properties that were utilized to create localized immune privilege in an in vitro islet cell culture system. Cellular constructs composed of human islets and AEC (islet/AEC) were bioengineered under defined rotational cell culture conditions. Insulin secretory capacity was validated by glucose challenge and immunomodulatory potential characterized using a peripheral blood lymphocyte (PBL) proliferation assay. Results were compared to control constructs composed of islets or AEC cultured alone. Studies employing AEC-conditioned medium examined the role of soluble factors, and fluorescence immunocytochemistry was used to identify putative mediators of the immunosuppressive response in isolated AEC monocultures. Sustained, physiologically appropriate insulin secretion was observed in both islets and islet/AEC constructs. Activation of resting PBL proliferation occurred on exposure to human islets alone but this response was significantly (p <0.05) attenuated by the presence of AEC and AEC-conditioned medium. Mitogen (phytohaemagglutinin, 5 µg/ml)-induced PBL proliferation was sustained on contact with isolated islets but abrogated by AEC, conditioned medium, and the islet/AEC constructs. Immunocytochemical analysis of AEC monocultures identified a subpopulation of cells that expressed the proapoptosis protein Fas ligand. This study demonstrates that human islet/AEC constructs exhibit localized immunosuppressive properties with no impairment of ß-cell function. The data suggest that transplanted islets may benefit from the immune privilege status conferred on them as a consequence of their close proximity to human AEC. Such an approach may reduce the need for chronic systemic immunosuppression, thus making islet transplantation a more attractive treatment option for the management of insulin-dependent diabetes.

Meta-analysis of the population and phenotypic expression of CYP2C9/2C19 polymorphism on drug metabolism in different ethnicities

The term "pharmacogenetics" has been defined as the scientific study of inherited factors that affect the human drug response. Many pharmacogenetie studies have been published since 1995 and have focussed on the principal enzyme family involved in drug metabolism, the cytochrome P450 family, particularly cytochrome P4502C9 and 2C19. In order to investigate the pharmacogenetic aspect of pharmacotherapy, the relevant studies describing the association of pharmacogenetic factor(s) in drug responses must be retrieved from existing literature using a systematic review approach. In addition, the estimation of variant allele prevalence for the gene under study between different ethnic populations is important for pharmacogenetic studies. In this thesis, the prevalence of CYP2C9/2C19 alleles between different ethnicities has been estimated through meta-analysis and the population genetic principle. The clinical outcome of CYP2C9/2C19 allelic variation on the pharmacotherapy of epilepsy has been investigated; although many new antiepileptic drugs have been launched into the market, carbamazepine, phenobarbital and phenytoin are still the major agents in the pharmacotherapy of epilepsy. Therefore, phenytoin was chosen as a model AED and the effect of CYP2C9/2C19 genetic polymorphism on phenytoin metabolism was further examined.An estimation of the allele prevalence was undertaken for three CYP2C9/2C19 alleles respectively using a meta-analysis of studies that fit the Hardy-Weinberg equilibrium. The prevalence of CYP2C9*1 is approximately 81%, 96%, 97% and 94% in Caucasian, Chinese, Japanese, African populations respectively; the pooled prevalence of CYP2C19*1 is about 86%, 57%, 58% and 85% in these ethnic populations respectively. However, the studies of association between CYP2C9/2C19 polymorphism and phenytoin metabolism failed to achieve any qualitative or quantitative conclusion. Therefore, mephenytoin metabolism was examined as a probe drug for association between CYP2C19 polymorphism and mephenytoin metabolic ratio. Similarly, analysis of association between CYP2C9 polymorphism and warfarin dose requirement was undertaken.It was confirmed that subjects carrying two mutated CYP2C19 alleles have higher S/R mephenytoin ratio due to deficient CYP2C19 enzyme activity. The studies of warfarin and CYP2C9 polymorphism did not provide a conclusive result due to poor comparability between studies.The genetic polymorphism of drug metabolism enzymes has been studied extensively, however other genetic factors, such as multiple drug resistance genes (MDR) and genes encoding ion channels, which may contribute to variability in function of drug transporters and targets, require more attention in future pharmacogenetic studies of antiepileptic drugs.

Drug information in general practice pharmacy

The drug information sources currently available to general practice pharmacists have been identified. The use of and attitudes to these sources were assessed as well as the perceived information needs of practising pharmacists. The special requirements of women pharmacists and pharmacists working part-time were studied. The relationship of the medical representative as an information source for pharmacists was evaluated. Participation in continuing education programmes as a vital means of ensuring current information awareness and knowledge for the practising profession has been considered. Investigations were mainly pursued by questionnaire survey, while computer facilities were used for the processing and the analyses of data. The desirability of collated and evaluated information from one or more independent authoritative sources has been discussed. The increasing advisory role of the general practice pharmacist and the needs of the patient and potential customer have been discussed, with projections for the pharmacist's future health care contribution.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

Background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

The efficacy and safety of imeglimin as add-on therapy in patientswith type 2 diabetes inadequately controlled with metformin monotherapy

OBJECTIVE - A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone. RESEARCH DESIGN AND METHODS - A total of 156 patients were randomized 1:1 to receive imeglimin (1,500mg twice a day) or placebo added to a stable dose of metformin (1,500-2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio. RESULTS - After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin was 20.44% (P <0.001). Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (20.91 mg/dL and 27.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin therapy was generally welltolerated with a comparable safety profile to metformin-placebo. CONCLUSIONS - Addition of imeglimin to metformin improved glycemic control and offers potential as a new treatment for type 2 diabetes. Copyright © 2013 by the American Diabetes Association.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

Set-up and maintenance of syringe drivers for subcutaneous drug administration in palliative care

Focal points: Details of syringe driver use were collected from 11 inpatient hospice units in the West Midlands and compared with predetermined standards set by a multidisciplinary group We recorded 294 syringe driver events which complied with standards for the choice of administration site, protection of the syringe driver from light and the reason for initiation of the infusion Issues of nurse training, variability in prescribing practices, provision of written information for patients, labelling and documentation of the diluent used were all identified as areas in which compliance with standards could be improved