Structurally similar allosteric modulators of α7 nicotinic acetylcholine receptors exhibit five distinct pharmacological effects.

Activation of nicotinic acetylcholine receptors (nAChRs) is associated with the binding of agonists such as acetylcholine to an extracellular site that is located at the interface between two adjacent receptor subunits. More recently, there has been considerable interest in compounds, such as positive and negative allosteric modulators (PAMs and NAMs), that are able to modulate nAChR function by binding to distinct allosteric sites. Here we examined a series of compounds differing only in methyl substitution of a single aromatic ring. This series of compounds includes a previously described α7-selective allosteric agonist, cis-cis-4-p-tolyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide (4MP-TQS), together with all other possible combinations of methyl substitution at a phenyl ring (18 additional compounds). Studies conducted with this series of compounds have revealed five distinct pharmacological effects on α7 nAChRs. These five effects can be summarized as: 1) nondesensitizing activation (allosteric agonists), 2) potentiation associated with minimal effects on receptor desensitization (type I PAMs), 3) potentiation associated with reduced desensitization (type II PAMs), 4) noncompetitive antagonism (NAMs), and 5) compounds that have no effect on orthosteric agonist responses but block allosteric modulation (silent allosteric modulators (SAMs)). Several lines of experimental evidence are consistent with all of these compounds acting at a common, transmembrane allosteric site. Notably, all of these chemically similar compounds that have been classified as nondesensitizing allosteric agonists or as nondesensitizing (type II) PAMs are cis-cis-diastereoisomers, whereas all of the NAMs, SAMs, and type I PAMs are cis-trans-diastereoisomers. Our data illustrate the remarkable pharmacological diversity of allosteric modulators acting on nAChRs

An analysis of Australian graduate critical care nurse education.

BACKGROUND: Preparation of specialist critical care nurses in Australia is at graduate level, although there remains considerable variation in courses offered in relation to qualification, content, assessment and outcomes. As higher education providers must now comply with the Australian Qualifications Framework (AQF) a study was conducted to examine existing critical care courses and graduate practice outcomes. METHODS: Twenty-two critical care courses were reviewed. Data sources included course provider, websites, course curricula and telephone interviews with course coordinators. A framework approach, was used consisting of five key stages: preliminary immersion of raw data, conceptualising a thematic framework, indexing, charting, mapping and interpretation of data. FINDINGS: Analysis revealed considerable variations in course delivery and graduate practice outcomes. Most courses used professional competency standards as a framework for course curricula and clinical assessment, with inconsistency in their translation to graduate practice outcomes. Twenty-one courses included clinical assessment at graduate certificate level with no clinical assessment conducted at master level. The expected practice outcome for fifteen courses was safe practice with graduates not expected to practice at a specialist or team leadership level. Minimum graduate practice standards were not included in three courses as an expected outcome. CONCLUSION: The AQF requires graduate nurse education to be compliant with academic outcome standards. The findings of our study indicate variations between courses and subsequent graduate practice outcomes. It is therefore timely to establish national critical care education graduate practice standards

Regarding “Development of a postgraduate interventional cardiac nursing curriculum” by Currey et al.

publisher: Elsevier articletitle: Regarding “Development of a postgraduate interventional cardiac nursing curriculum” by Currey et al. journaltitle: Australian Critical Care articlelink: http://dx.doi.org/10.1016/j.aucc.2015.12.038 content_type: simple-article copyright: © 2015 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved

The effect of the introduction of a standard monitoring protocol on the investigations performed on the metabolic control of type 2 diabetes at Addington Hospital Medical Outpatients Department, Durban, South Africa

Background: A comprehensive approach to the control of type 2 diabetes is required to reduce mortality and morbidity. To improve diabetes management, in 2005 a protocol for the monitoring and management of type 2 diabetes, aligned to the 2003 Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) guidelines, was introduced atAddington Hospital Medical Outpatients Department, Durban, South Africa.Method: Data were collected from 120 randomly selected patients with type 2 diabetes. The number of glycated haemoglobin (HbA1c) and lipid estimations, blood pressure (BP) measurements and body mass indices (BMIs) recorded in 2005 was compared with those recorded in 2008 and 2009. The mean levels of these parameters and the number of patients reaching goal in 2008 were compared with the figures for 2009.Results: In 2005, 18.8% of patients had HbA1c levels measured compared with 82.9% in 2009 (P < 0.01). The mean HbA1c was 6.9% (± 1.9) in 2008 and 6.4% (± 2.0) in 2009 (P = 0.1). BP and BMI was measured in over 93% of patients in 2005, 2008 and 2009. BP goals were attained by 21% of patients in 2008 and 30% in 2009 (P = 0.65). The mean BMI in 2008was 29.4 kg/m2 (24% achieved goal), and in 2009 it was 28.6kg/m2 (29% achieved goal; P = 0.267). Lipid estimations rose significantly from 26% in 2005 to 73% in 2009 (P < 0.01). There was no improvement in the number of patients reaching target lipid levels between 2008 and 2009.Conclusion: The monitoring protocol improved adherence to the SEMDSA 2003 guidelines from 2005 to 2009. Overall glycaemic control was within target, but attainment of most nonglycaemic goals was suboptimal and did not improve over the study period

Assessment of causal link between psychological factors and symptom exacerbation in inflammatory bowel disease:a protocol for systematic review of prospective cohort studies

Background Inflammatory bowel disease is an idiopathic chronic disease that affects around 28 million people worldwide. Symptoms are distressing and have a detrimental effect on patients’ quality of life. A possible link between exacerbation of symptoms and psychological factors has been suspected but not established. Previous reviews concerned with this link had conceptual and methodological limitations. In this paper we set out a protocol that lays the foundations for a systematic review that will address these shortcomings. The aim of this review is to provide researchers and clinicians with clarity on the role of psychological factors in inflammatory bowel disease symptom exacerbation.Method/design We will identify all original, published, peer reviewed studies relevant to the topic and published in English from inception to November 2012. The databases MEDLINE, EMBASE, CINAHL and PsychINFO will be systematically searched. The search terms will include: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, psychological stress, mental stress, life stress, family stress, hassles, social stress, coping, mood disorders, anxiety and depression in sequential combinations.Studies will be screened according to predetermined inclusion and exclusion criteria by two reviewers. We will include clinical prospective cohort studies of all human participants aged 18 years or over with a diagnosis of inflammatory bowel disease. All eligible papers will be independently and critically appraised using the Critical Appraisal Skills Programme (CASP) tool by two reviewers. Two reviewers will independently extract and synthesise data from the studies using a predefined data extraction sheet. Disagreements will be resolved by discussion between reviewers and a third party will be consulted if agreement is not reached. Synthesised data will be analysed using Bradford Hill criterion for causality. If data permits, meta-analysis will be performed.Discussion This study will provide the most comprehensive review and synthesis of current evidence around the link between psychological factors and symptom exacerbation in inflammatory bowel disease. Results will inform clinicians in appropriate intervention development for this patient group that would reduce symptom exacerbation and therefore improve patients’ quality of life

Development of <scp>A</scp>ustralian clinical practice outcome standards for graduates of critical care nurse education

Aims and objectivesTo develop critical care nurse education practice standards.BackgroundCritical care specialist education for registered nurses in Australia is provided at graduate level. Considerable variation exists across courses with no framework to guide practice outcomes or evidence supporting the level of qualification.DesignAn eDelphi technique involved the iterative process of a national expert panel responding to three survey rounds.MethodsFor the first round, 84 statements, organised within six domains, were developed from earlier phases of the study that included a literature review, analysis of critical care courses and input from health consumers. The panel, which represented the perspectives of four stakeholder groups, responded to two rating scales: level of importance and level of practice.ResultsOf 105 experts who agreed to participate, 92 (88%) completed survey round I; 85 (92%) round II; and 73 (86%) round III. Of the 98 statements, 75 were rated as having a high level of importance – median 7 (IQR 6–7); 14 were rated as having a moderate level of importance – median 6 (IQR 5–7); and nine were rated as having a low level of importance – median 4 (IQR 4–6)–6 (IQR 4–6). The majority of the panel rated graduate level of practice as ‘demonstrates independently’ or ‘teaches or supervises others’ for 80 statements. For 18 statements, there was no category selected by 50% or more of the panel. The process resulted in the development of 98 practice standards, categorised into three levels, indicating a practice outcome level by the practitioner who can independently provide nursing care for a variety of critically ill patients in most contexts, using a patient‐ and family‐focused approach.Conclusion/relevance to clinical practiceThe graduate practice outcomes provide a critical care qualification definition for nursing workforce standards and can be used by course providers to achieve consistent practice outcomes.</jats:sec

Development of Australian clinical practice outcome standards for graduates of critical care nurse education.

AIMS AND OBJECTIVES: To develop critical care nurse education practice standards. BACKGROUND: Critical care specialist education for registered nurses in Australia is provided at graduate level. Considerable variation exists across courses with no framework to guide practice outcomes or evidence supporting the level of qualification. DESIGN: An eDelphi technique involved the iterative process of a national expert panel responding to three survey rounds. METHODS: For the first round, 84 statements, organised within six domains, were developed from earlier phases of the study that included a literature review, analysis of critical care courses and input from health consumers. The panel, which represented the perspectives of four stakeholder groups, responded to two rating scales: level of importance and level of practice. RESULTS: Of 105 experts who agreed to participate, 92 (88%) completed survey round I; 85 (92%) round II; and 73 (86%) round III. Of the 98 statements, 75 were rated as having a high level of importance - median 7 (IQR 6-7); 14 were rated as having a moderate level of importance - median 6 (IQR 5-7); and nine were rated as having a low level of importance - median 4 (IQR 4-6)-6 (IQR 4-6). The majority of the panel rated graduate level of practice as 'demonstrates independently' or 'teaches or supervises others' for 80 statements. For 18 statements, there was no category selected by 50% or more of the panel. The process resulted in the development of 98 practice standards, categorised into three levels, indicating a practice outcome level by the practitioner who can independently provide nursing care for a variety of critically ill patients in most contexts, using a patient- and family-focused approach. CONCLUSION/RELEVANCE TO CLINICAL PRACTICE: The graduate practice outcomes provide a critical care qualification definition for nursing workforce standards and can be used by course providers to achieve consistent practice outcomes

Developing and Testing the Standard of Practice and Evaluation of Critical-Care-Nursing Tool (SPECT) for Critical Care Nursing Practice.

BACKGROUND: Nurses working in critical care often undertake specialty education. There are no uniform practice outcomes for critical care programs, and consumer input to practice standards has been lacking. METHODS: A structured multiphase project was undertaken to develop practice standards and an assessment tool informed by critical care nursing stakeholders as well as patients and families-the Standards of Practice and Evaluation of Critical-Care-Nursing Tool (SPECT). RESULTS: Testing of the SPECT revealed adequate content validity index (CVI), domain CVI (range, 0.772 to 0.887), and statement CVI (range, 0.66 to 1.00). Reliability was adequate in terms of internal consistency (Cronbach's α > 0.864) and test-retest Spearman rank correlation (range, 0.772 to 0.887); intra-rater kappa agreement was significant for 102 of 104 statements with moderate agreement for 94.2% of statements. CONCLUSION: The SPECT appears to have clinical feasibility, preliminary validity and reliability, and provides a clear definition for the expected practice level for graduates of a critical care education program

The use of mindfulness-based cognitive therapy for improving quality of life for inflammatory bowel disease patients:study protocol for a pilot randomised controlled trial with embedded process evaluation

Background: Inflammatory bowel disease (IBD) is a chronic condition with an unpredictable disease course. Rates of anxiety and depression among IBD patients in relapse (active disease symptoms) as well as in remission are higher than in the general population. Previous studies suggest that the prolonged effect of pain, anxiety, distress and depression have a detrimental effect on patients’ quality of life (QoL). Poor QoL in itself is associated with further symptom relapse. Mindfulness based cognitive therapy (MBCT) is a psychological group intervention that has the potential to improve QoL. When used in other chronic conditions, it demonstrated reduced negative effect from pain and psychological factors at completion of an 8-week MBCT course. The effect of MBCT has never been researched in IBD. The aim of this study is to obtain the information required to design a full scale randomised controlled trial (RCT) that will examine the effectiveness of MBCT in improving quality of life for IBD patients.Methods/Design: This is an exploratory RCT with embedded process evaluation. Forty IBD patients will be recruited from NHS outpatient gastroenterology clinics and will be randomised to either a MBCT (intervention) group or to await-list (control) group. All participants will undergo 16 h of structured group training over an 8-week period, with the control group starting 6 months later than the intervention group. Primary outcomes are recruitment, completion/retention rates and adherence and adaptation to the MBCT manual for IBD patients. The secondary outcome is to assess the feasibility of collecting reliable and valid data on proposed outcome measures such as quality of life, anxiety, depression, disease activity and mindful awareness. The process evaluation will use a survey and focus groups to assess the acceptability of the intervention and trial procedures for IBD patients.Discussion: The outcomes of this study will help define the barriers, uptake and perceived benefits of MBCT program for IBD patients. This information will enable the design of a full-scale study assessing the effect of MBCT on quality of life for IBD patients