Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Within- and between-day repeatability and variability in children's physiological responses during submaximal treadmill exercise

The purpose of this study was to verify within- and between-day repeatability and variability in children's oxygen uptake (VO^sub 2^), gross economy (GE; VO^sub 2^ divided by speed) and heart rate (HR) during treadmill walking based on self-selected speed (SS). Fourteen children (10.1 ± 1.4 years) undertook three testing sessions over 2 days in which four walking speeds, including SS were tested. Within- and between-day repeatability were assessed using the Bland and Altman method, and coefficients of variability (CV) were determined for each child across exercise bouts and averaged to obtain a mean group CV value for VO^sub 2^, GE, and HR per speed. Repeated measures analysis of variance showed no statistically significant differences in within- or between-day CV for VO^sub 2^, GE, or HR at any speed. Repeatability within- and between-day for VO^sub 2^, GE, and HR for all speeds was verified. These results suggest that submaximal VO^sub 2^ during treadmill walking is stable and reproducible at a range of speeds based on children's SS.

Cost-effectiveness of an intervention to reduce emergency re-admissions to hospital among older patients

Background. The objective is to estimate the cost-effectiveness of an intervention that reduces hospital readmission among older people at high risk. A cost-effectiveness model to estimate the costs and health benefits of the intervention was implemented. Methodology/Principal Findings. The model used data from a randomised controlled trial conducted in an Australian tertiary metropolitan hospital. Participants were acute medical admissions aged >65 years with at least one risk factor for readmission: multiple comorbidities, impaired functionality, aged >75 years, 30 recent multiple admissions, poor social support, history of depression. The intervention was a comprehensive nursing and physiotherapy assessment and an individually tailored program of exercise strategies and nurse home visits with telephone follow-up; commencing in hospital and continuing following discharge for 24 weeks. The change to cost outcomes, including the costs of implementing the intervention and all subsequent use of health care services, and, the change to health benefits, represented by quality adjusted life years, were estimated for the intervention as compared to existing practice. The mean change to total costs and quality 38 adjusted life years for an average individual over 24 weeks participating in the intervention were: cost savings of $333 (95% Bayesian credible interval $-1,932:1,282) and 0.118 extra quality adjusted life years (95% Bayesian credible interval 0.1:0.136). The mean net41 monetary-benefit per individual for the intervention group compared to the usual care condition was $7,907 (95% Bayesian credible interval $5,959:$9,995) for the 24 week period. Conclusions/Significance. The estimation model that describes this intervention predicts cost savings and improved health outcomes. A decision to remain with existing practices causes unnecessary costs and reduced health. Decision makers should consider adopting this 46 program for elderly hospitalised patients.

Testing the effectiveness of a Practice Development intervention on changing the culture of evidence based practice in an acute care environment

In this age of evidence-based practice, nurses are increasingly expected to use research evidence in a systematic and judicious way when making decisions about patient care practices. Clinicians recognise the role of research when it provides valid, realistic answers in practical situations. Nonetheless, research is still perceived by some nurses as external to practice and implementing research findings into practice is often difficult. Since its conceptual platform in the 1960s, the emergence and growth of Nursing Development Units, and later, Practice Development Units has been described in the literature as strategic, organisational vehicles for changing the way nurses think about nursing by promoting and supporting a culture of inquiry and research-based practice. Thus, some scholars argue that practice development is situated in the gap between research and practice. Since the 1990s, the discourse has shifted from the structure and outcomes of developing practice to the process of developing practice, using a Practice Development methodology; underpinned by critical social science theory, as a vehicle for changing the culture and context of care. The nursing and practice development literature is dominated by descriptive reports of local practice development activity, typically focusing on reflection on processes or outcomes of processes, and describing perceived benefits. However, despite the volume of published literature, there is little published empirical research in the Australian or international context on the effectiveness of Practice Development as a methodology for changing the culture and context of care - leaving a gap in the literature. The aim of this study was to develop, implement and evaluate the effectiveness of a Practice Development model for clinical practice review and change on changing the culture and context of care for nurses working in an acute care setting. A longitudinal, pre-test/post-test, non-equivalent control group design was used to answer the following research questions: 1. Is there a relationship between nurses' perceptions of the culture and context of care and nurses' perceptions of research and evidence-based practice? 2. Is there a relationship between engagement in a facilitated process of Practice Development and change in nurses' perceptions of the culture and context of care? 3. Is there a relationship between engagement in a facilitated process of Practice Development and change in nurses' perceptions of research and evidence-based practice? Through a critical analysis of the literature and synthesis of the findings of past evaluations of Nursing and Practice Development structures and processes, this research has identified key attributes consistent throughout the chronological and theoretical development of Nursing and Practice Development that exemplify a culture and context of care that is conducive to creating a culture of inquiry and evidence-based practice. The study findings were then used in the development, validation and testing of an instrument to measure change in the culture and context of care. Furthermore, this research has also provided empirical evidence of the relationship of the key attributes to each other and to barriers to research and evidence-based practice. The research also provides empirical evidence regarding the effectiveness of a Practice Development methodology in changing the culture and context of care. This research is noteworthy in its contribution to advancing the discipline of nursing by providing evidence of the degree to which attributes of the culture and context of care, namely autonomy and control, workplace empowerment and constructive team dynamics, can be connected to engagement with research and evidence-based practice.

A pilot randomised control trial of general practitioner and exercise physiologist interventions to reduce primary cardiovascular risk in overweight patients [Abstract]

Aims & Rationale/Objectives: With the knowledge that overweight is a major public health concern in Australia, that a multidisciplinary team approach to the management of lifestyle-related conditions is supported, and that the Australian Government recently recognised the role of the exercise physiologist (EP) in reducing the health burden of disease by their inclusion for reimbursement under the Medicare Plus scheme, this study sought to undertake a pilot RCT to compare GP and EP interventions to reduce primary cardiovascular risk in the overweight general practice population. Methods and Measures: Overweight patients recruited by a convenience sample of GPs were randomised into one of three arms: the control group, or the GP or EP intervention group (in which patients received either five GP or five EP consultations over 24 weeks). Patients had baseline, 12- and 24-week measures of body composition and cardio-respiratory fitness, and completed baseline and end-of-study surveys, fasting lipids and glucose. GPs and EPs completed an end-of-study survey. Results:Sixty-seven patients attended the baseline assessment. Overall retention rate was 67%. Patients were generally satisfied with the effectiveness of the interventions and their weight reduction. Favourable trends in BMI, weight, glucose and exercise levels for GP and EP intervention groups and in physical activity levels for all groups Conclusions: This study supports the feasibility of a RCT of GP and EP interventions for decreasing primary cardiovascular risk in the overweight general practice population.

Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise

Background: It has been proposed that adenosine triphosphate (ATP) released from red blood cells (RBCs) may contribute to the tight coupling between blood flow and oxygen demand in contracting skeletal muscle. To determine whether ATP may contribute to the vasodilatory response to exercise in the forearm, we measured arterialised and venous plasma ATP concentration and venous oxygen content in 10 healthy young males at rest, and at 30 and 180 seconds during dynamic handgrip exercise at 45% of maximum voluntary contraction (MVC). Results: Venous plasma ATP concentration was elevated above rest after 30 seconds of exercise (P < 0.05), and remained at this higher level 180 seconds into exercise (P < 0.05 versus rest). The increase in ATP was mirrored by a decrease in venous oxygen content. While there was no significant relationship between ATP concentration and venous oxygen content at 30 seconds of exercise, they were moderately and inversely correlated at 180 seconds of exercise (r = -0.651, P = 0.021). Arterial ATP concentration remained unchanged throughout exercise, resulting in an increase in the venous-arterial ATP difference. Conclusions: Collectively these results indicate that ATP in the plasma originated from the muscle microcirculation, and are consistent with the notion that deoxygenation of the blood perfusing the muscle acts as a stimulus for ATP release. That ATP concentration was elevated just 30 seconds after the onset of exercise also suggests that ATP may be a contributing factor to the blood flow response in the transition from rest to steady state exercise.

Comprehensive standardized data definitions for acute coronary syndrome research in emergency departments in Australasia

Patients with chest discomfort or other symptoms suggestive of acute coronary syndrome (ACS) are one of the most common categories seen in many Emergency Departments (EDs). While the recognition of patients at high-risk of ACS has improved steadily, identifying the majority of chest pain presentations who fall into the low-risk group remains a challenge. Research in this area needs to be transparent, robust, applicable to all hospitals from large tertiary centres to rural and remote sites, and to allow direct comparison between different studies with minimum patient spectrum bias. A standardised approach to the research framework using a common language for data definitions must be adopted to achieve this. The aim was to create a common framework for a standardised data definitions set that would allow maximum value when extrapolating research findings both within Australasian ED practice, and across similar populations worldwide. Therefore a comprehensive data definitions set for the investigation of non-traumatic chest pain patients with possible ACS was developed, specifically for use in the ED setting. This standardised data definitions set will facilitate ‘knowledge translation’ by allowing extrapolation of useful findings into the real-life practice of emergency medicine.

Establishing content validity of a survey research instrument : the older patients in acute care survey - United States

Geriatric nursing competency in the acute care setting is a social mandate for the 21st century. This article reports on the content validation of an Australian research instrument, the Older Patients in Acute Care Survey (OPACS) that examines the attitudes, the knowledge, and the practices of nurses working with acute care patients. The OPACS tool was developed primarily to assist nurse educators to assess attitudes, knowledge, and practices of nursing staff in caring for older patients in the acute care setting; to evaluate the implementation of institution-specific educational interventions; and to improve quality of care given to older patients. An overall content validity index (CVI) for the OPACS was calculated (CVI = .918), revealing high content validity. Opinions (CVI = .92) and practices (CVI = .97) subconstructs revealed high content validity as well. Therefore, results indicate that the OPACS has high content validity in the U.S. acute care setting and could assist nurse educators in establishing and enhancing nurse competency in the care for geriatric patients in the future.

Mechanisms of change in negative thinking and urinary monoamines in depressed patients during acute treatment with group cognitive behavior therapy and antidepressant medication

This naturalistic study investigated the mechanisms of change in measures of negative thinking and in 24-h urinary metabolites of noradrenaline (norepinephrine), dopamine and serotonin in a sample of 43 depressed hospital patients attending an eight-session group cognitive behavior therapy program. Most participants (91%) were taking antidepressant medication throughout the therapy period according to their treating Psychiatrists' prescriptions. The sample was divided into outcome categories (19 Responders and 24 Non-responders) on the basis of a clinically reliable change index [Jacobson, N.S., & Truax, P., 1991. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12–19.] applied to the Beck Depression Inventory scores at the end of the therapy. Results of repeated measures analysis of variance [ANOVA] analyses of variance indicated that all measures of negative thinking improved significantly during therapy, and significantly more so in the Responders as expected. The treatment had a significant impact on urinary adrenaline and metadrenaline excretion however, these changes occurred in both Responders and Non-responders. Acute treatment did not significantly influence the six other monoamine metabolites. In summary, changes in urinary monoamine levels during combined treatment for depression were not associated with self-reported changes in mood symptoms.

Oral ibuprofen for acute postoperative pain

In this short communication we wanted to find out what is the analgesic effect of single dose oral Ibuprofen for adults with postoperative pain? Ibuprofen at 200mg and 400mg are effective in producing at least 50% pain relief in patients with moderate to severe postoperative pain (at least 30mm on a VAS). They are safe to use without common adverse effects. The use of Ibuprofen 200mg or 400mg should be considered as standard practice or protocol for pain relief in post-operative settings. Clinicians should consider a range of factors before prescribing or administering Ibuprofen for acute post-operative pain, including but not limited to, the duration of pain relief with Ibuprofen of different doses, Ibuprofen formulation, cost and patient preference.

Psychosocial outcomes of Hong Kong Chinese diagnosed with acute coronary syndromes: a prospective repeated measures study.

BACKGROUND: Western studies have suggested that emotional stress and distress impacted on the morbidity and mortality in people following acute coronary events. Symptoms of anxiety and depression have been associated with re-infarction and death, prolonged recovery and disability and depression may precipitate the client's low self-esteem. This study examined perceived anxiety, depression and self-esteem of Hong Kong Chinese clients diagnosed with acute coronary syndrome (ACS) over a 6-month period following hospital admission. OBJECTIVES: To examine: DESIGN: A prospective, repeated measures design with measures taken on two occasions over a 6-month period; (1) within the 1st week of hospital admission following the onset of ACS and (2) at 6 months follow up. SETTING AND PARTICIPANTS: Convenient sample of 182 voluntary consented clients admitted with ACS to a major public hospital in Hong Kong who could communicate in Chinese, complete questionnaires, cognitive intact, and were haemodynamically stable and free from acute chest pain at the time of interview. METHODS: Baseline data were obtained within 1 week after hospital admission. The follow-up data was collected 6 months after hospital discharge. The Chinese version of the Hospital Anxiety and Depression Scale (HADS), State Self-esteem Scale (SSES), and Rosenberg's Self-Esteem Scale (RSES) were used to assess anxiety and depression, state self-esteem, and trait self-esteem, respectively. RESULTS: Findings suggested gender differences in clients' perception in anxiety, depression and self-esteem. Improvements in clients' perception of these variables were evident over the 6-month period following their acute coronary events. CONCLUSION: The study confirmed the western notion that psychosocial problems are common among coronary clients and this also applies to Hong Kong Chinese diagnosed with ACS. Further studies to explore effective interventions to address these psychosocial issues are recommended.

Modeling factors that influence exercise and dietary change among midlife Australian women: results from the Healthy Aging of Women Study

The objective of this study was to investigate the factors that influence midlife women to make positive exercise and dietary changes. In late 2005 questionnaires were mailed to 866 women aged 51–66 years from rural and urban locations in Queensland, Australia and participating in Stage 2 of the Healthy Aging of Women Study. The questionnaires sought data on socio-demographics, body mass index (BMI), chronic health conditions, self-efficacy, exercise and dietary behavior change since age 40, and health-related quality of life. Five hundred and sixty four (69%) were completed and returned by early 2006. Data analysis comprised descriptive and bivariate statistics and structural equation modeling. The results showed that midlife is a significant time for women to make positive health behavior changes. Approximately one-third of the sample (34.6%) indicated that they had increased their exercise and around 60% had made an effort to eat more healthily since age 40. Modeling showed self-efficacy to be important in making both exercise and dietary changes. Although education appeared to influence self-efficacy in relation to exercise change, this was not the case for dietary change. The study has application for programs promoting healthy aging among women, and implies that those with low education, high BMI and poor mental health may need considerable support to improve their lifestyles.

A naturalistic inquiry of registered nurses' perspectives and expectations of psychodynamic therapeutic care in acute psychiatric inpatient facilities

Within contemporary inpatient mental health nursing practice, the psychodynamic model of care considered previously to be central to the nurse-patient relationship now seems a radical concept. It appears to exist only within primary care facilities and public health care practice settings. This naturalistic inquiry aimed to explicate mental health nurses' perspectives and expectations of providing psychodynamic therapeutic care in acute inpatient psychiatric facilities. Ten registered nurses working in acute inpatient mental health facilities were interviewed. Five themes emerged: a career for life, relating in a psychodynamic manner, swimming against the current, adopting a position of difference, and hopeful expectancy.

The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat

Context: The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic and anorexigenic peptides. ---------- Objective: The aim of the study was to investigate the effects of medium-term exercise on fasting/postprandial levels of appetite-related hormones and subjective appetite sensations in overweight/obese individuals. ---------- Design and Setting: We conducted a longitudinal study in a university research center. ---------- Participants and Intervention: Twenty-two sedentary overweight/obese individuals (age, 36.9 ± 8.3 yr; body mass index, 31.3 ± 3.3 kg/m2) took part in a 12-wk supervised exercise programme (five times per week, 75% maximal heart rate) and were requested not to change their food intake during the study. ---------- Main Outcome Measures: We measured changes in body weight and fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite. ---------- Results: Exercise resulted in a significant reduction in body weight and fasting insulin and an increase in AG plasma levels and fasting hunger sensations. A significant reduction in postprandial insulin plasma levels and a tendency toward an increase in the delayed release of glucagon-like peptide-1 (90–180 min) were also observed after exercise, as well as a significant increase (127%) in the suppression of AG postprandially. ---------- Conclusions: Exercise-induced weight loss is associated with physiological and biopsychological changes toward an increased drive to eat in the fasting state. However, this seems to be balanced by an improved satiety response to a meal and improved sensitivity of the appetite control system.