Estrogen replacement, muscle composition, and physical function: The health ABC study

Purpose: Although the beneficial effects of estrogen use on cardiovascular and cognitive function in postmenopausal women have been recently discredited, controversy remains regarding its usefulness for maintaining skeletal muscle mass or strength. Therefore, the purpose of this study was to determine whether estrogen use is associated with enhanced muscle composition and, if so, whether this translates into improved strength and physical function. Methods: Cross-sectional analysis of 840 well-functioning community-dwelling white women (current estrogen replacement therapy (ERT) users = 259, nonusers = 581) aged 70-79 yr participating in the Health, Aging and Body Composition Study. Muscle composition of the midthigh by computed tomography included cross-sectional area (CSA) of the quadriceps, hamstrings, intermuscular fat and subcutaneous fat, and muscle attenuation in Hounsfield units (HU) as a measure of muscle density. Isometric hand grip and isokinetic knee extensor strength were assessed by dynamometry. Physical function was assessed using a summary scale that included usual 6-m walk and narrow walk speed, repeated chair stands, and standing balance. Results: In analyses of covariance adjusted for relevant confounders. quadriceps muscle CSA and HU were greater in Current ERT than non-ERT women (P < 0.05). Grip strength was also greater (P < 0.05) in women taking ERT while knee extensor strength approached significance (P < 0.10). However, differences in muscle composition and strength were modest at <= 3.3%. There was no difference by ERT status for the hamstring, muscles. fat CSA. or for physical function. Conclusion: The associations between ERT and muscle composition and strength were minor and did not translate into improved physical function. Initiation of ERT for preservation of muscle composition and function may not be indicated.

Hormones down under: Hormone therapy use after the women's health initiative

Aims: The primary objective was to describe the usage pattern of hormone therapy (HT) in a sample of urban Australian women in 2001 and to assess the characteristics of users vs. non-users. The second objective was to determine whether there had been any change in usage since the publication of the results of the combined oestrogen plus progestagen arm of the Women's Health Initiative (WHI) in 2002. Methods: A cohort of 374 postmenopausal women aged 50-80 years participated in this substudy of the LAW (Longitudinal Assessment of Ageing in Women) project: a 5-year multidisciplinary, observational study. Participants completed an annual medical assessment including details of the use of HT and the reasons for use, as well as demographic and psychosocial data. Results: In December 2001, 30.8% of the participants were using HT, whereas 55.4% were ever users. The management of vasomotor symptoms and mood disturbance were the primary reasons for use. Of those who had been using HT in December 2001 (24.4%) women ceased using HT in the 3 months following publication of the WHI results. The percentage of women using HT in December 2003 (13.9%) was less than half of that of December 2001. Conclusion: The rate of HT use and the reasons for use, in 2001 in Brisbane was similar to that of other Australian regions. Usage of HT decreased since the publication of the WHI results in 2002 which may reflect changing attitudes by patients and practitioners regarding HT.

A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham elderly thyroid study

Context: Subclinical hypothyroidism (SCH) and cognitive dysfunction are both common in the elderly and have been linked. It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit. Objective: Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function. Design and Setting: We conducted a double-blind placebo-controlled randomized controlled trial in the context of United Kingdom primary care. Patients: Ninety-four subjects aged 65 yr and over (57 females, 37 males) with SCH were recruited from a population of 147 identified by screening. Intervention: T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 µg T4 per day for 12 months. Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm. Fifty-two subjects received T4 (31 females, 21 males; mean age 73.5 yr, range 65–94 yr); 42 subjects received placebo (26 females, 16 males; mean age 74.2 yr, 66–84 yr). Main Outcome Measures: Mini-Mental State Examination, Middlesex Elderly Assessment of Mental State (covering orientation, learning, memory, numeracy, perception, attention, and language skills), and Trail-Making A and B were administered. Results: Eighty-two percent and 84% in the T4 group achieved euthyroidism at 6- and 12-month intervals, respectively. Cognitive function scores at baseline and 6 and 12 months were as follows: Mini-Mental State Examination T4 group, 28.26, 28.9, and 28.28, and placebo group, 28.17, 27.82, and 28.25 [not significant (NS)]; Middlesex Elderly Assessment of Mental State T4 group, 11.72, 11.67, and 11.78, and placebo group, 11.21, 11.47, and 11.44 (NS); Trail-Making A T4 group, 45.72, 47.65, and 44.52, and placebo group, 50.29, 49.00, and 46.97 (NS); and Trail-Making B T4 group, 110.57, 106.61, and 96.67, and placebo group, 131.46, 119.13, and 108.38 (NS). Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months. Conclusions: This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function.

Palliative care challenges : implications for nurses' practice in renal settings

The very act of withdrawing dialysis places renal nurses in a unique practice setting requiring a sudden shift in care delivery from one of providing Ife-sustaining, active treatment to that of palliation. The impact of this act on the renal nurse remains largely invisible. Minimal research has been conducted that explores the significant issues and challenges that exist for renal nurses in the delivery of palliation following withdrawal of dialysis treatment. This paper attempts to highlight the issues and challenges that do exist for renal nurses in providing palliation and the subsequent lack of available research knowledge to inform practice in the renal setting. It recommends further research be conducted into the renal setting so as to inform the development of appropriate education to support renal nurses practice in the future.

Understanding the role of knowledge in the practice of expert nephrology nurses in Australia

This paper, which is abstracted from a larger study into the acquisition and exercise of nephrology nursing expertise, aims to explore the role of knowledge in expert practice. Using grounded theory methodology, the study involved 17 registered nurses who were practicing in a metropolitan renal unit in New South Wales, Australia. Concurrent data collection and analysis was undertaken, incorporating participants' observations and interviews. Having extensive nephrology nursing knowledge was a striking characteristic of a nursing expert. Expert nurses clearly relied on and utilized extensive nephrology nursing knowledge to practice. Of importance for nursing, the results of this study indicate that domain-specific knowledge is a crucial feature of expert practice.

Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer

Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life.

Drugs for diabetes and obesity

14.1 Drugs for diabetes 14.1.1 Diabetes mellitus 14.1.2 Physiology of the pancreas 14.1.3 Insulin replacement therapy 14.1.4 Metformin 14.1.5 Acarbose 14.1.6 Sulfonylureas 14.1.7 Glitazones 14.1.8 Glucagon-like peptide-1, exenatide and sitagliptin 14.2 Drugs for obesity 14.2.1 Introduction 14.2.2 Amphetamine 14.2.3 Phentermine 14.2.5 Orlistat

Smoking cessation

21. Smoking cessation 21.1 Epidemiology of cigarette smoking 21.2 Nicotine, addiction and pharmacokinetics 21.3 Nicotine replacement therapy 21.4 Varenicline 21.5 Bupropion

What information-related activities do people with ESKD use?

Background Information practice is an emerging area of research that seeks to reveal how people learn to connect with the complex multimodal information landscapes that informs their ability to make decisions. Previous research has identified that people with end stage kidney disease (ESKD) tend to adopt a ‘received’ or ‘engaged’ view of information but little is known about the activities of information practice. Objectives This research project sought to identify the: i) information-related activities; and ii) how information is used. Methods Using a constructivist qualitative methodology, ten people with ESKD living in a large metropolitan city were purposively selected and interviewed. Data was subject to thematic analysis by researchers from nursing and information science. Saturation of themes was achieved. Results Participants were between 38 and 72 years, had been receiving kidney replacement therapy from 2 weeks to 31 years. Eight participants reported having access to the internet but none participated in chat rooms. The activities were conceptualized into themes as listening, seeking, searching, sharing and observing. These activities enabled people to create, reflect on and evaluate the information needed to inform their decision-making Conclusion/Application to Clinical Practice The information practice research approach will enable a better understanding of the underlying relationship between information, knowledge and experience to be better understood. For renal nurses who are involved in patient education being able to recognise the way people use information will assist in individualizing educational sessions and tailoring teaching strategies to make it more meaningful.

Narrative review of changing medical and feminist perspectives on menopause : from femininity and ageing to risk and choice

Meanings and descriptions of menopause have shifted focus over the past century and a half; more particularly the past sixty years has seen a shift from descriptions of hormone decline and its relation to ageing, femininity and symptoms of menopause since the 1960's to the possibility for preventive medicine afforded by menopause. Medicine is not a static field in its construction of menopause. It has changed, not least by its engagement (positively or negatively) with critique from both within (epidemiological) and without (feminist and social sciences). In this review we identify three recent changes: (1) Increasing concern with women's decision-making. (2) The emergence from within medicine of the rejection of the use of language which defines menopause as a condition of deficiency. (3) New insights from postmodern and poststructural analyses of menopause that examine the epistemological foundations of medical and feminist concepts of menopause and contest fixed descriptions of the experience of menopause. Key aspects of a ‘medical menopause’ nevertheless remain constant: menopause is a loss of hormones that results in predictable effects and risks and may be ameliorated by hormone replacement therapy. A question therefore emerges about how and to what effect medical practitioners have engaged with critiques of the medical menopause?

Feminist ethics and menopause : autonomy and decision-making in primary medical care

The construction of menopause as a long-term risk to health and the adoption of discourses of prevention has made necessary a decision by women about medical treatment; specifically regarding the use of hormone replacement therapy. In a study of general practitioners’ accounts of menopause and treatment in Australia, women's ‘choice’, ‘informed decision-making’ and ‘empowerment’ were key themes through which primary medical care for women at menopause was presented. These accounts create a position for women defined by the concept of individual choice and an ethic of autonomy. These data are a basis for theorising more generally in this paper. We critically examine the construct of ‘informed decision-making’ in relation to several approaches to ethics including bioethics and a range of feminist ethics. We identify the intensification of power relations produced by an ethic of autonomy and discuss the ways these considerations inform a feminist ethics of decision-making by women. We argue that an ‘ethic of autonomy’ and an ‘offer of choice’ in relation to health care for women at menopause, far from being emancipatory, serves to intensify power relations. The dichotomy of choice, to take or not to take hormone replacement therapy, is required to be a choice and is embedded in relations of power and bioethical discourse that construct meanings about what constitutes decision-making at menopause. The deployment of the principle of autonomy in medical practice limits decision-making by women precisely because it is detached from the construction of meaning and the self and makes invisible the relations of power of which it is a part.

Menopause as a long-term risk to health : implications of general practitioner accounts of prevention for women’s choice and decision-making

Over the past two decades medical researchers and modernist feminist researchers have contested the meaning of menopause. In this article we examine various meanings of menopause in major medical and feminist literature and the construction of menopause in a semi-structured interview study of general practitioners in rural South Australia. Three discursive themes are identified in these interviews; (i) the hormonal menopause – symptoms, risk, prevention; (ii) the informed menopausal woman; and (iii) decision-making and hormone replacement therapy. By using the discourse of prevention, general practitioners construct menopause in relation to women's health care choices, empowerment and autonomy. We argue that the ways in which these concepts are deployed by general practitioners in this study produces and constrains the options available to women. The implications of these general practitioner accounts are discussed in relation to the proposition that medical and feminist descriptions of menopause posit alternative but equally-fixed truths about menopause and their relationship with the range of responses available to women at menopause. Social and cultural explanations of disease causality (c.f.Germov 1998, Hardey 1998) are absent from the new menopause despite their being an integral part of the framework of the women's health movement and health promotion drawn on by these general practitioners. Further, the shift of responsibility for health to the individual woman reinforces practice claims to empower women, but oversimplifies power relations and constructs menopause as a site of self-surveillance. The use of concepts from the women's health movement and health promotion have nevertheless created change in both the positioning of women as having ‘choices’ and the positioning of some general practitioners in terms of greater information provision to women and an attention to the woman's autonomy. In conclusion, we propose that a new menopause has evolved from a discursive shift in medicine and that there exists within this new configuration, claiming the empowerment of women as an integral part of health care for menopause, the possibility for change in medical practice which will broaden, strengthen, and maintain this position.