Showing papers by "University of Auckland published in 1997"

Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women

Abstract: Objective: To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women. Design: Randomised controlled trial of an individually tailored programme of physical therapy in the home (exercise group, n=116) compared with the usual care and an equal number of social visits (control group, n=117). Setting: 17 general practices in Dunedin, New Zealand. Subjects: Women aged 80 years and older living in the community and registered with a general practice in Dunedin. Main outcome measures: Number of falls and injuries related to falls and time between falls during one year of follow up; changes in muscle strength and balance measures after six months. Results: After one year there were 152 falls in the control group and 88 falls in the exercise group. The mean (SD) rate of falls was lower in the exercise than the control group (0.87 (1.29) v 1.34 (1.93) falls per year respectively; difference 0.47; 95% confidence interval 0.04 to 0.90). The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 (0.52 to 0.90). The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 (0.39 to 0.97). After six months, balance had improved in the exercise group (difference between groups in change in balance score 0.43 (0.21 to 0.65). Conclusions: An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older. Key messages Modifiable risk factors for falls in elderly people have been well defined; they include loss of muscle strength and impaired balance A programme to improve strength and balance in women aged 80 years and older can be set up safely with four home visits from a physiotherapist This programme reduced falls and moderate injuries appreciably over the subsequent year in Dunedin, New Zealand The benefit was most noticeable in elderly people who fell often

A Taxonomy of Obfuscating Transformations

Abstract: It has become more and more common to distribute software in forms that retain most or all of the information present in the original source code. An important example is Java bytecode. Since such codes are easy to decompile, they increase the risk of malicious reverse engineering attacks. In this paper we review several techniques for technical protection of software secrets. We will argue that automatic code obfuscation is currently the most viable method for preventing reverse engineering. We then describe the design of a code obfuscator, a tool which converts a program into an equivalent one that is more diicult to understand and reverse engineer. The obfuscator is based on the application of code transformations, in many cases similar to those used by compiler optimizers. We describe a large number of such transformations, classify them, and evaluate them with respect to their potency (To what degree is a human reader confused?), resilience (How well are automatic deobfuscation attacks resisted?), and cost (How much overhead is added to the application?). We nally discuss some possible deobfuscation techniques (such as program slicing) and possible countermeasures an obfuscator could employ against them.

Strategy Retold: Toward a Narrative View of Strategic Discourse

Abstract: Using narrative theory, this article explores strategic management as a form of fiction. After introducing several key narrative concepts, we discuss the challenges strategists have faced in making strategic discourse both credible and novel and consider how strategic narratives may change within the "virtual" organization of the future. We also provide a number of narrativist-oriented research questions and methodological suggestions.

Mental time travel and the evolution of the human mind.

Abstract: This article contains the argument that the human ability to travel mentally in time constitutes a discontinuity between ourselves and other animals. Mental time travel comprises the mental reconstruction of personal events from the past (episodic memory) and the mental construction of possible events in the future. It is not an isolated module, but depends on the sophistication of other cognitive capacities, including self-awareness, meta-representation, mental attribution, understanding the perception-knowledge relationship, and the ability to dissociate imagined mental states from one's present mental state. These capacities are also important aspects of so-called theory of mind, and they appear to mature in children at around age 4. Furthermore, mental time travel is generative, involving the combination and recombination of familiar elements, and in this respect may have been a precursor to language. Current evidence, although indirect or based on anecdote rather than on systematic study, suggests that nonhuman animals, including the great apes, are confined to a "present" that is limited by their current drive states. In contrast, mental time travel by humans is relatively unconstrained and allows a more rapid and flexible adaptation to complex, changing environments than is afforded by instincts or conventional learning. Past and future events loom large in much of human thinking, giving rise to cultural, religious, and scientific concepts about origins, destiny, and time itself.

Quantum dynamics of an atomic Bose-Einstein condensate in a double-well potential

Abstract: We consider the quantum dynamics of a neutral atom Bose-Einstein condensate in a double-well potential, including many-body hard-sphere interactions. Using a mean-field factorization we show that the coherent oscillations due to tunneling are suppressed when the number of atoms exceeds a critical value. An exact quantum solution, in a two-mode approximation, shows that the mean-field solution is modulated by a quantum collapse and revival sequence.

Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC)

Abstract: Background: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australasia, North and South America Subjects: 257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries Methods: Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever Results: The prevalence of rhinitis with itchy-watery eyes (“rhinoconjunctivitis”) in the past year varied across centres from 08%(to 149% in the 6-7-year-olds and from 14% to 397% in the 13-14-year-olds Within each age group, the global pattem was broadly consistent across each of the symptom categories In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe south and central Asia High prevalences were reported from centres in several regions Conclusion: These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study These differences, if real, may offer important clues to environmental influences on allergy

Immunoreactive amino‐terminal pro‐brain natriuretic peptide (NT‐PROBNP): a new marker of cardiac impairment

Abstract: OBJECTIVE Human brain natriuretic peptide-32 (BNP) (i.e. proBNP(77–108)), the mature form of BNP and secreted predominantly by the cardiac ventricle, is formed from a high molecular weight precursor, proBNP(1–108). We have recently identified the aminoterminal form proBNP(1–76) (NT-proBNP) in human plasma but its source, metabolism and production in circulatory disorders are unknown. We have investigated the relationship between immunoreactive (IR) NT-proBNP and BNP-32 in normal and hypertensive subjects and in patients with cardiac impairment, as well as the regional plasma concentrations in patients undergoing routine cardiac catheterization. DESIGN AND PATIENTS Plasma hormone measurements were made in 26 normal subjects, 20 subjects with untreated mild hypertension and 111 treated patients with a history of coronary heart disease and documented cardiac impairment (left ventricular ejection fraction (LVEF) < 45% (mean 29%); 25 NYHA Class I, 65 Class II and 21 Class III). Regional blood sampling from the femoral artery, femoral vein, renal vein and coronary sinus was undertaken in 14 patients presenting for left and right cardiac catheterization studies in the course of standard investigation for a range of cardiac disorders. MEASUREMENTS Plasma samples were assayed for IR NT-proBNP and IR BNP-32 (and atrial natriuretic peptide (ANP) in the regional blood samples). In the patients with cardiac impairment, LVEF was determined by gated radionuclide ventriculography, exercise capacity was measured using a modified Naughton multistage protocol and creatinine clearance was calculated from plasma creatinine, age and weight. In the regional study, extraction ratios across the kidney and lower limb (and step-ups across the heart) were calculated from plasma peptide concentrations. RESULTS In normal subjects mean IR NT-proBNP levels (10.8 ± 1.3 pmol/L) were similar to levels of IR BNP-32 (9.7 ± 0.5 pmol/L). In hypertensive patients the levels of IR NT-proBNP and IR BNP-32 tended to be higher than but were not significantly different from normal subjects. Both IR NT-proBNP and IR BNP-32 were raised in NYHA Classes I, II and III compared with normals (P < 0.001 for all) with higher levels of both BNP forms seen with increasing cardiac impairment. The levels of IR NT-proBNP were greater than IR BNP-32 in all NYHA Classes (P < 0.001) for all). Overall, the levels of IR NT-proBNP (129 ± 12 pmol/L) were 4-fold higher than concomitant BNP-32 levels (29 ± 2 pmol/L). Multivariate analysis showed that LVEF, exercise test time and creatinine clearance were independent predictors of IR NT-proBNP. In all study groups, the levels of IR NT-proBNP and IR BNP-32 levels were highly correlated. Regional plasma sampling showed similar step-ups in IR NT-proBNP and IR BNP-32 levels across the heart, together with similar extraction of both BNP forms across the kidney and lower limb. For both BNP forms, these changes across tissues were significantly less than for ANP. CONCLUSIONS Plasma levels of immunoreactive amino terminal-proBNP are raised in cardiac impairment, including NYHA Class I, and rise with increasing cardiac decompensation. Metabolism and tissue uptake of immunoreactive amino terminal-proBNP and immunoreactive BNP-32 appear similar. In cardiac impairment the proportional and absolute increment above normal levels of the aminoterminal BNP peptide exceeds that for BNP-32 and suggest that amino terminal-proBNP may be a more discerning marker of early cardiac dysfunction than BNP-32.

Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs.

Abstract: Hypothermia has been proposed as a neuroprotective strategy. However, short-term cooling after hypoxia-ischemia is effective only if started immediately during resuscitation. The aim of this study was to determine whether prolonged head cooling, delayed into the late postinsult period, improves outcome from severe ischemia. Unanesthetized near term fetal sheep were subject to 30 min of cerebral ischemia. 90 min later they were randomized to either cooling (n = 9) or sham cooling (n = 7) for 72 h. Intrauterine cooling was induced by a coil around the fetal head, leading initially to a fall in extradural temperature of 5-10 degrees C, and a fall in esophageal temperature of 1.5-3 degrees C. Cooling was associated with mild transient systemic metabolic effects, but not with hypotension or altered fetal heart rate. Cerebral cooling reduced secondary cortical cytotoxic edema (P < 0.001). After 5 d of recovery there was greater residual electroencephalogram activity (-5.2+/-1.6 vs. -15.5+/-1.5 dB, P < 0.001) and a dramatic reduction in the extent of cortical infarction and neuronal loss in all regions assessed (e.g., 40 vs. 99% in the parasagittal cortex, P < 0.001). Selective head cooling, maintained throughout the secondary phase of injury, is noninvasive and safe and shows potential for improving neonatal outcome after perinatal asphyxia.

The lateral line can mediate rheotaxis in fish

Abstract: Rheotaxis is a behavioural orientation to water currents1. It has been demonstrated physiologically that some lateral-line receptors are particularly well suited to provide information on water currents2, but their contribution to rheotaxis has been largely overlooked. The accepted view is that rheotaxis is mediated by visual and tactile cues1, and that in rheotactic orientation “the lateral lines play only a minor role”3. Here we provide a direct demonstration that rheotaxis can be mediated by the lateral line, and indeed by one specific receptor class of this system. In three diverse fish species, pharmacological block of the entire lateral-line system substantially increases the velocity threshold for rheotactic behaviour. The same effect is observed when only superficial neuromasts are ablated, whereas blockade of the other receptor class, canal neuromasts, has no such effect. Our results therefore demonstrate that superficial neuromasts make an important contribution to rheotactic behaviour in fish.

Dietary fat and asthma: is there a connection?

Abstract: The last two decades have seen an increase in the prevalence of asthma, eczema, and allergic rhinitis in developed countries. This increase has been paralleled by a fall in the consumption of saturated fat and an increase in the amount of polyunsaturated fat in the diet. This is due to a reduction in the consumption of animal fat and an increase in the use of margarine and vegetable oils containing omega-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid. There is also evidence for a decrease in the consumption of oily fish which contain omega-3 PUFAs, such as eicosapentaenoic acid. In a number of countries, there are social class and regional differences in the prevalence of allergic disease, which are associated with differences in the consumption of PUFAs. Linoleic acid is a precursor of arachidonic acid, which can be converted to prostaglandin E2 (PGE2), whereas eicosapentaenoic acid inhibits the formation of PGE2. PGE2 acts on T-lymphocytes to reduce the formation of interferon-gamma (IFN-gamma) without affecting the formation of interleukin-4 (IL-4). This may lead to the development of allergic sensitization, since IL-4 promotes the synthesis of immunoglobulin E (IgE), whereas IFN-gamma has the opposite effect. Changes in the diet may explain the increase in the prevalence of asthma, eczema and allergic rhinitis. The effects of diet may be mediated through an increase in the synthesis of prostaglandin E2 which in turn can promote the formation of immunoglobulin E.

Insulin resistance in short children with intrauterine growth retardation.

Abstract: Epidemiological studies have demonstrated an association between intrauterine growth retardation and an increased risk of adult diseases that include essential hypertension, noninsulin-dependent diabetes mellitus, and ischemic heart disease. A common feature of these diseases is insulin resistance. To investigate whether abnormal insulin sensitivity was a characteristic of subjects with intrauterine growth retardation (IUGR), we compared two groups of short prepubertal children: a group with IUGR (birth weight less than the tenth percentile; n = 15) and a normal birth weight group (n = 12). Subjects underwent a modified frequently sampled iv glucose tolerance test that permitted calculation of the acute insulin response, insulin sensitivity index, and glucose effectiveness. A marked difference in the insulin sensitivity index was noted between groups, with the IUGR group being less insulin sensitive [6.9 vs. 16.9 10(-4)min-1.(microU/mL); P = 0.0048]. The acute insulin response was also significantly different between groups, with IUGR subjects having higher insulin levels (445 vs. 174 microU/mL; P = 0.005). There was no difference in glucose effectiveness between groups. Short prepubertal IUGR children have a specific impairment in insulin sensitivity compared to their normal birth weight peers. In short IUGR children, impaired insulin sensitivity is a potential marker for the early identification and intervention in the development of late adult-onset noninsulin-dependent diabetes mellitus.

Acceleration of iterative image restoration algorithms.

Abstract: A new technique for the acceleration of iterative image restoration algorithms is proposed. The method is based on the principles of vector extrapolation and does not require the minimization of a cost function. The algorithm is derived and its performance illustrated with Richardson-Lucy (R-L) and maximum entropy (ME) deconvolution algorithms and the Gerchberg-Saxton magnitude and phase retrieval algorithms. Considerable reduction in restoration times is achieved with little image distortion or computational overhead per iteration. The speedup achieved is shown to increase with the number of iterations performed and is easily adapted to suit different algorithms. An example R-L restoration achieves an average speedup of 40 times after 250 iterations and an ME method 20 times after only 50 iterations. An expression for estimating the acceleration factor is derived and confirmed experimentally. Comparisons with other acceleration techniques in the literature reveal significant improvements in speed and stability.

Structure and function of the vertebrate magnetic sense

Abstract: Some vertebrates can navigate over long distances using the Earth's magnetic field, but the sensory system that they use to do so has remained a mystery. Here we describe the key components of a magnetic sense underpinning this navigational ability in a single species, the rainbow trout ( Oncorhynchus mykiss). We report behavioural and electrophysiological responses to magnetic fields and identify an area in the nose of the trout where candidate magnetoreceptor cells are located. We have tracked the sensory pathway from these newly identified candidate magnetoreceptor cells to the brain and associated the system with a learned response to magnetic fields.

Application of Thermomechanical Principles to the Modelling of Geotechnical Materials

Abstract: A thermodynamic framework is presented for the plasticity modelling of geotechnical materials. The framework is capable of modelling rigorously both friction and non-associated flow, and the strong connection between these phenomena is demonstrated. The formulation concentrates on the development of constitutive models from hypotheses about the form of an energy potential and a dissipation function. The reformulation of previous work, in which the Helmholtz free energy was used, to a new approach starting from the Gibbs free energy is found to be valuable. The relationship between the new functions and classical plasticity concepts (yield surface, plastic potential, isotropic and kinematic hardening, friction, dilation) is demonstrated. Comments are made on elastic-plastic coupling. Implications of the new approach for critical state soil models are discussed.

Towards a paradigm shift in marketing? An examination of current marketing practices

Abstract: In recent years, the traditional Transaction approach to marketing has been challenged to the point where a number of authors have suggested that a “paradigm shift” is occurring. The “newparadigm” is commonly referred to as Relationship Marketing, and has been used to reflect a number of different types of relational marketing activity, including Database, Interaction and Network marketing. This paper investigates current marketing practice to clarify the relevance of these alternative approaches using four case studies and a survey of 134 firms. The results do not support the notion of a complete “paradigm shift”. Rather, the findings show that for many firms, transactional marketing is relevant and practised concurrently with various types of relational marketing. It is concluded that while relational marketing issues are currently receiving attention from academics and practitioners alike, the role of transactional marketing should not be ignored or underestimated.

Association between Polycystic Ovaries and Extent of Coronary Artery Disease in Women Having Cardiac Catheterization

Abstract: Background: Women with polycystic ovaries have associated risk factors for coronary artery disease. It is unknown whether women with more extensive coronary artery disease are more likely to have p...

Risk Factors for Sudden Infant Death Syndrome Following the Prevention Campaign in New Zealand: A Prospective Study

Abstract: Objectives To identify the risk factors for sudden infant death syndrome (SIDS) following a national campaign to prevent SIDS. Methods For 2 years (October 1, 1991 through September 30, 1993) data were collected by community child health nurses on all infants born in New Zealand at initial contact and at 2 months. Results There were 232 SIDS cases in the postneonatal age group (2.0/1000 live births) and these were compared with 1200 randomly selected control subjects. Information was available for 127 cases (54.7%) and 922 (76.8%) of controls. The previously identified modifiable risk factors were examined. The prevalence of prone sleeping position of the infant was very low (0.7% at initial contact and 3. 0% at 2 months), but was still associated with an increased risk of SIDS. In addition, the side sleeping position was also found to have an increased risk of SIDS compared with the supine sleeping position (at 2 months: adjusted odds ratio (OR) = 6.57; 95% confidence interval (CI) = 1.71, 25.23). Maternal smoking was found to be the major risk factor for SIDS. Bed sharing was also associated with an increased risk of SIDS. There was an interaction between maternal smoking and bed sharing on the risk of SIDS. Compared with infants not exposed to either bed sharing or maternal smoking, the adjusted OR for infants of mothers who smoked was 5.01 (95% CI = 2.01, 12.46) for bed sharing at the initial contact and 5.02 (95% CI = 1.05, 24. 05) for bed sharing at 2 months. In this study breastfeeding was not associated with a statistically significant reduction in the risk of SIDS. The other risk factors for SIDS identified were: unmarried mother, leaving school at a younger age, young mother, greater number of previous pregnancies, late attendance for antenatal care, smoking in pregnancy, male infant, Maori ethnicity, low birth weight, and shorter gestation. Conclusions After adjustment for potential confounders, prone and side sleeping positions, maternal smoking, and the joint exposure to bed sharing and maternal smoking were associated with statistically significant increased risk of SIDS. A change from the side to the supine sleeping position could result in a substantial reduction in SIDS. Maternal smoking is common in New Zealand and with the reduction in the prevalence of prone sleeping position is now the major risk factor in this country. However, smoking behavior has been difficult to change. Bed sharing is also a major factor but appears only to be a risk to infants of mothers who smoke. Addressing bed sharing among mothers who smoke could reduce SIDS by at least one third. Breastfeeding did not appear to offer a statistically significant reduction in SIDS risk after adjustment of potential confounders, but as breastfeeding rates are comparatively good in New Zealand, this result should be interpreted with caution as the power of this study to detect a benefit is small.

Understanding contemporary marketing: Development of a classification scheme

Abstract: The term Relationship Marketing has been used in a multitude of ways to describe and define marketing in the contemporary environment. This has led to the term being loosely defined and applied in the literature, resulting in frustration for both researchers and practitioners. Therefore, a classification scheme is developed from analysis of the extant literature, and used to systematically examine the meaning of marketing across twelve dimensions which reflect issues related to marketing practice. From this scheme, the authors identify two ‘perspectives’ of marketing, which encompass four distinguishable ‘types’ of marketing. Implications for future research in the area are discussed.

Laminar structure of the heart: a mathematical model

Abstract: A mathematical description of cardiac anatomy is presented for use with finite element models of the electrical activation and mechanical function of the heart. The geometry of the heart is given in terms of prolate spheroidal coordinates defined at the nodes of a finite element mesh and interpolated within elements by a combination of linear Lagrange and cubic Hermite basis functions. Cardiac microstructure is assumed to have three axes of symmetry: one aligned with the muscle fiber orientation (the fiber axis); a second set orthogonal to the fiber direction and lying in the newly identified myocardial sheet plane (the sheet axis); and a third set orthogonal to the first two, in the sheet-normal direction. The geometry, fiber-axis direction, and sheet-axis direction of a dog heart are fitted with parameters defined at the nodes of the finite element mesh. The fiber and sheet orientation parameters are defined with respect to the ventricular geometry such that 1) they can be applied to any heart of known dimensions, and 2) they can be used for the same heart at various states of deformation, as is needed, for example, in continuum models of ventricular contraction.

Glucocorticoid osteoporosis--mechanisms and management.

Abstract: Glucocorticoids are potent osteopenic agents, producing negative calcium and bone balance via actions at many sites. The most significant adverse effects of glucocorticoid drugs on the skeleton are probably a direct inhibition of matrix synthesis by the osteoblast, reductions in calcium absorption in both the gut and the renal tubule, and the production of hypogonadism, particularly in men. Reductions in bone density of 10-40% result, the loss being more marked in trabecular bone and in patients receiving a high cumulative dose of the steroid. Fractures occur in about 30% of individuals who take these drugs for an average of 5 years. Bone loss is reversible when glucocorticoid treatment is withdrawn. Bone density can also be increased by sex hormone replacement in those with demonstrable deficiency, by bisphosphonates, and possibly by vitamin D metabolites. All patients treated with glucocorticoids for more than 6 months should be considered for bone densitometry and be offered appropriate drug treatment if values are towards the lower end of the young normal range or if there is already evidence of fractures occurring after minimal trauma. With this approach, the significant morbidity associated with steroid osteoporosis might be substantially avoided.

Neural pathways for the control of birdsong production

Abstract: As in humans, song production in birds involves the intricate coordination of at least three major groups of muscles: namely, those of the syrinx, the respiratory apparatus, and the upper vocal tract, including the jaw. The pathway in songbirds that controls the syrinx originates in the telencephalon and projects via the occipitomesencephalic tract directly upon vocal motoneurons in the medulla. Activity in this pathway configures the syrinx into phonatory positions for the production of species typical vocalizations. Another component of this pathway mediates control of respiration during vocalization, since it projects upon both expiratory and inspiratory groups of premotor neurons in the ventrolateral medulla, as well as upon several other nuclei en route. This pathway appears to be primarily involved with the control of the temporal pattern of song, but is also importantly involved in the control of vocal intensity, mediated via air sac pressure. There are extensive interconnections between the vocal and respiratory pathways, especially at brain-stem levels, and it may be these that ensure the necessary temporal coordination of syringeal and respiratory activity. The pathway mediating control of the jaw appears to be different from those mediating control of the syrinx and respiratory muscles. It originates in a different part of the archistriatum and projects upon premotor neurons in the medulla that appear to be separate from those projecting upon the syringeal motor nucleus. The separateness of this pathway may reflect the imperfect correlation of jaw movements with the dynamic and acoustic features of song. The brainstem pathways mediating control of vocalization and respiration in songbirds have distinct similarities to those in mammals such as cats and monkeys. However, songbirds, like humans, but unlike most other non-songbirds, have developed a telencephalic vocal control system for the production of learned vocalizations.

Prevalence of Stroke and Stroke-Related Disability Estimates From the Auckland Stroke Studies

Abstract: Background and Purpose To provide estimates of the prevalence of stroke and stroke-related disability for international comparisons and for planning purposes. Methods Estimates of prevalence were derived from two population-based studies conducted 10 years apart in Auckland, New Zealand. The first, carried out in 1981, included information on survival and stroke-related disability to 14 years after stroke, and the second, undertaken in 1991 to 1992, included this information up to 3 years after stroke. An actuarial model was developed that took into account changes in incidence, long-term survival, and population structure. Results Overall, it was estimated that 7491 people (3793 men and 3698 women) living in Auckland (total population 945 000) in 1991 had experienced a stroke at some stage in the past. This represents an age-standardized rate of 833 per 100 000 (991 per 100 000 in men and 706 per 100 000 in women) in the population aged 15 years and older. When only those who have made an incomplete reco...

Effects of beta-blocker therapy on mortality in patients with heart failure : A systematic overview of randomized controlled trials

Abstract: Aims Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. Methods and results Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2 P =0·0035), representing an absolute reduction in mean annual mortality from 9·7% to 7·5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were nonsignificantly greater (2 P =0·09) than those of standard agents (18% reduction SD 15), principally metoprolol. Conclusion Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.