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BACKGROUND: The evidence-based approach to medical care involves the explicit use of evidence on the magnitude of the effects of interventions to inform diagnostic and treatment decisions. This article critiques current mainstream guidelines on the management of hypertension in the elderly (aged 60 years and over) and presents an alternative evidence-based approach. METHODS: Three major national and international guidelines for the management of hypertension from the United Kingdom (UK), the United States (US) and from a joint World Health Organisation/International Society of Hypertension (WHO/ISH) Working Party were appraised and the evidence on which they were based was reviewed. The relevant evidence was also assessed to determine the likely magnitude of risks and benefits of anti-hypertensive treatment in older people and an alternative approach to making treatment decisions, based on the New Zealand guidelines for the management of hypertension, is described. RESULTS: Hypertension management guidelines from the UK, US and WHO/ISH made similar recommendations about which elderly patients should be treated, although there were some ambiguities in their advice. Treatment recommendations were based primarily on blood pressure levels which were set at about 160 mm Hg systolic and/or 90 mm Hg diastolic. The threshold levels were based mainly on the cut-off blood pressure levels used in randomised trials of anti-hypertensive drug treatment, rather than the estimated magnitude of treatment benefit. Each of the guidelines acknowledged the important effect of associated cardiovascular disease (CVD) risk factors on the likely benefits of treatment, but did not expand on the magnitude of this effect. No patient-specific estimates of the likely absolute benefits of treatment were provided in any of the guidelines. In contrast the New Zealand guidelines for the management of hypertension recommend the use of explicit estimates of absolute CVD risks and benefits to inform treatment decisions. They were designed to provide practitioners with estimates of the likely absolute risk of CVD in patients with different risk factor profiles and with estimates of the absolute benefits of treatment. The New Zealand guidelines recommend that drug treatment be considered in patients with a 5-year risk of CVD of about 10-15% or more; approximately 25 patients with a 10-15% risk would require treatment for 5 years to prevent one CVD event. As elderly patients are generally at higher absolute CVD risk than younger people, the New Zealand recommendation give priority to the treatment of older patients. In order to take account of differences in life expectancy and the medical costs of caring for elderly people, absolute risk-based guidelines can be improved by incorporating potential years of life gained from treatment and the cost-effectiveness of treatment expressed as $/quality adjusted life years gained. Preliminary analyses indicate that the cost-effectiveness of treatment is generally greatest in patients in their 60s and early 70s. Treatment in younger people is not usually very cost-effective because of their low absolute risk of CVD and the cost-effectiveness of treatment in people over about 75 years declines because of the increasing cost of non-CVD morbidity. CONCLUSIONS: The explicit assessment of absolute CVD risks and likely treatment benefits in patients with hypertension can usefully inform treatment decisions and provide a more rational basis for initiating therapy than blood pressure levels alone. This approach highlights the generally greater CVD risk and potential treatment benefits in older compared with younger hypertensive patients. The absolute risk-based approach can be further enhanced by providing decision makers with patient-specific data on the potential life years gained from treatment and its cost-effectiveness. (ABSTRACT TRUNCATED)  相似文献   
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Chronic butylated hydroxytoluene (BHT) treatment after a single administration of a carcinogen increases lung tumor multiplicity in some inbred strains of mice. We report that BALB/cOla and BALB/cByJ mice given a low dose (10 microg/g of body weight) of 3-methylcholanthrene (MCA) develop no lung tumors unless this is followed by chronic BHT exposure. Slightly higher MCA doses (15 and 25 microg/g) induce low lung tumor multiplicities (0.6 and 1.9 tumors/mouse, respectively) that are increased 12-26-fold by chronic BHT administration. This low-dose MCA/BHT model in BALB mice will facilitate the identification of genes regulating susceptibility to lung tumor promotion and pulmonary chemopreventative agents that act at a postinitiation site.  相似文献   
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The P2X3 receptor subunit, a member of the P2X family of ATP-gated ion channels, is almost exclusively localized in sensory neurons. In the present study, we sought to gain insight into the role of P2X3 and P2X3-containing neurons in sensory transmission, using immunohistochemical approaches. In rat dorsal root ganglia (DRG), P2X3-immunoreactivity (-ir) was observed in small- and medium-sized neurons. Approximately 40% of DRG neuronal profiles in normal rats contained P2X3-ir. In rats that had received neonatal capsaicin treatment, the number of P2X3-positive neurons was decreased by approximately 70%. Analysis of the colocalization of P2X3-ir with cytochemical markers of DRG neurons indicated that approximately 94% of the P2X3-positive neuronal profiles were labelled by isolectin B4 from Bandeiraea simplicifolia, while only 3% contained substance P-ir, and 7% contained somatostatin-ir. In dorsal horn of rat spinal cord, P2X3-ir was observed in the inner portion of lamina II and was reduced subsequent to dorsal rhizotomy, as well as subsequent to neonatal capsaicin treatment. Finally, P2X3-ir accumulated proximal to the site of sciatic nerve ligation, and was seen in nerve fibres in skin and corneal epithelium. In summary, our results suggest that P2X3 is expressed by a functionally heterogeneous population of BSI-B4-binding sensory neurons, and is transported into both central and peripheral processes of these neurons.  相似文献   
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The clinical consequences of single or multiple exposure of pregnant gilts to porcine reproductive and respiratory syndrome virus (PRRSV) at various stages of gestation were determined. Thirty-three pregnant gilts were allotted to 6 experimental groups (5 to 7 gilts/group). Gilts of groups 1 to 5 were exposed to strain NADC-8 of PRRSV at the following times: group 1, gestation day (GD) 1; group 2, GDs 1 and 90; group 3, GD 30; group 4, GDs 30 and 90; group 5, GD 90. Virus exposure was by either intrauterine (GD 1) or oronasal (GDs 30 and 90) inoculation. Gilts of group 6 were kept as nonexposed controls. Gilts were either necropsied on or about GD 111 (groups 1 to 5) or were allowed to farrow (group 6). The detection of PRRSV in serum of fetuses and piglets (within 12 hof birth) was considered evidence of transplacental infection. Transplacental infection and virus-induced death were and were not confirmed for groups 3, 4, and 5 and for groups 1, 2, and 6, respectively. Collectively, the results indicated that intrauterine exposure to PRRSV at GD 1 was without clinical effect (groups 1 and 2) and provided protection against subsequent exposure to the same strain of virus at GD 90 (group 2). The highest incidence of transplacental infection and fetal death followed a single exposure to PRRSV at GD 90 (group 5).  相似文献   
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