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Background Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long-term mortality in an elderly hypertensive population. Methods and Results We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24-hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow-up). Weighted day-night systolic BPV was calculated for both baseline and follow-up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: -0.37±1.95; 95% CI, -0.54 to -0.19; P<0.001) in weighted day-night systolic BPV between baseline and follow-up. Having constant stable: high BPV was associated with an increase in all-cause mortality (hazard ratio: 3.03; 95% CI, 1.67-5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62-8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow-up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow-up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long-term mortality.

Background: Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long-term mortality in an elderly hypertensive population. Methods and Results: We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24-hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow-up). Weighted day-night systolic BPV was calculated for both baseline and follow-up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: −0.37±1.95; 95% CI, −0.54 to −0.19; P<0.001) in weighted day-night systolic BPV between baseline and follow-up. Having constant stable: high BPV was associated with an increase in all-cause mortality (hazard ratio: 3.03; 95% CI, 1.67–5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62–8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow-up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions: Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow-up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long-term mortality.

Aim To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). Methods Six hundred twenty-nine subjects with CVD who smoked ≥10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. Results Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{<}0.001\) \end{document}). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{<}0.001\) \end{document}). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((P{<}0.001)\) \end{document}. In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants \batchmode \documentclass[fleqn,10pt,legalpaper]{article}

Aim: To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). Method(s): Six hundred twenty-nine subjects with CVD who smoked >=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. Result(s): Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19). Conclusion(s): After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations. © 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.

Objective: A patient survey was conducted by questionnaire to evaluate patient acceptance and perceptions of efficacy with zanamivir (Glaxo Wellcome), the first in a new class of neuraminidase inhibitors that are active against both influenza A and influenza B. The survey was also designed to provide rapid feedback to physicians prescribing zanamivir within the winter period when influenza was likely to be prevalent. Setting(s): Patients with clinically diagnosed influenza were enrolled by participating general practitioners (GPs) during the 1999 influenza season in Australia. Courses of medication with a questionnaire were prescribed by participating GPs. Patient(s): A total of 1408 patients returned completed questionnaires, 60% were employed or were students and 238 had had a current influenza immunisation, mostly patients > 65 years. Myalgia, headache and feverishness were reported by at least 80% of patients. Result(s): Symptom relief was reported by more than 50% of patients within 24 hours and by 77% of patients within 48 hours; satisfaction with treatment was high and 65% of patients returned to normal activities within 72 hours. Older patients reported a slightly less rapid response to zanamavir in terms of symptom relief, but nevertheless were able to return quickly to normal activities. A total of 378/477 (79%) patients who were very satisfied with their treatment experienced symptom relief in 24 hours. Of the 400 at-risk patients aged > 65 years or with co-morbidities, 78% were satisfied with their treatment, with 235/400 (59%) experiencing symptom relief within 24 hours. Patients found the Diskhaler(TM) device easy to use irrespective of age and reported rapid symptom relief, which may reflect the targeted delivery of high concentrations of zanamivir to the site of viral replication in the respiratory tract. Conclusion(s): Overall, the survey indicated that zanamivir was associated with an early return to normal activities and confirmed that the benefit

Objective. This study examined, in a group of older patients, (a) the effectiveness of an invitation to participate in a program providing individualized physical activity advice in a primary care setting and (b) the changes in self-reported physical activity and symptoms in patients with osteoarthritis (OA). Methods. Healthy, sedentary community-dwelling men and women aged 60 years or more were invited to participate. Following random allocation, the intervention group received individualized physical activity advice at baseline and at 3, 6, and 12 months followup. Results. Of the 299 people who satisfied the study's inclusion criteria, a subgroup of 69 people reported pain and stiffness of the hip or knee at baseline. These patients reported increases in frequency and time of walking and vigorous exercise (all P<0.001), with no change to OA symptom scores (pain and stiffness), and a small decline in physical functioning was reported at 12 months followup in the control group only (P=0.027). At the 12-month followup more intervention participants than control participants (P=0.013) reported a greater intention to exercise. Conclusions. An offer of primary care-based physical activity advice, with an emphasis on the benefits for general health (rather than "treatment" for OA), will attract individuals with OA symptoms. Although the present study was unable to demonstrate intervention-control group differences for the majority of outcomes, intention to exercise did appear to be positively influenced.

Advice from doctors, structured interventions from nurses, and individual and group counselling are effective interventions. Generic self help materials are no better than brief advice but more effective than doing nothing; personalised materials are more effective than standard materials. All forms of nicotine replacement therapy are effective. The antidepressants bupropion and nortriptyline increased quit rates in a small number of trials; the usefulness of the antihypertensive drug clonidine is limited by side effects. Anxiolytics and lobeline are ineffective. The effectiveness of aversion therapy, mecamylamine, acupuncture, hypnotherapy and exercise is uncertain.

Influenza outbreaks occur annually on a seasonal basis, usually in the winter, and are responsible for substantial global morbidity and mortality, particularly amongst patients at high risk of complications. Influenza also places a significant clinical and economic burden on the healthcare system and management is largely the responsibility of primary-care practitioners (PCPs), who are often the first point of contact for patients. Diagnosis is usually made on clinical grounds, which is 60 to 70% accurate when influenza is known to be circulating locally. Vaccination remains the cornerstone for influenza management and protects the majority of at-risk patients, but vaccine effectiveness depends on correct prediction of the circulating strain and it is reduced in immunosuppressed and elderly patients. Until recently the options for treatment of influenza were very limited, with the primary recommendations being bedrest and treatment of symptoms only. In some countries the amantadine and rimantadine antiviral drugs have been available to treat influenza for some years, but use of these agents is limited by the incidence of adverse events, rapid development of resistance, and the fact that their activity is restricted to influenza A. Zanamivir (RelenzaTM, Glaxo Wellcome) is the first neuraminidase inhibitor to be approved for use in the treatment of influenza A and B. Oseltamivir (TamifluTM, F. Hoffmann-La Roche) is similarly active against influenza A and B, and in clinical trials both drugs were shown reduce the median time to alleviation of influenza symptoms by 1 to 2.5 days (zanamivir) and 1.2 to 1.3 days (oseltamivir). Both agents were well tolerated, zanamivir having a safety profile similar to placebo and oseltamivir. producing mild nausea and vomiting in some patients. Zanamivir is administered by oral inhalation delivering the drug directly to the respiratory tract, and oseltamivir, a prodrug, is taken in the form of a pill. In short-term use, no resistance t

Background: Although systematic reviews of health care interventions are an invaluable tool for health care providers and researchers, many potential authors never publish reviews. This study attempts to determine why some people with interest in performing systematic reviews do not subsequently publish a review; and what steps could possibly increase review completion. Method(s): Cross-sectional survey by email and facsimile of the 179 participants in Australasian Cochrane Centre training events between 1998 and 2000. Result(s): Ninety-two participants responded to the survey (51 percent). Response rate of deliverable surveys was 82 percent (92/112). The remainder of the participants had invalid or no contact information on file. More than 75 percent of respondents felt that the current workshops met their needs for training. The most critical barriers to completion of a Cochrane review were: lack of time (80 percent), lack of financial support (36 percent), methodological problems (23 percent) and problems with group dynamics (10 percent). Conclusion(s): Strategies to protect reviewer time and increase the efficiency of the review process may increase the numbers of trained reviewers completing a systematic review.

BACKGROUND: Although systematic reviews of health care interventions are an invaluable tool for health care providers and researchers, many potential authors never publish reviews. This study attempts to determine why some people with interest in performing systematic reviews do not subsequently publish a review; and what steps could possibly increase review completion. METHOD(S): Cross-sectional survey by email and facsimile of the 179 participants in Australasian Cochrane Centre training events between 1998 and 2000. RESULT(S): Ninety-two participants responded to the survey (51 percent). Response rate of deliverable surveys was 82 percent (92/112). The remainder of the participants had invalid or no contact information on file. More than 75 percent of respondents felt that the current workshops met their needs for training. The most critical barriers to completion of a Cochrane review were: lack of time (80 percent), lack of financial support (36 percent), methodological problems (23 percent) and problems with group dynamics (10 percent). CONCLUSION(S): Strategies to protect reviewer time and increase the efficiency of the review process may increase the numbers of trained reviewers completing a systematic review.

BACKGROUND: Health care professionals frequently advise patients to improve their health by stopping smoking. Such advice may be brief, or part of more intensive interventions. OBJECTIVE(S): The aims of this review were to assess the effectiveness of advice from physicians in promoting smoking cessation; to compare minimal interventions by physicians with more intensive interventions; to assess the effectiveness of various aids to advice in promoting smoking cessation and to determine the effect of anti-smoking advice on disease specific and all cause mortality. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register and the Cochrane Controlled Trials Register. Date of the most recent searches: October 2000. SELECTION CRITERIA: Randomized trials of smoking cessation advice from a medical practitioner in which abstinence was assessed at least six months after advice was first provided. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the setting in which advice was given, type of advice given (minimal or intensive), and whether aids to advice were used, the outcome measures, method of randomization and completeness of followup. The main outcome measures were abstinence from smoking after at least six months follow-up and mortality. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. Subjects lost to follow-up were counted as smokers. Where possible, meta-analysis was performed using a fixed effects model. MAIN RESULTS: We identified thirty four trials, conducted between 1972 and 1999, including over 27,000 smokers. In some trials, subjects were at risk of specified diseases (chest disease, diabetes, ischaemic heart disease), but most were from unselected populations. The most common setting for delivery of advice was primary care. Other settings included hospital wards and outpatient clinics, and industrial clinics. Pooled data from 16 trials of brief advice vers

BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine from cigarettes. This reduces withdrawal symptoms associated with smoking cessation thus helping resist the urge to smoke cigarettes. OBJECTIVE(S): The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; and to determine its effectiveness compared to other pharmacotherapies. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register in April 2000. SELECTION CRITERIA: Randomized trials in which NRT was compared to placebo or no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow-up of less than six months. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and duration and form of nicotine therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model. MAIN RESULTS: We identified one hundred trials; of the 88 with a non NRT control group, 48 trials were of nicotine gum, 30 of transdermal nicotine patch, four of intranasal nicotine spray, four of inhaled nicotine and two of nicotine sublingual tablet. Four trials compared combinations of two forms of nicotine therapy with

BACKGROUND: Health care professionals frequently advise patients to improve their health by stopping smoking. Such advice may be brief, or part of more intensive interventions. OBJECTIVE(S): The aims of this review were to assess the effectiveness of advice from physicians in promoting smoking cessation; to compare minimal interventions by physicians with more intensive interventions; to assess the effectiveness of various aids to advice in promoting smoking cessation and to determine the effect of anti-smoking advice on disease specific and all cause mortality. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register and the Cochrane Controlled Trials Register. Date of the most recent searches: October 1998. SELECTION CRITERIA: Randomised trials of smoking cessation advice from a medical practitioner in which abstinence was assessed at least six months after advice was first provided. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the setting in which advice was given, type of advice given (minimal or intensive), and whether aids to advice were used, the outcome measures, method of randomisation and completeness of followup. The main outcome measure was abstinence from smoking after at least six months follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. Subjects lost to follow-up were counted as smokers. Where possible, meta-analysis was performed using a fixed effects model. MAIN RESULTS: We identified thirty-one trials, conducted between 1972 and 1997, including over 26,000 smokers. In some trials, subjects were at risk of specified diseases (chest disease, diabetes, ischaemic heart disease), but most were from unselected populations. The most common setting for delivery of advice was primary care. Other settings included hospital wards and outpatient clinics, and industrial clinics. Pooled data from 16 trials of brief advice versus no advice (or