A Question of Social Justice: How Policies of Profit Negate Engagement of Developing World Bioethicists and Undermine Global Bioethics.

We identify the ways the policies of leading international bioethics journals limit the participation of researchers working in the resource-constrained settings of low- and middle-income countries (LMICs) in the development of the field of bioethics. Lack of access to essential scholarly resources makes it extremely difficult, if not impossible, for many LMIC bioethicists to learn from, meaningfully engage in, and further contribute to the global bioethics discourse. Underrepresentation of LMIC perspectives in leading journals sustains the hegemony of Western bioethics, limits the presentation of diverse moral visions of life, health, and medicine, and undermines aspirations to create a truly "global" bioethics. Limited attention to this problem indicates a lack of empathy and moral imagination on the part of bioethicists in high-income countries, raises questions about the ethics of bioethics, and highlights the urgent need to find ways to remedy this social injustice.

Hormone therapy for preventing cardiovascular disease in post-menopausal women.

BACKGROUND: Evidence from systematic reviews of observational studies suggest that hormone replacement therapy (HT) may have beneficial effects in reducing the incidence of cardiovascular disease (CVD) events in post-menopausal women. This is an updated version of a Cochrane review first published in 2005 (Gabriel-Sanchez 2005). OBJECTIVES: To assess the effects of HT for the prevention of CVD in post-menopausal women, and whether there are differential effects between use of single therapy alone compared to combination HT and use in primary or secondary prevention. SEARCH METHODS: We searched the following databases to April 2010: Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE and LILACS. SELECTION CRITERIA: Randomised controlled trials (RCTs) of women comparing orally administered HT with placebo with a minimum of six-months follow-up. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Risk Ratios (RR) with 95% confidence intervals were calculated for each outcome. Results were combined using fixed-effect meta-analyses, and where possible, further stratified analyses conducted to assess the effect of time on treatment. Additionally, univariate meta-regression analyses were undertaken to assess whether length of trial follow-up, single or combination treatment, or whether treatment for primary or secondary prevention were potential predictors for a number of CVD outcomes in the trials. MAIN RESULTS: Four new trials were identified through the update; one trial included in the previous review was excluded. Therefore the review included 13 trials with a total of 38,171 post-menopausal women. Overall, single and combination HT in both primary and secondary prevention conferred no protective effects for all cause mortality, CVD death, non-fatal MI, or angina. There were no significant differences in the number of coronary artery by-pass procedures or angioplasties performed between the trial arms. However there was an increased risk of stroke for both primary and secondary prevention when combination and single HT was combined, RR 1.26 (95% CI 1.11 to 1.43), in venous thromboembolic events, RR 1.89 (95% CI 1.58 to 2.26) and in pulmonary embolism RR 1.84 (95% CI 1.42 to 2.37) relative to placebo. The associated numbers needed-to-harm (NNH) were 164, 109 and 243 for stroke, venous thromboembolism and pulmonary embolism respectively. AUTHORS' CONCLUSIONS: Treatment with HT in post-menopausal women for either primary or secondary prevention of CVD events is not effective, and causes an increase in the risk of stroke, and venous thromboembolic events. HT should therefore only be considered for women seeking relief from menopausal symptoms. Short-term HT treatment should be at the lowest effective dose, and used with caution in women with predisposing risk factors for CVD events.

Evolution of the evidence on the effectiveness and cost-effectiveness of acetylcholinesterase inhibitors and memantine for Alzheimer's disease: systematic review and economic model.

INTRODUCTION: in 2007 the National Institute of Health and Clinical Excellence (NICE) restricted the use of acetylcholinesterase inhibitors and memantine. METHODS: we conducted a health technology assessment (HTA) of the effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of AD to re-consider and up-date the evidence base used to inform the 2007 NICE decision. The systematic review of effectiveness targeted randomised controlled trials. A comprehensive search, including MEDLINE, Embase and the Cochrane Library, was conducted from January 2004 to March 2010. All key review steps were done by two reviewers. Random effects meta-analysis was conducted. The cost-effectiveness was assessed using a cohort-based model with three health states: pre-institutionalised, institutionalised and dead. The perspective was NHS and Personal Social Services and the cost year 2009. RESULTS: confidence about the size and statistical significance of the estimates of effect of galantamine, rivastigmine and memantine improved on function and global impact in particular. Cost-effectiveness also changed. For donepezil, galantamine and rivastigmine, the incremental cost per quality-adjusted life year (QALY) in 2004 was above £50,000; in 2010 the same drugs 'dominated' best supportive care (improved clinical outcome at reduced cost). This was primarily because of changes in the modelled costs of introducing the drugs. For memantine, the cost-effectiveness also improved from a range of £37-53,000 per QALY gained to a base-case of £32,000. CONCLUSION: there has been a change in the evidence base between 2004 and 2010 consistent with the change in NICE guidance. Further evolution in cost-effectiveness estimates is possible particularly if there are changes in drug prices.

Levels and predictors of exercise referral scheme uptake and adherence: a systematic review.

BACKGROUND: The effectiveness of exercise referral schemes (ERS) is influenced by uptake and adherence to the scheme. The identification of factors influencing low uptake and adherence could lead to the refinement of schemes to optimise investment. OBJECTIVES: To quantify the levels of ERS uptake and adherence and to identify factors predictive of uptake and adherence. METHODS: A systematic review and meta-analysis was undertaken. MEDLINE, EMBASE, PsycINFO, Cochrane Library, ISI WOS, SPORTDiscus and ongoing trial registries were searched (to October 2009) and included study references were checked. Included studies were required to report at least one of the following: (1) a numerical measure of ERS uptake or adherence and (2) an estimate of the statistical association between participant demographic or psychosocial factors (eg, level of motivation, self-efficacy) or programme factors and uptake or adherence to ERS. RESULTS: Twenty studies met the inclusion criteria, six randomised controlled trials (RCTs) and 14 observational studies. The pooled level of uptake in ERS was 66% (95% CI 57% to 75%) across the observational studies and 81% (95% CI 68% to 94%) across the RCTs. The pooled level of ERS adherence was 49% (95% CI 40% to 59%) across the observational studies and 43% (95% CI 32% to 54%) across the RCTs. Few studies considered anything other than gender and age. Women were more likely to begin an ERS but were less likely to adhere to it than men. Older people were more likely to begin and adhere to an ERS. LIMITATIONS: Substantial heterogeneity was evident across the ERS studies. Without standardised definitions, the heterogeneity may have been reflective of differences in methods of defining uptake and adherence across studies. CONCLUSIONS: To enhance our understanding of the variation in uptake and adherence across ERS and how these variations might affect physical activity outcomes, future trials need to use quantitative and qualitative methods.

Preventing unintentional injuries to children under 15 years in the outdoors: a systematic review of the effectiveness of educational programs.

INTRODUCTION: Unintentional injuries to children in the outdoors have a significant impact on child mortality, development and healthcare costs. This paper presents the findings of a systematic review about the effectiveness of programs that provided information, advice or education about the prevention of unintentional injuries to children under 15 years during outdoor play and leisure. METHODS: A structured search strategy was conducted in a range of databases. All report titles and abstracts were screened using pre-defined criteria. Included reports were quality appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) tool. All quality appraisals and data extraction were checked by a second reviewer. If not provided in the original reports, ORs and mean differences were calculated, where sufficient data were available. RESULTS: Twenty-three studies met the inclusion criteria. There was a paucity of robust study designs. The majority of studies only reported a short-term follow-up of intermediate outcome measures. Only two studies measured injury rates; both reported a reduction, but both studies also had considerable methodological weaknesses. The five studies that measured the use of protective equipment reported mixed results, although there is some evidence that suggests that more extensive educational programs (such as health fairs and media campaigns) increase their use. The 20 studies that measured behaviour, attitude or knowledge outcomes reported highly mixed results. DISCUSSION: Methodological weaknesses of the included studies limit support for a particular course of action. To better inform policy and practice, future research should (1) use robust study designs and (2) not rely on short-term proxy outcome measures.

Cost-effectiveness of dasatinib and nilotinib for imatinib-resistant or -intolerant chronic phase chronic myeloid leukemia.

OBJECTIVES: To estimate the cost-effectiveness of dasatinib and nilotinib compared with high-dose imatinib for people with chronic phase chronic myeloid leukemia, which are resistant to normal-dose imatinib and compared with interferon-α for people intolerant to imatinib, from the perspective of the UK National Health Service. METHODS: An an area under the curve partitioned survival model was developed to estimate the cost-effectiveness of dasatinib and nilotinib. Clinical effectiveness evidence was taken mostly from single-arm trials. RESULTS: Both progression-free survival and overall survival are highly uncertain. In the base case, patients take nilotinib for much less time than dasatinib. Nilotinib is expected to dominate high-dose imatinib, yielding slightly more (0.32) quality-adjusted life years (QALYs) at slightly less cost (£11,100 [pound sterling]) per person. Dasatinib is predicted to provide slightly more (0.53) QALYs at substantially greater cost (£48,900), yielding a very high incremental cost-effectiveness ratio of £91,500 QALY against high-dose imatinib. Cost-effectiveness, however, changes radically under the plausible assumption that the drugs are taken for the same time. For people intolerant to imatinib, nilotinib is expected to yield an incremental cost-effectiveness ratio of £104,700/QALY, and dasatinib £82,600/QALY compared with interferon-α. Further, both drugs represent poor value for money for a range of plausible structural assumptions. CONCLUSIONS: The model should be viewed as an exploratory analysis of the cost-effectiveness of dasatinib and nilotinib because it relies on many assumptions. Whilst clinical data remains immature, the cost-effectiveness of dasatinib and nilotinib for imatinib-resistant people is highly uncertain. Both nilotinib and dasatinib are highly unlikely to be cost-effective versus interferon-α for people intolerant to imatinib.

Psychological interventions for coronary heart disease.

BACKGROUND: Psychological symptoms are strongly associated with coronary heart disease (CHD), and many psychological treatments are offered following cardiac events or procedures. OBJECTIVES: Update the existing Cochrane review to (1) determine the independent effects of psychological interventions in patients with CHD (principal outcome measures included total or cardiac-related mortality, cardiac morbidity, depression, and anxiety) and (2) explore study-level predictors of the impact of these interventions. SEARCH STRATEGY: The original review searched Cochrane Controleed Trials Register (CCTR, Issue 4, 2001), MEDLINE, EMBASE, PsycINFO, and CINAHL to December 2001. This was updated by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, PsycINFO and CINAHL from 2001 to January 2009. In addition, we searched reference lists of papers, and expert advice was sought for the original and update review. SELECTION CRITERIA: Randomised controlled trials of psychological interventions compared to usual care, administered by trained staff. Only studies estimating the independent effect of the psychological component with a minimum follow-up of six months. Adults with specific diagnosis of CHD. DATA COLLECTION AND ANALYSIS: Titles and abstracts of all references screened for eligibility by two reviewers independently; data extracted by the lead author and checked by a second reviewer. Authors contacted where possible to obtain missing information. MAIN RESULTS: There was no strong evidence that psychological intervention reduced total deaths, risk of revascularisation, or non-fatal infarction. Amongst a smaller group of studies reporting cardiac mortality there was a modest positive effect of psychological intervention (relative risk: 0.80 (95% CI 0.64 to 1.00)). Furthermore, psychological intervention did result in small/moderate improvements in depression, standardised mean difference (SMD): -0.21 (95% CI -0.35, -0.08) and anxiety, SMD: -0.25 (95% CI -0.48 to -0.03). Results for mortality indicated some evidence of small-study bias, though results for other outcomes did not. Meta regression analyses revealed four significant predictors of intervention effects on depression were found: (1) an aim to treat type-A behaviours (ß = -0.32, p = 0.03) were more effective than other interventions. In contrast, interventions which (2) aimed to educate patients about cardiac risk factors (ß = 0.23, p = 0.03), (3) included client-led discussion and emotional support as core therapeutic components (ß = 0.31, p < 0.01), or (4) included family members in the treatment process (ß = 0.26, p < 0.01) were significantly less effective. AUTHORS' CONCLUSIONS: Psychological treatments appear effective in treating psychological symptoms of CHD patients. Uncertainly remains regarding the subgroups of patients who would benefit most from treatment and the characteristics of successful interventions.

Reduced dietary salt for the prevention of cardiovascular disease: a meta-analysis of randomized controlled trials (Cochrane review).

BACKGROUND: Although meta-analyses of randomized controlled trials (RCTs) of salt reduction report a reduction in the level of blood pressure (BP), the effect of reduced dietary salt on cardiovascular disease (CVD) events remains unclear. METHODS: We searched for RCTs with follow-up of at least 6 months that compared dietary salt reduction (restricted salt dietary intervention or advice to reduce salt intake) to control/no intervention in adults, and reported mortality or CVD morbidity data. Outcomes were pooled at end of trial or longest follow-up point. RESULTS: Seven studies were identified: three in normotensives, two in hypertensives, one in a mixed population of normo- and hypertensives and one in heart failure. Salt reduction was associated with reductions in urinary salt excretion of between 27 and 39 mmol/24 h and reductions in systolic BP between 1 and 4 mm Hg. Relative risks (RRs) for all-cause mortality in normotensives (longest follow-up-RR: 0.90, 95% confidence interval (CI): 0.58-1.40, 79 deaths) and hypertensives (longest follow-up RR 0.96, 0.83-1.11, 565 deaths) showed no strong evidence of any effect of salt reduction CVD morbidity in people with normal BP (longest follow-up: RR 0.71, 0.42-1.20, 200 events) and raised BP at baseline (end of trial: RR 0.84, 0.57-1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause mortality in those with heart failure (end of trial RR 2.59, 1.04-6.44, 21 deaths).We found no information on participant's health-related quality of life. CONCLUSIONS: Despite collating more event data than previous systematic reviews of RCTs (665 deaths in some 6,250 participants) there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or CVD morbidity. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small BP reduction achieved.

Exercise-based cardiac rehabilitation for coronary heart disease.

BACKGROUND: The burden of coronary heart disease (CHD) worldwide is one of great concern to patients and healthcare agencies alike. Exercise-based cardiac rehabilitation aims to restore patients with heart disease to health. OBJECTIVES: To determine the effectiveness of exercise-based cardiac rehabilitation (exercise training alone or in combination with psychosocial or educational interventions) on mortality, morbidity and health-related quality of life of patients with CHD. SEARCH STRATEGY: RCTs have been identified by searching CENTRAL, HTA, and DARE (using The Cochrane Library Issue 4, 2009), as well as MEDLINE (1950 to December 2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), and Science Citation Index Expanded (1900 to December 2009). SELECTION CRITERIA: Men and women of all ages who have had myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA), or who have angina pectoris or coronary artery disease defined by angiography. DATA COLLECTION AND ANALYSIS: Studies were selected and data extracted independently by two reviewers. Authors were contacted where possible to obtain missing information. MAIN RESULTS: This systematic review has allowed analysis of 47 studies randomising 10,794 patients to exercise-based cardiac rehabilitation or usual care. In medium to longer term (i.e. 12 or more months follow-up) exercise-based cardiac rehabilitation reduced overall and cardiovascular mortality [RR 0.87 (95% CI 0.75, 0.99) and 0.74 (95% CI 0.63, 0.87), respectively], and hospital admissions [RR 0.69 (95% CI 0.51, 0.93)] in the shorter term (< 12 months follow-up) with no evidence of heterogeneity of effect across trials. Cardiac rehabilitation did not reduce the risk of total MI, CABG or PTCA. Given both the heterogeneity in outcome measures and methods of reporting findings, a meta-analysis was not undertaken for health-related quality of life. In seven out of 10 trials reporting health-related quality of life using validated measures was there evidence of a significantly higher level of quality of life with exercise-based cardiac rehabilitation than usual care. AUTHORS' CONCLUSIONS: Exercise-based cardiac rehabilitation is effective in reducing total and cardiovascular mortality (in medium to longer term studies) and hospital admissions (in shorter term studies) but not total MI or revascularisation (CABG or PTCA). Despite inclusion of more recent trials, the population studied in this review is still predominantly male, middle aged and low risk. Therefore, well-designed, and adequately reported RCTs in groups of CHD patients more representative of usual clinical practice are still needed. These trials should include validated health-related quality of life outcome measures, need to explicitly report clinical events including hospital admission, and assess costs and cost-effectiveness.

Reduced dietary salt for the prevention of cardiovascular disease.

BACKGROUND: An earlier Cochrane review of dietary advice identified insufficient evidence to assess effects of reduced salt intake on mortality or cardiovascular events. OBJECTIVES: 1. To assess the long term effects of interventions aimed at reducing dietary salt on mortality and cardiovascular morbidity.2. To investigate whether blood pressure reduction is an explanatory factor in any effect of such dietary interventions on mortality and cardiovascular outcomes. SEARCH STRATEGY: The Cochrane Library (CENTRAL, Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effect (DARE)), MEDLINE, EMBASE, CINAHL and PsycInfo were searched through to October 2008. References of included studies and reviews were also checked. No language restrictions were applied. SELECTION CRITERIA: Trials fulfilled the following criteria: (1) randomised with follow up of at least six-months, (2) intervention was reduced dietary salt (restricted salt dietary intervention or advice to reduce salt intake), (3) adults, (4) mortality or cardiovascular morbidity data was available. Two reviewers independently assessed whether studies met these criteria. DATA COLLECTION AND ANALYSIS: Data extraction and study validity were compiled by a single reviewer, and checked by a second. Authors were contacted where possible to obtain missing information. Events were extracted and relative risks (RRs) and 95% CIs calculated. MAIN RESULTS: Seven studies (including 6,489 participants) met the inclusion criteria - three in normotensives (n=3518), two in hypertensives (n=758), one in a mixed population of normo- and hypertensives (n=1981) and one in heart failure (n=232) with end of trial follow-up of seven to 36 months and longest observational follow up (after trial end) to 12.7 yrs. Relative risks for all cause mortality in normotensives (end of trial RR 0.67, 95% CI: 0.40 to 1.12, 60 deaths; longest follow up RR 0.90, 95% CI: 0.58 to 1.40, 79 deaths) and hypertensives (end of trial RR 0.97, 95% CI: 0.83 to 1.13, 513 deaths; longest follow up RR 0.96, 95% CI; 0.83 to 1.11, 565 deaths) showed no strong evidence of any effect of salt reduction. Cardiovascular morbidity in people with normal blood pressure (longest follow-up RR 0.71, 95% CI: 0.42 to 1.20, 200 events) or raised blood pressure at baseline (end of trial RR 0.84, 95% CI: 0.57 to 1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause death in those with congestive heart failure (end of trial relative risk: 2.59, 95% 1.04 to 6.44, 21 deaths). We found no information on participants health-related quality of life. AUTHORS' CONCLUSIONS: Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Further RCT evidence is needed to confirm whether restriction of sodium is harmful for people with heart failure. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.

Effectiveness of search strategies for qualitative research about barriers and facilitators of program delivery.

Electronic database search strategies have developed substantially over the course of the past two decades, but their optimal use within a broader search strategy remains unclear. This article evaluates the use of a range of search strategies to identify qualitative evidence on the implementation of cardiovascular disease (CVD) prevention programs. Within the time-limited context of the production of a policy-relevant systematic review, the authors found the protocol-driven, targeted, and reference-checking search strategies to be the most effective, while obtaining authors' suggestions proved to be a resource-intensive process with negligible results. Weaknesses in the indexing of qualitative research in electronic literature databases mean that the sensitivity of searches may need to be reduced to allow time for other search strategies to be implemented. Expert knowledge may be optimally used through involving experts in the design and implementation of a search strategy, rather than solely as a source of citations.

Preventing unintentional injuries to children in the home: a systematic review of the effectiveness of programmes supplying and/or installing home safety equipment.

In children under the age of five, the majority of unintentional injuries occur in the home, with higher levels of injury morbidity and mortality being found among those from more deprived backgrounds. This paper presents the findings of a systematic review about the effectiveness of programmes in decreasing unintentional injury rates to children (aged up to 15 years) in the home. The effectiveness of the provision of home safety equipment with or without installation, safety education or a home risk assessment is presented by outcome: injury rates, installation of smoke alarms and installation of other home safety equipment. Analysis of the statistically significant evidence suggests that few programmes reduce injury rates in children except where home safety equipment is supplied in conjunction with a home risk assessment, although this effect was only evident in households where a child had previously suffered an unintentional injury. The distribution of smoke alarms alone is insufficient for improving installation rates; programmes containing an education component showed more success. Interventions integrated into wider health programmes, where trusting relationships with householders were cultivated and/or where specific safety issues identified by a community were responded to also showed greater success in increasing smoke alarm installation rates. The evidence of effectiveness on installation rates of other home safety equipment is highly mixed, although there is some evidence to suggest that installation rates always decrease after 6 months. Where stair gates are both supplied and installed, inequalities in rates of use may be reduced.

Promoting patient uptake and adherence in cardiac rehabilitation.

BACKGROUND: Cardiac rehabilitation is an important component of recovery from coronary events but uptake and adherence to such programmes are below the recommended levels. This aim is to update a previous non-Cochrane systematic review which examined interventions that may potentially improve cardiac patient uptake and adherence in rehabilitation or its components and concluded that there is insufficient evidence to make specific recommendations. OBJECTIVES: To determine the effects of interventions to increase patient uptake of, and adherence to, cardiac rehabilitation. SEARCH STRATEGY: A previous systematic review identified studies published prior to June 2001. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 4 2007), MEDLINE (2001 to January 2008), EMBASE (2001 to January 2008), CINAHL (2001 to January 2008), PsycINFO (2001 to January 2008), Web of Science: ISI Proceedings (2001 to April 2008), and NHS Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)) from 2001 to January 2008. Reference lists of identified systematic reviews and randomised control trials (RCTs) were also checked for additional studies. SELECTION CRITERIA: Adults with myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, heart failure, angina, or coronary heart disease eligible for cardiac rehabilitation and randomised or quasi-randomised trials of interventions to increase uptake or adherence to cardiac rehabilitation or any of its component parts. Only studies reporting a measure of adherence were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts of all identified references were screened for eligibility by two reviewers independently and full papers of potentially relevant trials were obtained and checked. Included studies were assessed for risk of bias by two reviewers. MAIN RESULTS: Ten studies were identified, three of interventions to improve uptake of cardiac rehabilitation and seven of interventions to increase adherence. Meta-analysis was not possible due to multiple sources of heterogeneity. All three interventions targeting uptake of cardiac rehabilitation were effective. Two of seven studies intended to increase adherence had a significant effect. Only one study reported the non-significant effects of the intervention on cardiovascular risk factors and no studies reported data on mortality, morbidities, costs or health care resource utilisation. AUTHORS' CONCLUSIONS: There is some evidence to suggest that interventions to increase the uptake of cardiac rehabilitation can be effective. Few practice recommendations for increasing adherence to cardiac rehabilitation can be made at this time. Interventions targeting patient identified barriers may increase the likelihood of success. Further high quality research is needed.

Exercise training for systolic heart failure: Cochrane systematic review and meta-analysis.

AIMS: To determine the effect of exercise training on clinical events and health-related quality of life (HRQoL) of patients with systolic heart failure. METHODS AND RESULTS: We searched electronic databases including Medline, EMBASE, and Cochrane Library up to January 2008 to identify randomized controlled trials (RCTs) comparing exercise training and usual care with a minimum follow-up of 6 months. Nineteen RCTs were included with a total of 3647 patients, the majority of whom were male, low-to-medium risk, and New York Heart Association class II-III with a left ventricular ejection fraction of <40%. There was no significant difference between exercise and control in short-term (

Exercise based rehabilitation for heart failure.

BACKGROUND: From previous systematic reviews and meta-analyses there is consensus about the positive effect of exercise training on exercise capacity; however, the effects on health-related quality of life, mortality and hospital admissions in heart failure remain uncertain. OBJECTIVES: To update the previous systematic review which determined the effectiveness of exercise-based interventions on the mortality, hospitalisation admissions, morbidity and health-related quality of life for patients with systolic heart failure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4). To update searches from the previous review, MEDLINE, EMBASE, CINAHL, and PsycINFO were searched (2001 to January 2008). ISI Proceedings and bibliographies of identified reviews were checked. SELECTION CRITERIA: Randomised controlled trials of exercise-based interventions with six months follow up or longer compared to usual medical care or placebo. The study population comprised adults of all ages (> 18 years) with evidence of chronic systolic heart failure. DATA COLLECTION AND ANALYSIS: All identified references were independently screened by two review authors and those that were clearly ineligible were rejected. Full papers of potentially relevant trials were obtained. Data were independantly extracted from the included trials and their risk of bias assessed by a single review author and checked by a second. MAIN RESULTS: Nineteen trials (3647 participants) met the inclusion criteria. One large trial recuited 2331 of the participants. There was no significant difference in pooled mortality between groups in the 13 trials with < 1 year follow up. There was evidence of a non-significant trend toward a reduction in pooled mortality with exercise in the four trials with > 1 year follow up. A reduction in the hospitalisation rate was demonstrated with exercise training programmes. Hospitalisations due to systolic heart failure were reduced with exercise and there was a significant improvement in health-related quality of life (HRQoL). The effect of cardiac exercise training on total mortality and HRQoL were independent of the degree of left ventricular dysfunction, type of cardiac rehabilitation, dose of exercise intervention, length of follow up, trial quality, and trial publication date. AUTHORS' CONCLUSIONS: The previous version of this review showed that exercise training improved exercise capacity in the short term in patients with mild to moderate heart failure when compared to usual care. This updated review provides evidence that in a similar population of patients, exercise does not increase the risk of all-cause mortality and may reduce heart failure-related hospital admissions. Exercise training may offer important improvements in patients' health-related quality of life.

Home-based versus centre-based cardiac rehabilitation.

BACKGROUND: The burden of cardiovascular disease world-wide is one of great concern to patients and health care agencies alike. Traditionally centre-based cardiac rehabilitation (CR) programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. OBJECTIVES: To determine the effectiveness of home-based cardiac rehabilitation programmes compared with supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life and modifiable cardiac risk factors in patients with coronary heart disease. SEARCH STRATEGY: We updated the search of a previous review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2007, Issue 4), MEDLINE, EMBASE and CINAHL from 2001 to January 2008. We checked reference lists and sought advice from experts. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes, in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Studies were selected independently by two reviewers, and data extracted by a single reviewer and checked by a second one. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Twelve studies (1,938 participants) met the inclusion criteria. The majority of studies recruited a lower risk patient following an acute myocardial infarction (MI) and revascularisation. There was no difference in outcomes of home- versus centre-based cardiac rehabilitation in mortality risk ratio (RR) was1.31 (95% confidence interval (C) 0.65 to 2.66), cardiac events, exercise capacity standardised mean difference (SMD) -0.11 (95% CI -0.35 to 0.13), as well as in modifiable risk factors (systolic blood pressure; diastolic blood pressure; total cholesterol; HDL-cholesterol; LDL-cholesterol) or proportion of smokers at follow up or health-related quality of life. There was no consistent difference in the healthcare costs of the two forms of cardiac rehabilitation. AUTHORS' CONCLUSIONS: Home- and centre-based cardiac rehabilitation appear to be equally effective in improving the clinical and health-related quality of life outcomes in acute MI and revascularisation patients. This finding, together with an absence of evidence of difference in healthcare costs between the two approaches, would support the extension of home-based cardiac rehabilitation programmes such as the Heart Manual to give patients a choice in line with their preferences, which may have an impact on uptake of cardiac rehabilitation in the individual case.

Home based versus centre based cardiac rehabilitation: Cochrane systematic review and meta-analysis.

OBJECTIVE: To compare the effect of home based and supervised centre based cardiac rehabilitation on mortality and morbidity, health related quality of life, and modifiable cardiac risk factors in patients with coronary heart disease. DESIGN: Systematic review. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, CINAHL, and PsycINFO, without language restriction, searched from 2001 to January 2008. REVIEW METHODS: Reference lists checked and advice sought from authors. Included randomised controlled trials that compared centre based cardiac rehabilitation with home based programmes in adults with acute myocardial infarction, angina, or heart failure or who had undergone coronary revascularisation. Two reviewers independently assessed the eligibility of the identified trials and extracted data independently. Authors were contacted when possible to obtain missing information. RESULTS: 12 studies (1938 participants) were included. Most studies recruited patients with a low risk of further events after myocardial infarction or revascularisation. No difference was seen between home based and centre based cardiac rehabilitation in terms of mortality (relative risk 1.31, 95% confidence interval 0.65 to 2.66), cardiac events, exercise capacity (standardised mean difference -0.11, -0.35 to 0.13), modifiable risk factors (weighted mean difference systolic blood pressure (0.58 mm Hg, -3.29 mm Hg to 4.44 mm Hg), total cholesterol (-0.13 mmol/l, -0.31 mmol/l to 0.05 mmol/l), low density lipoprotein cholesterol (-0.15 mmol/l, -0.31 mmol/l to 0.01 mmol/l), or relative risk for proportion of smokers at follow-up (0.98, 0.73 to 1.31)), or health related quality of life, with the exception of high density lipoprotein cholesterol (-0.06, -0.11 to -0.02) mmol/l). In the home based participants, there was evidence of superior adherence. No consistent difference was seen in the healthcare costs of the two forms of cardiac rehabilitation. CONCLUSIONS: Home and centre based forms of cardiac rehabilitation seem to be equally effective in improving clinical and health related quality of life outcomes in patients with a low risk of further events after myocardial infarction or revascularisation. This finding, together with the absence of evidence of differences in patients' adherence and healthcare costs between the two approaches, supports the further provision of evidence based, home based cardiac rehabilitation programmes such as the "Heart Manual." The choice of participating in a more traditional supervised centre based or evidence based home based programme should reflect the preference of the individual patient.

Cost-effectiveness of temsirolimus for first line treatment of advanced renal cell carcinoma.

OBJECTIVES: To estimate the cost-effectiveness of temsirolimus compared to interferon-alpha for first line treatment of patients with advanced, poor prognosis renal cell carcinoma, from the perspective of the UK National Health Service. METHODS: A decision-analytic model was developed to estimate the cost-effectiveness of temsirolimus. The clinical effectiveness of temsirolimus compared with interferon-alpha and the utility values (using EQ-5D tariffs) were taken from a recent phase III randomized clinical trial. Cost data were obtained from published literature and based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses. RESULTS: Compared to interferon-alpha, temsirolimus treatment resulted in an incremental cost per QALY gained of pound94,632; based on an estimated mean gain of 0.24 quality-adjusted life years (QALYs) per patient, at a mean additional cost of pound22,331 (inflated to 2007/8). The cost per QALY for patient subgroups ranged from pound74,369 to pound154,752. The probability that temsirolimus is cost-effective compared to interferon-alpha at a willingness to pay threshold of pound30,000 per QALY for all patient groups is expected to be close to zero. The cost per QALY was sensitive to the clinical effectiveness parameters, health state utilities, drug costs and the cost of administration of temsirolimus. CONCLUSIONS: Temsirolimus has been shown to be clinically effective compared to interferon-alpha offering additional health benefits, however, with a cost per QALY in excess of pound90,000, it may not be regarded as a cost-effective use of resources in some health care settings.

Cost-effectiveness of sorafenib for second-line treatment of advanced renal cell carcinoma.

OBJECTIVES: To estimate the cost-effectiveness of sorafenib (Nexavar, Bayer, Leverkusen, Germany) versus best supportive care (BSC) for second-line treatment of advanced renal cell carcinoma from the perspective of the UK National Health Service. METHODS: A decision analytic model was developed to estimate the cost-effectiveness of sorafenib. The clinical effectiveness of sorafenib versus BSC was taken from a recent randomized phase III trial. Utility values were taken from a phase II trial of sunitinib, using EQ-5D tariffs. Cost data were obtained from published literature and were based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses. RESULTS: Compared to BSC, sorafenib treatment resulted in an incremental cost per quality-adjusted life year (QALY) gained of pound75,398, based on an estimated mean gain of 0.27 QALYs per patient, at a mean additional cost of pound20,063 (inflated to 2007/2008). The probability that sorafenib is cost-effective compared to BSC at a willingness to pay threshold of pound30,000 per QALY is 0.0%. In sensitivity analysis, estimates of cost per QALY were sensitive to changes in the clinical effectiveness parameters, and to health state utilities and drug costs. CONCLUSIONS: Sorafenib has been shown to be clinically effective compared to BSC, offering additional health benefits; however, with a cost per QALY in excess of pound70,000, it may not be regarded as a cost-effective use of resources in some health-care settings.