Rimonabant improves obesity but not the overall cardiovascular risk and quality of life; results from CARDIO-REDUSE (CArdiometabolic Risk reDuctIOn by Rimonabant: the Effectiveness in Daily practice and its USE).

BACKGROUND: Rimonabant treatment, examined in Phase 3 trials, showed improvement of cardiovascular risk factors in obese patients. OBJECTIVE: The objective of this Phase 4 trial is to assess the effectiveness of rimonabant plus lifestyle counselling when used in daily practice, namely in the general practice. The hypothesis was that the effectiveness in Phase 4 would be smaller than the efficacy in Phase 3 due to different patient selection and treatment conditions. At the end of this trial, rimonabant was suspended of all markets due to psychiatric side effects. METHODS: This trial randomly assigned 222 patients with enlarged waist circumferences and hyperglycaemia or diabetes mellitus type 2, recruited from Dutch general practices, to double-blinded therapy with either placebo or rimonabant (20 mg/day) for 1 year in addition to lifestyle counselling. RESULTS: Compared with placebo, the rimonabant group showed significant improvements in body weight, body mass index, high-density lipoprotein (HDL) cholesterol and the main outcome waist circumference after 1 year. The United Kingdom Prospective Diabetes Study risk calculation showed no significant difference. The rimonabant group showed statistically deterioration, compared with the placebo group, in the quality of life in the EuroQol and two domains of the SF-36: role limitations due to physical health problems and bodily pain. CONCLUSIONS: The unique real life data of this Phase 4 trial showed that the effectiveness of rimonabant in daily practice is indeed lower than in controlled circumstances (Phase 3). Rimonabant treatment showed improvement of obesity and the HDL cholesterol, but had no positive effect on the other cardiovascular risk factors and the quality of life.

Healthcare financing systems for increasing the use of tobacco dependence treatment.

BACKGROUND: We hypothesized that provision of financial assistance for smokers trying to quit, or reimbursement of their care providers, could lead to an increased rate of successful quit attempts. OBJECTIVES: The primary objective of this review was to assess the impact of reducing the costs of providing or using smoking cessation treatment by health care financing interventions on abstinence from smoking and utilization of smoking cessation treatment. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction group specialized register; the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2008; MEDLINE (from January 1966 to August 2008) and EMBASE (from January 1980 to August 2008) to identify trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled trials involving financial benefit interventions to smokers or their health care providers or both. DATA COLLECTION AND ANALYSIS: Three reviewers independently extracted data and assessed the quality of the included studies. Rate ratios (RR) were calculated for individual studies on an intention-to-treat basis and meta-analysis was performed using a random effects model. We included economic evaluations when a study presented the costs and effects of two or more alternatives. MAIN RESULTS: We found nine trials involving financial interventions directed at smokers and two studies directed at health care providers.There was a statistically significant favourable effect of full financial interventions directed at smokers on continuous abstinence compared to no interventions with a risk ratio (RR) of 4.38 (95% CI 1.94 to 9.87). There was also a significant effect of full financial interventions when compared to no interventions on the number of participants making a quit attempt (RR 1.19; 95% CI 1.07 to 1.32; N = 3). There was a significant effect of financial interventions directed at health care providers in increasing the utilization of behavioural interventions for smoking cessation (RR 1.33; 95% CI 1.01 to 1.77). Comparison of full benefit with partial or no benefit resulted in costs per additional quitter ranging from $260 to $1453. AUTHORS' CONCLUSIONS: Full financial interventions directed at smokers when compared to no financial interventions could increase the proportion quitting, quit attempts and utilization of pharmacotherapy by smokers. Although the absolute differences were small the costs per additional quitter were low. The methodological qualities of the included studies need to be taken into consideration in interpreting the conclusions.

Mono and multifaceted inhalant and/or food allergen reduction interventions for preventing asthma in children at high risk of developing asthma.

BACKGROUND: Allergen exposure is one of the environmental factors seemingly associated with the development of asthma. If asthma is a multi-factorial disease, it is hypothesised that prevention might only prove effective if most or all relevant environmental factors are simultaneously avoided. OBJECTIVES: To assess effect(s) of monofaceted and multifaceted interventions compared with control interventions in preventing asthma and asthma symptoms in high risk children. SEARCH STRATEGY: We searched the Cochrane Airways Trials Register (December 2008). SELECTION CRITERIA: Randomised controlled trials of allergen exposure reduction for the primary prevention of asthma in children. Interventions were multifaceted (reducing exposure to both inhalant and food allergens) or monofaceted (reducing exposure to either inhalant or food allergens) Follow up had to be from birth (or during pregnancy) up to a minimum of two years of age. DATA COLLECTION AND ANALYSIS: We included in the analysis studies assessing the primary outcome (current diagnosis: asthma) and/or one of the secondary outcomes (current respiratory symptoms: wheezing, nocturnal coughing and dyspnoea). We pooled multifaceted and monofaceted intervention trials separately. We made an indirect comparison of their effects using tests for interaction to calculate relative odds ratios. MAIN RESULTS: We included three multifaceted and six monofaceted intervention studies (3271 children). Physician diagnosed asthma in children less than five years, and asthma as defined by respiratory symptoms and lung function criteria in children aged five years and older, both favoured treatment with a multifaceted intervention compared to usual care (< 5 years: odds ratio (OR) 0.72, 95% confidence interval (CI) 0.54 to 0.96, and > 5 years: OR 0.52, 95% CI 0.32 to 0.85). However, there was no significant difference in outcome between monofaceted intervention and control interventions (< 5 years: OR 1.12, 95% CI 0.76 to 1.64, and > 5 years: OR 0.83, 95% CI 0.59 to 1.16). Indirect comparison between these treatments did not demonstrate a significant difference between multiple interventions and mono-interventions in reducing the frequency of asthma diagnosis in children under five years (relative OR 0.64 (95% CI 0.40 to 1.04, P = 0.07) or five years and older (relative OR 0.63, 95% CI 0.35 to 1.13, P = 0.12). There was also no significant difference between either mono- and multifaceted intervention and control in reducing the likelihood of symptoms of nocturnal coughing at follow up. Wheezing, however, showed a significant difference between multifaceted and mono-interventions (relative OR 0.59, 95% CI 0.35 to 0.99, P = 0.04), but the significance was lost when data on treatment only was analysed. AUTHORS' CONCLUSIONS: The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children.

Encouraging smokers to quit: the cost effectiveness of reimbursing the costs of smoking cessation treatment.

BACKGROUND: Smoking cessation should be encouraged in order to increase life expectancy and reduce smoking-related healthcare costs. Results of a randomised trial suggested that reimbursing the costs of smoking cessation treatment (SCT) may lead to an increased use of SCT and an increased number of quitters versus no reimbursement. OBJECTIVE: To assess whether reimbursement for SCT is a cost-effective intervention (from the Dutch societal perspective), we calculated the incremental costs per quitter and extrapolated this outcome to incremental costs per QALY saved versus no reimbursement. METHODS: In the reimbursement trial, 1266 Dutch smokers were randomly assigned to the intervention or control group using a randomised double consent design. Reimbursement for SCT was offered to the intervention group for a period of 6 months. No reimbursement was offered to the control group. Prolonged abstinence from smoking was determined 6 months after the end of the reimbursement period. The QALYs gained from quitting were calculated until 80 years of age using data from the US. Costs (year 2002 values) were determined from the societal perspective during the reimbursement period (May-November 2002). Benefits were discounted at 4% per annum. The uncertainty of the incremental cost-effectiveness ratios was estimated using non-parametric bootstrapping. RESULTS: Eighteen participants in the control group (2.8%) and 35 participants in the intervention group (5.5%) successfully quit smoking. The costs per participant were 291 euro and 322 euro, respectively. If society is willing to pay 1000 euro or 10,000 euro for an additional 12-month quitter, the probability that reimbursement for SCT would be cost effective was 50% or 95%, respectively. If society is willing to pay 18,000 euro for a QALY, the probability that reimbursement for SCT would be cost effective was 95%. However, the external validity of the extrapolation from quitters to QALYs is uncertain and several assumptions had to be made. CONCLUSION: Reimbursement for SCT may be cost effective if Dutch society is willing to pay 10,000 euro for an additional quitter or 18,000 euro for a QALY.

Productivity cost calculations in health economic evaluations: correcting for compensation mechanisms and multiplier effects.

Productivity costs related to paid work are commonly calculated in economic evaluations of health technologies by multiplying the relevant number of work days lost with a wage rate estimate. It has been argued that actual productivity costs may either be lower or higher than current estimates due to compensation mechanisms and/or multiplier effects (related to team dependency and problems with finding good substitutes in cases of absenteeism). Empirical evidence on such mechanisms and their impact on productivity costs is scarce, however. This study aims to increase knowledge on how diminished productivity is compensated within firms. Moreover, it aims to explore how compensation and multiplier effects potentially affect productivity cost estimates. Absenteeism and compensation mechanisms were measured in a randomized trial among Dutch citizens examining the cost-effectiveness of reimbursement for smoking cessation treatment. Multiplier effects were extracted from published literature. Productivity costs were calculated applying the Friction Cost Approach. Regular estimates were subsequently adjusted for (i) compensation during regular working hours, (ii) job dependent multipliers and (iii) both compensation and multiplier effects. A total of 187 respondents included in the trial were useful for inclusion in this study, based on being in paid employment, having experienced absenteeism in the preceding six months and completing the questionnaire on absenteeism and compensation mechanisms. Over half of these respondents stated that their absenteeism was compensated during normal working hours by themselves or colleagues. Only counting productivity costs not compensated in regular working hours reduced the traditional estimate by 57%. Correcting for multiplier effects increased regular estimates by a quarter. Combining both impacts decreased traditional estimates by 29%. To conclude, large amounts of lost production are compensated in normal hours. Productivity costs estimates are strongly influenced by adjustment for compensation mechanisms and multiplier effects. The validity of such adjustments needs further examination, however.

If you try to stop smoking, should we pay for it? The cost-utility of reimbursing smoking cessation support in the Netherlands.

BACKGROUND: Smoking cessation can be encouraged by reimbursing the costs of smoking cessation support (SCS). The short-term efficiency of reimbursement has been evaluated previously. However, a thorough estimate of the long-term cost-utility is lacking. OBJECTIVES: To evaluate long-term effects of reimbursement of SCS. METHODS: Results from a randomized controlled trial were extrapolated to long-term outcomes in terms of health care costs and (quality adjusted) life years (QALY) gained, using the Chronic Disease Model. Our first scenario was no reimbursement. In a second scenario, the short-term cessation rates from the trial were extrapolated directly. Sensitivity analyses were based on the trial's confidence intervals. In the third scenario the additional use of SCS as found in the trial was combined with cessation rates from international meta-analyses. RESULTS: Intervention costs per QALY gained compared to the reference scenario were approximately euro1200 extrapolating the trial effects directly, and euro4200 when combining the trial's use of SCS with the cessation rates from the literature. Taking all health care effects into account, even costs in life years gained, resulted in an estimated incremental cost-utility of euro4500 and euro7400, respectively. In both scenarios costs per QALY remained below euro16 000 in sensitivity analyses using a life-time horizon. CONCLUSIONS: Extrapolating the higher use of SCS due to reimbursement led to more successful quitters and a gain in life years and QALYs. Accounting for overheads, administration costs and the costs of SCS, these health gains could be obtained at relatively low cost, even when including costs in life years gained. Hence, reimbursement of SCS seems to be cost-effective from a health care perspective.

The cost-effectiveness of antidepressants for smoking cessation in chronic obstructive pulmonary disease (COPD) patients.

OBJECTIVES: In healthy smokers, antidepressants can double the odds of cessation. Because of its four times lower costs and comparable efficacy in healthy smokers, nortriptyline appears to be favourable compared to bupropion. We assessed which of both drugs was most effective and cost-effective in stopping smoking after 1 year compared with placebo among smokers at risk or with existing chronic obstructive pulmonary disease (COPD). METHODS: A total of 255 participants, aged 30-70 years, received smoking cessation counselling and were assigned bupropion, nortriptyline or placebo randomly for 12 weeks. Prolonged abstinence from smoking was defined as a participant's report of no cigarettes from week 4 to week 52, validated by urinary cotinine. Costs were calculated using a societal perspective and uncertainty was assessed using the bootstrap method. RESULTS: The prolonged abstinence rate was 20.9% with bupropion, 20.0% with nortriptyline and 13.5% with placebo. The differences between bupropion and placebo [relative risk (RR) = 1.6; 95% confidence interval (CI) 0.8-3.0] and between nortriptyline and placebo (RR = 1.5; 95% CI 0.8-2.9) were not significant. Severity of airway obstruction did not influence abstinence significantly. Societal costs were 1368 euros (2.5th-97.5th percentile 193-5260) with bupropion, 1906 euros (2.5th-97.5th 120-17 761) with nortriptyline and 1212 euros (2.5th-97.5th 96-6602) with placebo. Were society willing to pay more than 2000 euros for a quitter, bupropion was most likely to be cost-effective. CONCLUSIONS: Bupropion and nortriptyline seem to be equally effective, but bupropion appears to be more cost-effective when compared to placebo and nortriptyline. This impression holds using only health care costs. As the cost-effectiveness analyses concern some uncertainties, the results should be interpreted with care and future studies are needed to replicate the findings.

IPCRG Consensus statement: tackling the smoking epidemic - practical guidance for primary care.

Tobacco use will become the world's foremost cause of premature death and disability within 20 years unless current trends are reversed. Many opportunities to reduce this epidemic are missed in primary care. This Discussion paper from the International Primary Care Respiratory Group (IPCRG) - which reflects the IPCRG's understanding of primary care practitioners' needs - summarises a new approach based on strong evidence for effective interventions. All primary care health professionals can increase smoking cessation rates among their patients, even when time and resources are limited. Medical and non-medical staff can support patients who choose to quit by providing information, referral to telephone counselling services, and behavioural counselling using motivational interviewing techniques, where resources permit. Drug therapy to manage nicotine dependence can significantly improve patients' chances of quitting successfully, and is recommended for people who smoke 10 or more cigarettes per day. All interventions should be tailored to the individual's circumstances and attitudes.

Is there any role for allergen avoidance in the primary prevention of childhood asthma?

In this article we discuss 3 hypotheses to attempt to understand why preventive measures thus far studied with the aim of preventing (or delaying) the development of asthma have shown such disappointing results. The most likely explanation is that the development of a multifactorial disease, such as asthma, is extremely difficult, if not impossible, to prevent by eliminating only one risk factor. In a meta-analysis we investigated the effect of a multifaceted and monofaceted intervention in 10 prospective birth cohorts of a total of 3473 children on a diagnosis of asthma. Multifaceted intervention studies had an odds ratio (OR) of 0.73 (95% CI, 0.55-0.97), whereas the monointervention studies had an OR of 1.22 (95% CI, 0.83-1.78) in patients younger than 5 years and an OR of 0.52 (95% CI, 0.32-0.84) versus 0.93 (95% CI, 0.66-1.31) in patients older than 5 years. We therefore hypothesize that studies with a multifaceted approach will have a much greater chance of being successful than studies using a monofaceted approach, with the latter being unlikely to yield a clinically relevant reduction of asthma.