2 Minute Medicine Rewind January 6-12, 2014

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In this section, we will highlight the key high-impact studies, updates, and analyses published in medicine during the past week.

Tobacco Control and the Reduction in Smoking-Related Premature Deaths in the United States, 1964-2012

Fifty years after the initiation of tobacco control in the United States, the smoking rate has declined from over 42% overall to less than 20%, according to the CDC. In this retrospective analysis, using data from several national surveys, researchers modeled the estimated number of premature deaths avoided and years of life saved by tobacco control by comparing smoking-related deaths and actual smoking rates to counterfactual scenarios (projected trends in smoking prevalence if no tobacco control existed).  The authors estimate that, overall, 8.0 million (credible range [CR] 7.4-8.3 million) or 31% (CR 29-32%) of premature smoking-related deaths were avoided from 1964-2012 as a result of tobacco control. Individuals under 65 (40% of lives saved, CR 37-41%) and women (37% of lives saved, CR 36-38%) have benefited the most, and the proportion of deaths avoided continues to increase (from 11% in the first decade to 56% in 2004-2012). Tobacco control is estimated to have improved overall life expectancy by 2.3 years (CR 1.8-2.5) for men and 1.6 years (CR 1.4-1.7) for women.

Trends in Smoking Among Adults with Mental Illness and Association Between Mental Health Treatment and Smoking Cessation

Despite significant overall reductions in smoking rates over the last several decades, individuals with mental illness continue to use tobacco at higher rates than the general population. In this retrospective study, investigators used data from two national surveys to compare recent (2004-2011) smoking trends among adults with and without probable mental illness and smoking cessation among those with or without mental health treatment. The smoking rate among individuals with mental illness was significantly higher than those with no mental illness (28% vs 17% respectively, p<0.001), although they were also significantly different demographically. After controlling for all covariates, there was a significant difference in difference (2.3%, 95%CI 0.7-3.9%, p=0.005) in the rate of decline of smoking among those with and without mental illness from 2010-2011, and those with mental illness saw no significant decline whatsoever (25.3% to 24.9%, p=0.5). In another survey, among 14,057 individuals with mental illness, those receiving mental health treatment were significantly more likely to quit than those who received no treatment (37.2% vs 33.1%, p=0.005), even after adjusting for mental illness severity and other covariates (p=0.04). Outpatient, but not inpatient, treatment was associated with quitting (p=0.006 vs p=0.27, respectively), which the authors attribute to lack of emphasis on smoking cessation in inpatient settings.

Upper-Airway Stimulation for Obstructive Sleep Apnea

Although continuous positive airway pressure (CPAP) and other therapies have been developed to treat obstructive sleep apnea (OSA), these methods often provide inconsistent efficacy or rely on patient adherence. In this multicenter, prospective, single-group trial sponsored by the developer (Inspire Medical Systems), 126 participants with nonadherence to CPAP therapy and moderate-to-severe OSA underwent surgery to implant an upper-airway neurostimulation system. Subsequently, at 12 months, 46 of the participants who had experienced a response to therapy were randomized to therapy-maintenance or therapy-withdrawal for 7 days. The primary outcomes were the change in severity of OSA as measured by the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) as well as the proportion of participants who had a 50% reduction in AHI score at 12 months. Median AHI score decreased significantly, from 29.3 events per hour at baseline to 9.0 events per hour at 12 months (p<0.001), as did the median ODI (25.4 to 7.4 events per hour, p<0.001), and 66% of participants experienced >50% reduction in AHI score from baseline. Those randomized to therapy-withdrawal on average experienced an increase in AHI score from 7.6 to 25.8 after one week, significantly different from those on therapy-maintenance (p<0.001). 

Prevention of Diabetes with Mediterranean Diets: A Subgroup Analysis of a Randomized Trial

Lifestyle modifications have been shown to effectively delay the onset of Type 2 diabetes mellitus, but prescribed changes are often intensive and difficult to adhere to. In this subgroup analysis of a randomized trial, 3541 Spanish individuals aged 55-80, without pre-existing diabetes but with 3 or more cardiovascular risk factors, were randomized to one of three diets, all without calorie restrictions or advice to increase physical activity: a Mediterranean diet supplemented with extra-virgin olive oil (EVOO), a Mediterranean diet supplemented with nuts, or advice for a low-fat diet (control) in order to measure the incidence of new-onset type 2 diabetes (a secondary outcome of the overall trial). During a median of 4.1 years of follow-up, 6.9% of the Mediterranean diet group supplemented with EVOO developed diabetes, compared to 7.4% of the group supplemented with nuts, and 8.8% of the control group. Compared to the control group, adjusted HR for diabetes was 0.60 (CI 0.43-0.85) in the EVOO group and 0.82 (CI 0.61-1.10) for the group supplemented with nuts, suggesting a 40% relative risk reduction in diabetes risk due to a Mediterranean diet composition supplemented with extra-virgin olive oil.

Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions

Treatment of chronic lymphocytic leukemia (CLL) with the monoclonal anti-CD20 antibody rituximab has been shown to prolong survival in physically fit patients with CLL, but not those with coexisting conditions. Obinutuzumab also targets CD20, but directly induces cell death rather than depending on complement-dependent cytotoxicity. In this phase 3, open-label, randomized trial, 781 patients with previously untreated CLL and at least one coexisting condition (defined by a Cumulative Illness Rating Scale score of higher than 6 on a scale of 0-56) were randomized 1:2:2 to receive chemotherapy (chlorambucil) alone, obinutuzumab-chlormabucil, or rituximab-chlorambucil. The primary outcome was progression-free survival, with secondary endpoints including response rates, event-free survival, overall survival, and adverse events. Median progression-free survival was 26.7 months in the obinutuzumab group vs 11.1 months for those receiving chlorambucil alone (HR 0.18, 95%CI 0.13-0.24, p<0.001) and 16.3 months for the rituximab-chlorambucil group (HR 0.44 vs chlorambucil alone, 95%CI 0.34-0.57, p<0.001). Patients in the obinutuzumab-chlorambucil group had significantly higher rates of complete or partial response at 3 months after treatment (p<0.001) than the rituximab-chlorambucil group. Overall survival at 36 months was highest in the obinutuzumab-chlorambucil group vs chlorambucil alone (HR 0.41, p=0.002), and there was greater though statistically insignificant overall survival when comparing obinutuzumab-chlorambucil and rituximab-chlorambucil group (HR 0.66, 95%CI 0.41-1.06, p=0.08).

By Kathleen Li and David Ouyang

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