Nicotine is the main addictive agent in cigarettes that sustains smoking. This, in turn, is responsible for most tobacco-related disease and premature death. The US Food and Drug Administration (FDA) recently issued an Advanced Notice of Proposed Rulemaking that would reduce nicotine in all cigarettes in the United States to minimally addictive levels. The aim of this randomized controlled study was to examine the potential effects of immediate versus gradual reduction from usual to very low nicotine content cigarettes, and to compare these groups with a usual nicotine content condition. As part of this study, research participants (n=1250) were randomized with 2 weeks of baseline smoking and 20 weeks of one of three interventions. The first intervention group underwent immediate nicotine reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; the second intervention was gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes, and the third intervention was maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes. The main outcomes were measures of 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT). Researchers found that there were significantly lower levels of exposure in the immediate versus gradual reduction group for CO with a mean difference of -4.06 parts per million (ppm) (95% Cl -4.89 ppm to -3.23 ppm, p<0.0055). The level of exposure to 3-HPMA was also significantly reduced (ratio of geometric means 0.83, 95% Cl 0.77 to 0.88, p <0.0055), as was exposure to PheT (ratio of geometric means 0.88, 95% Cl 0.83 to 0.93, p<0.0055). This study therefore shows that immediate reduction in nicotine content of cigarettes provides the greatest reduction in biomarkers of smoke exposure over time. Further studies of longer duration are needed to study the long-term effect of reduced nicotine content cigarettes.
An increasingly common alternative payment model for Medicare is bundled payments, however there is limited evidence regarding the effectiveness of this model. This study aimed to study outcomes from the first year of implementation of a bundled payment model for lower extremity joint replacement (LEJR). As part of a 5-year mandatory participation randomized trial conducted by the Centers for Medicare Services, eligible metropolitan statistical areas (MSAs) were randomized to the Comprehensive Care for Joint Replacement (CJR) bundled payment model for LEJR episodes or to a control group. The primary outcome was the share of LEJR admissions discharged to institutional post-acute care. Researchers found that the mean percentage of LEJR admissions discharged to institutional post-acute care was 33.7% in the control group, and 2.9 percentage points lower in the CJR group (95% Cl -4.96% to -0.90%). In addition, mean Medicare spending for institutional post-acute care per LEJR episode was $3,871 in the control group and $307 lower in the CJR group (95% Cl -$587 to -$27). Mean overall Medicare spending per LEJR episode was $22,872 in the control group and $453 lower in the CJR group (95% Cl -$909 to $3). This study therefore shows that hospitals that adopted the Comprehensive Care for Joint Replacement bundled payment model for LEJR among Medicare beneficiaries had significantly fewer discharges to institutional post-acute care, although this did not result in a significant difference in total Medicare spending per LEJR episode.
There is a lack of effective antiviral agents for the treatment and prevention of influenza virus infections. Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease, and has demonstrated therapeutic activity in preclinical models. In this study, researchers conducted 2 randomized controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. In the first study, patients were randomized to receive single doses of baloxavir (10 mg, 20 mg, or 40 mg) or placebo. In the second study, patients were randomized to receive a single oral dose of baloxavir (40 mg for patients weighing <80 kg or 80 mg for those weighing >80 kg), oseltamivir at a dose of 75 mg twice daily for 5 days, or matching placebos Based on the results of the first study, researchers found that the median time to alleviation of influenza symptoms was 23.4 hours to 28.2 hours shorter in the baloxavir groups than in the placebo group (p<0.05). In the subsequent study, the median time to alleviation of symptoms was 53.7 hours (95% CI 49.5 hours to 58.5 hours) with baloxavir, as compared with 80.2 hours (95% CI 72.6 hours to 87.1 hours, p<0.001) with placebo. The time to alleviation of symptoms was similar between baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively. This study therefore shows that a single-dose of baloxavir marboxil is safe and superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.
Diet during pregnancy and early life has been shown to be an important contributor to a child’s development and health. This randomized controlled trial aimed to examine the effect of fish oil supplementation with n-3 long chain polyunsaturated fatty acids (n-2 LCPUFA) in pregnancy on anthropometry, proportions of the human body and body composition in offspring. Research participants, consisting of 736 pregnant women and their offspring, were randomized to receive fish oil or a control (olive oil) daily from pregnancy week 24 until one week after birth. The main outcome measures were height/length, weight, head, and waist measurements and body composition from dual energy X–ray absorptiometry. Researchers found that the mean body mass index (BMI) z-score was increased between age 0 and 6 years in the fish oil supplementation group compared to the control group (mean difference 0.14, 95% Cl 0.04 to 0.23, p=0.006). At 6 years, supplementation was also associated with a higher BMI z-score (mean difference 0.19, 95% Cl 0.06 to 0.32, p=0.004), a higher weight/height (p=0.03), and a larger waist circumference (p=0.04). The dual energy X-ray absorptiometry scan performed at age 6 years showed a higher total mass in the intervention group compared to the control group (mean difference 395.4 g (86.6 g to 704.3 g), p=0.01), explained by a higher lean body mass (p=0.002) and a higher bone mineral content (p=0.01), without any significant differences in total body fat or lean mass percentage. This study therefore shows that fish oil supplementation with n-3 LCPUFA from the 24th week of pregnancy may lead to a higher BMI in offspring from 0 to 6 years of age, without an increased risk of obesity in the early years. The proportional increase in lean and bone mass indicates that n-3 LCPUFA may have a general growth-stimulating effect.
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