2 Minute Medicine Rewind May 24 – May 31, 2015

Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults

Herpes zoster continues to be a menacing disease especially for patients who are 50 years of age or older, resulting in more frequent post infectious complications in this population including post herpetic neuralgia. The current live-attenuated vaccine for herpes zoster, Zostavax (Merck), is approved for use in patients over 50 years of age. However, the vaccine has an overall 51.3% efficacy against herpes zoster that decreases with age. In this phase 3 trial, researchers tested the efficacy of a new recombinant subunit vaccine that features the VZV glycoprotein E. In this randomized control trial, 15,411 patients who were older than 50 years of age were randomized to receive either 2 doses of the vaccine or a placebo spaced 2 months apart. After a median follow-up of 3.2 years, the incidence of confirmed herpes zoster infection was 0.3 per 1000 person-years in the intervention group compared to 9.1 per 1000 person-years in the control group. The overall vaccine efficacy was between 96.6% and 97.9% across the three age groups: 50-59, 60-69, and > 69 years old. The rate of serious adverse events and potential immune-mediated diseases was similar between the intervention and control groups. This phase 3 trial therefore demonstrates that this recombinant subunit vaccine appears to substantially reduce the incidence of herpes zoster in patients aged 50 years and older with a minimal side effect profile.

Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study

To date, the results of observational, genetic, and clinical research on the role of HDL cholesterol in reducing the risk of coronary artery disease (CAD) have been conflicting. More recent studies have suggested that cholesterol efflux capacity, a measure of the ability of HDL to promote cholesterol removal from lipid-laden macrophages, may provide additional information to help clarify the link between HDL and CAD risk in a way not achieved by measuring static HDL levels alone. In this case-control study, researchers sought to clarify the association between cholesterol efflux capacity and cardiovascular outcomes by studying 1745 patients with incident CAD in the EPIC-Norfolk cohort, compared to 1749 control patients free of cardiovascular disorders. Investigators found that cholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r = 0.40, p < 0.0001) and apoA-I concentration (r = 0.22, p < 0.0001). It was inversely correlated with type 2 diabetes (r = -0.18, p < 0.0001) and positively correlated with alcohol consumption (r = 0.12, p < 0.0001). When comparing the top and bottom tertiles, cholesterol efflux capacity was independently inversely associated with incident CAD events even after adjustment for age, sex, diabetes, hypertension, smoking, alcohol use, waist:hip ratio, BMI, LDL levels, triglyceride levels, as well as both HDL and apoA-I concentrations levels (OR 0.64, 95% CI 0.51-0.80). This study therefore shows that cholesterol efflux capacity appears to be an important measure of the ability of HDL cholesterol to reduce CAD risk and warrants further consideration as a diagnostic test and potential pathway for future therapeutics.

Randomized Trial of Four Financial-Incentive Programs for Smoking Cessation

Using financial incentives to promote behavioral health change is becoming an increasingly popular mechanism used by governments, employers, and insurers. A variety of different methods for structuring these incentives exist, but have not been well evaluated for promoting change in certain health behaviors such as smoking. In this randomized trial, researchers randomized 2538 CVS Caremark employees to either usual care or one of four different financial incentive programs for smoking cessation. In the individual-reward group, the individual received a $200 reward for smoking abstinence at each time point. In the individual-deposit group, the individual received the same reward structure but was additionally required to make an initial $150 deposit, which was lost unless the patient successfully quit smoking. In the collaborative-reward group, individuals were grouped with 5 other individuals and received increasing payments per time point with each additional individual in the group who remained abstinent. In the collaborative-deposit group, each individual paid an initial $150 deposit. At each time point, a total of $3600 was redistributed among the individuals in the group who remained abstinent. Researchers found that all four financial incentive groups had higher rates of smoking cessation at 6 months (ranging from 9.4 to 10.0%) than usual care (6.0%)(p < 0.05 for all comparisons). There was no difference in 6-month abstinence rates between group-oriented and individual-oriented programs (13.7% vs. 12.1% respectively, p = 0.29). There was a 90.0% rate of acceptance of reward-based programs versus a 13.7% acceptance of deposit-based programs (p < 0.001), which was reflected in a significantly higher rate of abstinence in the reward based programs at 6 months compared to deposit-based programs (15.7% vs. 10.2%, p < 0.001). However, in an analysis of individuals who actually participated in a program, the 6-month abstinence rate was 13.2 percentage points higher in the deposit-based program. This study shows that financial incentive programs can be more effective than usual care in promoting smoking cessation and that reward strategies appear to be more effective than deposit strategies with no difference between the group versus individual oriented structures researched in this study.

Copy Number Variations and Cognitive Phenotypes in Unselected Populations

There are approximately 2.4 million known DNA copy number variations (CNV) in the human genome. CNVs have been shown to influence RNA transcription and contribute to individual differences across a number of traits and conditions. However, they have been for the most part studied only in the context of genomic disorders in pediatric cohorts with known cognitive impairments. As such, the effects of pathological CNVs in the normal adult carrier population are not well understood. Additionally, the clinical effects of rarer intermediate-size autosomal CNVs (defined as CNVs between 250 and 500kb in size) in the adult population have also been poorly studied. In this study, researchers randomly selected 7877 individuals from an Estonian population biobank and looked at associations between CNVs and adult cognitive outcomes including level of educational attainment and prevalence of intellectual disability. The investigators identified 56 carriers of CNVs associated with known syndromes and found that their phenotypes were similar to those described in carriers found in clinical cohorts. They also discovered that 10.5% of the cohort had at least one rare autosomal intermediate-size CNV. Individuals with a deletion of at least 250kb had an odds ratio of 3.16 for having an intellectual disability when compared with the overall cohort (95% CI 1.51-5.98, p = 1.5e-03). And those with a duplication of at least 1Mb had an odds ratio of 3.67 for having an intellectual disability compared with the overall cohort (95% CI 1.29-8.54, p = 0.008). Similarly, mean education attainment was significantly lower and rates of dropping out from high school were higher among those with a deletion or duplication CNV when compared with the overall cohort. These associations were further corroborated by analyzing additional cohorts of adults from Italy and the United States. This study therefore shows that known pathogenic CNVs have clear clinical effects in seemingly normal adult carriers and that additionally,relatively common intermediate-size CNVs can have negative cognitive outcomes, suggesting a role for additional study of these CNVs.

Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial

Alpha-1 proteinase inhibitor (A1P1) augmentation treatment has shown promise for slowing the progression of lung disease in alpha-1 antitrypsin deficiency but has yet to be studied in a randomized control trial. In this study, 180 non-smokers with severe alpha-1 antitrypsin deficiency and a forced expiratory volume in 1 second (FEV1) between 35-70% predicted were randomized to receive either A1PI treatment or placebo. Researchers found that the annual rate of lung density loss at total lung capacity (TLC) and functional residual capacity (FRC) combined, as assessed by CT, did not differ significantly between the intervention and placebo groups (-1.50g/L/yr vs. -2.12 g/L/yr, difference 0.62 g/L/yr, 95% CI -0.02-1.26, p = 0.06). However, when looking at lung density loss at TLC alone, there was a significant decrease in the rate of lung density loss in the A1PI group when compared to the placebo group (difference 0.74 g/L/yr, 95% CI 0.06-1.42, p = 0.03). There was no significant increase in adverse events in the intervention group. This study therefore shows that use of A1PI augmentation treatment can slow the progression of emphysema in patients with severe alpha-1 antitrypsin deficiency as assessed by measuring lung density at TLC.

Image: PD

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