2 Minute Medicine Rewind April 10, 2017


Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma

Over the last decade, the use of proteasome inhibitors and immunomodulatory drugs has increased rates of complete response in multiple myeloma. However, the role of autologous stem-cell transplantation in conjunction with these drugs is unclear. This study aimed to investigate whether transplantation affects progression-free survival when used in conjunction with lenalidomide, bortezomib, and dexamethasone (RVD). After receiving three 21-day cycles of RVD, 700 multiple myeloma patients were randomly assigned to receive either high-dose melphalan and stem cell transplantation followed by two additional cycles of RVD, or five additional cycles of RVD. All patients also received lenalidomide maintenance therapy for one year after their respective courses of treatment. Researchers found that the rate of complete response was 48% in the RVD-alone group versus 59% in the transplantation group (p = 0.03), with minimal residual disease detected in significantly fewer patients from the transplantation group (p<0.001). The transplantation group also had an average progression-free survival of 50 months versus 36 months in the group that did not receive a stem cell transplant, yielding a statically significant hazard ratio of 0.65 (95% CI 0.53 to 0.80, p<0.001) for the transplant group. However, neutropenia, infections, and grade 3 and 4 gastrointestinal complications were also more common in the transplant group. Overall, survival at 4 years did not differ between the two groups. This study therefore shows that autologous stem-cell transplantation in conjunction with lenalidomide, bortezomib, and dexamethasone therapy is associated with increased progression-free survival, but is not without significant adverse effects and does not improve overall 4-year survival.

Association Between Early Low-Dose Hydrocortisone Therapy in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years of Age

Dexamethasone, when used in the prevention of bronchopulmonary dysplasia in preterm infants, is associated with an increased risk of neurodevelopmental adverse effects, such as cerebral palsy. This study aimed to investigate the incidence of neurodevelopmental adverse events when using early hydrocortisone therapy, an alternative to dexamethasone previously shown to increase survival without bronchopulmonary dysplasia. This secondary analysis utilized data from the PREMILOC randomized clinical trial, where 379 neonates were randomized to receive either hydrocortisone or placebo after birth, and subsequently evaluated for neurodevelopmental delay at a median corrected age of 22 months. For the primary outcome of neurodevelopmental delay, there were no statistically significant differences between the two treatment groups (p = 0.33).  The incidence of cerebral palsy and the incidence of other major neurological impairments were also not significantly different between the two groups. This study therefore shows that early low-dose hydrocortisone in the prevention of bronchopulmonary dysplasia in preterm infants, is not associated with increased risk for neurodevelopmental impairments at 2 years.

Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015

Worldwide, smoking is a leading risk factor for both early death and disability. In this systematic analysis, data from 2818 sources was reviewed in order to evaluate changes in prevalence and disease burden in 195 countries from 1990-2015. These results were also explored with respect to gender and birth year, as well as socio-demographic index (SDI), a measure of level of development in the area. Results showed a worldwide daily smoking prevalence of 25% for men (95% CI 24.2-25.7%) and 5.4% for women (95% CI 5.1 to 5.7%). The percentage of countries achieving significant annualized decline in prevalence was greater from 1990 to 2005 than from 2005 to 2015. In 2015, 11.5% of global deaths were attributable to smoking, which emerged as one of the top five risk factors for disease burden based on disability-adjusted life years (DALYs) and mortality in 109 of the 195 countries evaluated. In low to middle-SDI areas, it was found that population growth and aging contributed to increases in overall smoking-attributable morbidity. Based on these findings, the authors indicate that it may be difficult to continue to meet past rates of decline in smoking and, in turn, smoking-attributable disease without concerted effort in promoting smoking cessation, including political commitment.

Cardiometabolic Abnormalities Among Normal-Weight Persons From Five Racial/Ethnic Groups in the United States: A Cross-Sectional Analysis of Two Cohort Studies

Being overweight or obese is a risk factor for cardiometabolic abnormality. However, the relationship between weight and these abnormalities may differ between races. This cross-sectional analysis aimed to investigate the prevalence of metabolic abnormality but normal weight (MAN) in South Asians, Chinese-Americans, whites, African-Americans, and Hispanics. MAN was defined as having normal weight and 2 or more of the following: high fasting glucose, low high-density lipoprotein (HDL), high triglyceride levels, or hypertension. This yielded a prevalence of 43.6% in South Asians (95% CI 36.8 to 50.6%), 32.2% in Chinese-Americans (95% CI 27.3 to 37.4%), 21% in whites (95% CI 18.4 to 23.9%), 31.1% in African-Americans (95% CI 26.3 to 36.3%), and 38.5% in Hispanics (95% CI 32.6 to 44.6%). These differences persisted after adjustment for ectopic body fat, demographics, and behavioral factors. This study therefore shows that non-whites have significantly higher rates of metabolic abnormalities despite normal weight. Opportunities to address metabolic abnormalities in individuals from these ethnic groups may be missed at higher rates compared to whites if screening is done on the basis of BMI criterion alone.

Body-Weight Fluctuations and Outcomes in Coronary Disease

Fluctuation in body weight is a risk factor for cardiovascular disease and death due to cardiovascular pathology. However, it is unclear whether or not weight fluctuation has a significant effect on outcomes in patients with known coronary artery disease (CAD).  In this post-hoc analysis of a randomized controlled trial involving 9509 patients with clinically-evidence CAD and levels of low-density lipoprotein (LDL) <130 mg/dL, the authors examined fluctuations in the weight of patients enrolled and the effects of the fluctuation on coronary events, including revascularization, angina, nonfatal myocardial infarction, and death from coronary heart disease. After adjusting for risk factors, lipid levels, body weight, and weight change, researchers found that each increase of 1 standard deviation (SD) in body-weight variability yielded an increase in the risk of any coronary event (HR 1.04, 95% CI 1.01 to 1.07, p = =0.01), any cardiovascular event (HR 1.04, 95% CI 1.02 to 1.07, p<0.001) and death (HR 1.09, 95% CI 1.07 to 1.12, p<0.001). Among patients with the highest amount of body weight variability, the incidence of coronary events was 64% higher. The risk for any cardiovascular event, including myocardial infarction and stroke, and the risk for death were also higher with an increase in body-weight variability. This study therefore shows that, irrespective of other risk factors, an increase in body-weight variability is associated with a higher incidence of coronary and cardiovascular events.

Image: PD

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