Publications

Overtreatment is pervasive in medicine and leads to potential patient harms and excessive costs in health care. Although evidence-based medicine is often derided as practice by rote algorithmic medicine, the appropriate application of key evidence-based medicine principles in clinical decision making is fundamental to preventing overtreatment and promoting high-value, individualized patient-centered care. Specifically, this article discusses the importance of (1) using absolute rather than relative estimates of benefits to inform treatment decisions; (2) considering the time horizon to benefit of treatments; (3) balancing potential harms and benefits; and (4) using shared decision making by physicians to incorporate the patient's values and preferences into treatment decisions. Here, we illustrate the application of these principles to considering the decision of whether or not to recommend intensive glycemic control to patients to minimize microvascular and cardiovascular complications in type 2 diabetes mellitus. Through this lens, this example will illustrate how an evidence-based medicine approach can be used to individualize glycemic goals and prevent overtreatment, and can serve as a template for applying evidence-based medicine to inform treatment decisions for other conditions to optimize health and individualize patient care.

BACKGROUND

Exposure to advertisements for tobacco products and tobacco warning labels evokes emotions. This study evaluated the association of discrete positive and negative emotions with interest in alternative tobacco products.

METHOD

In 2013, 1,226 U.S. adult nonsmokers and current smokers viewed advertisements for moist snuff, snus, and electronic cigarettes (e-cigarettes) with various warning labels and then indicated their emotional responses in terms of anger, anxiety, sadness, guilt, disgust, discouragement, hope, and contentment. Outcomes were openness to using moist snuff, snus, and e-cigarettes in the future and interest in a free sample of each product. Data were analyzed in 2016.

RESULTS

Hope was positively associated with openness and interest across all alternative tobacco products as was contentment for moist snuff and snus. Anger was negatively associated with openness to moist snuff and e-cigarettes, disgust negatively to moist snuff and snus, and anxiety negatively to e-cigarettes. Being a current smoker, ever trying a corresponding product, being male, and younger age were associated with greater openness to and interest in moist snuff and snus. For e-cigarettes, being a current smoker, ever trying e-cigarettes, and being female were associated with greater openness, and being a current smoker was associated with greater odds of selecting a free sample.

CONCLUSIONS

Positive emotions, particularly hope, were consistently positively associated with interest in alternative tobacco products. Hope is widely used by tobacco and e-cigarette companies to advertise their products. Antitobacco messages should aim to lower hope associated with tobacco products but increase hope for cessation or life without tobacco.

In 2010, the American Heart Association introduced a new conceptual framework to encourage a focus on primary prevention and provided a definition for "ideal cardiovascular health". In this study we examined the relationship between positive childhood experience and ideal cardiovascular health in mid-life, and the extent to which education, depression, and social support mediate this association. Data are from participants in the Midlife and Aging in the United States study who completed a clinic-based assessment of health (N=1255, aged 34-84years, 2004-2005). We created a positive childhood experiences index based on retrospective report of eight childhood experiences, and calculated a continuous ideal cardiovascular health score for each participant following the American Heart Association's definition of ideal, intermediate and poor cardiovascular health across seven health metrics (analyses conducted in 2015-2016). Positive childhood experiences were associated with ideal cardiovascular health: compared to individuals in the lowest quartile, respondents in the second, third, and fourth quartile of positive childhood experiences scored 0.42 (standard error (SE)=0.18), 0.92 (SE=0.18) and 1.04 (SE=0.18) units higher on ideal cardiovascular health, adjusting for age, sex, and race. Respondent's education, depression status, and social support fully mediated the direct effect of positive childhood experiences on ideal cardiovascular health, with the largest indirect effect for education. These results suggest that positive childhood experiences are associated with ideal cardiovascular health in midlife. Strategies to promote cardiovascular wellbeing may benefit from a focus on social interventions early in life; educational attainment, major depression, and social support may represent key points of intervention.

PURPOSE

To image late mechanical activation and identify effective left-ventricular (LV) pacing sites for cardiac resynchronization therapy (CRT). There is variability in defining mechanical activation time, with some studies using the time to peak strain (TPS) and some using the time to the onset of circumferential shortening (TOS). We developed improved methods for imaging mechanical activation and evaluated them in heart failure (HF) patients undergoing CRT.

MATERIALS AND METHODS

We applied active contours to cine displacement encoding with stimulated echoes (DENSE) strain images to detect TOS. Six healthy volunteers underwent magnetic resonance imaging (MRI) at 1.5T, and 50 patients underwent pre-CRT MRI (strain, scar, volumes) and echocardiography, assessment of the electrical activation time (Q-LV) at the LV pacing site, and echocardiography assessment of LV reverse remodeling 6 months after CRT. TPS at the LV pacing site was also measured by DENSE.

RESULTS

The latest TOS was greater in HF patients vs. healthy subjects (112 ± 28 msec vs. 61 ± 7 msec, P < 0.01). The correlation between TOS and Q-LV was strong (r > 0.75; P < 0.001) and better than between TPS and Q-LV (r < 0.62; P ≥ 0.006). Twenty-three of 50 patients had the latest activating segment in a region other than the mid-ventricular lateral wall, the most common site for the CRT LV lead. Using a multivariable model, TOS/QRS was significantly associated with LV reverse remodeling even after adjustment for overall dyssynchrony and scar (P < 0.05), whereas TPS was not (P = 0.49).

CONCLUSION

Late activation by cine DENSE TOS analysis is associated with improved LV reverse remodeling with CRT and deserves further study as a tool to achieve optimal LV lead placement in CRT.

LEVEL OF EVIDENCE

1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:887-896.

Hyperalgesic priming, a sexually dimorphic model of transition to chronic pain, is expressed as prolongation of prostaglandin E2-induced hyperalgesia by the activation of an additional pathway including an autocrine mechanism at the plasma membrane. The autocrine mechanism involves the transport of cyclic adenosine monophosphate (AMP) to the extracellular space, and its conversion to AMP and adenosine, by ecto-5'phosphodiesterase and ecto-5'nucleotidase, respectively. The end product, adenosine, activates A1 receptors, producing delayed onset prolongation of prostaglandin E2 hyperalgesia. We tested the hypothesis that the previously reported, estrogen-dependent, sexual dimorphism observed in the induction of priming is present in the mechanisms involved in its expression, as a regulatory effect on ecto-5'nucleotidase by estrogen receptor α (EsRα), in female rats. In the primed paw AMP hyperalgesia was dependent on conversion to adenosine, being prevented by ecto-5'nucleotidase inhibitor α,β-methyleneadenosine 5'-diphosphate sodium salt and A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. To investigate an interaction between EsRα and ecto-5'nucleotidase, we treated primed female rats with oligodeoxynucleotide antisense or mismatch against EsRα messenger RNA. Whereas in rats treated with antisense AMP-induced hyperalgesia was abolished, the A1 receptor agonist N-cyclopentiladenosine still produced hyperalgesia. Thus, EsRα interacts with this autocrine pathway at the level of ecto-5'nucleotidase. These results demonstrate a sexually dimorphic mechanism for the expression of priming.

PERSPECTIVE

This study presents evidence of an estrogen-dependent mechanism of expression of chronic pain in female rats, supporting the suggestion that differential targets must be considered when establishing protocols for the treatment of painful conditions in men and women.