Extended Central Tendency Measure and difference plot for heart rate variability analysis.

Heart rate variability (HRV) is a non-invasive alternative to analyze the role of the autonomic nervous system (ANS) on heart functioning. Many tools have been developed to analyze collected cardiac data. Among them, the Central Tendency Measure (CTM) is a quantitative method for variability analysis of RR intervals. The values of the CTM must be between 0 and 1 (inclusive) for different radius, which follows the intrinsic characteristics of each time series. Using the conventional CTM, the successive differences of the time series may be calculated, and it can classify and differentiate the disturbances in the ANS involving HRV. This method was extended (e-CTM) to analyze the differences between RR interval time series. In this extension, a new parameter is added, which allows analysis of long time intervals, instead of successive and adjacent RR intervals. The ability of the e-CTM to differentiate the groups of the RR interval time series was verified with 145 RR interval time series divided into three groups: subjects with congestive heart failure, healthy subjects, and nurses during one hour of their workday. Results evidence that the new parameter added differentiates the group with pathology (and subsequent impairment of ANS) and group under stress at work (temporary impairment of ANS). These results suggest that the e-CTM is capable of detection long-term variations in the HRV according to the ANS impairment.

International Multicenter Validation of an Intermediate Risk Subclassification of Prostate Cancer Managed with Radical Treatment without Hormone Therapy.

PURPOSE: The NCCN Guidelines® recently endorsed a subclassification of intermediate risk prostate cancer into favorable and unfavorable subgroups. However, this subclassification was developed in a treatment heterogeneous cohort. Thus, to our knowledge the natural history of androgen deprivation treatment naïve favorable and unfavorable intermediate risk prostate cancer cases remains unknown. MATERIALS AND METHODS: Groups at 3 academic centers pooled data on patients with intermediate risk prostate cancer treated with radical monotherapy (dose escalated external beam radiotherapy, brachytherapy or radical prostatectomy) without combined androgen deprivation treatment. We used the cumulative incidence with competing risk analysis to estimate biochemical recurrence, distant metastasis and prostate cancer specific mortality. RESULTS: A total of 2,550 men at intermediate risk were included in study, of whom 1,063 and 1,487 were at favorable and unfavorable risk, respectively. Of the men 1,149 underwent radical prostatectomy, 1,143 underwent dose escalated external beam radiotherapy and 258 underwent brachytherapy. Median followup after the different treatments ranged from 60.4 to 107.4 months. The 10-year cumulative incidence of distant metastasis in the favorable vs unfavorable risk groups was 0.2% (95% CI 0.2-0.2) vs 11.6% (95% CI 7.7-15.5) for radical prostatectomy (p <0.001), 2.8% (95% CI 0.8-4.8) vs 13.5% (95% CI 9.6-17.4) for dose escalated external beam radiotherapy (p <0.001) and 3.5% (95% CI 0-7.4) vs 10.2% (95% CI 4.3-16.1) for brachytherapy (p = 0.063). The 10-year rate of prostate cancer specific mortality in the favorable vs unfavorable risk groups was 0% (95% CI 0-0) vs 3.7% (95% CI 1.7-5.7) for radical prostatectomy (p = 0.016), 0.5% (95% CI 0.5-0.5) vs 5.6% (95% CI 3.6-7.6) for dose escalated external beam radiotherapy (p = 0.015) and 0% (95% CI 0-0) vs 2.5% (95% CI 0.5-4.5) for brachytherapy (p = 0.028). CONCLUSIONS: This multicenter international effort independently validates the prognostic value of the intermediate risk prostate cancer subclassification in androgen deprivation treatment naïve cases across all radical treatment modalities. It is unlikely that treatment intensification would meaningfully improve oncologic outcomes in men at favorable intermediate risk.