Background-Sympathetic and parasympathetic systems are considered the principal rapidly reacting systems that control heart rate. Methods and Results-We propose a symbolic analysis series to quantify the prevalence of sympathetic or parasympathetic cardiac modulation. This analysis decomposes the heart rate variability series in patterns lasting 3 beats and classifies them into 3 categories: nonvariable, variable, and very variable patterns referred to as 0V, 1V, and 2V patterns. First, we applied this method to experimental and pharmacological conditions characterized by sympathetic activation (tilt test, handgrip, nitroprusside, and high-dose atropine administration) or parasympathetic activation (phenylephrine and low-dose atropine administration) in 60 healthy subjects. An increase in sympathetic modulation and a vagal withdrawal elicited a significant increase in 0V patterns and a decrease in 2V patterns, whereas parasympathetic dominance induced the opposite, reflecting a reciprocal sympathovagal balance. The second part of the study considered a series of 300 beats before the onset of major arrhythmic events in patients with an implantable cardioverterdefibrillator. Symbolic analysis detected an increase in the percentage of 0V patterns before the onset of major arrhythmias compared with baseline (41.6Ϯ3.9% and 24.4Ϯ2.9%, respectively; PϽ0.01), indicating a sympathetic prevalence. On the other hand, the 2V patterns did not decrease before major arrhythmias, suggesting the presence of nonreciprocal autonomic modulations. Conclusions-Symbolic analysis of 3 beat sequences takes into account the different time course of sympathetic and parasympathetic cardiac modulations and seems appropriate for elucidating the neural pathophysiological mechanisms occurring during the short periods that precede acute cardiac events.

Summary. Background: Pretest probability assessment is necessary to identify patients in whom pulmonary embolism (PE) can be safely ruled out by a negative D-dimer without further investigations. Objective: Review and compare the performance of available clinical prediction rules (CPRs) for PE probability assessment. Patients/methods: We identified studies that evaluated a CPR in patients with suspected PE from Embase, Medline and the Cochrane database. We determined the 95% confidence intervals (CIs) of prevalence of PE in the various clinical probability categories of each CPR. Statistical heterogeneity was tested. Results: We identified 9 CPR and included 29 studies representing 31215 patients. Pooled prevalence of PE for three-level scores (low, intermediate or high clinical probability) was: low, 6% (95% CI, 4-8), intermediate, 23% (95% CI, 18-28) and high, 49% (95% CI, 43-56) for the Wells score; low, 13% (95% CI, 8-19), intermediate, 35% (95% CI, 31-38) and high, 71% (95% CI, 50-89) for the Geneva score; low, 9% (95% CI, 8-11), intermediate, 26% (95% CI, 24-28) and high, 76% (95% CI, 69-82) for the revised Geneva score. Pooled prevalence for two-level scores (PE likely or PE unlikely) was 8% (95% CI,6-11) and 34% (95% CI,29-40) for the Wells score, and 6% (95% CI, 3-9) and 23% (95% CI, 11-36) for the Charlotte rule. Conclusion: Available CPR for assessing clinical probability of PE show similar accuracy. Existing scores are, however, not equivalent and the choice among various prediction rules and classification schemes (three-versus two-level) must be guided by local prevalence of PE, type of patients considered (outpatients or inpatients) and type of D-dimer assay applied.

The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the more recently proposed vitamin D serum concentration are two novel predictors of the response to antiviral treatment in chronic hepatitis C virus (HCV) infection. This study aimed to verify whether the IL-28B rs12979860 C/T polymorphism and pretreatment serum vitamin D levels have independent or complementary roles in predicting the rates of sustained viral response (SVR). The present study included 211 consecutive, treatment-naïve chronic HCV patients who had their pretreatment serum 25-OH vitamin D level and IL-28B rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%) patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA, cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV genotypes were analyzed separately, the SVR was predicted by the IL-28B rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area under the ROC curve of 0.836. Moreover, by categorizing these latter patients into four groups-C/C homozygotes with vitamin D levels >20 ng/mL (group A) or 20 ng/mL (group B) and C/T heterozygotes or T/T homozygotes with vitamin D levels >20 ng/mL (group C) or 20 ng/mL (group D)-a significant linear trend was observed, with SVR rates in the following descending order: group A, 18/21 (85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40 (22.5%) (P < 0.0001). Conclusion: Vitamin D serum levels are complementary to the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of the SVR in treatment-naïve chronic hepatitis C. (HEPATOLOGY 2011;53:1118-1126