Predictors of Early or Delayed Diastolic Dysfunction After Anthracycline-Based or Nonanthracycline Chemotherapy: A Pharmacological Appraisal

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Cigarette smoking affects the differences between male and female phenotypes

Sex-gender medicine focuses on differences and similarities in health and disease between men and women. The present study focused on the existence of male and female phenotypes when routine demographic, biochemical and haematological data are considered and aimed to determine the influence of smoking on phenotypes and evaluate the role of body weight on sex-gender differences in view of the fact that some of them can be utilized as biomarkers of diagnosis, diseases and therapeutic response

Allergenius, an expert system for the interpretation of allergen microarray results

BACKGROUND: An in vitro procedure based on a microarray containing many different allergen components has recently been introduced for use in allergy diagnosis. Recombinant and highly purified allergens belonging to different allergenic sources (inhalants, food, latex and hymenoptera) are present in the array. These components can either be genuine or cross-reactive, resistant or susceptible to heat and low pH, and innocuous or potentially dangerous. A large number of complex and heterogeneous relationships among these components has emerged, such that sometimes these interactions cannot be effectively managed by the allergist. In the 1960s, specialized languages and environments were developed to support the replacement of human experts with dedicated decision-making information systems. Currently, expert systems (ES) are advanced informatics tools that are widely used in medicine, engineering, finance and trading. METHODS: We developed an ES, named Allergenius ®, to support the interpretation of allergy tests based on microarray technology (ImmunoCAP ISAC ®). The ES was implemented using Flex, a LPA Win-Prolog shell. Rules representing the knowledge base (KB) were derived from the literature and specialized databases. The input data included the patient’s ID and disease(s), the results of either a skin prick test or specific IgE assays and ISAC results. The output was a medical report. RESULTS: The ES was first validated using artificial and real life cases and passed all in silico validations. Then, the opinions of allergists with experience in molecular diagnostics were compared with the ES reports. The Allergenius reports included all of the allergists’ opinions and considerations, as well as any additional information. CONCLUSIONS: Allergenius is a trustable ES dedicated to molecular tests for allergy. In the present version, it provides a powerful method to understand ISAC results and to obtain a comprehensive interpretation of the patient’s IgE profiling

Cox regression and survival analysis from the tauro-urso-deoxycholic trial in amyotrophic lateral sclerosis

Recent phase II pilot clinical trials suggested that tauro-urso-deoxycholic acid (TUDCA) might slow functional decline and increase survival in patients with amyotrophic lateral sclerosis (ALS). We performed a multivariate analysis of the original TUDCA cohort to better define the treatment effect and allow comparability with other trials. Linear regression slope analysis showed statistical differences in the decline rate, favoring the active treatment arm (p-value < 0.01; −0.262 for the TUDCA group and −0.388 for the placebo group). Mean survival time, estimated by the Kaplan–Meier analysis, showed a 1-month difference, favoring active treatment (log-rank test p-value = 0.092). Cox regression analysis demonstrated that placebo treatment was associated with a higher risk of death (p-value = 0.055). These data further support the disease-modifying effect of TUDCA monotherapy and raise the question of what could be the additional effect of combining TUDCA with sodium phenylbutyrate

Cardioprotective role of zofenopril in patients with acute myocardial infarction: a pooled individual data analysis of four randomised, double-blind, controlled, prospective studies

Early administration of zofenopril following acute myocardial infarction (AMI) proved to be prognostically beneficial in the four individual randomised, double-blind, parallel-group, prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. In the present analysis, we evaluated the cumulative efficacy of zofenopril by pooling individual data from the four SMILE studies

Cardioprotective role of zofenopril in hypertensive patients with acute myocardial infarction: a pooled individual data analysis of the SMILE studies

Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angiotensin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients. Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisinopril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks. Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p = .003 and .60, .36–.99; p = .049, respectively) and normotensive patients (0.56, 0.42–0.75; p = .0001 and .51, .28–.90; p = .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p = .918; normotensives: 0.91, 0.59–1.41; p = .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p = .045), but not in normotensive patients (0.77; 0.55–1.10; p = .150). Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril

Efficacy of zofenopril in combination with thiazide diuretics in patients with acute myocardial infarction: A pooled individual data analysis of four randomized, double-blind, controlled, prospective studies

Background: In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs). Methods: This was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD. Results: Among 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD-). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD-(16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74\u20131.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55\u20130.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46\u20130.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP). Conclusion: In post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients