A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p

Sindrome di Alienazione Genitoriale: Contributo Casistico

One of the more harmful possible outcomes resulting from conflict between parents is the phenomenon of parental alienation syndrome (PAS). This disorder often goes undetected, and is not well recognized in Italy although it is the subject of many studies in the United States.Due to the ever-increasing attention given to PAS in cases regarding separation and divorce, where conflict involving child custody is often involved, the authors set about studying this topic by analyzing the files and records pertaining to 18 cases of PAS from four family counseling centers in Apulia, Italy.Using an intentionally elaborate questionnaire, we set out to investigate the particular features of PAS. In particular, this questionnaire allowed us to obtain information on the nuclear family as well as on the dynamics of separation and divorce. These elements are useful in determining parental fitness and can serve to offer insight into the behaviors of both the alienating and alienated parent. Furthermore, such information may offer insight into the effects of PAS on the children based on its three types (mild, moderate, and severe).The article concludes with some annotations, reflections, and proposals regarding the possible deleterious effects that parental conflicts may produc

HEART FAILURE IN INFECTIVE ENDOCARDITIS: A REPORT FROM THE MULTICENTER, PROSPECTIVE, OBSERVATIONAL STUDY ON ENDOCARDITIS IN ITALY (SEI)

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