Multicentric survey on dose reduction/interruption of cancer drug therapy in 12.472 patients: Indicators of suspected adverse reactions

Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012.Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events.Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012. Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events

Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Ecografia in gravidanza: studio della co-genitorialità

RIASSUNTO: Obiettivo: Il presente lavoro è uno studio esplorativo sui comportamenti delle coppie in attesa del primo figlio mentre osservano l’ecografia 4D dell’ultimo trimestre di gravidanza. In particolare si vuole verificare se le madri ed i padri riconoscono il bambino attraverso l’ecografia, se mostrano comportamenti genitoriali intuitivi diretti al bambino e se attribuiscono a se stessi ed al partner un’identità genitoriale. Metodo: Sono state osservate 18 coppie non referred in attesa del primo figlio mediante una procedura osservativa mutuata dalla versione prenatale del Lausanne Trilogue Play che utilizza come stimolo il video dell’ecografia 4D. È stata effettuata un’analisi del contenuto dei dialoghi dei genitori ed un’analisi microanalitica della durata di sorrisi e dialoghi diretti al bambino nell’ecografia ed al partner. Risultati: Questa procedura permette di osservare alcuni aspetti dell’identità genitoriale e co-genitoriale per le coppie in gravidanza, come nominare se stessi ed il partner “mamma” e “papà”. Inoltre si osserva l’attribuzione di un’identità al bambino nell’ecografia e comportamenti diretti al bambino come sorrisi ed imitazione. Conclusioni: Si conferma il ruolo dell’ecografia nella transizione alla genitorialità e nella formazione della relazione co-genitoriale. Si evidenziano le implicazioni cliniche di un assessment precoce utile per interventi di prevenzione e di sostegno alla genitorialità

Eco-LTP: ecografia ostetrica e alleanze cogenitoriali

Il Capitolo descrive l'esperienza di ricerca intervento con coppie di neo-genitori durante la gravidanza. E' stata ideata una procedura di osservazione prenatale durante la quale i genitori interagiscono con il figlio immaginario "osservandolo" nel video dell'ecografia a 3 dimensioni. altri strumenti hanno consentito di valutare l'alleanza cogenitoriale in via di costruzione durante la gravidanza e successivamente le neo-famiglie hanno partecipato al LTP per evidenziare la coordinazione familiare dopo la nascita