Imberti R.,Direzione Scientifica |
Pietrobono L.,Servizio di Radiodiagnostica |
Klersy C.,Servizio di Biomedica e Statistica
Minerva Anestesiologica | Year: 2012
Surgery of spontaneous supratentorial intracerebral hemorrhage (ICH), especially if performed early, can be complicated by rebleeding, a condition that can worsen the outcome. We evaluated the effect of recombinant activated factor VII (rFVIIa) on postoperative rebleeding. Methods. In this randomized, open-label, single-blinded study, 21 patients with spontaneous supratentorial ICH diagnosed by computed tomography (CT) scan were treated with intravenous rFVIIa (100 mcg/Kg b.w., N=13) or placebo (N=8). Hematoma volume was assessed using CT scan immediately, 18-30 hours, and 5-7 days after hematoma evacuation. The primary endpoint was a hematoma volume at 18-30 hours after surgery. All CT scans were evaluated at one center by the same investigator who was unaware of the treatment. Hematoma volume was measured using dedicated software. Results. At baseline, the hematoma volume was 59.2±27.4 and 71.5±32.1 mL in the rFVIIa and placebo group, respectively. Hematoma evacuation resulted in significantly smaller ICH volumes that were similar in the rFVIIa and placebo group at 18-30 hours after surgery (15.9±14.2 mL and 18±15.1 mL, respectively; mean difference 2.1 mL, 95% confidence interval -12.1 to 16.2, P=0.76 (0.03 mL after adjustment for baseline value)). The frequencies of deep venous thrombosis, myocardial infarction, troponin I elevation and cerebral ischemia were similar in both groups. Conclusion. In this pilot study, intraoperative, intravenous rFVIIa administration did not modify hematoma volume after early ICH surgery. However, the 95% CI was wide, which indicates considerable uncertainty. Therefore, our results do not disprove the potential benefit of rFVIIa administration, which could be shown in a larger study. Copyright© 2012 Edizioni Minerva Medica.
Imberti R.,Direzione Scientifica |
Cusato M.,Laboratory of Clinical Pharmacokinetics |
Villani P.,Laboratory of Clinical Pharmacokinetics |
Carnevale L.,Fondazione IRCCS |
And 4 more authors.
Chest | Year: 2010
Background: Infections caused by multidrug-resistant gram-negative bacteria have caused a resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients, and no attempts have been made to evaluate its concentration in BAL. Methods: In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulfonate (CMS) IV, 2 million International Units (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 h. Colistin was measured by a selective, sensitive high-performance liquid chromatography-based method. Pharmacokinetic parameters were determined by noncompartmental analysis. Results: Patients received 2.19 ± 0.38 mg/kg (range, 1.58-3.16) of CMS per dose. At steady state, mean ± SD plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21 ± 1.08 and 1.03 ± 0.69 μg/mL, respectively. Mean ± SD area under the plasma concentration-time curve from 0 to 8 h (AUC 0-8), apparent elimination half-life, and apparent volume of distribution were 11.5 ± 6.2 μg×h/mL, 5.9 ± 2.6 h, and 1.5 ± 1.1 L/kg, respectively. Cmax/minimum inhibitory concentration (MIC) ratio and AUC 0-24/MIC ratio (MIC = 2 μg/mL) were 1.1 ± 0.5 and 17.3 ± 9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed. Conclusions: Although the pharmacodynamic parameters that better predict the efficacy of colistin are not known in humans, in critically ill adult patients the IV administration of CMS 2 million International Units (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin, which is undetectable in BAL. A better understanding of the pharmacokinetic- pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen. © 2010 American College of Chest Physicians.
Imberti R.,Direzione Scientifica |
Cusato M.,Unit of Clinical Pharmacokinetics in Transplantation and Autoimmune Diseases |
Accetta G.,Fondazione IRCCS Policlinico San Matteo |
Marino V.,Anesthesia and Neuro Intensive Care Unit |
And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2012
Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2λ) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of >5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Ciammella P.,Radiotherapy Unit |
Fiorentino A.,Centro Of Riferimento Oncologico Regionale |
Franco P.,TomoTherapy |
Cavuto S.,Direzione Scientifica |
And 3 more authors.
Cancer Investigation | Year: 2013
Few data exist about the prevalence of burnout syndrome among young radiation oncologists. A national survey to assess its prevalence among junior members (under 40 yrs of age) of the Italian Society of Radiation Oncology was conducted. One hundred and twelve young radiation oncologists completed the questionnaire: the prevalence of burnout syndrome was 35%, and it was related to the presence of different personal, organizational, and work-related aspects, with an impact also on the private life (p < .005). Burnout syndrome is relatively common among young Italian radiation oncologists, and specific educational tools to help improve the management of workload and stress are needed. © 2013 Informa Healthcare USA, Inc.
Onder G.,University Cattolica Sacro Cuore |
Liperoti R.,University Cattolica Sacro Cuore |
Foebel A.,University Cattolica Sacro Cuore |
Fialova D.,Charles University |
And 7 more authors.
Journal of the American Medical Directors Association | Year: 2013
Introduction: Older adults with advanced cognitive impairment have a limited life expectancy and the use of multiple drugs is of questionable benefit in this population. The aim of the present study was to assess if, in a sample of nursing home (NH) residents with advanced cognitive impairment, the effect of polypharmacy on mortality differs depending on estimated life expectancy. Methods: Data were from the Services and Health for Elderly in Long TERm care (SHELTER) project, a study collecting information on residents admitted to 57 NHs in 8 European countries. Polypharmacy was defined as the concomitant use of 10 or more drugs. Limited life expectancy was estimated based on an Advanced Dementia Prognostic Tool (ADEPT) score of 13.5 or more. A Cognitive Performance Scale score of 5 or more was used to define advanced cognitive impairment. Participants were followed for 1 year. Results: Mean age of 822 residents with advanced cognitive impairment entering the study was 84.6 (SD 8.0) years, and 630 (86.6%) were women. Overall, 123 participants (15.0%) had an ADEPT score of 13.5 or more (indicating limited life expectancy) and 114 (13.9%) were on polypharmacy. Relative to residents with ADEPT score less than 13.5, those with ADEPT score of 13.5 or higher had a lower use of benzodiazepines, antidementia drugs, and statins but a higher use of beta-blockers, digoxin, and antibiotics. Polypharmacy was associated with increased mortality among residents with ADEPT score of 13.5 or more (adjusted hazard ratio [HR] 2.19, 95% confidence interval [CI]: 1.15-4.17), but not among those with ADEPT score less than 13.5 (adjusted HR 1.10, 95% CI: 0.71-1.71). Discussion: Polypharmacy is associated with increased mortality in NH residents with advanced cognitive impairment at the end of life. Conclusion: These findings underline the need to assess life expectancy in older adults to improve the prescribing process and to simplify drug regimens. © 2013 American Medical Directors Association, Inc.
Bedogni G.,University of Trieste |
Bedogni G.,University of Milan |
Gastaldelli A.,CNR Institute of Clinical Physiology |
Manco M.,Direzione Scientifica |
And 4 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2012
Background and aims: Early onset type 2 diabetes mellitus (T2DM) is associated with obesity, insulin resistance and impaired beta-cell function. Non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for T2DM. We investigated the relationship between NAFLD and glucose metabolism in a large sample of obese children. Methods and Results: A total of 571 obese children (57% males and 43% females) aged 8-18 years were consecutively studied at a tertiary care centre specialised in paediatric obesity. Liver ultrasonography was used to diagnose NAFLD after exclusion of hepatitis B and C and alcohol consumption. Oral-glucose tolerance testing (OGTT) was performed; insulin sensitivity was evaluated by using the insulin sensitivity index (ISI) and beta-cell function by using the ratio between the incremental areas under the curve (AUC) of insulin and glucose (incAUCins/incAUCglu). A total of 41% of the obese children had NAFLD. Impaired glucose tolerance or T2DM was present in 25% of the children with NAFLD versus 8% of those without it (p< 0.001). Children with NAFLD had higher body mass index (BMI), fasting glucose, 120-min OGTT glucose, incAUCins/incAUCglu and lower ISI as compared with children without NAFLD (p≤ 0.002). At bootstrapped multivariable median regression analysis controlling for gender, age, pubertal status and BMI, NAFLD was an independent predictor of 120-min OGTT glucose and ISI, but not of incAUCins/incAUCglu. Similar findings were obtained using continuous liver steatosis as the predictor, instead of dichotomous NAFLD. Conclusion: NAFLD was present in 41% of our obese children and was associated with higher insulin resistance, but not with impaired beta-cell function. © 2010 Elsevier B.V.
Candela S.,Servizio di Epidemiologia |
Pergolizzi S.,Servizio di Epidemiologia |
Ragni P.,Servizio di Epidemiologia |
Cavuto S.,Direzione Scientifica |
And 5 more authors.
Vaccine | Year: 2013
Introduction: An observational, non-comparative, prospective, surveillance study of individuals vaccinated with the MF59-adjuvanted A/H1N1 influenza vaccine, Focetria®, (Novartis Vaccines & Diagnostics, Siena, Italy), was performed in Italy during the 2009 A/H1N1 influenza pandemic. Method: This study assessed the short-term (six-week) safety profile of the investigational vaccine in real time. After vaccination (N=. 7943), adverse events (AE) were assessed using both active (telephone) and passive (healthcare database) follow-up in enrolled vaccinated subjects, including infants (6-23 months), pregnant women, and the immunosuppressed. The treating physicians of all subjects experiencing AEs post-vaccination were consulted for clinical information on the conditions reported. All AEs were coded according to ICD-10. Results: A total of 1583 AEs occurred during the study, 67 (4.2%) of which were serious adverse events (SAEs). One SAE was considered to be possibly related to vaccination (transitory and ill-defined neurologic disorder experienced by a 16-year-old asthmatic male). Three adverse events of special interest (AESI) were identified (convulsions experienced by two epileptic subjects), none of which were considered to be vaccine-related. Six individuals died during the study period, in each case the cause of death was not related to vaccination (four cases of severe underlying co-morbidity, one case of psychoactive drug misuse, and one case of acute myocardial infarction). Conclusions: No cases of clinically relevant AEs, SAEs, or AESI were observed within a six-week period of vaccine administration. In accordance with existing clinical and post-marketing safety data, the results of this active surveillance study demonstrate a good safety profile for the MF59-adjuvanted A/H1N1 vaccine, Focetria, within the general population. © 2012 Elsevier Ltd.
Deandrea S.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri |
Deandrea S.,University of Milan |
Corli O.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri |
Consonni D.,Unit of Epidemiology |
And 3 more authors.
Journal of Pain and Symptom Management | Year: 2014
Context. Despite the large body of literature on breakthrough cancer pain (BTcP), an accurate estimate of BTcP prevalence is still not available. Objectives. To provide an estimate of BTcP prevalence and investigate the association between different prevalence rates and possible determinants. Methods. We conducted MEDLINE and EMBASE searches for studies published from 1990 to 2012 reporting data on BTcP prevalence in adult cancer populations. Pooled prevalence rates from observational studies with an acceptable methodological quality were computed. The association between BTcP prevalence and possible predictors was investigated using subgroup analyses and meta-regression. Results. Twenty-seven observational studies were identified. When quality criteria were applied, only 19 studies were included in the pooled analysis. The overall pooled prevalence was 59.2%, with high heterogeneity. The lowest prevalence rates were detected in studies conducted in outpatient clinics (39.9%), and the highest prevalence was reported in studies conducted in hospice (80.5%). The association between BTcP prevalence and other determinants such as publication year, age, gender, metastatic disease prevalence, or baseline pain intensity did not reach statistical significance. Conclusion. In the context of a large between-studies heterogeneity, more than one in two patients with cancer pain also experiences BTcP, with some variability according to clinical and organizational variables. © 2014 U.S. Cancer Pain Relief Committee.
Caso V.,University of Perugia |
Santalucia P.,Direzione Scientifica |
Acciarresi M.,University of Perugia |
Pezzella F.R.,Uo Medicina Durgenza Stroke Unit |
Paciaroni M.,University of Perugia
European Journal of Internal Medicine | Year: 2012
Stroke is a leading cause of death worldwide and the first cause of disability in the Western world. Over the last 20 years, antiplatelet agents have reduced overall stroke rates in primary and secondary prevention in men. However, this has not been the case for women. In this narrative review, the most widely used antiplatelet therapies for primary and secondary prevention in stroke, excluding cardioembolic stroke, will be outlined. First, the largest randomised controlled trials will be analysed as well as the enrolment percentages of women. Second, analyses on sex-interaction effects in each study will be examined. Moreover, the Authors will discuss the need to develop targeted antiplatelet therapies specifically for women. Based on current results, the most randomised clinical trials and meta-analyses on antiplatelet agents in cerebrovascular disease have not performed sub-analyses on sex-related differences and this is mainly because women were underrepresented. Despite this, antiplatelet agents are considered to be equally effective for both sexes in primary and secondary stroke prevention. Finally, aspirin is the most widely studied antiplatelet in women and has been shown to provide greater benefit for women as primary prevention of ischemic stroke without a significant increased risk in haemorrhage. © 2012 European Federation of Internal Medicine.
Apolone G.,Direzione Scientifica
European journal of pain (London, England) | Year: 2012
Transdermal delivery systems containing fentanyl or buprenorphine, despite the relatively lack of comparative studies, have reached an impressive share of the market in several countries. In the context of a wider observational study, we applied the propensity score to test the comparative effectiveness of the two routes of administration (oral vs. transdermal). We applied the propensity score in a subgroup of patients (starting the World Health Organization third step therapy during the scheduled follow-up of 28 days) using pre-planned primary (pain intensity change) and secondary endpoints, such as increase in doses, need for switching and safety profile. Univariate and multivariate analyses were carried out. Three-hundred sixty-six eligible cases were analysed. We found a difference among the two groups in terms of variables potentially associated with therapy choice and outcomes. After adjusting for propensity score, results were in favour of transdermal delivery systems for the primary endpoint (odds ratio 1.68; p = 0.04). A similar trend was also present for the other secondary endpoints. Only in the case of nausea and vomiting, patients receiving transdermal delivery systems reported a higher frequency of events. The application of the propensity score has helped understand better the actual effectiveness of transdermal delivery systems that are at least equivalent to the oral opioids, and even more effective for pain intensity reduction. © 2011 European Federation of International Association for the Study of Pain Chapters.