Clinical Epidemiology and Biometric Unit

Pavia, Italy

Clinical Epidemiology and Biometric Unit

Pavia, Italy
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De Gregori M.,University of Pavia | Allegri M.,IRCCS Policlinico San Matteo | De Gregori S.,Unit of Clinical Pharmacokinetics | Garbin G.,University of Pavia | And 4 more authors.
Current Drug Metabolism | Year: 2010

Cytochromes P450 are members of a superfamily of hemoproteins that catalyze a variety of oxidative reactions in the metabolism of endogenous and exogenous hydrophobic substrates. Fifty-eight cytochrome P450 (CYP) isoenzymes belonging to 18 families have been identified in human cells; the corresponding genes are highly polymorphic, and genetic variability underlies interindividual differences in drug response. The polymorphisms of CYP2D6 significantly affect the pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6 substrates. The number of functional CYP2D6 alleles per genome determines the existence of four different phenotypes, i.e. poor, intermediate, extensive, and ultrarapid metabolizers. CYP2D6 genetic variants include copy number variations, single nucleotide substitutions, frameshift and insertion/deletion mutations. This review reports some of the different methodological approaches used to screen for CYP2D6 variants and focuses on methods that have improved variation detection, from conventional techniques to more recent microarray technology and high throughput DNA sequencing. In addition, this review reports some results on clinical relevance of CYP2D6 polymorphisms and provides examples of variability in drug response associated with interindividual phenotypic differences. © 2010 Bentham Science Publishers Ltd.


Sainz-Barriga M.,Ghent University | Scudeller L.,Clinical Epidemiology and Biometric Unit | Costa M.G.,University of Udine | De Hemptinne B.,Ghent University | Troisi R.I.,Ghent University
Liver Transplantation | Year: 2011

The portal vein flow (PVF), portal vein pressure (PVP), and hepatic venous pressure gradient (HVPG) were prospectively assessed to explore their relationships and to better define hyperflow and portal hypertension (PHT) during liver transplantation (LT). Eighty-one LT procedures were analyzed. No correlation between PVF and PVP was observed. Increases in the central venous pressure (CVP) were transmitted to the PVP (58%, range = 25%-91%, P = 0.001). Severe PHT (HVPG â?¥ 15 mm Hg) showed a significant reciprocal association with high PVF (P = 0.023) and lower graft survival (P = 0.04). According to this initial experience, an HVPG value â?¥ 15 mm Hg is a promising tool for the evaluation of hemodynamic stress potentially influencing outcomes. An algorithm for graft inflow modulation based on flows, gradients, and systemic hemodynamics is provided. In conclusion, the evaluation of PHT severity with PVP could be delusive because of the influence of CVP. PVF and PVP do not correlate and should not be used individually to assess hyperflow and PHT during LT. Copyright © 2011 American Association for the Study of Liver Diseases.


Rossi G.C.M.,University of Pavia | Pasinetti G.M.,Instituto Beato Palazzolo | Scudeller L.,Clinical Epidemiology and Biometric Unit | Bianchi P.E.,University of Pavia
Journal of Ocular Pharmacology and Therapeutics | Year: 2013

Purpose: To record signs and symptoms of ocular surface disease (OSD) in patients treated with Intra Ocular Pressure (IOP)-lowering medications; to evaluate the relationship between signs and symptoms; and to identify how to diagnose and follow OSD and its impact on the quality of life in such patients. Methods: A prospective observational study of enrolled consecutive topically treated open-angle glaucoma or ocular hypertension patients: patients presenting systemic or ocular conditions that could interfere with ocular surface status were excluded. Enrolled patients underwent a complete ophthalmic examination comprehensive of evaluation of tear film break-up time (TF-BUT) and fluorescein corneal staining (keratitis punctatae) and who completed the Italian version of both the National Eye Institute-Visual Function Questionnaire (NEI-VFQ) 25 and the Glaucoma Symptom Scale (GSS) questionnaires. Results: 233 patients adhered to a study protocol. Punctatae keratitis was detected in 70 (30%) eyes; abnormal TF-BUT in 67 (28.8%) patients: 97 patients (42.1%) presented an OSD. The abnormal values were gender-independent, keratitis was statistically related to age (P=0.01) and number of instillations/die (P=0.0007). TF-BUT was related to the IOP value (P<0.0001). The NEI ocular pain subscale was statistically related to TF-BUT (P=0.017); GSS was both related to TF-BUT and punctatae keratitis (P<0.00001). Conclusions: Many patients present an OSD related to therapy, and this affects their quality of life. The use of fixed combinations to reduce surface exposition and of benzalkonium chloride-free formulations should be encouraged to reduce and contain the onset or worsening of this secondary condition in glaucoma patients. The GSS has shown a good relation to signs and should be routinely used to evaluate the impact of OSD on the quality of life. © Copyright 2013, Mary Ann Liebert, Inc. 2013.


Rossi G.C.M.,University of Pavia | Pasinetti G.M.,Instituto Beato Palazzolo | Scudeller L.,Clinical Epidemiology and Biometric Unit | Raimondi M.,University of Pavia | And 2 more authors.
European Journal of Ophthalmology | Year: 2013

Purpose. To identify risk factors for developing ocular surface disease (OSD), to verify the prevalence of OSD, and to record efficacy of questionnaires in identifying symptoms' impact on patients' quality of life. Methods. This was an observational, cross-sectional study of patients with topically treated glaucoma. Tear film break-up time (TFBUT) and punctate keratitis were evaluated; 2 quality-of-life questionnaires (National Eye Institute-Visual Function Questionnaire 25 and Glaucoma Symptom Scale) were submitted to all patients. Class of previous and current intraocular pressure (IOP)-lowering drugs, number of drugs, number of drops/day, and total and current benzalkonium chloride (BAK) exposure were collected. results. A total of 233 patients completed the study. TFBUT was abnormal in 71 (30.5%) eyes; punctate keratitis was present in 74 (31.7%). Keratitis was more frequent with increasing number of eye-drops (p=0.008) and number of instillations per day (p=0.009). Ocular surface disease was present in 97 (41.6%) patients and was statistically related to number of medications used (p=0.026). The univariate analysis pointed out that patients with OSD were older (p=0.04), had lower IOP values (p=0.03), were topically treated for more time (p<0.0001), had assumed more BAK (p<0.0001), and presented worst quality of life (p<0.01). The multivariate analysis found that OSD was related to number of medications used (p=0.002), prolonged use of preserved medications (p=0.005), and total BAK exposure (p<0.001). Conclusions. There is clinical evidence that the number of medications, their prolonged use, and the total BAK exposure are risk factors to develop OSD in patients with glaucoma. To prevent OSD onset, BAK exposure and the number of topical medications should be reduced. © 2012 Wichtig Editore.


Sainz-Barriga M.,University of Udine | Reyntjens K.,University of Udine | Costa M.G.,University of Udine | Scudeller L.,Clinical Epidemiology and Biometric Unit | And 4 more authors.
American Journal of Transplantation | Year: 2010

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered. 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.


Ferraioli G.,University of Pavia | Tinelli C.,Clinical Epidemiology and Biometric Unit | Lissandrin R.,University of Pavia | Zicchetti M.,University of Pavia | And 3 more authors.
World Journal of Gastroenterology | Year: 2014

AIM: To assess the performance of controlled attenuation parameter (CAP) in patients with chronic viral hepatitis. METHODS: CAP is a new technique that measures the attenuation in the liver of an ultrasound beam, which is directly related to lipid accumulation. Consecutive patients undergoing liver biopsy for chronic viral hepatitis were studied using the M probe of FibroScan device (Echosens, Paris, France). The device estimates liver steatosis steatosis in decibel per meter (dB/m). An expert operator performed all measurements. Steatosis was graded according to Kleiner's classification. Pearson or Spearman rank coefficient was used to test correlation between two study variables. Linear regression was used for multivariate model to assess the association between CAP and other variables. Receiver operating characteristic curve analysis was performed to calculate area under the curve (AUROC) for S0 vs S1-S3 and S0-S1 vs S2-S3. RESULTS: 115 subjects (85 males and 30 females) were prospectively studied. The mean values of CAP were 227.1 ± 43.1 for S0; 254.6 ± 38.9 for S1; 297.8 ± 49.4 dB/m for S2-S3. In univariate analysis CAP showed a significant correlation with age, body mass index (BMI), degree of steatosis, and cholesterol. Multivariate regression analysis confirmed the correlation with the degree of steatosis [coefficient, 1.2 (0.60-1.83); P < 10-5] and BMI [coefficient, 4.1 (0.5-7.8); P = 0.03] but not with all other variables. Optimal cutoff values for S ≥ 1 and S ≥ 2 were 219 dB/m [AUROC, 0.76 (0.67-0.84); sensitivity, 91.1% (78.8-97.5); specificity, 51.6% (38.7-64.2); positive predictive value, 56.9% (44.7-68.6); negative predictive value, 89.2% (74.3-97.0); positive likelihood ratio, 1.88 (1.4-2.5); negative likelihood ratio, 0.17 (0.07-0.5)] and 296 dB/m [AUROC, 0.82 (0.74-0.89); sensitivity, 60.0% (32.3-83.7); specificity, 91.5% (83.9-96.3); positive predictive value, 52.9% (27.8-77.0); negative predictive value, 93.5% (86.3-97.6); positive likelihood ratio, 7.05 (3.2-15.4); negative likelihood ratio, 0.44 (0.2-0.8)], respectively. CONCLUSION: Controlled attenuation parameter could be a useful tool in the clinical management of patients with chronic viral hepatitis for detecting liver steatosis. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Ferraioli G.,University of Pavia | Tinelli C.,Clinical Epidemiology and Biometric Unit | Dal Bello B.,Fondazione IRCCS Policlinico San Matteo | Zicchetti M.,University of Pavia | And 2 more authors.
Hepatology | Year: 2012

Real-time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single-center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty-one patients met inclusion criteria. On the same day, real-time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix-en-Provence, France), TE using FibroScan (Echosens, Paris, France), and US-assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0-F1 versus F2-F4, F0- F2 versus F3-F4, and F0-F3 versus F4 for both real-time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85-0.96) for SWE and 0.84 (95% CI: 0.76-0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94-1.00) for SWE and 0.96 (95% CI: 0.90-0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93-1.00) for SWE and 0.96 (95% CI: 0.91-0.99) for TE (P = 0.48), when comparing F0-F1 versus F2- F4, F0- F2 versus F3-F4, and F0 -F3 versus F4, respectively. Conclusion: The results of this study show that real-time SWE is more accurate than TE in assessing significant fibrosis (≥F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B-mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information. © 2012 American Association for the Study of Liver Diseases.


Pagella F.,University of Pavia | Pusateri A.,University of Pavia | Giourgos G.,University of Pavia | Tinelli C.,Clinical Epidemiology and Biometric Unit | Matti E.,University of Pavia
American Journal of Rhinology and Allergy | Year: 2014

Background: In the literature, the global endoscopic sinus surgery (ESS) success in the treatment of sinonasal inverted papilloma (IP) is 95%. This study was designed to describe a conservative endoscopic approach, based on research of the tumor's pedicle and treatment concentrated on its site of attachment, and to compare the results of this technique with the outcome of standard endoscopic treatment. Methods: Retrospective analysis of the patients treated in our institution for paranasal inverted papilloma (IP), between 2002 and 2011 with a minimum of 18 months follow-up was performed. Group A received a standard ESS including whole sinus demucosization (maxillary, ethmoid, frontal, or sphenoid sinus) and bony wall drilling. Group B patients instead underwent pedicle-oriented endoscopic surgery (POES); in this group, bony demucosization and drilling were selectively conducted around the site of pedicle attachment of the tumor. Results: The cohort included 73 patients (median age, 60.5 years; median follow-up, 58 months). Group A/group B consisted of 37/36 patients. IP persistence - recurrence for group A/group B was 0/1 cases. Oncological success for global endoscopic/group A/group B was 98.6% (72/73)/100% (37/37)/97.2% (35/36). We noticed a significant difference in surgical operative time and postoperative complication rate among the groups, in favor of POES technique. Conclusion: Our data confirm the efficacy of the endonasal endoscopic treatment for sinonasal IP. Moreover, the even more conservative endoscopic treatment proposed (POES) seems to offer good control of the disease, shorter operating times, avoidance of unnecessary surgery with respect to uninvolved structures, and permits a follow-up aimed at the site of the pedicle attachment. Copyright © 2014, OceanSide Publications, Inc.


Ferraioli G.,University of Pavia | Tinelli C.,Clinical Epidemiology and Biometric Unit | Lissandrin R.,University of Pavia | Zicchetti M.,University of Pavia | And 3 more authors.
European Radiology | Year: 2014

Objectives: To evaluate reproducibility of measurements of spleen stiffness (SS) and liver stiffness (LS) at several sites by using point shear wave elastography (pSWE) and to investigate any training effect. Methods: Healthy volunteers were consecutively enrolled. Measurements of SS and LS were performed by an expert (observer 1) and a novice (observer 2) at three different sites of liver and spleen. To assess the effect of training the study was conducted in two periods (period 1 and period 2). Concordance correlation coefficient was used to assess intra-observer and inter-observer reproducibility. Results: A total of 92 subjects (67 men and 25 women) were enrolled in the study. Both intra-observer and inter-observer agreement were higher for the liver than for the spleen. Overall, the highest intra-observer and inter-observer agreement were obtained for the assessment of LS through intercostal space, and for measurements at this site there was a significantly better performance of observer 2 after the training period. For both observers, training improved the repeatability of SS measurements at all sites. A good intra-observer agreement was obtained only for measurements at the spleen lower pole. Conclusions: The results of this study show that a learning curve in pSWE acquisition should be taken into account both for SS and LS measurements. Key Points: • Reproducibility of SS measurements depends on the expertise of the operator. • To achieve good reproducibility between measurements a training period is required. • A learning curve in pSWE acquisition should be taken into account. • SS measurements are less reproducible than LS measurements. © European Society of Radiology 2014.


Ferraioli G.,University of Pavia | Tinelli C.,Clinical Epidemiology and Biometric Unit | Lissandrin R.,University of Pavia | Zicchetti M.,University of Pavia | And 3 more authors.
World Journal of Gastroenterology | Year: 2014

AIM: To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness. METHODS: This was a single-center, cross-sectional study. Consecutive patients with chronic viral hepatitis scheduled for liver biopsy (LB) (Group 1) and healthy volunteers (Group 2) were studied. In each subject 10 consecutive point shear-wave elastography (PSWE) measurements were performed using the iU22 ultrasound system (Philips Medical Systems, Bothell, WA, United States). Patients in Group 1 underwent PSWE, transient elastography (TE) using FibroScan (Echosens, Paris, France) and ultrasound-assisted LB. For the assessment of PSWE reproducibility two expert raters (rater 1 and rater 2) independently performed the examinations. The performance of PSWE was compared to that of TE using LB as a reference standard. Fibrosis was staged according to the METAVIR scoring system. Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve (AUC) for F ≥ 2, F ≥ 3 and F = 4. The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin's concordance correlation coefficient. RESULTS: To assess the performance of PSWE, 134 consecutive patients in Group 1 were studied. The median values of PSWE and TE (in kilopascals) were 4.7 (IQR = 3.8-5.4) and 5.5 (IQR = 4.7-6.5), respectively, in patients at the F0-F1 stage and 3.5 (IQR = 3.2-4.0) and 4.4 (IQR = 3.5-4.9), respectively, in the healthy volunteers in Group 2 (P < 10-5). In the univariate analysis, the PSWE and TE values showed a high correlation with the fibrosis stage; low correlations with the degree of necroinflammation, aspartate aminotransferase and gamma-glutamyl transferase (GGT); and a moderate negative correlation with the platelet count. A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables. The following AUC values were found: 0.80 (0.71-0.87) for PSWE and 0.82 (0.73-0.89) for TE (P = 0.42); 0.88 (0.80-0.94) for PSWE and 0.95 (0.88-0.98) for TE (P = 0.06); and 0.95 (0.89-0.99) for PSWE and 0.92 (0.85-0.97) for TE (P = 0.30) for F ≥ 2, F ≥ 3 and F = 4, respectively. To assess PSWE reproducibility, 116 subjects were studied, including 47 consecutive patients scheduled for LB (Group 1) and 69 consecutive healthy volunteers (Group 2). The intraobserver agreement ranged from 0.83 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 1 and from 0.84 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 2. The interobserver agreement yielded values from 0.83 (95%CI: 0.78-0.88) to 0.93 (95%CI: 0.91-0.95). CONCLUSION: PSWE is a reproducible method for assessing liver stiffness, and it compares with TE. Compared with patients with nonsignificant fibrosis, healthy volunteers showed significantly lower values. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

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