Liver-related and extrahepatic events in patients with non-alcoholic fatty liver disease: a retrospective competing risks analysis.

Background & Aim: Non-alcoholic fatty liver disease (NAFLD), and especially fibrotic non-alcoholic steatohepatitis, is associated with high risks of liver-related events (LRE) and extrahepatic events (EHE). We evaluated the competitive risk occurrence of LRE and EHE in a large cohort of biopsy-proven NAFLD stratified according to baseline severity of fibrosis. Methods: Two thousand one hundred thirty-five patients with biopsy-proven NAFLD were enrolled. Observed cumulative incidence functions (CIFs) were used to evaluate the risk of LRE and EHE; cause-specific Cox model and predicted CIFs were fitted to identify predictors of LRE and EHE. A replication cohort of NAFLD patients with live…

From South to North? Mobility of Southern Italian Students at the Transition from the First to the Second Level University Degree

In the last decades, the Italian University System has encountered several structural reforms aimed at making it more internationally competitive. Among them, the introduction of the University financial autonomy has triggered an “internal” competition among Universities to attract students from the entire country. Students’ enrollment at the first level has decreased significantly especially after the economic crisis of 2008, while the students’ migration from the South to the Central and Northern regions of the country has increased. These phenomena have created further inequalities within the country and a cultural and socio-economic loss for the South that does not appear to slow down. …

Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation

Background Transarterial chemoembolisation (TACE) is first-line treatment in unresectable hepatocellular carcinoma (HCC) and rescue treatment after failure of radical treatments in early stage HCC. Prognostic tools for HCC using time-fixed Cox models may be unreliable in patients treated with TACE because time-varying predictors interact. Aim To explore time-dependent variables as survival predictors in patients with HCC receiving TACE as first-line or second-line treatment. Methods Eighty four consecutive patients with HCC (mean age 68; male gender 62%; Child-Pugh class: A n = 73, B n = 11; Barcelona Clinic Liver Cancer class: A n = 44, B n = 24, C n = 16) treated with TACE were enrolled. …

Centile estimation for a proportion response variable.

This paper introduces two general models for computing centiles when the response variable Y can take values between 0 and 1, inclusive of 0 or 1. The models developed are more flexible alternatives to the beta inflated distribution. The first proposed model employs a flexible four parameter logit skew Student t (logitSST) distribution to model the response variable Y on the unit interval (0, 1), excluding 0 and 1. This model is then extended to the inflated logitSST distribution for Y on the unit interval, including 1. The second model developed in this paper is a generalised Tobit model for Y on the unit interval, including 1. Applying these two models to (1-Y) rather than Y enables model…

Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis.

BACKGROUND/AIMS: Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis. METHODS: MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourtee…

Influence diagnostics for generalized linear mixed models: a gradient-like statistic

In the literature, many influence measures proposed for Generalized Linear Mixed Models (GLMMs) require the information matrix that can be difficult to calculate. In the present paper, a known influence measure is approximated to get a simpler form, for which the information matrix is no more necessary. The proposed measure is showed to have a form similar to the gradient statistic, recently introduced. Good performances have been obtained through simulation studies.

Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation

Aliment Pharmacol Ther 2011; 34: 196–204 Summary Background  Transarterial chemoembolisation (TACE) is first-line treatment in unresectable hepatocellular carcinoma (HCC) and rescue treatment after failure of radical treatments in early stage HCC. Prognostic tools for HCC using time-fixed Cox models may be unreliable in patients treated with TACE because time-varying predictors interact. Aim  To explore time-dependent variables as survival predictors in patients with HCC receiving TACE as first-line or second-line treatment. Methods  Eighty four consecutive patients with HCC (mean age 68; male gender 62%; Child-Pugh class: A n = 73, B n = 11; Barcelona Clinic Liver Cancer class: A n = 44, B…

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in post-operative Crohn's disease

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease. Renna S, Cammà C, Modesto I, Cabibbo G, Scimeca D, Civitavecchia G, Mocciaro F, Orlando A, Enea M, Cottone M. Dipartimento di Medicina, Pneumologia e Fisiologia della Nutrizione Umana, Università di Palermo, Palermo, Italy. BACKGROUNDS & AIMS: The benefit of therapy for prevention of postoperative recurrence of Crohn's disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurr…

The Performance of the Gradient-Like Influence Measure in Generalized Linear Mixed Models

A gradient-like statistic, recently introduced as an influence measure, has been proven to work well in large sample, thanks to its asymptotic properties. In this work, through small-scale simulation schemes, the performance of such a diagnostic measure is further investigated in terms of concordance with the main influence measures used for outlier identification. The simulation studies are performed by using generalized linear mixed models (GLMMs).

Assessing the importance of nursery areas of European hake (Merluccius merluccius) using a body condition index

Abstract In this study, we analysed the variability of reserve storage in juvenile European hake (Merluccius merluccius) off the western coasts of Italy (Central Mediterranean Sea). Reserve storage was measured by the hepatosomatic index (HSI), in relation to environmental and population covariates. HSI has been proved to be a consistent measure of energy storage in gadoids, thus reflecting quantity and quality of food availability for growth. Generalized Additive Models for Location, Scale and Shape (GAMLSS) were used to model the effect of depth, bottom temperature, bottom currents, fish density and fish body size on HSI of juvenile European hake. The results revealed that reserve storage…

Penalized inference in multivariate ordered logistic models: theory and applications

School Bike Sharing Program: will it Succeed?

Abstract Encouraging active and sustainable transport modes in order to limit the excessive use of cars, as well as reducing pollutant emissions and creating livable urban environments, has become one of the priorities for policymakers in recent years. The introduction of innovative systems increasingly being introduced in modern cities, such as bike sharing, can certainly contribute to the spread of cycling and thus allow a radical change in the mobility habits of their citizens. This can be especially true for high-school students who are often otherwise accompanied by their parents with private cars. This article aims to assess the influence that a bike sharing program for students has o…

A Genetic and Metabolic Staging System for Predicting the Outcome of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver-related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis-4 (FIB-4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinom…

Modelling the effects of more selective trawl nets on the productivity of European hake (Merluccius merluccius) and deep-water rose shrimp (Parapenaeus longirostris) stocks in the Strait of Sicily

Single-species Gadget models were used to assess the effects of using a sorting grid mounted on the traditional trawl net used by Sicilian trawlers to exploit the deep-water rose shrimp in the Strait of Sicily. The main commercial by-catch species of this fleet is the European hake (Merluccius merluccius), often caught at sizes well below the minimum conservation reference size. Selectivity curves based on the results of an experimental survey carried out in the area using a commercial trawler equipped with an ad hoc-designed sorting grid were incorporated into single-species Gadget models to forecast the effects of changing fishery selectivity on the performance of the two stocks in terms …

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

Background: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D). Methods: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by dec…

Predicting in-hospital mortality from Coronavirus Disease 2019: A simple validated app for clinical use

Backgrounds Validated tools for predicting individual in-hospital mortality of COVID-19 are lacking. We aimed to develop and to validate a simple clinical prediction rule for early identification of in-hospital mortality of patients with COVID-19. Methods and findings We enrolled 2191 consecutive hospitalized patients with COVID-19 from three Italian dedicated units (derivation cohort: 1810 consecutive patients from Bergamo and Pavia units; validation cohort: 381 consecutive patients from Rome unit). The outcome was in-hospital mortality. Fine and Gray competing risks multivariate model (with discharge as a competing event) was used to develop a prediction rule for in-hospital mortality. D…

A cholestatic pattern predicts major liver-related outcomes in patients with non-alcoholic fatty liver disease

NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO).

Bivariate logistic models for the analysis of the students' University "success"

We analyze the students’ success at University by considering their performance in terms of both “qualitative performance”, measured by their grade average, and “quantitative performance”, measured by University Credits accumulated. To jointly model both marginal and association relationships with covariates, the analysis has been carried out by fitting a bivariate ordered logistic model (BOLM), in a nonparametric fashion, by penalized maximum likelihood estimation. The advantages of such model are in terms of parsimony and parameters interpretation, while preserving goodness-of-fit. The application regards an engineering student (ES) cohort from the University of Palermo.

Modelling a proportion response variable using generalised additive models for location scale and shape

In this paper two alternative approaches are proposed to model a response variable Y measured on the interval from zero to one, including both zero and one. The first proposed model employs a flexible four parameter distribution for 0 < Y < 1, for example a logit skew exponential power distribution, inflated by including point probabilities at 0 and 1. The second proposed model is a generalised Tobit model, obtained from a flexible four parameter distribution on (-infinity;+infinity), for example the skew exponential power distribution, by censoring below 0 and above 1. The proposed models are applied to a real data set and compared with current popular models.

RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study: SIMPLE: Scoring Index to Monitor Progression of Low-risk Esophageal varices.

Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria).All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-H…

A Cholestatic Pattern Predicts Liver-Related Events in Patients with Nonalcoholic Fatty Liver Disease

Background & Aims: Liver test alteration patterns can be categorized as: predominantly hepatocellular(H), with an ALT/ALP ratio>5; predominantly cholestatic pattern(C) with a ratio 55 years(HR2.55,95%C.I.1.17-5.54;p=0.01), platelets<150,000/mmc(HR0.14,95%C.I.0.06-0.32;p<0.001), albumin<4g/L(HR0.62,95%C.I.0.35-1.08;p=0.09), C vs M pattern(HR7.86,95%C.I.1.03-60.1;p=0.04), C vs H pattern(HR12.1,95% C.I.1.61-90.9;p=0.01) and fibrosis F3-F4(HR35.8,95%C.I.4.65-275.2;p<0.001) were independent risk factors for LRE occurrence. C vs M pattern(HR14.3,95%C.I.1.90-105.6;p=0.008) and C vs H pattern(HR15.6,95%C.I. 2.10-115.1;p=0.0068) were confirmed independently associated with LRE occurrence in the vali…

Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study

Objective The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC.Design Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V-0 and V-1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of su…

Peginterferon-Α_2B plus ribavirin is more effective than peginterferon-Α_2A plus ribavirin in menopausal women with chronic hepatitis C

Summary.  Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naive patients (431 men, 315 women) treated with Peg-IFNα-2a (180 μg/week) or Peg-IFNα-2b (1.5 μg/kg/week) plus ribavirin (800–1400  mg/day) for 24 or 48 weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44…

Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitis.

BACKGROUND: In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM. AIMS: To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis. METHODS: Nondiabetic patients with genotype 1 CHC (n = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemi…

Survival of unresectable hepatocellular carcinoma: A meta-analysis of the control arms of 28 randomized trials

A gradient-based deletion diagnostic measure for generalized linear mixed models

ABSTRACTA gradient-statistic-based diagnostic measure is developed in the context of the generalized linear mixed models. Its performance is assessed by some real examples and simulation studies, in terms of ability in detecting influential data structures and of concordance with the most used influence measures.

Mortality after transjugular intrahepatic portosystemic shunt in older adult patients with cirrhosis: A validated prediction model

Background and Aims Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in patients with cirrhosis with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (greater than or equal to 70 years) is debated, and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults. Approach and Results We prospectively enrolled 411 consecutive patients observed at four referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of va…

Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease

Background and aims: Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G&gt;C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholi…

A century of fishery data documenting the collapse of smooth-hounds (Mustelusspp.) in the Mediterranean Sea

Conservation and management of shark populations is increasingly becoming important in many marine regions, since there is a growing body of evidence showing that several species are threatened and continuing to decline because of unregulated fishing. Quantifying the extent of sharks' decline, the risk of species extinction, and the consequences for marine ecosystems have been challenging and controversial, mostly due to data limitations. In this study, more than one century of multiple-sources of bibliographic records on presence and frequency of occurrence of three species of commercial sharks, the smooth-hounds Mustelus spp., in the Mediterranean Sea were compiled and analysed. Generaliz…

Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data

Summary Background There is clear evidence from two systematic reviews that radiotherapy (RT) reduces the risk of local recurrence in patients with resectable rectal cancer, though the data on survival are still equivocal. Objective To assess the effects of chemotherapy combined concomitantly with radiotherapy (CRT) on the increase of overall survival, and on the prevention of local recurrence and distant metastases. Data sources Computerized bibliographic searches of MEDLINE and CANCERLIT (1970–2008) were supplemented with hand searches of reference lists. Study selection Studies were included if they were randomized controlled trials (RCTs) comparing preoperative or postoperative CRT to p…

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Survival of patients treated with sorafenib for hepatocellular carcinoma recurrence after liver transplantation: A systematic review and meta-analysis

Background: Data on survival and safety of sorafenib for hepatocellular carcinoma recurrence after liver transplant are still equivocal. Aim: We performed a meta-analysis of published studies, with the aim of estimating the 1-year rates of survival, analysing the variability in survival rates and, finally, identifying the factors associated with a longer survival. Methods: Data from 8 of the 17 selected studies were pooled, while the other 9 were excluded because survival rates were missing. All included studies were retrospective. Results: Overall, the 1-year survival ranged from 18% to 90%. Tumour progression was the main cause of death. The second cause was bleeding, reported only in pat…

Analisi della predittività dei test d’accesso per Economia

Questo lavoro sulla predittività dei test di accesso TOLC-E e TOLC-I si inserisce, a pieno titolo, in due progetti di ricerca promossi da alcuni autori di questo rapporto. Il primo, del 2016, è il “Protocollo di Ricerca per lo studio della mobilità universitaria (MS) e delle carriere universitarie” tra gli atenei di Palermo, Napoli Federico II, Firenze, Torino, Cagliari, Sassari e Siena e il Miur. Il secondo è un Progetto di Rilevanza Nazionale 2017HBTK5P dal titolo “From high school to job placement: micro-data life course analysis of university student mobility and its impact on the Italian North-South divide”, linea Sud, finanziato nel 2019 con la partecipazione degli atenei sottoscritto…

Modeling confidential data via modified hurdle mixed models

Modelling students' mobility in Italy: an analysis of the determinants by combining individual and aggregated data

The migratory phenomenon consisting in the enrolment of some students in a University different from the one nearest to their place of origin goes under the name of students’ mobility (SM). This phenomenon can be studied for different territorial aggregations, depending on the aims and the availability of data. In Italy several analyses have been carried out to detect the determinants of such a phenomenon. Two approaches are mostly followed. The former considers the analysis of aggregate data (AD) flows, and it is aimed at detecting the characteristics of the Universities and the territories in which they are situated, the latter analyzes the determinants of SM on the grounds of the student…

Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites: A Meta-analysis of Individual Patient Data

Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shunt (TIPS) with large-volume paracentesis in cirrhotic patients with refractory ascites. Although all agree that TIPS reduces the recurrence rate of ascites, survival is controversial. The aim of this study was to compare the effects of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites by means of meta-analysis of individual patient data from 4 randomized controlled trials.The study population consisted of 305 patients: 149 allocated to TIPS and 156 to paracentesis. Cumulative probabilities of transplant-free survival and of hepatic encephalopathy (HE) were estimated…

Mortality in patients with hepatocellular carcinoma predicted by six scoring: none is the winner

A penalized approach for the bivariate ordered logistic model with applications to social and medical data

Bivariate ordered logistic models (BOLMs) are appealing to jointly model the marginal distribution of two ordered responses and their association, given a set of covariates. When the number of categories of the responses increases, the number of global odds ratios to be estimated also increases, and estimation gets problematic. In this work we propose a non-parametric approach for the maximum likelihood (ML) estimation of a BOLM, wherein penalties to the differences between adjacent row and column effects are applied. Our proposal is then compared to the Goodman and Dale models. Some simulation results as well as analyses of two real data sets are presented and discussed.

Some issues concerning the statistical evaluation of a screening test: the ARFI ultrasound case

In this paper we analyze some issues concerning the statistical evaluation of a screening test for classification. The case study is ARFI, an ultrasound device recently introduced, and used for the evaluation of liver fibrosis. First, we present a simple statistical evaluation based on a novel index that compare two competitors with respect to a gold standard, and then we propose a procedure that determines a table with the “acceptable” number of measurements to get an “accurate” diagnosis using the ARFI device.

Fibrosis staging in chronic hepatitis C: Analysis of discordance between transient elastography and liver biopsy

Summary.  In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir ≥ F2) is variable. Constitutional and liver disease-related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)-RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy-six of 286 (26.6%) had stage ≥F2 and TE < 7.1 kPa (false negat…

ANALISI DELLE CARRIERE UNIVERSITARIE NELLE LAUREE SCIENTIFICHE DI BASE IN ITALIA NELL’ULTIMO DECENNIO

An analysis of italian university science students’ careers in the last decade · This paper deals with the study of Italian university science careers by analyzing administrative longitudinal data from the Italian Ministry of Education. Three freshmen cohorts enrolled in a three-year degree course 2011/12, 2014/15, and 2016/17 are analyzed in three time points : at enrolment, in order to assess their choices with respect to their individual characteristics ; at the beginning of the second year, in order to assess who moves to another course and who drops out ; at the fourth year, in order to determine the “best” students’ profiles. The students’ variables involved are gender, type of school…

Appendice A

Questo lavoro sulla predittività dei test di accesso TOLC-E e TOLC-I si inserisce, a pieno titolo, in due progetti di ricerca promossi da alcuni autori di questo rapporto. Il primo, del 2016, è il “Protocollo di Ricerca per lo studio della mobilità universitaria (MS) e delle carriere universitarie” tra gli atenei di Palermo, Napoli Federico II, Firenze, Torino, Cagliari, Sassari e Siena e il Miur. Il secondo è un Progetto di Rilevanza Nazionale 2017HBTK5P dal titolo “From high school to job placement: micro-data life course analysis of university student mobility and its impact on the Italian North-South divide”, linea Sud, finanziato nel 2019 con la partecipazione degli atenei sottoscritto…

Personalized cost-effectiveness of boceprevir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C

Abstract Background We assessed the cost-effectiveness of boceprevir-based triple therapy compared to peginterferon alpha and ribavirin dual therapy in untreated patients with genotype 1 chronic hepatitis C; patients were discriminated according to the combination of baseline plus on-treatment predictors of boceprevir-based triple therapy. Methods Cost-effectiveness analysis performed according to data from the available published literature. The target population was composed of untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C, and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian Nati…

Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE).

AbstractAn accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality…

Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis

Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, ca…

Centile estimation for a proportion response variable

This paper introduces two general models for computing centiles when the response variable Y can take values between 0 and 1, inclusive of 0 or 1. The models developed are more flexible alternatives to the beta inflated distribution. The first proposed model employs a flexible four parameter logit skew Student t (logitSST) distribution to model the response variable Y on the unit interval (0, 1), excluding 0 and 1. This model is then extended to the inflated logitSST distribution for Y on the unit interval, including 1. The second model developed in this paper is a generalised Tobit model for Y on the unit interval, including 1. Applying these two models to (1-Y) rather than Y enables model…

An association model for bivariate data with application to the anlysis of university students' success.

The academic success of students is a priority for all universities. We analyze the students' success at university by considering their performance in terms of both ‘qualitative performance’, measured by their mean grade, and ‘quantitative performance’, measured by university credits accumulated. These data come from an Italian University and concern a cohort of students enrolled at the Faculty of Economics. To jointly model both the marginal relationships and the association structure with covariates, we fit a bivariate ordered logistic model by penalized maximum likelihood estimation. The penalty term we use allows us to smooth the association structure and enlarge the range of possible …

First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Seque…

Gender differences in Italian STEM degree courses: a discrete-time competing-risks model

In this paper, we highlight possible gender differences in performance of students attending Italian university STEM degree courses, controlling for sociodemographic and territorial variables.We used the micro-data from the Italian Ministry of Education, Universities and Research database of the 2011-12 freshmen cohort enrolled at an Italian bachelor university degree course. The analysis was dealt with by fitting a discrete-time competing-risks model. Bachelor degree graduation, dropout, and change to non-STEM courses were considered as competing events. The aim is to highlight gender gaps in the student performance, and the STEM courses where this gap is more critical.

Fitting linear models and generalized linear models with large data sets in R

We present an estimating algorithm to fit linear and generalized linear models not involving the QR decomposition. Some new R functions are presented and discussed. For large data sets, comparisons with respect to the well-known lm() and glm(), as well as to biglm() and bigglm() from the package biglm, show that the proposed functions speed up computation while preserving numerical stability and accuracy

AGILE 3+ Score for the Diagnosis of Advanced Fibrosis and for Predicting Liver-related Events in NAFLD.

Background &amp; aims: We aimed to assess the diagnostic accuracy of AGILE 3+, a recently developed score based on the combination of aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, age, and liver stiffness measurement (LSM) by transient elastography, when compared with Fibrosis-4 (FIB-4) and LSM, for the diagnosis of advanced fibrosis and for the prediction of liver-related events (LREs) occurrence in patients with NAFLD. Methods: A total of 614 consecutive patients with biopsy-proven NAFLD or clinical diagnosis of NAFLD-related compensated cirrhosis were enrolled. LREs were recorded during follow-up. FIB-4, LSM by transient elastography (Fi…

Error factors for transient elastography in chronic hepatitis C

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems

Summary Background  A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. Aim  To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. Methods  We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. Results  One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated p…

Appendice C

Questo lavoro sulla predittività dei test di accesso TOLC-E e TOLC-I si inserisce, a pieno titolo, in due progetti di ricerca promossi da alcuni autori di questo rapporto. Il primo, del 2016, è il “Protocollo di Ricerca per lo studio della mobilità universitaria (MS) e delle carriere universitarie” tra gli atenei di Palermo, Napoli Federico II, Firenze, Torino, Cagliari, Sassari e Siena e il Miur. Il secondo è un Progetto di Rilevanza Nazionale 2017HBTK5P dal titolo “From high school to job placement: micro-data life course analysis of university student mobility and its impact on the Italian North-South divide”, linea Sud, finanziato nel 2019 con la partecipazione degli atenei sottoscritto…

NR1H4 rs35724 G>C variant modulates liver damage in nonalcoholic fatty liver disease

Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G&gt;C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G&gt;C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n = 124). Results: The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic conf…

Influence Diagnostics for Meta-Analysis of Individual Patient Data Using Generalized Linear Mixed Models

In meta-analysis, generalized linear mixed models (GLMMs) are usually used when heterogeneity is present and individual patient data (IPD) are available, while accepting binary, discrete as well as continuous response variables. In the present paper some measures of influence diagnostics based on log-likelihood are suggested and discussed. A known measure is approximated to get a simpler form, for which the information matrix is no more necessary. The performance of the proposed measure is assessed through a diagnostic analysis on simulated data reproducing a possible meta-analytical context of IPD with influential outliers. The proposed measure is showed to work well and to have a form sim…

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: An individual patient data meta-analysis

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk fac…

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems

A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately.To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC.We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model.One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among…

Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C

We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…

Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients with Non-alcoholic Fatty Liver Disease

Background & Aims Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk for liver-related complications, such as decompensation, hepatocellular carcinoma (HCC), and death; the severity of liver fibrosis and metabolic comorbidities are the main risk factors. A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3 (PNPLA3) gene is associated with higher prevalence of liver damage and HCC, but there are no data from prospective studies of outcomes of patients with this polymorphism. We investigated whether the common rs738409 variant in PNPLA3 gene associates with the occurrence of liver-related events and death in a large cohort of patients w…

Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C.

BACKGROUND AND AIMS: Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assess the cost-effectiveness of TT compared to DT in the treatment of untreated patients with G1 CHC. METHODS: We created a Markov Decision Model to evaluate, in an untreated Caucasian patients aged 50 years, weight 70 kg, with G1 CHC and Metavir F2 liver fibrosis score, for a time horizon of twenty years, the cost-effectiveness of the following 5 competing strategie…

A penalized approach to the bivariate logistic regression model for the association between ordinal responses

Bivariate ordered logistic models (BOLMs) are appealing to jointly model the marginal distribution of two ordered responses and their association, given a set of covariates. When the number of categories of the responses increases, the number of global odds ratios (or their re-parametrizations) to be estimated also increases and estimating the association structure becomes crucial for this type of data. In fact, such data could be too "rich" to be fully modelled with an ordinary BOLM while, sometimes, the well-known Dale's model could be too parsimonious to provide a good fit. In addition, when the cross-tabulation of the responses contains some zeros, for a number of model configurations, …

Are radiological endpoints surrogate outcomes of overall survival in hepatocellular carcinoma treated with transarterial chemoembolization?

Background&amp; Aims: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. Methods: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS …

The impact of radiotherapy on survival in resectable gastric carcinoma: A meta-analysis of literature data.

Summary Background The benefit of external radiotherapy for gastric carcinoma has been extensively studied, but data on survival are still equivocal. Objective To assess the effectiveness of surgery combined with preoperative radiotherapy or postoperative chemoradiotherapy in the reduction of all-cause mortality in patients with resectable gastric carcinoma. Methods Computerised bibliographic searches of MEDLINE and CANCERLIT (1970–2006) were supplemented with hand searches of reference lists. Study selection Studies were included if they were randomised controlled trials (RCTs) comparing mortality of surgery combined with preoperative radiotherapy or postoperative chemoradiotherapy to surg…

Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis

Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis.MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourteen trials were included in t…

Appendice B

Questo lavoro sulla predittività dei test di accesso TOLC-E e TOLC-I si inserisce, a pieno titolo, in due progetti di ricerca promossi da alcuni autori di questo rapporto. Il primo, del 2016, è il “Protocollo di Ricerca per lo studio della mobilità universitaria (MS) e delle carriere universitarie” tra gli atenei di Palermo, Napoli Federico II, Firenze, Torino, Cagliari, Sassari e Siena e il Miur. Il secondo è un Progetto di Rilevanza Nazionale 2017HBTK5P dal titolo “From high school to job placement: micro-data life course analysis of university student mobility and its impact on the Italian North-South divide”, linea Sud, finanziato nel 2019 con la partecipazione degli atenei sottoscritto…

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

[Background & Aims] Patients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events.

Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma

The purpose was to assess the cost-effectiveness of sorafenib in the treatment of hepatocellular carcinoma (HCC) patients incorporating current prices and the results of the recent published field practice SOraFenib Italian Assessment (SOFIA) study. We created a Markov Decision Model to evaluate, in a hypothetical cohort of Caucasian male patients, aged 67 years with Barcelona Clinic Liver Cancer (BCLC) C HCC, or BCLC B HCC who were unfit or failed to respond to locoregional therapies, well compensated cirrhosis, and with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG), the cost-effectiveness of the following strategies: (1) full or dose-adjusted sorafenib for …

Student mobility in higher education: Sicilian outflow network and chain migrations

The most important student mobility (SM) flow in Italy is from the Southern to the Central-Northern regions, a phenomenon that has been magnified by an increasing number of outgoing students from Sicily over the last decade. In this paper, we rely upon micro-data of university enrollment and students' personal records for three cohorts of freshmen, in order to investigate preferential patterns of SM from Sicily toward universities in other regions. Our main goal is to reveal the existence of chain migrations, where students from a particular geographical area move towards a particular destination to follow other students that have previously moved. The paper provides aspects that are innova…

Efficacy of lumen-apposing metal stents or self-expandable metal stents for endoscopic ultrasound-guided choledochoduodenostomy: a systematic review and meta-analysis

Abstract Background Endoscopic ultrasound (EUS)-guided biliary drainage is becoming an option for palliation of malignant biliary obstruction. Lumen-apposing metal stents (LAMS) are replacing self-expandable metal stents (SEMS). The aim of this meta-analysis was to evaluate the efficacy and safety of LAMS and SEMS for EUS-guided choledochoduodenostomy (EUS-CDS). Methods A meta-analysis was performed using PRISMA protocols. Electronic databases were searched for studies on EUS-CDS. The primary outcome was clinical success. Secondary outcomes were technical success, reintervention, and adverse events. We used the random effects model with the DerSimonian–Laird estimation, and the results were…

Radiomics Analysis on Gadoxetate Disodium-Enhanced MRI Predicts Response to Transarterial Embolization in Patients with HCC

Objectives: To explore the potential of radiomics on gadoxetate disodium-enhanced MRI for predicting hepatocellular carcinoma (HCC) response after transarterial embolization (TAE). Methods: This retrospective study included cirrhotic patients treated with TAE for unifocal HCC naïve to treatments. Each patient underwent gadoxetate disodium-enhanced MRI. Radiomics analysis was performed by segmenting the lesions on portal venous (PVP), 3-min transitional, and 20-min hepatobiliary (HBP) phases. Clinical data, laboratory variables, and qualitative features based on LI-RADSv2018 were assessed. Reference standard was based on mRECIST response criteria. Two different radiomics models were construc…

Penalized inference in multivariate ordered logistic models: theory and applications

Mortality in patients with hepatocellular carcinoma predicted by six scoring systems: None is the winner

Longitudinal investigation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older patients in the province of Palermo (Southern Italy) during the early wave of the pandemic.

IntroductionClinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in old adults from Southern Italy is little known. This study aims to investigate the mortality risk related to risk factors, therapy and clinical course and to suggest prognostic indicators based on day-to-day follow-up of clinical and laboratory findings.Material and methodsIt was designed as a retrospective longitudinal cohort study of adult SARS-CoV-2 patients admitted at Partinico COVID Hospital in Palermo, Southern Italy. Patients were recruited between 4 March and 25 April and followed up until 31 May 2020, day-to-day until death or hospital discharge. Clinical data, laboratory…

Effect of pharmacological interventions and placebo on liver Histology in nonalcoholic steatohepatitis: A network meta-analysis

Background: The aims of this study were to quantify the histological improvement and its risk factors in patients with NASH enrolled in the placebo arms of randomized controlled trials (RCTs), and to indirectly compare the effect of several investigational drugs for NASH on validated histological outcomes.Data synthesis: A comprehensive search was conducted to detect phase 2 and 3 RCTs comparing pharmacological interventions in patients with NASH. According to Food and Drug Administra-tion (FDA) recommendations, primary outcomes included: 1) NASH resolution without wors-ening of fibrosis; 2) At least 1-point reduction in fibrosis without worsening of NASH. Meta -analysis and meta-regression…

Diagnostics for meta-analysis based on generalized linear mixed models

Meta-analysis is the method to combine data coming from multiple studies, with the aim to provide an overall event-risk measure of interest summarizing information coming from the studies. In meta-analysis generalized linear mixed models (GLMM) are particularly used for a number of measures of interest since they allow the true effect size to differ from study to study while accepting binary, discrete as well as continuous response variable. In the present paper some strategies of influence diagnostics based on log-likelihood are suggested and discussed. These are considered for Individual Patient Data, Aggregate Data and their compounding.

A flexible approach for modelling a proportion response variable: Loss given default

Loss given default (LGD) is a proportion of a credit exposure that is lost if the obligor defaults on a loan. Response variable LGD contains values between 0 and 1 including both 0 and 1, where 0 means that the balance is fully recovered while 1 means total loss of exposure at default. This article addresses two alternative semi parametric approaches for modelling loss given default, which is measured on the interval [0,1]. The class of models are very flexible and can accommodate skewness and bimodal characteristics of LGD data. The dependence of the predictors of each of the parameters (of the proposed model distribution for LGD) on explanatory variables can be additive P-splines, regress…

Modeling sequential systemic therapy for unresectable hepatocellular carcinoma in the era of immunotherapy: What comes next?

324 Background: Atezolizumab plus Bevacizumab represents the new best performing first-line approach for unresectable hepatocellular carcinoma (u-HCC). However, the best sequential strategy after every first-line failure (for progression or intolerance) remains elusive, and options for retreating patients failing Atezolizumab plus Bevacizumab with multi-kinase inhibitors (MKI) or immune checkpoint inhibitor (ICI) are yet undefined. Methods: We developed a Markov model to analyze simulated-Overall Survival (s-OS) of second-line ICIs or MKIs after first-line Atezolizumab plus Bevacizumab over a lifetime horizon. For first-line therapy, PFS of Atezolizumab plus Bevacizumab was extracted from …

Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C

We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…

GEMS, a GEnetic and Metabolic Staging predicting the outcome of non-alcoholic fatty liver disease

Background and Aim: Non-alcoholic fatty liver disease(NAFLD) is an emergent cause of liver-related events(LRE). We have assessed the ability of a composite score based on clinical features, metabolic comorbidities and genetic background, to predict LRE. Methods: 546 consecutive patients with NAFLD were recruited and stratified according to FIB-4(low risk <1.3;intermedium-high risk ≥1.3). LRE were defined as occurrence of HCC or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LRE. Results: Over a median follow-up of 73.8 months, 58 patients experienced LRE(only 1 in the cohort of patients with FIB-4 65 years(HR 17.96), plat…

Endothelial angiopoietin-2 overexpression in explanted livers identifies subjects at higher risk of recurrence of hepatocellular carcinoma after liver transplantation

BackgroundThough the precise criteria for accessing LT are consistently being applied, HCC recurrence (HCC-R_LT) still affects more than 15% of the patients. We analyzed the clinical, histopathological, and biological features of patients with HCC to identify the predictive factors associated with cancer recurrence and survival after LT.MethodsWe retrospectively analyzed 441 patients with HCC who underwent LT in our center. Overall, 70 (15.8%) of them developed HCC-R_LT. We matched them by age at transplant and etiology with 70 non-recurrent patients. A comparable cohort from the Liver Transplant Centre of Bologna served as validation. The clinical and biochemical characteristics and pre-LT…

Analisi della predittività dei test d’accesso per Ingegneria

Questo lavoro sulla predittività dei test di accesso TOLC-E e TOLC-I si inserisce, a pieno titolo, in due progetti di ricerca promossi da alcuni autori di questo rapporto. Il primo, del 2016, è il “Protocollo di Ricerca per lo studio della mobilità universitaria (MS) e delle carriere universitarie” tra gli atenei di Palermo, Napoli Federico II, Firenze, Torino, Cagliari, Sassari e Siena e il Miur. Il secondo è un Progetto di Rilevanza Nazionale 2017HBTK5P dal titolo “From high school to job placement: micro-data life course analysis of university student mobility and its impact on the Italian North-South divide”, linea Sud, finanziato nel 2019 con la partecipazione degli atenei sottoscritto…

Impact of virus eradication in patients with compensated hepatitis C virus-related cirrhosis: competing risks and multistate model

BACKGROUND & AIMS No published study to date has provided a careful analysis of the effects of a sustained viral response (SVR) on the outcomes of patients with compensated hepatitis C virus (HCV)-related cirrhosis in relation to the degree of portal hypertension. Therefore, we estimated the impact of achieving SVR on disease progression, hepatocellular carcinoma (HCC) development and mortality in a large cohort of HCV patients with cirrhosis with or without oesophageal varices (OVs) at the start of antiviral therapy. METHODS A total of 535 Caucasian patients were prospectively recruited to this study. All patients had a clinical or histological diagnosis of compensated HCV-related cirrhosi…

Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16–152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver a…

The pblm package: semiparametric regression for bivariate categorical responses in R

We present an R package to fit semiparametric regression models for two categorical responses. It works for both nominal and ordered responses and several types of logits can be specified. Proportional, non-proportional and partial proportional odds models can be fitted, with marginal and association parameters estimated in a parametric or semiparametric way, via penalized maximum likelihood estimation. An application to show the potential of the package is carried out on a data set of Italian university students.

Cost effectiveness of boceprevir or telaprevir for previously treated patients with genotype 1 chronic hepatitis C.

Background & Aims Randomised controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype 1 (G1) chronic hepatitis C (CHC) patients with previous relapse (RR), partial response (PAR), and null-response (NR). We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC. Methods The available published literature provided the data source. The target population was made up of previously treated Caucasian patients with G1 CHC and these were evaluated over a lifetime horizo…

A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma.

Knowing the spontaneous outcome of hepatocellular carcinoma (HCC) is important for designing randomized controlled trials (RCTs) of new therapeutic approaches; however, survival of patients in the absence of treatment is highly variable, and prognostic factors influencing outcomes are incompletely defined. The aims of this meta-analysis were to estimate the 1-year and 2-year survival rates of untreated HCC patients enrolled in RCTs of palliative treatments, and to identify prognostic factors. RCTs evaluating therapies for HCC with placebo or no-treatment arms were identified on MEDLINE through April 2009. Data were combined in a random effect model. Primary outcomes were 1-year and 2-year s…

Peginterferon-Α_2B plus ribavirin is more effective than peginterferon-Α_2A plus ribavirin in menopausal women with chronic hepatitis C.

Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naïve patients (431 men, 315 women) treated with Peg-IFNα-2a (180 μg/week) or Peg-IFNα-2b (1.5 μg/kg/week) plus ribavirin (800–1400 mg/day) for 24 or 48 weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44.2% of Peg-…

Progression-Free Survival Early Assessment Is a Robust Surrogate Endpoint of Overall Survival in Immunotherapy Trials of Hepatocellular Carcinoma

Background: Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods. Methods: A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan&nd…

La mobilità degli studenti universitari nell'ultimo decennio in Italia

La mobilità degli studenti dal Sud e dalle Isole verso il Centro-Nord ha creato e crea ulteriori disuguaglianze e una perdita di capitale umano che non sembra rallentare negli ultimi anni. In questo quadro si colloca il nostro studio sulla mobilità universitaria, i cui effetti non sono limitati al sistema universitario nazionale, ma hanno implicazioni sociali ed economiche sull’intero Paese.

Dalla triennale alla magistrale: continua la “fuga dei cervelli” dal Mezzogiorno d'Italia

Guardando alla geografia della mobilità degli studenti meridionali negli anni accademici dal 2014/15 al 2017/18 nel passaggio dalla laurea triennale a quella magistrale, Massimo Attanasio, Marco Enea e Alessandro Albano rilevano che la fuga, già evidente nel passaggio dalle superiori all’università, continua anche in seguito: gli atenei del Mezzogiorno continuano a perdere iscritti potenziali a favore degli atenei del Centro-Nord.

Quali atenei scelgono i diplomati del Mezzogiorno d’Italia?

La geografia della mobilità degli studenti meridionali nel passaggio dalle superiori all’università è qui analizzata nel periodo che va dal 2011/12 al 2016/17 (anni scolastici o accademici). I dati, analizzati da Massimo Attanasio, Marco Enea e Andrea Priulla mostrano una fuga allarmante, e persino crescente nel tempo, dal Mezzogiorno verso gli atenei del Centro- Nord.