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Background In Italy there is evidence of a large variability in health care services and health outcomes. This multi-regional project is funded on Ministry of Health and Health Regional Authorities (code NET-2016-02364191). The aims are: 1) To test the effectiveness of Audit and Feedback (A&F) interventions in improving health professional practices and patients' outcomes in different settings using both a quantitative and a qualitative approach. 2) To examine factors that may explain variations in the effectiveness of A&F. 3) To evaluate the impact of A&F in reducing avoidable differences in access to effective health care interventions in socioeconomically disadvantaged populations. Methods In the 7 participating Regions (about 33 million inhabitants) experimental study designs have been implemented in different clinical areas (e.g. before-after controlled study, cluster randomized trial): in Lazio emergency care and chronic diseases care, in Friuli Venezia Giulia emergency care, in Piemonte oncology care, in Emilia Romagna chronic disease care, in Lombardia cardiovascular care, in Calabria deliveries and maternal health, in Sicilia emergency care. The effectiveness of different types of A&F are compared in term of outcomes using health information system databases. Results Preliminary results show large heterogeneity in developing and conducting A&F, in term of team project composition, type of intervention, clinicians' behavior to be changed, outcomes indicators, professionals involved, structure and timing of data reporting, actions to be implemented after the intervention. Limited awareness and interest of clinicians in A&F interventions was found. Conclusions The project represents a unique opportunity to explore how A&F interventions could be better designed. Different A&F strategies will be compared in term of clinical outcomes. The identification of barriers/facilitating factors will supply knowledge on mechanisms and tools to enhance A&F effectiveness. Key messages The project supports providers in reducing gap between knowledge and practice. The project promotes culture of interprofessional collaboration as a key point for high quality care.

Summary Background Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of clinical conditions, actually representing an emerging disease of great clinical interest. Currently, its diagnosis requires liver biopsy, an invasive procedure not free from potential complications. However, several non-invasive diagnostic strategies have been proposed as potential diagnostic alternatives, each with different sensitivities and accuracies. Aim To review non-invasive diagnostic parameters and tools for NAFLD diagnosis and to formulate a diagnostic and prognostic algorithm for a better classification of patients. Methods A literature search was carried out on MEDLINE, EMBASE, Web of Science and Scopus for articles and abstracts in English. The search terms used included ‘NAFLD’, ‘non invasive method and NAFLD’, ‘transient elastography’ and ‘liver fibrosis’. The articles cited were selected based on their relevancy to the objective of the review. Results Ultrasonography still represents the first-line diagnostic tool for simple liver steatosis; its sensitivity could be enhanced by the complex biochemical score SteatoTest. Serum cytokeratin-18 is a promising and accurate non-invasive parameter (AUROCs: 0.83; 0.91) for the diagnosis of non-alcoholic steatohepatitis (NASH). The staging of liver fibrosis still represents the most important prognostic problem: the most accurate estimating methods are FibroMeter, FIB-4, NAFLD fibrosis score (AUROCs: 0.94; 0.86; 0.82) and transient elastography (AUROC: 0.84–1.00). Conclusions Different non-invasive parameters are available for the accurate diagnosis and prognostic stratification of non-alcoholic fatty liver disease which, if employed in a sequential algorithm, may lead to a reduced use of invasive methods, i.e. liver biopsy.

Road accidents represent an enormous burden to society and an immeasurable human cost. During the last 30 years the overall volume of traffic has tripled and injuries after road accidents are today a major public health problem. Road accidents are predictable and preventable and many interventions may reduce the most severe events. The Commission of the European Union has recently proposed an action to halve the number of deaths after road accidents by 2010; all parts involved in road safety are committed to take action in this direction. Alcohol is one of the most important risk factors, being responsible for about 10,000 deaths each year in the European Union. The number of fatalities might be reduced by 5-40% by stopping driving with blood alcohol concentration over the legal limits of 0.5 mg/ml. Several factors may add to alcohol to determine the risk of road accidents and the severity of injury. The most important are high speed, male sex and young age, driving inexperience, fatigue, use of psychotropic legal and illicit drugs, weekend night, misuse of seat belts or helmets. Alcohol may impair the patho-physiological response to injury, but the putative mechanisms are not definitely proved. Also at low concentrations, it may influence both the diagnostic process and the final outcome of patients after injury. At first evaluation, the degree of injury may be overestimated in intoxicated patients, prompting a greater number of diagnostic manoeuvres and invasive procedures. Alcohol positive patients are more likely to need intensive care, surgery, blood transfusion, and longer hospital stay, because of more severe acute medical complications (infections, respiratory failure and shock). In patients with positive blood alcohol concentrations previously unsuspected injuries are more likely to be diagnosed during follow-up. The recidivism rate for road accidents is larger in patients with chronic alcohol abuse, independently of the driver or passenger status. Physicians who provide care to injured patients after road accidents have an important role in preventing alcohol-related injury and death. They can refer patients suspected for drinking and driving for treatment after a road accident, when their motivation is definitely increased. Brief interventions in the emergency room decrease alcohol consumption and decrease the incidence of further events caused by driving under the influence of alcohol.

BACKGROUND AND AIMS: There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. MATERIALS AND METHODS: One hundred seventy-four consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements. One hundred seventy-four patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of > 1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. RESULTS: Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (p55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; p=0.51). CONCLUSION: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients.

Background and Aim: We evaluated the relationship between insulin resistance (IR) and insulin secretion with the metabolic syndrome (MS) in 885 subjects (377 men/508 women, age 49 11 years, BMI 29 5.2 kgm2) at risk of diabetes enrolled in the genetics, pathophysiology and evolution of type 2 diabetes (GENFIEV) study. Methods and Results: All subjects underwent a 75-g oral glucose tolerance test (OGTT) for the estimation of plasma levels of glucose and C-peptide, as well as fasting insulin and lipid profile. IR was arbitrarily defined as HOMA-IR value above the 75th centile of normal glucose tolerance (NGT) subjects. Overall MS prevalence (National Cholesterol Treatment Panel-Adult Treatment Panel (NCEP-ATPIII) criteria) was 33%, 19% in subjects with NGT, 42% in impaired fasting glucose (IFG), 34% in impaired glucose tolerance (IGT), 74% in IFG + IGT subjects, and 56% in newly diagnosed diabetic patients. Prevalence was slightly higher with IDF criteria. MS prevalence was >50% in subjects with 2 h glucose >7.8 mmol l-1, independently of fasting plasma glucose. IR prevalence was higher in subjects with MS than in those without (63% vs. 23%; p < 0.0001) and increased from 54% to 73% and 88% in the presence of three, four or five traits, respectively. IR occurred in 42% of subjects with non-diabetic alterations of glucose homeostasis, being the highest in those with IFG + IGT (IFG + IGT 53%, IFG 45%, IGT 38%; p < 0.0001). Individuals with MS were more IR irrespective of glucose tolerance (p < 0.0001) with no difference in insulinogenic index. Hypertriglyceridaemia (OR: 3.38; Confidence Interval, CI: 2.294.99), abdominal obesity (3.26; CI: 2.18-4.89), hyperglycaemia (3.02; CI: 1.80-5.07) and hypertension (1.69; CI: 1.12-2.55) were all associated with IR. Conclusions: These results show that in subjects with altered glucose tolerance (in particular IFG + IGT) MS prevalence is high and is generally associated to IR. Some combinations of traits of MS may significantly contribute to identify subjects with IR.

INTRODUCTION: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are part of the same metabolic defect, both having insulin resistance as the main pathogenic mechanism and sharing similar outcomes (i.e., cardiovascular and liver-related mortality). The prevalence of NAFLD is expected to rise, owing to the increasing worldwide prevalence of obesity and MetS; therefore, the identification of factors responsible for disease progression is essential to devise therapeutic strategies. AREAS COVERED: The available and potential future treatments for NAFLD in combination with MetS are reviewed in this paper, following an extensive literature search and personal experience. EXPERT OPINION: All NAFLD patients should be evaluated for their metabolic, cardiovascular and liver-related risk. Weight loss through lifestyle intervention remains the most comprehensive and safe treatment of NAFLD and associated MetS; however, > 50% of patients fail to achieve target weight loss. Pharmacologic treatment seems to be important for these patients and for NAFLD cases with more advanced liver disease. It temporarily reverses metabolic alterations, but liver disease progresses after the treatment is stopped. Although current treatments are unsatisfactory, new drugs have been proposed and a few innovative compounds are in the pipeline of pharmaceutical companies. Before pharmacologic treatment can be routinely recommended for NAFLD, long-term randomized trials are needed, along with assessments of the safety and benefits of drugs on proper histological outcomes or validated surrogate markers. The intensive control of individual features of MetS remains mandatory.

The effectiveness of cognitive-behavior treatment (CBT) in nonalcoholic fatty liver disease (NAFLD), largely related to overweight/obesity and considered the hepatic expression of the metabolic syndrome (MS), has so far been tested in very limited samples. In a tertiary referral center, consecutively observed NAFLD subjects were offered a CBT program aimed at weight loss and increased physical activity, based on 13 group sessions; 68 cases entered the treatment protocol, those who refused (n = 82) were given recommendations for diet and physical activity. Treatment goals (weight loss ≥7% initial birth weight, normalization of liver enzymes, and improved parameters of MS) were tested by logistic regression at 6 months (all cases) and at 2 years, both on intention-to-treat and in completers (Diet, 78; CBT, 65). The results were adjusted for the propensity score of attending the CBT program, based on civil, anthropometric and clinical variables. At baseline the CBT group had a larger prevalence of obesity and more severe insulin resistance (homeostasis model assessment (HOMA)). At follow-up, CBT was associated with a higher probability of weight loss and normal liver enzymes (6-month: odds ratio (OR), 2.56; 95% confidence interval (CI), 1.15–5.69; 2-year intention-to-treat: OR, 3.57, 95% CI, 1.59–8.00), after adjustment for propensity and changes in body weight. A similar trend was observed in the outcome goals of insulin resistance and the score of MS, which were both reduced. In conclusion, subjects with NAFLD participating in a CBT program significantly improve their general and liver parameters. The beneficial effects are largely maintained at 2-year follow-up, in keeping with the lifestyle-related pathogenesis of disease.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are increasingly relevant public health issues owing to their close association with the worldwide epidemics of diabetes and obesity. NAFLD/NASH is one of the most common chronic liver diseases and increases the 5-year direct and indirect health care costs by an estimated 26% [1]. Although evidencebased clinical practice guidelines for this condition are badly needed, currently not enough evidence is available to formulate guidelines in an unbiased, responsible, and unequivocal way. This position statement summarizes the proceedings of the 2009 EASL Special Conference on NAFLD/NASH and proposes expert opinion for different aspects of the clinical care of these patients.

Background The effect of pre-injury antiplatelet treatment in the risk of intracranial lesions in subjects after mild head injury (Glasgow Coma Scale (GCS) 14–15) is uncertain. Methods The potential risk was determined, considering its increasing use in guidelines on cardiovascular disease prevention, and ageing of the trauma population in Europe. Patients The interaction of antiplatelet therapy with the prediction variables of main decision aids was analysed in 14 288 consecutive adolescent and adult subjects with mild head injury. Measurements Any intracranial lesion at CT scan was selected as an outcome measure in a multivariable logistic regression analysis. Results Intracranial lesions were demonstrated in 880 cases (6.2%), with an unfavourable outcome at 6 months in 86 (0.6%). Antiplatelet drugs were recorded in 10% of the entire cohort (24.7% in the group over 65 years). They increased the risk of intracranial lesions in the univariate analysis (OR 2.6; 95% CI 2.2 to 3.1), interacting with age in the multivariate analysis (antiplatelet OR 2.7 (1.9 to 3.7); age ≥75 years 1.4 (1.0 to 1.9)). The inclusion of these two variables with those included in previous decision aids for CT scanning (GCS, neurodeficit, post-traumatic seizures, suspected skull fracture, vomiting, loss of consciousness, coagulopathy) predicted intracranial lesions with a sensitivity of 99.7% (95% CI 98.9 to 99.8) and a specificity of 54.0% (95% CI 53.1 to 54.8), with a CT ordering rate of 49.3% (undetermined events 0.2:1000). Interpretation Antiplatelet drugs need to be considered in future prediction models on mild head injury, considering their increasing use and progressive ageing of the trauma population.

Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. NAFLD is considered the hepatic component of the metabolic syndrome and insulin resistance represents its pathophysiological hallmark. Insulin resistance in NAFLD is characterized by reduced whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanism(s) underlying the accumulation of fat in the liver may include excess dietary fat, increased delivery of free fatty acids to the liver, inadequate fatty acid oxidation, and increased de novo lipogenesis. Liver fat is highly correlated with all the components of the metabolic syndrome, independent of obesity, and NAFLD may increase the risk of type 2 diabetes and atherosclerosis. Overproduction of glucose, very low-density lipoproteins, C-reactive protein and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease. The reason(s) why some patients will develop NASH are poorly understood. Circulating free fatty acids may be cytotoxic by inducing lipid peroxidation and hepatocyte apoptosis. Insulin resistance is often associated with chronic low-grade inflammation, and numerous mediators released from immune cells and adipocytes may contribute liver damage and liver disease progression. Understanding the molecular mediators of liver injury would promote the development of mechanism-based therapeutic interventions. This article briefly summarizes the recent advances in our understanding of the relationship between NAFLD/NASH, insulin resistance and the metabolic syndrome.

The effects of cognitive-behavioral therapy (CBT) on central dopamine (DA), noradrenaline (NE) and serotonin (5-HT) secretion were studied in a group of 50 female inpatients, of which 14 suffered from anorexia nervosa restricted type (AN-R), 14 from anorexia nervosa bingeing-purging type (AN-BP), and 22 from bulimia nervosa (BN). The aim of the study was to see whether or not CBT modifies the secretion of central DA (blood homovanillic acid=HVA), NE (blood 3-methoxy-4-hydroxy-phenylglycol=MHPG) and the 5-HT transporter (as evaluated by the platelet paroxetine binding=[(3)H]-Par-binding), if the physical and psychological effects of CBT correlate with changes of the neurotransmitter secretion; and if the biological effects of CBT are linked to specific psychopathological aspect of the disorders. The treatment lasted 20 weeks. Body-mass Index, bingeing and purging, specific AN-BN psychopathological (EDE 12-OD), depression (Beck Inventory), anxiety (STAY Form-Y-1), impulsiveness (Barratt Impulsiveness Scale), self-esteem (Rosenberg Self-Biochemical Scale) and temperament (Temperament and Character Inventory, Cloninger Scale) were assessed at baseline and at the end of the treatment. CBT significantly improved the psychophysical aspects of the diseases. HVA and MHPG concentrations did not change. The [(3)H]-Par-binding parameters, the maximum binding capacity (B(max)) and dissociation constant (K(d)) values did not change in either AN-R or AN-BP patients, while the [(3)H]-Par B(max) (and not the K(d)) increased significantly in BN patients. Correlations emerged between basal and final [(3)H]-Par B(max) values and psychopathological scores, but not between CBT-induced differences between basal and final values. Our data suggest that only in BN CBT may act through changes in 5-HT system function.

Background & Aims Mutations in the hemochromatosis gene ( HFE ) (C282Y and H63D) lead to parenchymal iron accumulation, hemochromatosis, and liver damage. We investigated whether these factors also contribute to the progression of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Methods We studied clinical, histologic (liver biopsy samples for hepatocellular iron accumulation), serologic (iron and enzyme levels), and genetic ( HFE genotype) data from 587 patients from Italy with NAFLD and 184 control subjects. Results Iron accumulation predominantly in hepatocyes was associated with a 1.7-fold higher risk of a fibrosis stage greater than 1 (95% confidence interval [CI]: 1.2–2.3), compared with the absence of siderosis (after adjustment for age, body mass index, glucose tolerance status, and alanine aminotransferase level). Nonparenchymal/mixed siderosis was not associated with moderate/severe fibrosis (odds ratio, 0.72; 95% CI: 0.50–1.01). Hepatocellular siderosis was more prevalent in patients with HFE mutations than in those without; approximately one third of patients with HFE mutations had parenchymal iron accumulation (range, 29.8%–35.7%, depending on HFE genotype). Predominantly hepatocellular iron accumulation occurred in 52.7% of cases of patients with HFE mutations. There was no significant association between either the presence of HFE mutations or specific HFE genotypes and the severity of liver fibrosis. Conclusions Iron deposition predominantly in hepatocyes is associated with more severe liver damage in patients with NAFLD. However, HFE mutations cannot be used to identify patients with hepatocellular iron accumulation.

Non-alcoholic fatty liver disease (NAFLD) is a clinical/biochemical condition associated with the metabolic syndrome. As the disease stems from excess calorie intake and lack of physical activity, the correction of unhealthy lifestyles is the background of any prevention and treatment strategy; drugs should remain a second-line treatment. Several studies have shown that weight loss and physical activity, the cornerstones of a healthy lifestyle, have a specific therapeutic role in NAFLD, preventing disease progression and reducing the burden of disease. Prescriptive diets have a limited long-term efficacy; after a short period, most patients resume their old habits and weight regain is the rule. Physical activity, usually in combination with diet, but also independent of weight loss, improves liver enzymes and reduces liver fat, with uncertain results on hepatic necroinflammation; however, making patients increase their physical activity is very difficult. Only a behavioral approach may give patients the practical instruments to achieve their eating and exercise goals, incorporate them into lifestyle, and maintain the results for a long period, thereby possibly guaranteeing long-term durability of change. Cognitive-behavior treatment should be provided to patients at risk of advanced liver disease, and this action should be coupled with prevention strategies at the population level. Only a synergistic approach and a global societal response might be effective in reducing the burden of advanced liver disease and premature death due to NAFLD/NASH (non-alcoholic steatohepatitis).

Background: Patient-reported outcomes such as HRQL have become increasingly important for patients with chronic liver disease (CLD). Aim: To explore the relative impact of different types of liver disease on HRQL as well as predictors of HRQL domains in CLD. Design: Our HRQL databases with Short-Form 36 data (SF-36) as well as clinico-demographic data were used. Scores for each of SF-36 scales (PF - physical functioning, RP - role functioning, BP - bodily pain, GH - general health, VT – vitality, SF - social functioning, RE - role emotional and MH - mental health, MCS- mental component score, PCS- physical component score) were compared between different types of CLD as well as other variables. SF-36 scales were compared using Wilcoxon tests. Spearman’s rank coefficient was used as a measure of age-HRQL correlations. For all tests and correlation estimations, p-values not exceeding 0.05 after Benjamini-Hochberg correction were considered to be statistically significant. Results: Complete data was available for 1103 CLD patients. Demographic and clinical data included: age 53.7±11.8 years, 39% female, 792 (65%) with cirrhosis [357 (45%) Child’s A, 274 (35%) Child’s B and 161 (20%) Child’s C)]. Analysis revealed that age correlated significantly (p

Self-induced vomiting is adopted by people with a variety of eating disorders (ED) to control body shape and weight. We tested the prevalence, the associated features and the role on treatment outcome of self-induced vomiting in 152 ED patients consecutively admitted to an inpatient cognitive-behavioral treatment (CBT), based on the transdiagnostic CBT for ED. The Eating Disorder Examination, together with the Beck Depression Inventory, the State-Trait Anxiety Inventory and the Temperament and Character Inventory were recorded at entry and at end of treatment. Self-induced vomiting was reported in 35.5% of cases, and 21.1% had multiple purging with vomiting. Individuals with vomiting and those with multiple purging had significantly higher BMI and a higher frequency of bulimic episodes, but individuals with multiple purging were also characterized by higher levels of depression, longer ED duration, more severe ED psychopathology and lower self-directness. Individuals with vomiting had higher eating concern and novelty seeking compared with those without purging behaviors. However, the three groups had similar dropout rates and outcomes in response to inpatient CBT, in keeping with the transdiagnostic theory of EDs.

Objective To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls. Design Prospective case-control study. Setting University-based practice. Patient(s) Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]). Intervention(s) Cardiovascular risk markers and hormonal parameters were assessed. Main Outcome Measure(s) Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS. Result(s) The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D. Conclusion(s) Weight and PCOS are two independent variables affecting the endothelial function.

The model of care for patients with mild-to-moderate head injury and CT-detected lesions that do not require an immediate intervention is a matter of debate. This study compared the effects on outcome of a model based either on observation in a neurosurgical unit (NSU) or in a peripheral hospital (PH), making use of neurosurgical expertise via a teleradiology system.The investigation reviewed the data that was prospectively collected in 865 cases with mild-to-moderate head injury and positive CT scan, not needing immediate neurosurgical evacuation. Outcome was determined at 6 months. The predictive value of location of observation on outcome was evaluated by logistic regression, after adjustment for the propensity score to the type of observation (calculated on main entry variables).700 subjects had a mild head injury, 105 had a moderate injury with GCS 13-11 and 60 with Glasgow Coma Scale (GCS) 10-9. Only 152/865 subjects (17.6%) were admitted to a NSU. During observation, neurosurgery was necessary in 117 cases (13.5%), 74/152 (48.7%) NSU-observed patients and 43/713 (6.0%; p0.001) PH-observed cases. The outcome was unfavourable in 18% of the NSU cases versus 10% of the PH cases (p = 0.143). After correction for propensity, no significant differences were found between models of observation (NSU vs. PH; odds ratio, 0.92; 95% confidence interval, 0.49 to 1.75).A model of care based on observation in PH with neurosurgical consult by teleradiology system, repeat CT scanning and transfer time 30-60 min to a NSU is not detrimental for subjects with initial non-neurosurgical lesions after mild-to-moderate head injury.

Subjects with nonalcoholic fatty liver disease are at risk of progressive liver failure. Lifestyle changes including weight-loss strategies and increased physical activity remain the first-line approach, but a few pharmacological treatments have also been successfully tested. Several drugs improve biochemistry, only a few improve histology; in all cases, the results were not sustained after treatment stop. Pharmacological treatment is not so far indicated outside controlled clinical trials with histological outcomes.

Objective The study was aimed at assessing the prevalence of compulsive exercising to control shape and weight in eating disorders (EDs) and its relationship with treatment outcome. Method Compulsive exercising to control shape and weight, defined according to a modified version of the Intense Exercising to Control Shape or Weight section of the Eating Disorder Examination (EDE), was assessed in 165 consecutive ED inpatients entering a protocol based on the transdiagnostic cognitive behavior theory and treatment of EDs. Baseline assessment also included anthropometry, the global EDE interview, the Beck Depression Inventory, the State-Trait Anxiety Inventory (STAI), the Eating Disorders Inventory–Perfectionism Scale, and the Temperament and Character Inventory. Results Of the patients, 45.5% were classified as compulsive exercisers, the prevalence being highest (80%) in restricting-type anorexia nervosa (AN), lowest in EDs not otherwise specified (31.9%), and intermediate in binge/purging AN (43.3%) and in purging-type bulimia nervosa (39.3%). Compulsive exercising to control shape and weight was independently predicted by the EDE restraint score (odds ratio, 1.32; 95% confidence interval, 1.06-1.64; P = .014) after adjustment for ED; the total amount of exercise was associated with EDE restraint, as well as with the Temperament and Character Inventory reward dependence. At follow-up, an improved EDE global score was predicted by lower baseline values, higher baseline STAI and STAI improvement, and lower amount of exercise in the last 4 weeks. Voluntary treatment discontinuation was not predicted by baseline exercise. Discussion Compulsive exercising to control shape and weight is a behavioral feature of restricting-type AN, associated with restraint and temperament dimensions, with influence on treatment outcome.

Background: Subjects with moderate head injury are a particular challenge for the emergency physician. They represent a heterogeneous population of subjects with large variability in injury severity, clinical course and outcome. We aimed to determine the early predictors of outcome of subjects with moderate head injury admitted to an Emergency Department (ED) of a general hospital linked via telemedicine to the Regional Neurosurgical Centre. Patients and methods: We reviewed, prospectively, 12 675 subjects attending the ED of a General Hospital between 1999 and 2005 for head injury. A total of 309 cases (2.4%) with an admission Glasgow Coma Scale (GCS) 9–13 were identified as having moderate head injury. The main outcome measure was an unfavourable outcome at 6 months after injury. The predictive value of a model based on main entry variables was evaluated by logistic regression analysis. Findings: 64.7% of subjects had a computed tomographic scan that was positive for intracranial injury, 16.5% needed a neurosurgical intervention, 14.6% had an unfavourable outcome at 6 months (death, permanent vegetative state, permanent severe disability). Six variables (basal skull fracture, subarachnoid haemorrhage, coagulopathy, subdural haematoma, modified Marshall category and GCS) predicted an unfavourable outcome at 6 months. This combination of variables predicts the 6-month outcome with high sensitivity (95.6%) and specificity (86.0%). Interpretation: A group of selected variables proves highly accurate in the prediction of unfavourable outcome at 6 months, when applied to subjects admitted to an ED of a General Hospital with moderate head injury.

OBJECTIVE To estimate if young polycystic ovary syndrome (PCOS) patients have subclinical risks of vascular disease compared with eumenorrheic polycystic ovary (PCO) women and healthy controls. METHODS Twenty-eight PCOS patients, 17 eumenorrheic PCO women, and 15 healthy eumenorrheic volunteers underwent medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; uteroovarian ultrasonographic analysis and color Doppler evaluation of uterine, stromal ovarian, and ophthalmic arteries; brachial artery flow-mediated vasodilatation; 24-hour ambulatory blood pressure monitoring. An oral glucose tolerance test was performed to analyze glucose, insulin, and C-peptide. RESULTS Doppler analysis revealed a significantly higher uterine pulsatility index in the PCOS group compared with controls. The lowest vascular resistances in the ovaries were found in PCOS and PCO compared with controls. The ophthalmic artery back pressure was significantly higher in women with PCOS than in controls. The brachial artery diameter, at baseline, was similar in all the participants. After the reactive hyperemia, a greater vasodilatation was observed in controls and PCO patients in comparison with PCOS women. Total cholesterol, triglycerides, and the atherogenic plasma index were significantly higher in PCOS than PCO and controls. Leukocytes and homocysteine were slightly higher in PCOS. The nitrites/nitrates plasma levels were lower in PCOS and PCO patients compared with controls. The insulin and C-peptide plasma values were higher in PCOS patients than controls. In PCOS patients the different estimates of insulin sensitivity and pancreatic beta-cell function were higher compared with PCO and controls. CONCLUSION Polycystic ovary syndrome is a condition associated with an increased vascular risk. LEVEL OF EVIDENCE II.

The risk of chronic liver disease and liver-related mortality is increased in patients with type 2 diabetes mellitus. Several cohort studies have suggested a metabolic pathway from nonalcoholic fatty liver, nonalcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. Although cardiovascular risk remains the major cause for excess mortality in type 2 diabetes mellitus, the risk of progressive liver disease should no longer be underscored.

Background: Very few data are available on psychological distress in morbidly obese subjects in relation to weight history. In subjects with childhood obesity, psychological distress might be better than in adult-onset obesity, because of progressive adaptation to the social stigma. Method: we tested psychological distress in relation to BMI at age 20 years (BMI-20), weight history and somatic comorbidities in 632 treatment-seeking, morbidly obese participants from the QUOVADIS cohort (130 men, 502 women; mean age 45.5 years). The number of dieting attempts/year, BMI increase and cumulative BMI loss since age 20 were calculated as weight cycling parameters. The Symptom Check List-90 (SCL-90), the Psychological General Well-Being (PGWB), the Binge-Eating Scale and the ORWELL-97 questionnaire were used to score psychometry and health-related quality of life. Complications were quantitatively assessed by a modified Charlson’s score. Results: BMI-20 was normal in 35% of cases and >35 kg/m2 in only 14%. Psychometric scores were not different in relation to BMI-20, when corrected for age, with the exception of the General Health scale of PGWB, showing a greater distress in subjects with normal BMI-20. In most cases, the prevalence of pathological results of questionnaires showed a J-shaped curve, with participants with normal BMI-20 or those with Class II-III obesity in early adulthood having the highest prevalence of psychological/ psychiatric distress and poor HRQL. Weight cycling was a risk factor for binge-eating, depression and interpersonal sensitivity at SCL-90, whereas somatic comorbidities adversely affected most SCL-90 and all PGWB scales. Conclusion: Weight cycling and somatic comorbidities, but not age of onset of obesity, are the main factors negatively influencing psychological health in treatment-seeking, morbidly obese subjects.

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common liver disorders claiming the urgent attention of both medical professionals and the public sphere because of the imminent epidemic of advanced liver injury that appendages epidemic of obesity. Recent research reveals simple triglyceride accumulation in hepatocytes (i.e., liver steatosis) frequently becoming complicated by inflammation (i.e., non-alcoholic steatohepatitis, or NASH) that may progress into more advanced stages of the disease including cirrhosis or, eventually, hepatocellular carcinoma. The exact mechanisms of the progression of NAFLD into overt NASH and advanced disease stages are largely unknown. There is urgent need in terms of both intensive research pursuits and effective practical measures to deal with this common threat.

Objectives To investigate the causes of attrition reported by obese patients treated by medical centres. Design Observational study. Setting Obese patients enrolled in a long-term study involving 18 Italian medical centres. Participants 940 obese patients (727 female; mean age, 49 yrs; mean BMI, 38.6 kg/m2) Measurements Causes of attrition reported by Droputs during a structured telephone interview Results After a median observation period of 41 months (range, 25 – 50), 766 of 940 patients (81.5%) discontinued treatment. 62% of total drop-out occurred in the first year of follow-up. 74% of Dropouts reported a single primary reasons for treatment interruption. Two primary reasons were reported by 22.4% of patients, and three reasons by 3.4%. Practical difficulties, alone or in combination, were reported by more than half of Dropouts (55%), and were the leading cause of attrition after perceived failure of treatment. Among practical difficulties, family problems or problems at work and logistics, coupled with health problems other than obesity, were the most frequent reasons of attrition, but also a perceived sense of abandonment or a bad interaction with therapists were frequently reported. Conclusion Practical difficulties and psychological problems are the most important reasons of attrition reported by patients. A therapeutic alliance addressing these issues has a large potential to reduce treatment interruption and to improve outcome in obesity.

Hepatic steatosis has been associated with fibrosis, but it is unknown whether the latter is independent of the etiology of fat infiltration. We analyzed the relationship between clinical characteristics, insulin resistance (HOMA-R) and histological parameters in 132 patients with "viral" steatosis caused by genotype 3 chronic hepatitis C (CHC-3) and 132 patients with "metabolic" steatosis caused by nonalcoholic fatty liver disease (NAFLD), matched by age, BMI, and degree of liver fat accumulation. Tests of liver function were comparable in the two study populations. The prevalence of features of insulin resistance was higher in NAFLD, as was HOMA-R (P = .008). Logistic regression analysis confirmed that steatosis was associated with a high viral load and low serum cholesterol in CHC-3, and with high aminotransferase, glucose, ferritin and hypertriglyceridemia in NAFLD. At univariate analysis, advanced fibrosis was associated with steatosis in NAFLD, but not in CHC-3. Other parameters related to fibrosis severity were HOMA-R and a low platelet count in CHC-3, and high aminotransferases, HOMA-R, ferritin and low HDL-cholesterol in NAFLD. On multivariate analysis, only low platelet count (OR = 0.78; 95% CI, 0.67-0.92) and HOMA-R (OR = 2.98; 1.13-7.89) were independent predictors of advanced fibrosis in CHC-3. In NAFLD, severe fibrosis was predicted by fat grading (OR = 3.03; 1.41-6.53), ferritin (OR = 1.13; 1.03-1.25) and HOMA-R (OR = 1.16; 1.02-1.31). In conclusion, insulin resistance is an independent predictor of advanced fibrosis in both NAFLD and CHC-3, but the extent of steatosis contributes to advanced disease only in NAFLD. Virus-induced hepatic steatosis as seen in CHC-3 does not contribute significantly to liver fibrosis.

Attrition in weight loss programs is a complex process, possibly influenced by several pretreatment patients’ characteristics and treatment variables, but available data reveal sometime contradictory results. Only a few pretreatment patients’ characteristics and treatment variables have been confirmed by more than one study as relevant risk factors, but recently new data of clinical utility emerged from “real world” large observational studies. Practical difficulties, unsatisfactory results, some psychological variables (e.g. lack of motivation, unrealistic weight loss expectations, overall level of stress, self-confidence in the ability to lose additional weight without professional help, and sense of abandonment from therapists), duration and type of treatment seem to play a crucial role in the patients’ decision of interrupting the weight loss treatment.

Clinical, epidemiological and biochemical data strongly support the concept that nonalcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome. Insulin resistance is the common factor connecting obesity, diabetes, hypertension and dyslipidemia with fatty liver and the progression of hepatic disease to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma.The association of nonalcoholic fatty liver disease with the features of the metabolic syndrome has been confirmed in several epidemiological studies. The diagnostic and clinical significance of raised liver enzymes has been questioned; advanced hepatic disease may also be present in individuals with ultrasonographically detected steatosis and normal aminotransferase levels. The role of adipokines (leptin, adiponectin) and cytokines (tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta) in disease progression is probably pivotal, mediated by oxidative stress. The importance of iron accumulation in this process has not been confirmed. Treatments aimed at weight loss remain a primary option; among pharmacological interventions, insulin sensitizers (glitazones and metformin) have confirmed beneficial effects on both biochemical and histological data, but new treatments are on the horizon.Nonalcoholic fatty liver disease prevalence in Western countries is high and there is a trend towards a further increase, with millions of people at risk of advanced liver disease. The epidemiological evidence, the lifestyle origin of the disease and the cost of pharmacotherapy make prevention a primary goal, and will contribute to making behavior therapy the background treatment. We need specific programs and carefully controlled, randomized studies to tackle simultaneously all the components of the metabolic syndrome.

Background. Previous studies reported an impairment of both the physical and mental dimensions of quality of life in patients with cirrhosis. Very few data are available on the psychological impact of the disease and its relation to liver function. Aim. To measure the psychological status of patients with cirrhosis in relation to the severity of the liver impairment. Patients and methods. One hundred and fifty-six patients with cirrhosis were studied. Two questionnaires (the Beck Depression Inventory and the Psychological General Well-Being Index) were self-administered in random order. Clinical and laboratory data were collected using standardised forms. Results. The global score of Psychological General Well-Being Index was severely reduced compared to Italian population norm. Among individual domains, the more severely affected was General Health, the less compromised was Positive Well-Being. A negative relation was found between Child–Pugh score (a comprehensive measure of disease severity) and global Psychological General Well-Being Index and several individual subscales. The Beck Depression Inventory scores were indicative of a depressed mood in over 50% of patients, in relation to the presence of clinical symptoms. Conclusions. Patients with cirrhosis have signs of psychological distress and depression, as assessed by Beck Depression Inventory and Psychological General Well-Being Index, in relation to the severity of liver disease. Accordingly, a non-negligible number of patients warrant treatment.

Nonalcoholic fatty liver disease (NAFLD) is systematically associated with features of metabolic syndrome, a condition carrying a high risk of cardiovascular events. We measured the percent vasodilation of brachial artery in response to ischemia (a test of endothelial function)(FMV) and cardiovascular risk profile in 52 NAFLD cases and 28 age- and gender-matched controls. The 10-year risk of coronary events was calculated according to the Framingham equation and the scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33 ± SD 5.93% in NAFLD vs. 12.22 ± 5.05% in controls (P < 0.0001), and higher in pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%)(P = 0.010). No differences were observed in flow-independent vasodilation (response to sublingual nitroglycerin). Percent FMV was negatively associated with insulin resistance (homeostasis model assessment) in the whole population (r = -0.243; P = 0.030). In logistic regression analysis, NAFLD was associated with a percent FMV in the lower tertile (odds ratio, 6.7; 95% confidence interval, 1.26-36.1), after adjustment for age, gender, BMI and insulin resistance. Among NAFLD patients, low FMV was associated with nonalcoholic steatohepatitis (adjusted-odds ratio, 6.8; 1.2-40.2). The 10-year probability of cardiovascular events was moderately increased in NAFLD, and particularly in nonalcoholic steatohepatitis. Our study provides evidence of endothelial dysfunction and increased risk of cardiovascular events in NAFLD. The risk of advanced liver disease is well-recognized in NAFLD patients, but the large majority of cases might probably experience cardiovascular disease in the long-term, indirectly limiting the burden of liver failure.

The obesity and diabetes epidemics are driving the NAFLD epidemic. Although the overall risk of HCC in NAFLD is lower than in liver disease of different etiology, the very high number of cases will constitute a worldwide challenge for National Health Systems. The diabetes-associated progression of NASH/cryptogenic cirrhosis to HCC is slow, but effective treatments are limited by comorbidities, which also reduce the inclusion in liver transplant lists. New diabetes treatments might help decrease the future burden of diabetes-associated HCC.

Nonalcoholic fatty liver disease (NAFLD) is a disease of affluence, and the epidemics of obesity and diabetes in the Western world put an increasing number of subjects at risk of liver-related morbidity and mortality in the coming years. Cross-sectional studies have suggested predictors of advanced disease, and the severity of steatosis per se, as well as insulin resistance and its clinical correlates are associated with greater risk. Only a few longitudinal studies are available [1,2], but data support the hypothesis that intervention programs are worth establishing to halt disease progression. What is the best treatment for NAFLD? Several pilot and uncontrolled studies on drug treatment have been published and a few randomized controlled studies are also available (for a recent review, see Bugianesi et al. [3]). Insulinsensitizing agents are the most promising drugs; there is evidence that both metformin [4,5] and glitazones [6,7] produce positive effects on biochemistry (alanine aminotransferase levels), as well as on histology. Following treatment, not only steatosis, but also necroinflammatory changes and fibrosis are of lower grade at follow-up liver biopsies. But some issues remain unanswered: (a) How long should treatment be continued? (b) Is treatment able to prevent terminal liver failure? It will take years before a definite answer is available. The evidence of NAFLD as part of the metabolic syndrome opens the possibility that both the onset of disease and disease progression may be prevented by changes in lifestyle. Obesity, type 2 diabetes and hypertension benefit from healthier lifestyles, and all guidelines suggest that pharmacological treatment should be started only when

The treatment of non-alcoholic fatty liver disease may be worthwhile to prevent progression to advanced liver failure, but no therapy is definitely evidence-based. Weight loss or lifestyle modifications remain the primary line of intervention, particularly in overweight or obese subjects. In adult non-alcoholic fatty liver disease, they are effective in the short-term, but require a multidisciplinary team approach that is rarely available in liver units. Insulin-sensitizing agents are probably the treatment of choice. They definitely reduce the insulin resistance that promotes steatosis. Several uncontrolled and controlled studies have documented an improvement in liver biochemistry and in histology, but the long-term results remain unsettled. This is an area where significant advances are expected in the next few years.

From a clinical point of view, our results, along with literature data, show that EFT, a psychotherapy focused on the cognitive and interpersonal experiential perspectives of emotions associated with DC, produces promising results on binge eating remission, weight loss, binge eating behavior and health-related quality of life in treatment-seeking BED patients with obesity. The data also suggest that the combination of EFT and DC might be a promising strategy to produce both an improvement of the eating disorder psychopathology and a healthy amount of weight loss. The main limitations of the study include the short-term follow-up, the different rates of dropout between groups and the nonrandom assignment to groups. Matching by propensity, the advantages and limits of which have been discussed elsewhere, may only partly overcome the allocation bias. Our data may be considered the basis for future confirmatory studies with long-term follow-up and a randomized controlled design.

Night eating syndrome is an eating disorder characterized by a delay in the circadian timing of food intake, which is remarkably reduced during the first part of the day and greatly increased after dinner, frequently with awakenings characterized by nocturnal food ingestion and morning anorexia. In the absence of standard diagnostic criteria, its prevalence is difficult to estimate. According to the most agreed criteria, the disorder affects approximately 1.5% of the general population, it is more common among obese persons and the prevalence increases with increasing adiposity. Longitudinal studies with adequate follow-up are needed to determine whether night eating contributes to weight gain and the development of obesity. The research should also aim to assess the interaction of genetic and environmental processes in the pathogenesis and in the maintenance of the disorder. There is no satisfactory treatment of night eating. Limited information is available on drug treatment (sertraline, topiramate). Lifestyle modifications aimed at weight loss are standard treatment whenever night eating is associated with obesity and have demonstrated a favorable effect, but more research is needed also in this area to optimize the protocols.

SUMMARY. Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate–severe if ‡20%. Patients underwent standard of care therapy with pegylated interferon and ribavirin. The severity of steatosis progressively increased according to sCD36 quartiles (P = 0.02); total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in patients in the lower quartile compared to all the others. Gamma-glutamyl transferase (P = 0.02), homoeostasis model assessment (HOMA) score (P = 0.002) and sCD36 (P = 0.04) were independently associated with the severity of steatosis as continuous variable. Multivariate logistic regression analysis showed that HOMA (OR 1.243, 95% CI 1.04–1.484, P = 0.01) and sCD36 (OR 1.445, 95%CI 1.135–1.839, P = 0.003) were independently linked to steatosis ‡20%. No association was found between sCD36 and SVR. CD36 is linked to steatosis and insulin resistance in patients with G1 CHC, but does not predict response to treatment. The potential of sCD36 as a surrogate marker of steatosis should be further investigated.

Subjects with chest pain and a negative diagnostic workup constitute a problem for emergency physicians. We tested the usefulness of clinical variables in predicting 30-day and 6-month outcome in subjects with chest pain of undifferentiated origin after a negative workup.Chest pain of undifferentiated origin was diagnosed by negative first-line (serial electrocardiograms, troponins assays, and 12- to 24-hour observation) and second-line evaluation (echocardiography, exercise tolerance test, stress scintigraphy, stress echocardiography, coronary angiography). Thirty-day and 6-month outcomes were considered unfavorable in the presence of any of the following: death, acute coronary syndrome, need for urgent coronary revascularization. The variables considered for risk stratification were age, sex, smoking, family history of coronary artery disease, presence of hypertension, high cholesterol levels, diabetes, chronic renal failure, cerebral vascular disease, and history of acute coronary syndrome, percutaneous transluminal angioplasty (PTA), coronary artery by pass graft, and heart failure.Five items (diabetes, chronic renal failure, history of PTA or bypass, history of heart failure) were associated with 30-day unfavorable outcome (31 events/1262 cases; 2.5%). The receiver operating characteristic area of the selected items was 0.726 (95% confidence interval [CI], 0.654-0.798); sensitivity was 90.3% (73.1-95.8) and specificity was 54.8% (52.0-57.6). A similar panel of items (older age, diabetes, chronic renal failure, history of PTA) predicted an unfavorable 6-month outcome (90 subjects [7.1%], with lower accuracy (receiver operating characteristic area, 0.610 [95% CI, 0.594-0.627, P.05]; sensitivity, 98.9% [95% CI, 93.1-99.6]; specificity, 21.6% [95% CI, 19.4-23.9]).In subjects with chest pain of undifferentiated origin, the risk of unfavorable outcome cannot be accurately predicted by the selected clinical items.

The impact of diabetes mellitus (DM) on public health is growing worldwide due to its increasing prevalence and the severity of complications. According to the ARNO observational study, a population-oriented database containing 20 years of medical prescriptions for over 10 million Italians in 30 Local Health Districts of 7 regions, the prevalence of pharmacologically treated DM increased from 3% to over 5% from 1997 to 2008; the associated direct costs may be estimated to be 54% higher per population unit compared to similar patients without DM. Over the years, pharmacological treatment has been modified according to the results of recent trials (metformin as initial treatment, larger use of cholesterol and blood pressure lowering drugs), but drug use remains far below the standards proposed by guidelines, and clinical targets are not systematically reached. More aggressive treatment based on both standard and innovative pharmacological approaches would be needed to reduce the clinical burden of the disease, but such a policy would increase the total cost of DM to levels largely incompatible with economic resources in an era of financial crisis. A policy that promotes primary prevention, involving decision makers at different levels, even outside the National Health System, is urgently needed.

Backgrounds & Aims: Healthy diet and physical activity are the treatment cornerstones of non-alcoholic fatty liver disease (NAFLD); their effectiveness is however limited by difficulties in implementing lifestyle changes. We aimed at determining the stage of change and associated psychological factors as a prerequisite to refine strategies to implement behavior changes. Methods: We studied 138 consecutive NAFLD patients (73% male, age 19-73 years). The diagnosis was confirmed by liver biopsy in 64 cases (steatohepatitis, 47%). All cases completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments (for diet and physical activity, respectively) and providing stages of change according to transtheoretical model. Logistic regression analysis was used to identify factors associated with stages making behavioral changes more demanding. Results: The individual profiles were variable; for diet, no cases had precontemplation as prevalent stage of change (highest score in individual profiles); 36% had contemplation. For physical activity, 50% were classified in either precontemplation or contemplation. Minor differences were recorded in relation to associated metabolic complications or steatohepatitis. Logistic regression identified male sex (odds ratio, 4.51; 95% confidence interval, 1.69-12.08) and age (1.70; 1.20-2.43 per decade) as the independent parameters predicting precontemplation or contemplation for diet. No predictors were identified for physical activity. Conclusions: NAFLD cases have scarce readiness to lifestyle changes, particularly with regard to physical activity. Defining stages of change and motivation offers the opportunity to improve clinical care of NAFLD people through individual programs exploiting the powerful potential of behavioral counseling, an issue to be tested in longitudinal studies. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Objective: To define the utility of the DSM-IV-TR definition of binge eating, as it applies to anorexia nervosa (AN) and underweight eating disorder not otherwise specified (ED-NOS). Method: We investigated the psychopathological features associated with bulimic episodes in 105 underweight individuals with eating disorders who reported regular objective bulimic episodes with or without subjective bulimic episodes (OBE group, n = 33), regular subjective bulimic episodes only (SBE group, n = 36) and neither objective nor subjective bulimic episodes (n = 36, no- RBE group). The Eating Disorder Examination (EDE), anxiety, depression, and personality tests were administered before and upon completion of inpatient cognitive behavior therapy (CBT) treatment 6 months later. Results: Compared with the SBE group, OBE subjects had higher body mass index, and more frequent self-induced vomiting, while both OBE and SBE groups had more severe eating disorder psychopathology and lower self-directness than the no-RBE group. Dropout rates and outcomes in response to inpatient CBT were similar in the three groups. Discussion: Despite a few significant differences at baseline, the similar outcome in response to CBT indicates that categorizing patients with underweight eating disorder on the basis of the type or frequency of bulimic episodes is of limited clinical utility.

L’epidemia di diabete di tipo 2 nel mondo non più solo occidentale trova le sue origini anche dalla combinazione di comportamenti non salutari e potrebbe largamente essere corretta da un’educazione a uno stile di vita più sano. Terminata la stagione dei grandi trial di prevenzione, si sta affermando la stagione dell’intervento nella popolazione con diabete, con tutte le difficoltà prevedibili considerando il numero delle persone sulle quali intervenire e le difficoltà nelle quali operano già le strutture diabetologiche. Così come in altri Paesi, anche dalla realtà italiana sono state pubblicate esperienze positive sia attraverso programmi specifici sia attraverso l’utilizzazione di sussidi che favoriscono la motivazione al cambiamento. Analogamente a quanto dimostrato nella terapia dell’obesità, la dieta prescrittiva può essere ormai considerata una metodologia obsoleta, non garantendo alcuna aderenza e risultato nel lungo termine. Occorre oggi ripensare l’organizzazione dei servizi di diabetologia e dei team diabetologici per fornire ai pazienti una cura più efficace. In questo lavoro vengono passate in rassegna le principali esperienze pubblicate, documentandone gli effetti favorevoli e le difficoltà che ancora si frappongono alla loro diffusione. SUMMARY Lifestyle interventions in diabetes – where are we now? The epidemics of type 2 diabetes, no longer involving exclusively western countries, is largely due to a combination of unhealthy lifestyles and might be corrected by healthy diet and physical activity. Following the results of the large intervention trials on diabetes prevention, the focus is now on diabetes treatment. Here, the very large number of cases to be treated and the paucity of resources may be an insurmountable limit for most diabetes unit. As well as in different Countries, also in Italy we do have successful experiences published in the literature. They have been carried out either by in-house developed programs or by the use of tools favoring behavior changes. The use of prescriptive diet, as also observed in the treatment of obesity, does not guarantee long-term adherence and weight loss maintenance. We need to reconsider the organization of the diabetes Unit and diabetes team, in order to provide more effective treatment. We review the most important experiences in the behavior treatment of diabetes, underlining the favorable effects and the limits totheir full implementation.

Background Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are both highly prevalent in the general population and associated with obesity and insulin resistance. We aimed to evaluate the prevalence of GD in a cross sectional study of NAFLD patients and to define whether the presence of GD is associated with diabetes and predicts more severe liver disease. Methodology/Principal Findings We merged databases of four Liver Units, comprising 524 consecutive biopsy-proven NAFLD (373 males) observed between January 2003 and June 2010. GD was diagnosed in 108 (20%), and 313 cases (60%) were classified by liver biopsy as nonalcoholic steatohepatitis (NASH). The GD subgroup was characterized by a significantly higher prevalence of females, prediabetes/diabetes, abdominal obesity and metabolic syndrome, older age, higher BMI, fasting glucose, HOMA-IR and lower ALT. The prevalence of GD progressively increased with advancing fibrosis and with the severity of necroinflammatory activity (p for trend = 0.0001 and = 0.01, respectively), without differences in the severity of steatosis. At multivariate analysis GD was associated with female gender (OR 1.37, 95% CI 1.04–1.8), age (OR 1.027, 95% CI1.003–1.05), fasting glucose (OR 1.21, 95% CI 1.10–1.33) and NASH (OR 1.40,95% CI 1.06–1.89), whereas ALT levels were associated with a lower GD risk (OR 0.98, 95% CI 0.97–0.99). When subjects with cirrhosis were excluded from analysis, the association between GD and fasting glucose, female gender, and NASH was maintained. Conclusion Patients with NAFLD have a high prevalence of GD, which characterizes subjects with altered glucose regulation and more advanced liver disease.

The restoration of a normal body weight is a key strategy in the treatment of eating disorders, in order to eliminate the adverse effects of starvation on health and on the eating disorder psychopathology. Unfortunately, weight regain is frequently hindered by changes in body shape, in particular a protrusion of the abdomen, which may lead underweight patients to stop their nutritional rehabilitation program. In adult patients with underweight eating disorders, studies using dual-energy X-ray absorptiometry, skinfold thickness, dual photon absorptiometry and circumference measurements found a preferential accumulation of body fat in the central regions rather than the extremities during the process of weight regain. These data, however, were not confirmed in adolescents and in young adults with eating disorders. To date, the mechanism(s) implicated in the preferential accumulation of abdominal fat (e.g., low level of estrogens, fast rate of weight regain) have not been settled by experimental research, nor is it settled whether the preferential accumulation is a transient phenomenon or it persists after complete and stable weight restoration. Available data indicate that weight regain produces an increase in bone mineral density, initially greater in the hip than in the spine, but in the long-term bone recovery is never complete, especially whenever the eating disorder starts during adolescence and peak bone mass has not been attained. As lack of exercising may contribute to decrease bone mass, to increase the risk for atherosclerosis and to decrease compliance with the program, clinicians tend to incorporate healthy and social exercising in the nutritional rehabilitation. Preliminary findings indicate that this procedure helps patients get out of the isolation of their disease, overcome the urge to exercise, accept weight gain and changes in shape, and increase lean body mass, while it does not reduce the short-term gain of body fat or BMI.

Background: Overweight and obesity prevention in childhood and adolescence represent a priority for public health; school is a privileged place for health promotion interventions. Objectives: The study aimed to test the effectiveness of a multicomponent 5-month intervention on the habits of primary school children, making the families aware of the importance of healthy choices. Methods: Two hundred nine children attending the fourth class of primary school, divided into interventional (n = 103) and control arm (n = 106) were included in the study. In the intervention group, parents and teachers received more intense lifestyle counseling, associated with weekly motivational telephone calls to families to motivate further their lifestyle changes. Standard deviation score (SDS) body mass index (BMI) was the primary outcome measure; on open-air games and TV watching were secondary outcomes. Results: At baseline, no differences were observed between groups. At 8-month follow-up, mean SDS BMI had decreased by 0.06 units in the intervention arm and increased by 0.12 in controls (time x treatment ANOVA, P < 0.002). Outdoor activities increased from 6.23 h week-1 to 9.93 in the intervention group (P < 0.001), not in controls. This change was associated differences in TV watching from baseline (intervention, -0.96 h week-1; P = 0.037; controls, +1.33 h week-1; P = 0.031). Conclusion: A multicomponent school-based intervention addressing the needs of children, teachers and families produced a significant and favourable short-term effect on overweight/obese schoolchildren.

A marked variability has been documented in the therapeutic approaches to diabetes by various countries, suggesting that the level of care currently delivered may not produce the expected health-related gains. We investigated quality of care indicators in a large, representative multiregional population-based cohort of people (the ARNO Observatory) living in four Italian regions (2 million inhabitants), assessing process indicators and hospital admissions as outcome indicators. Diabetic individuals were identified in 2010 through record linkage among prescriptions, hospital admissions, and local diabetes registries. The guidelines of the Italian scientific societies recommend that risk factors such as lipids and microalbuminuria should be tested at least once a year in all patients with type 2 diabetes, and HbA1c should be tested at least twice a year, even in people with stable glycemic control over time and more frequently in insulin-treated and -complicated people. Of 126,163 diabetic individuals (prevalence of diabetes 5.8%, mean age 71 years), as many as 42% did not have their HbA1c measured for over a year. Even considering only insulin-treated people, this frequency remains disappointingly high (35%). The proportion of people having at least two annual tests for HbA1c was low (32.7%; 43.1% among insulin-treated patients).

OBJECTIVE To ascertain to which extent the use of HbA1c and oral glucose tolerance test (OGTT) for diagnosis of glucose tolerance could identify individuals with different pathogenetic mechanisms and cardiovascular risk profile. RESEARCH DESIGN AND METHODS A total of 844 subjects (44%men; age 49.5 +- 11 years; BMI 29 +- 5 kg/m2) participated in this study. Parameters of b-cell functionwere derived from deconvolution of the plasma C-peptide concentration after a 75-g OGTT and insulin sensitivity assessed by homeostasismodel assessment of insulin resistance (IR). Cardiovascular risk profile was based on determination of plasma lipids and measurements of body weight, waist circumference, and blood pressure. Glucose regulation categories byOGTT and HbA1c were comparedwith respect to insulin action, insulin secretion, and cardiovascular risk profile. RESULTS OGTT results showed 42% of the subjects had prediabetes and 15% had type 2 diabetes mellitus (T2DM), whereas the corresponding figures based on HbA1c were 38 and 11%, with a respective concordance rate of 54 and 44%. Subjects meeting both diagnostic criteria for prediabetes presented greater IR and impairment of insulin secretion and had aworse cardiovascular risk profile than those with normal glucose tolerance at both diagnostic methods. In a logistic regression analyses adjusted for age, sex, and BMI, prediabetic subjects, and even more T2DM subjects by OGTT, had greater chance to have IR and impaired insulin secretion. CONCLUSIONS HbA1c identifies a smaller proportion of prediabetic individuals and even a smaller proportion of T2DM individuals than OGTT, with no difference in IR, insulin secretion, and cardiovascular risk profile. Subjects fulfilling both diagnostic methods for prediabetes or T2DM are characterized by a worse metabolic profile.

Summary. The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate–severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004–1.070, P = 0.02), higher WC (1.031; 1.004–1.060; P = 0.02) and higher TyG (11.496; 3.163–41.784; P

OBJECTIVE To analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications. RESEARCH DESIGN AND METHODS Case/noncase bladder cancer reports associated with antidiabetic drug use were retrieved from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR). RESULTS Ninety-three reports of bladder cancer were retrieved, corresponding to 138 drug-reaction pairs (pioglitazone, 31; insulin, 29; metformin, 25; glimepiride, 13; exenatide, 8; others, 22). ROR was indicative of a definite risk for pioglitazone (4.30 [95% CI 2.82–6.52]), and a much weaker risk for gliclazide and acarbose, with very few cases being treated with these two drugs (6 and 4, respectively). CONCLUSIONS In agreement with preclinical and clinical studies, AERS analysis is consistent with an association between pioglitazone and bladder cancer. This issue needs constant epidemiologic surveillance and urgent definition by more specific studies.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is becoming one of the most common causes of chronic liver disease worldwide. The economic and social cost of disease is very high and there is a need for effective treatments. Areas covered: The available and potential future treatments for NAFLD are reviewed. Expert opinion: Weight loss remains the cornerstone of treatment of hepatic steatosis, but difficult to pursue. A pragmatic approach relies on generic recommendations for weight loss and physical activity in the whole population and limiting interventions to subject at risk of disease progression, but the type of preferred treatment remains a matter of debate. The large number and mechanistic diversity of drugs that have so far been investigated bear testimony to the lack of a specific, effective agent. Insulin resistance remains the pivotal alteration responsible for liver disease and its progression and insulin sensitizers are regarded as the treatment of choice. Several ongoing studies are testing the effectiveness of new approaches on histological outcomes and new metabolic pathways are under scrutiny.