Management of dairy heifers: can operant conditioning be an effective and feasible tool to decrease stress and ease animals' close contact and handling?

Beside health monitoring, a regular check of dairy heifers' growth rate is desirable, but it is rarely done since procedures that require restraint and handling can be associated with substantial stress for both animals and farmers. Inexperienced heifers, especially if they are highly responsive to humans, may find restraint and handling potentially aversive. This study investigated whether training heifers of different age and responsiveness toward humans (RTH), through operant conditioning, could reduce stress in animals, ease close contact and handling, and be feasible in terms of farmer's effort. We assessed 60 Holstein heifers of 2 age classes (Young, n = 29, 291 ± 39; Old, n = 31, 346 ± 62 d) according to the Avoidance Distance Test (ADT) and classified them as Confident (C, n = 20), Neutral, (N, n = 21) or Non-confident (NC, n = 19). Half of the heifers of each age and RTH class was trained (Tr, n = 29), whereas the other half was not (NTr, n = 31). The Tr heifers were subjected to target training for 8 sessions and positively reinforced with feed to allow being touched on the muzzle, rump and perineum. In case a heifer refused positive reinforcement, the trainer stepped back as negative reinforcement. In the last week of the experiment the effect of training on the reaction to handling was assessed in all heifers. We measured heart rate (HR), root mean square of successive inter-beat interval differences (RMSSD) and fecal cortisol metabolites (FCMs). The presence of behavioral distress signs was recorded as well. The ADT was performed a second time 24 h after the measuring session. All the trained heifers, regardless of RTH class, successfully accomplished the target training task in 6 sessions, spending on average 25.3 s per session, each. All the trained heifers allowed to be touched on the rump and perineum at the end of the 4th session. Training NC heifers required more time compared with the others. Trained heifers showed higher RMSSD (14.2 vs. 16.9), indicating a lower vagal tone, and thus, a slightly lower stress level than NTR. Training did not lead to differences in HR, FCMs or presence of stress behavioral signs. NC heifers had the highest mean baseline FCM values (38.4 vs. 30.3 vs. 29.1 ng/g) compared with N and C. NC heifers showed also the lowest value of FCMs, 12 h after the measuring session (36.7 vs. 44.6 vs. 49.7 ng/g), likely due to a decreased responsiveness of the adrenal gland to a stressor. The average avoidance distance decreased between the beginning and the end of the experiment, especially for N and NC heifers, regardless whether they were trained or not. These results show how using operant conditioning on some heifers, not only decreased their vagal tone, but reduced the responsiveness to humans of all the animals, trained and not trained; in the latter case, through non-associative learning, such as habituation.

Impact of migration on diabetes burden: audit in the metropolitan area of Bologna, Italy.

PURPOSE: To investigate the impact of diabetes in immigrants on the Italian healthcare system, as well as their compliance with standard protocols of control and treatment. METHODS: The prevalence of immigrants with diabetes living in the metropolitan area of Bologna (about 1 million inhabitants) in 2019 was investigated using a database containing all subjects in active follow-up for diabetes, based on antidiabetic drug use, disease-specific copayment exemption, ICD-9 codes, continuous care in diabetes units. Country of origin was derived from fiscal code. RESULTS: The overall prevalence of diabetes (n = 53,941; 51.8% males, median age 64) was 6.1% in both Italy-born and immigrant cohorts. Immigrant prevalence was 12.4%, moderately higher than that observed in the total population (12.2%). Diabetes risk was increased in the whole immigrant cohort (odds ratio (OR) 1.74; 95% Confidence Interval (CI) 1.69-1.79). Among cases with incident diabetes, the proportion of immigrants (median age, 49 vs. 65 in Italy-born individuals) increased progressively from 11.7% to 26.5% from 2011 to 2019 (males, 8.9-21.0%; females, 14.9-32.8%) in all age groups, particularly in young adults, but also in older subjects. Metabolic control was lower in immigrants, as was adherence to shared diagnostic and therapeutic protocols, without systematic differences in antidiabetic drug use, but much lower use of drugs for comorbid conditions. CONCLUSIONS: The population with diabetes in the metropolitan area of Bologna is rapidly changing. Quality improvement initiatives are needed to reduce the burden for the universalistic Italian health care system generated by the rapidly-growing high-risk immigrant population.

A Survey of Dog Owners' Attitudes toward Treats.

Commercially available dog treats have become very popular and a common part of the pet's diet, yet very little is known about peoples' opinions and feeding habits; therefore, a survey was shared on a popular social network.Most of the self-selected interviewed owners (n = 1833, 83%) use treats regularly, mainly to reward their dog's behavior or during training-sports activities. Owners usually buy several types of treats, of which biscuits and dental care sticks are the most common, and usually hand out one to five pieces to their dogs every day. Most owners read the labels of the treats to seek the ingredients list and the claimed health benefits; contrarily, many owners look for non-nutritional values, such as flavor (n = 321, 18%), brand (n = 72, 4%) or shape (n = 46, 3%). Seventy-five percent of the owners (n = 1369) follow the feeding instructions provided by the producers on the label.Treat feeding is a common practice among dog owners and there is great variability among regimens (e.g., types and quantities provided). Understanding the owner's attitudes could help veterinarians educate them to manage treats in the dog's diet.

Type 2 diabetes treatment and progression of chronic kidney disease in Italian family practice.

AIMS: Progressive chronic kidney disease represents a dreadful complication of type 2 diabetes mellitus (T2DM). We tested the pattern of use and the renal effects of old glucose-lowering drugs in T2DM patients cared for by Italian general practitioners (GPs). METHODS: Data of 2606 T2DM patients were extracted from the databases of GPs, who do not have access to the most recent glucose-lowering drugs in Italy. The rate of kidney function decline was calculated by CKD-EPIcr, based on two consecutive creatinine values. RESULTS: Metformin was used in 55% of cases, either alone or with sulfonylureas/repaglinide, across the whole spectrum of CKD (from 66% in stage G1 to only 8% in G4). Sulfonylurea use peaked at 21-22% in stage G2-G3a, whereas repaglinide use significantly increased from 8% in G1 to 22% in G4. The median rate of CKD decline was - 1.64 mL/min/1.73 m2 per year; it was higher in G1 (- 3.22 per year) and progressively lower with CKD severity. 826 cases (31.7%) were classified as fast progressors (eGFR decline more negative than - 5 mL/min/1.73 m2 per year). The risk of fast progressing CKD was associated with increasing BMI, albuminuria, and sulfonylurea use, alone (OR, 1.47; 95% confidence interval, 1.16-1.85), or in association with metformin (OR, 1.40; 95% CI 1.04-1.88). No associations were demonstrated for metformin, cardiovascular and lipid lowering drug use. CONCLUSION: In the setting of Italian family practice, sulfonylurea use is associated with progressive CKD in patients with T2DM. Metformin, at doses progressively reduced according to CKD stages, as recommended by guidelines, is not associated with fast progression.

Pharmacovigilance of sodium-glucose co-transporter-2 inhibitors: What a clinician should know on disproportionality analysis of spontaneous reporting systems.

Sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) have consistently demonstrated a clinically significant reduction of cardiovascular mortality. However, their safety in clinical practice is still incompletely characterized, and post-marketing monitoring is required considering the expected increase in clinical use. Different analyses of international spontaneous reporting systems, known as disproportionality analyses (DAs), have highlighted the occurrence of ketoacidosis, amputations, acute renal failure and skin toxicity. In this viewpoint, we critically appraise these pharmacovigilance data on SGLT2-Is, with the aim of supporting clinicians in proper interpretation of these studies, and discussing their risk-benefit profile. To this aim, we offer a broad perspective on basic technical aspects subtending DAs of spontaneous reporting databases (describing peculiarities of the Food and Drug Administration Adverse Event Reporting System), their common and evolving uses, key pitfalls in presenting study results (in terms of "risk" or "association") and relevant strategies to account for major confounders. This will also facilitate reviewers and editors in proper evaluation of DAs, and prompt pharmacovigilance experts in converging towards a set of minimum requirements in standardization of design, performance and reporting of DAs. A consensus on quality assessment of DAs will finally establish their transferability to clinical practice. It is anticipated that DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient.

Sense of coherence, self-esteem, and health locus of control in subjects with type 1 diabetes mellitus with/without satisfactory metabolic control.

BACKGROUND: Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. AIM: To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. SUBJECTS AND METHODS: Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels <7%-53 mmol/mol). RESULTS: In the overall population, SOC was negatively associated with BMI and average HbA1c, as was the association of self-esteem with HbA1c. Subjects attaining the desired metabolic target were characterized by higher SOC scores, higher Internal HLOC and prevalent Internal vs. Powerful-others HLOC. Compared to subjects in good metabolic control, subjects with unsatisfactory control had lower scores of SOC, Internal HLOC and Self-esteem, with no difference in Powerful others, or Chance HLOC. In the same group, SOC in the upper tertile was significantly associated with self-esteem (OR 1.35; 95% CI 1.08-1.69) and PHLOC (OR 1.24; 95% CI 1.03-1.49), after adjustment for age, sex, educational level, and comorbidities. CONCLUSIONS: Patients who fail to reach a satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis of international spontaneous reporting systems.

BACKGROUND AND AIMS: We assessed post-marketing safety of sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) by analyzing adverse events (AEs) reported in international pharmacovigilance databases. METHODS AND RESULTS: Eudravigilance, WHO-Vigibase (as of Feb 25, 2017) and the FDA Adverse Event Reporting System (FAERS, from 2004 to 2016 second quarter) were queried to extract AEs recording SGLT2-Is as suspect. Disproportionality analyses (case/non-case method) were performed in FAERS by calculating the reporting odds ratios (RORs) from System Organ Classes (SOCs) to Preferred Terms (PTs) (precise clinical entities). Potential signals were defined by statistically-significant ROR (lower limit of the 95% confidence interval - LL95%CI - >1) undetected by literature analysis (as of December 2016). SGLT2-Is were recorded in 7972, 19,775, 11,137 reports (Eudravigilance, WHO-Vigibase and FAERS, respectively); in FAERS, statistically significant ROR emerged for the following SOCs: "infections and infestations" (N = 2162; LL95%CI = 3.25), "metabolism and nutrition disorders" (2278; 1.36), "renal and urinary disorders" (1665; 2.31), "reproductive system and breast disorders" (471; 4.85), "skin and subcutaneous tissue disorders" (1136; 1.52). Skin toxicity emerged as potential signal (e.g., rash, photosensitivity, urticaria as PTs), both for SGLT2-Is as a class and as individual drugs. Severe adverse skin events (81 reports, 7% of the skin cases) mainly occurred in females aged 18-65 using SGLT2-Is as single antidiabetic regimen. CONCLUSION: Among antidiabetics, SGLT2-Is are associated with higher reporting of infections, metabolism, renal and reproductive AEs, corroborating clinical trial evidence. Their large reporting patterns and the unexpected signal of skin toxicity justify active vigilance by clinicians and "real-time" monitoring by pharmacovigilance experts.

Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). AIM: To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. METHODS: We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass index ≤37 in males and ≤28 in females. RESULTS: The prevalence of sarcopenia showed a linear increase with the severity of fibrosis, and severe fibrosis (F3-F4) was more than doubled in sarcopenia (48.3% vs. 20.4% in fibrosis ≤F2, P < 0.001). After adjusting for confounders, the association of sarcopenia with severe fibrosis was maintained (OR 2.36, CI 1.16-4.77, P = 0.01), together with age > 50 (OR 6.53, CI 2.95-14.4, P < 0.001), IFG/Diabetes (OR 2.14, CI 1.05-4.35, P = 0.03) and NASH (OR 13.3, CI 1.64-108.1, P = 0.01). Similarly, a significant association was found between sarcopenia and NASH (P = 0.01), steatosis severity (P = 0.006), and ballooning (P = 0.01), but only the association with severe steatosis was maintained (OR 2.02, CI 1.06-3.83, P = 0.03) after adjusting for confounders. CONCLUSIONS: In Western patients with NAFLD, with high prevalence of metabolic disorders and advanced liver disease, sarcopenia was associated with the severity of fibrosis and steatosis, independently of hepatic and metabolic risk factors. Studies are needed to assess the impact of interventions to reduce sarcopenia on NAFLD progression.

Incidence, prevalence, costs and quality of care of type 1 diabetes in Italy, age 0-29 years: The population-based CINECA-SID ARNO Observatory, 2002-2012.

BACKGROUND AND AIMS: To assess temporal trend in incidence (2003-12) and prevalence (2002-12) of type 1 diabetes in children and young adults, direct costs and selected indicators of quality of care under the coverage of the universalistic Italian National Health System (NHS). METHODS AND RESULTS: The ARNO Observatory, a healthcare monitoring system based on administrative data, identified a population-based multiregional cohort of subjects aged 0-29 years. Type 1 diabetes was defined by at least two prescriptions of insulin over 12 months and continuous insulin-treatment in the following year. Indicators of quality of care and directs costs were assessed in persons with diabetes and in people without diabetes, individually matched for age, gender and health unit (1:4 ratio). We identified 2357 incident cases of type 1 diabetes aged 0-29 years (completeness of ascertainment, 99%). Incidence rates were similar in ages 0-14 (15.8, 95% CI 14.9-16.8) and 15-29 years (16.3, 15.4-17.2), with no significant trend. Prevalence increased from 137 to 166.9/100,000, particularly in the age 15-29 years. Direct costs accounted for € 2117 in persons with diabetes and € 292 in control individuals. A statistically significant decreasing trend in hospitalization for acute complications was evident (p < 0.001), which was almost completely due to ketoacidosis. People with at least one HbA1c measurement over the year were 48.5%. CONCLUSION: We showed high incidence and increasing prevalence of type 1 diabetes in young adults in Italy, which impact on direct costs under the universalistic coverage of the NHS.

Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference.

BACKGROUND: Blood tests of liver injury are less well validated in non-alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis. AIMS: To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading. METHODS: We pre-included new NAFLD patients with biopsy and blood tests from a single-centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary-ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing. RESULTS: A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864-0.892) for FibroTest and fibrosis stages, 0.846 (0.830-0.862) for ActiTest and activity grades, and 0.822 (0.804-0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820-0.852; P = 0.0001), FIB4 (0.845; 0.829-0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850-0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05). CONCLUSIONS: In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non-invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis.

The relative burden of diabetes complications on healthcare costs: The population-based CINECA-SID ARNO Diabetes Observatory.

BACKGROUND AND AIMS: In the present population-based study, we aimed to describe the per patient annual healthcare cost of people with diabetes in 2007-2012, to assess the relative burden of diabetes complications and other potential determinants on healthcare costs in the 2012 cohort, and to describe and analyse the determinants of the cost of incident cases diagnosed in 2012. METHODS AND RESULTS: We analysed data from a retrospective cohort of residents in four Italian areas that were served by Local Health Units participating in the ARNO Observatory. Per patient annual healthcare costs (Euros) were estimated as the sum of all the resources supplied during that year (drugs, outpatient care, and hospitalisations). The mean per patient annual healthcare cost increased from €2752 in 2007 to €3191 in 2010, before decreasing to €2791 in 2012. The largest component of these costs was represented by hospitalisations (around €1550, on average; 51.7% of total cost), followed by outpatient care (€422; 14.6%) and drugs (€973; 33.7%). In 2012, the most relevant cost determinants were chronic diabetes complications, with an additional cost due to nephropathy/end stage renal disease (€4683), amputations (€5042), lower extremity revascularization (€4808), and cerebrovascular diseases (€3861). Costs associated with incidence cases were higher than those associated with prevalent. CONCLUSION: The present study provides evidence on the excess of healthcare costs due to diabetes complications in both prevalent and incident cases.

Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. Over the last 10years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes.

Dipeptidyl peptidase-4 inhibitors and heart failure: Analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System.

BACKGROUND AND AIMS: We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). METHODS: FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query "Cardiac failure". Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders. RESULTS: HF during DPP4-I use was recorded in 390 reports (4.4% of total reports). In exploratory analysis, statistically significant ROR emerged for DPP-4-I as a class (ROR = 1.17; 95% CI = 1.05-1.29), saxagliptin (1.68; 1.29-2.17), vildagliptin (2.39; 1.38-4.14), and rosiglitazone (13.98; 13.30-14.70). In consolidated analyses, the ROR for saxagliptin (2.60; 1.92-3.50) and vildagliptin (4.07; 2.28-7.27) increased, and became also significant for sitagliptin (1.61; 1.40-1.86). Concomitant drugs were reported in more than 50% of cases; the adjusted RORs of saxagliptin (2.30; 1.70-3.10), vildagliptin (3.15; 1.76-5.63), and sitagliptin (1.48; 1.28-1.71) were nonetheless significant. CONCLUSION: FAERS data are consistent with clinical studies on a possible association between saxagliptin and HF. The disproportionate reporting of HF with sitagliptin, conflicting with a recent phase IV trial, suggests that cardiovascular safety requires close post-marketing vigilance by clinicians of individual DPP-4-I in the community until the issue of class effect is solved.

Costs associated with emergency care and hospitalization for severe hypoglycemia.

BACKGROUND AND AIMS: We aimed to determine the direct economic cost of the management of severe hypoglycemia among people with diabetes in Italy. METHODS AND RESULTS: Data of cases with an acceptance diagnosis of hypoglycemia between January 2011 and June 2012 were collected in 46 Emergency Departments (EDs). Emergency care costs were computed by estimating the average cost per ambulance service, ED visit and short-term (<24 h) observation period. Hospitalization expenditure was estimated using the average cost reimbursed by the Italian healthcare system for hospital admission per patient with diabetes in a specific hospital ward. We retrieved 3516 hypoglycemic episodes occurring in subjects with diabetes. Half the cases (51.8%) required referral to EDs by means of the emergency ambulance services. A total of 1751 cases (49.8%) received an ED visit followed by discharge; 604 cases (17.2%) received a short-term observation period; 1161 (33.1%) were hospitalized. Unit costs for emergency care management were estimated at €205 for an ambulance call, €23 for an ED visit, and €220 for a short-term observation. The mean hospitalization cost was estimated at €5317; the average cost per each severe hypoglycemic event totaled €1911. From a base case assumption, the total direct cost of severe hypoglycemia in patients with diabetes in Italy was estimated to be approximately €23 million per year. CONCLUSION: Severe hypoglycemia in patients with diabetes constitutes a remarkable economic burden for national healthcare systems. Measures for preventing hypoglycemia are mandatory in diabetes management programs considering the impact on patients and on health spending.

Personality, attrition and weight loss in treatment seeking women with obesity.

Studies on small samples or in single units applying specific treatment programmes found an association between some personality traits and attrition and weight loss in individuals treated for obesity. We aimed to investigate whether pre-treatment personality traits were associated with weight loss outcomes in the general population of women with obesity. Attrition and weight loss outcomes after 12 months were measured in 634 women with obesity (mean age, 48; body mass index (BMI), 37.8 kg m(-2)) seeking treatment at eight Italian medical centres, applying different medical/cognitive behavioural programmes. Personality traits were assessed with the Temperament and Character Inventory (TCI), eating disorder features with the Binge Eating Scale (BES) and Night Eating Questionnaire (NEQ). Within the 12-month observation period, 32.3% of cases were lost to follow-up. After adjustment for demographic confounders and the severity of eating disorders, no TCI personality traits were significantly associated with attrition, while low scores of the novelty seeking temperament scale remained significantly associated with weight loss ≥ 10% (odds ratio, 0.983; 95% confidence interval, 0.975-0.992). Additional adjustment for education and job did not change the results. We conclude that personality does not systematically influence attrition in women with obesity enrolled into weight loss programmes in the community, whereas an association is maintained between novelty seeking and weight loss outcome. Studies adapting obesity interventions on the basis of individual novelty seeking scores might be warranted to maximize the results on body weight.

Drug utilization, safety, and effectiveness of exenatide, sitagliptin, and vildagliptin for type 2 diabetes in the real world: data from the Italian AIFA Anti-diabetics Monitoring Registry.

BACKGROUND AND AIMS: In Italy, the reimbursed use of incretin mimetics and incretin enhancers was subject to enrollment of patients into a web-based system recording the general demographic and clinical data of patients. We report the utilization data of glucagon-like peptide 1 (GLP1) receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors in clinical practice as recorded by the Italian Medicines Agency (AIFA) Monitoring Registry. METHODS AND RESULTS: From February 2008 to August 2010, 75,283 patients with type 2 diabetes were entered into the registry and treated with exenatide, sitagliptin, or vildagliptin. The treatment was administered to patients in a wide range of ages (≥75 years, n = 6125 cases), body mass index (BMI) (≥35 kg/m(2), n = 22,015), and metabolic control (HbA(1c) ≥ 11% ((96 mmol/mol), n = 3151). Overall, 1116 suspected adverse drug reactions were registered, including 12 cases of acute pancreatitis (six on exenatide). Hypoglycemic episodes mainly occurred in combination with sulfonylureas. Treatment discontinuation for the three drugs (logistic regression analysis) was negatively associated with the male gender and positively with baseline HbA1c, diabetes duration, and, limitedly to DPP-4 inhibitors, with BMI. Treatment discontinuation (including loss to follow-up, accounting for 21-26%) was frequent. Discontinuation for treatment failure occurred in 7.7% of cases (exenatide), 3.8% (sitagliptin), and 4.1% (vildagliptin), respectively, corresponding to 27-40% of all discontinuations, after excluding lost to follow-up. HbA1c decreased on average by 0.9-1.0% (9 mmol/mol). Body weight decreased by 3.5% with exenatide and by 1.0-1.5% with DPP-4 inhibitors. CONCLUSIONS: In the real world of Italian diabetes centers, prescriptions of incretins have been made in many cases outside the regulatory limits. Nevertheless, when appropriately utilized, incretins may grant results at least in line with pivotal trials.

The management of severe hypoglycemia by the emergency system: the HYPOTHESIS study.

BACKGROUND AND AIMS: Severe hypoglycemia is not rare in diabetes and markedly impacts on health resource use. We aimed to describe the characteristics of patients attending emergency departments (EDs) following a severe episode of hypoglycemia, the factors associated with the management of events and the final outcome. METHODS AND RESULTS: We carried out a retrospective analysis of cases attending 46 Italian EDs for hypoglycemia from January 2011 to June 2012. A total of 3753 records were retrieved from the databases of the participating centers, part of a network repeatedly involved in collaborative studies; 3516 episodes occurred in subjects with diabetes (median age, 76 years; range, 1-102). Comorbidities were recorded in 2320 (65.9%) diabetes cases; association with trauma or road accidents in 287 (8.2%) and 47 (1.3%), respectively. Patients were treated with insulin (49.8%), oral agents (31.4%), or combination treatment (15.1%). The event required assistance by the out-of-hospital Emergency services in 1821 cases (51.8%). Following the ED visit, admission to hospital departments was deemed necessary in 1161 cases (33.1%). Diabetes treatment (oral agents: OR, 1.63; 95% confidence interval (CI), 1.37-1.94), increasing age (OR, 1.39; 95% CI, 1.31-1.48) and the number of comorbidities (OR, 1.51; 95% CI, 1.38-1.66) were the main drivers of admission. The in-hospital death rate was 10%, associated with the number of comorbidities (OR, 1.28; 95%CI, 1.01-1.63). CONCLUSION: Severe hypoglycemia requiring referral to EDs is associated with a significant work-up of the Emergency services and a remarkable in-hospital death rate in frail individuals with diabetes.

Liver in the analysis of body composition by dual-energy X-ray absorptiometry.

OBJECTIVE: To investigate the predictive value for hepatic steatosis of a new software for the quantification of visceral fat by dual-energy X-ray absorptiometry (DXA) and to design new regions of interest (ROIs). METHODS: Adult volunteers were prospectively screened for hepatic steatosis by ultrasonography to obtain a well-balanced population according to the presence/absence of the disease. 90 adult patients without steatosis and 90 with steatosis (mild, 53.3%; moderate, 37.7%; and severe, 10.0%) were recruited. On the same day, all subjects were submitted to blood testing and to anthropometric and whole-body DXA for body composition evaluation. A new software for android visceral fat assessment was employed, and six new "liver-suited" ROIs as well as two modified android ROIs were designed. Their association with steatosis grade was tested by correlation analysis. RESULTS: Fat mass (FM) of the new ROIs showed the highest correlation coefficients with steatosis grade (ρ = 0.610-0.619; p < 0.001), which was also confirmed by multivariate analysis. On the whole population, the new ROIs maintained the highest predictive role for liver steatosis, with areas under the receiver operating characteristic curve up to 0.820 ± 0.032. Inter- and intra-operator agreement for the new ROIs was excellent (k = 0.915-1.000 and k = 0.927-1.000). CONCLUSION: New ROIs could be designed, standardized and implemented in DXA whole-body scan to provide more specific and predictive values of hepatic lipid content. ADVANCES IN KNOWLEDGE: This is the first study to investigate the predictive value for hepatic steatosis of visceral and regional FM assessed on the hepatic site by DXA in comparison with ultrasonography, anthropometry and surrogate markers derived by previously validated algorithms (fatty liver index).