Flavia Lombardo

Incidence of Coronary Heart Disease in Type 2 Diabetic Men and Women Impact of microvascular complications, treatment, and geographic location

OBJECTIVE—Cardiovascular disease (CVD) is the main cause of morbidity/mortality in diabetes. We set forth to determine incidence and identify predictors (including microvascular complications and treatment) of first coronary heart disease (CHD) event in CVD-free type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A cohort of 6,032 women and 5,612 men, sampled from a nationwide network of hospital-based diabetes clinics, was followed up for 4 years. Baseline assessment included retinopathy, nephropathy, and foot ulcers. First CHD events (myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and electrocardiogram-proven angina) were analyzed for 29,069 person-years. RESULTS—The age-standardized incidence rate (per 1,000 person-years) of first CHD event (n = 881) was 28.8 (95% CI 5.4–32.2) in men and 23.3 (20.2–26.4) in women. Major CHD (myocardial infarction, coronary artery bypass grafting, and percutaneous transluminal coronary angioplasty) was less frequent in women (5.8 [4.3–7.2]) than in men (13.1 [10.9–15.4]; a sex ratio of 0.5 [0.4–0.6]). Incidence rates of all outcomes were higher in patients with microvascular complications (for major CHD, age-adjusted rate ratios were 1.6 [1.2–2.21] in men and 1.5 [1.0–2.2] in women). By multivariate Cox analysis, age and diabetes duration were risk predictors common in both sexes. In men, glycemic control and treated hypertension were additional independent risk factors, but residing in the south was associated with a significant 29% risk reduction. In women, higher triglycerides/lower HDL cholesterol and microvascular complications were independent risk factors. CONCLUSIONS—In CVD-free patients with type 2 diabetes, risk of first CHD event depends on sex, geographic location, and presence of microvascular disease. Hyperglycemia and hypertension, particularly in men, and diabetic dyslipidemia, especially in women, are risk factors amenable to more aggressive treatment.

Recurrence of Cardiovascular Events in Patients With Type 2 Diabetes : Epidemiology and risk factors

OBJECTIVE—The purpose of this study was to assess incidence of and risk factors for recurrent cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND METHODS—We estimated the incidence of recurrent cardiovascular events in type 2 diabetic patients, aged 40–97 years, followed by a network of diabetes clinics. The analysis was conducted separately for 2,788 patients with CVD at enrollment (cohort A) and for 844 patients developing the first episode during the observation period (cohort B). RESULTS—During 4 years of follow-up, in cohort A the age-adjusted incidence of a recurrent event (per 1,000 person-years) was 72.7 (95% CI 58.3–87.1) in men and 32.5 (21.2–43.7) in women, whereas in cohort B it was 40.1 (17.4–62.9) in men and 22.4 (12.9–32.0) in women. After controls were included for potential predictors (familial CVD, obesity, smoking, diabetes duration, glycemic control, microvascular complications, geographic area, and antihypertensive and lipid-lowering treatment), male sex, older age, and insulin use were significant independent risk predictors (cohort A) and serum triglyceride levels ≥1.69 mmol/l emerged as the only metabolic (negative) prognostic factor (cohort B). In both cohorts, a prior CVD episode, especially myocardial infarction, was by far the strongest predictor of recurrent CVD. CONCLUSIONS—Approximately 6% of unselected diabetic patients in secondary prevention develop recurrent major CVD every year. Those with long-standing previous CVD show a higher incidence of recurrence. Male sex, age, high triglyceride levels, and insulin use are additional predictors of recurrence.

Lower extremity amputations in persons with and without diabetes in Italy: 2001-2010.

Objective To analyze hospitalization for lower extremity amputations (LEAs) and amputee rates in persons with and without diabetes in Italy. Research Design and Methods All patients with LEAs in the period 2001–2010 were identified analyzing the National Hospital Discharge Record database. For each year, amputee and hospitalization rates for LEAs were calculated either for persons with diabetes or without. Time trend for major and minor amputations were analysed. Results From 2001 to 2010 a mean annual number of 11,639 individuals underwent a lower extremity amputation: 58.6% had diabetes accounting for 60.7% of total hospitalizations. In 2010, the crude amputee rate for LEAs was 20.4 per 100,000 inhabitants: 247.2 for 100.000 persons with diabetes, and 8.6 for those without diabetes. Having diabetes was associated to an increased risk of amputation (Poisson estimated RR 10.9, 95%CI 9.4–12.8). Over the whole period, a progressive reduction of amputee rates was observed for major amputations either among persons with diabetes (−30.7%) or without diabetes (−12.5%), while the rates of minor amputations increased progressively (+22.4%) among people without diabetes and were nearly stable in people with diabetes (−4.6%). A greater number of minor amputations were performed among persons with than without diabetes: in 2010, the minor-to-major ratio among persons with diabetes (2.5) was more than twice than in those without diabetes (1.0). Conclusions The nationwide analyses confirm a progressive reduction of hospitalization and amputee rates for major LEAs, suggesting an earlier and more diffuse approach aimed at limb salvage.

Temporal trend in hospitalizations for acute diabetic complications: a nationwide study, Italy, 2001-2010.

Background We investigated temporal trends and geographic variations in both hospitalizations and in-hospital mortality rates for acute diabetic complications (ADC) in the Italian universal health care system. Methods and Findings A retrospective review of the medical records of patients with either primary or secondary discharge diagnosis of hyperglycaemic acute complications (ICD-9-CM codes 250.1, 250.2, 250.3) or hypoglycemic coma (ICD-9-CM code 251.0) was performed in period 2001–2010. Standardized rates by age and gender on 2001 Italian population and by diabetic population were calculated. We identified 7,601.883 diabetes-related hospital discharges. Out of them, 266,374 (3.5%) were due to ADC, either ketoacidosis/hyperosmolarity (94.4%) or hypoglycemic coma (5.6%). The rate of discharge for ADC decreased by 51.1% from 2001 to 2010 (14.4 vs. 7.1 discharge rate/1,000 diabetic people; 5.7% decrease per year, test for trend, p<0.001) with a similar trend for both hyperglycemic and hypoglycemic complications. Diabetic people in the younger age groups (≤19 and 20–44 years old) had a significantly greater rate of discharge for ADC than people aged 65 years and over (≤19 10-fold increase; 20–44: 2-fold increase). In-hospital mortality rate was 7.6%, with 211 preventable deaths in younger diabetic people (≤44 years old). There was a large variability among Italian Regions and the ratio between the highest and the lowest regional discharge rate reached 300% in 2010. Conclusions Decreasing temporal trend in hospitalizations for preventable ADC suggests improving outpatient care. In younger diabetic patients, however, both hospitalization rates and in-hospital mortality are still a matter of concern.

Prevalence and risk factors of HCV infection in a metropolitan area in southern Italy: Tail of a cohort infected in past decades.

Data on the prevalence of HCV infection in Italy are often outdated and from non‐urban populations. This study assessed the prevalence and risk factors for HCV infection in a large metropolitan area in southern Italy. A random 1:3 systematic sample of the adult general population of Naples was selected from three general practitioner patient registers in three different city districts. Socioeconomic indicators and risk factors for HCV infection were collected. Anti‐HCV and HCV‐RNA assays were performed. Logistic regression analysis was used to identify independent predictors of HCV infection. Of 1,500 randomly selected subjects, 1,315 (87.7%) participated in the study. Forty subjects (3.0%; 95%CI: 2.1–4.0) were anti‐HCV‐positive, with HCV‐RNA detected by PCR in 31 (77.5%) of these. Anti‐HCV prevalence increased with age, peaking (8.2%) in people born during the years 1945–1955. It was 1.7% in people residing in the better socioeconomic districts; but 5.7% in those residing in the district with lower socioeconomic status (P < 0.01). In multivariate analysis, age ≥60 years (OR 2.8, 95%CI: 1.3–6.1) and lower educational level (OR 3.6; 95%CI: 1.4–9.3), which is a proxy of low socioeconomic status, were the only independent predictors of the likelihood of anti‐HCV positivity. Overall, 22.5% of anti‐HCV positive subjects were previously unaware of their status. In the large city of Naples, infection with HCV is most common in people aged older than 60 years. Differences in socioeconomic conditions have played an important role in the spread of this infection. HCV positive subjects born during the years 1945–1955 are those who may benefit, to a greater extent, to be identified in order to receive the new effective therapy. J. Med. Virol. 89:291–297, 2017.

The impact of a vaccination campaign against hepatitis B on the further decrease of hepatitis B virus infection in a southern Italian town over 14 years

BACKGROUND Hepatitis B virus infection has decreased in Italy. The aims of this study were to identify changes, if any, in the epidemiological pattern of HBV infection in a southern Italian town first surveyed in 1996 and to assess the effectiveness of vaccination campaign against hepatitis B. METHODS In 2010, subjects were selected from the census by a systematic 1:4 random sampling procedure. Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti-HBc) were detected by ELISA. Associations (odds ratios) linking exposure to hepatitis B virus infection to potential risk factors were estimated by univariate and multivariate analyses. RESULTS Of the 1100 eligible subjects, 1020 (92.0%) agreed to participate. The prevalences of HBsAg (0.6%) and anti-HBc (15.2%) were significantly lower than in 1996 (0.8% and 21.5%) (p<0.01). No subject below 30 years of age (those that had been targeted for compulsory immunization) had been exposed to HBV infection. At multiple logistic regression analysis, age>45 years (OR=9.8; 95% CI=5.1-18.7) and past use of glass syringes (OR=1.9; 95% CI=1.2-3.1) independently predicted the likelihood of anti-HBc positivity. CONCLUSIONS These results, albeit obtained in a small town and thus not generalizable, confirm the continuous decreasing trend of HBV infection and demonstrate the effectiveness of the Italian hepatitis B vaccination program.

Evidence for the presence of autochthonous (locally acquired) cases of acute hepatitis E virus infections in Italy since the 80s

BACKGROUND Autochthonous (locally acquired) cases of acute hepatitis E virus have been recently reported in several developed countries. AIM To evidence cases, if any, and characteristics of acute hepatitis E virus infections in North-East of Italy several years ago. METHODS In 2014, stored sera of 165 nonA-nonB acute hepatitis referred to the hospital of Padua during the period 1978-1991 were tested for hepatitis C virus antibodies by EIA III and for anti-hepatitis E virus IgM by Wantai HEV IgM ELISA. Anti-hepatitis E virus IgM positive sera were tested by Real Star HEV RT-PCR kit (Altona Diagnostics, Hamburg, Germany). RESULTS Ninety-six (58.1%) sera resulted anti-HCV positive, and thus classified as acute C hepatitis. None of these subjects was anti-HEV IgM positive. Out of the 69 anti-HCV negative cases, 4 (5.8%) resulted anti-HEV IgM positive (one case hepatitis E virus-RNA positive), with an increasing trend from 2.8% during the years 1978-1984 to 9.1% during the years 1985-1991. All cases occurred in Italian patients with no travel abroad history. CONCLUSIONS There is evidence for the presence of autochthonous cases of acute hepatitis E virus infections in Italy since 80s.

Historical study of acute hepatitis B in subjects with or without hepatitis C infection.

BACKGROUND The epidemiological pattern of hepatitis B virus infection in Italy has greatly changed over the past decades. The aim of the study was to evaluate during time the epidemiological features of acute hepatitis B cases referred to an Infectious Disease Unit in North-East of Italy between 1978 and 1995. PATIENTS AND METHODS Stored sera of 183 cases were tested for HBV markers, HBV genotypes, anti-Delta and anti-HCV. RESULTS Anti-HBcIgM was positive in all cases. Mean age increased from 30.2 years in 1978 to 37.5 in 1995 (P<0.01). Significant increase was observed in proportion of cases reporting intravenous drug use from 11.5% to 29.6% (P<0.03). Chronicity rate was as low as 1.1%. Mean days of hospitalization significantly decreased. HBV genotype determination showed that majority of cases was infected by genotype D, but its prevalence decreased from 88.2% in 1978 to 75.0% in 1995. Delta coinfection was present in 8.2%. The prevalence of HCV in patients with acute HBV was 35.0%; it fluctuated from 26.2% to 44.2%, mostly related (53.1%) to intravenous drug use. Dual infection did not lead to a more severe course of disease. CONCLUSIONS From this retrospective study, remarkable fluctuations in the prevalence of dual HBV-HCV infection before the implementation of HBV vaccination were observed. Presence of anti-HCV did not affect the course of acute HBV.

Prevalence of and risk factors for HBV infection in a metropolitan Southern Italian area: Evidence for the effectiveness of universal Hepatitis B vaccination

BACKGROUND Available data on HBV prevalence in Italy are outdated and assessed with studies conducted in small towns. We aimed to evaluate prevalence of and risk factors for HBV infection in the metropolitan area of Naples, 24 years after the introduction of mass vaccination campaign against Hepatitis B in Italy. METHODS A random systematic sample of the adult general population of Naples was selected from the register of 3 general practitioners in 3 different socio-economic districts. Independent predictors of the likelihood of HBV infection were identified by logistic regression analysis. RESULTS Among 900 selected subjects, 772 (85.8%) participated in the study. The overall HBsAg and anti-HBc prevalences were 1.7% and 14.4%, respectively. Both markers were more likely detected in the district at low socioeconomic status than in those at medium-high status (p<0.01). Anti-HBc prevalence linearly increased from 0% in subjects 30 years old or younger to 28.0% in those older than 60 years of age (p<0.01). At multivariate analysis, age >60 years (OR3.38; 95%CI:1.98-5.74), low socioeconomic district of residence (OR3.26; 95%CI:1.72-6.18), and low educational qualification (OR2.73; 95%CI:1.45-5.16) were independent predictors of anti-HBc positivity. CONCLUSION Differences in socioeconomic conditions have played a major role in the past spread of HBV infection in Naples. Hepatitis B vaccination has resulted very effectively in preventing HBV infection, regardless of the district of residence, as none of the subjects in the vaccinated cohorts was exposed to the infection.

Lack of evidence that adherence to standard of care therapy improves survival in subjects with hepatocellular carcinoma in clinical practice

Currently, the BCLC classification, which links tumor stage with treatment option, is the standard system for clinical management of HCC. Thus far, this approach has been considered the standard of care worldwide. This study aimed to evaluate the survival of patients with HCC according to the BCLC Stage, surveillance, and adherence to standards of care. A 3‐year prospective study enrolled 92 consecutive patients with HCC in the Gastroenterology Unit of the University of Naples “Federico II”. Predictors of the likelihood of death were evaluated by the multivariate Cox model. Forty out of 92 (43%) subjects died during three years of follow up. The overall mortality rate per 100 person–years was 16.7, while the mortality rate for hepatic causes was only 14.2; it was lower in subjects under surveillance (11.4 vs. 28.2), in subjects adherent to standards of care (12.0 vs. 21.1), and in those who were in a better BCLC stage (10.6 vs. 45.8). The multivariate Cox model showed that advanced BCLC stage (HR 4.1, 95%C.I. = 1.8–9.4) was the sole independent predictor of the likelihood of mortality. In this regard, we observed lack of evidence that the adherence to the BCLC recommendations reduces the mortality of patients with HCC; and that the BCLC system cannot be accepted as a “commandment” to be invariably followed in everyday practice. Strategies to help improve adherence to international guidelines for HCC in clinical practice are required. J. Med. Virol. 87:1368–1376, 2015.