Ferdinando di Orio

Attributable risk for symptomatic liver cirrhosis in Italy

BACKGROUNDS/AIMS Knowledge of the proportion of liver cirrhosis attributable to the main risk factors is largely based on methodologically questionable clinical reports. METHODS The proportion of newly diagnosed cases of symptomatic liver cirrhosis attributable to known risk factors was estimated by a case-control study performed during 1989-1996 in 23 medical divisions of several hospitals distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted for the first time for liver decompensation. Controls were 651 patients admitted during the same period and to the same hospitals as the cases, for acute diseases unrelated to alcohol and virus infection. The proportion of symptomatic liver cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the combination of these was expressed as the population attributable risk. RESULTS Attributable risks were 67.9% (95% confidence interval (CI): 53.8-79.4) for alcohol, 40.1% (95% CI: 35.3-45.2) for hepatitis C virus and 4.4% (95% CI: 2.5-7.6) for hepatitis B virus. The three factors together explained 98.1% (95% CI: 81.6-99.6) of cases in men and 67.0% (95% CI: 50.4-85.8) in women. CONCLUSIONS Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis risk in Italy. From a public health viewpoint, with the elimination of the well-known risk factors (particularly alcohol and hepatitis C virus), liver cirrhosis should become a rare disease.

Proportion of Older People in the Community as a Predictor of Increasing Stroke Incidence

Objectives: To compare stroke incidence rates among comparable registries and to make correlations with aging of the resident populations. Methods: This correlation study included all comparable stroke registries maintained in industrialized countries (Italy, France, United Kingdom, Denmark, Norway, United States, and Australia). Eleven community-based stroke registries with similar high proportions of radiologically confirmed diagnoses based on standard definitions were identified. Incidence rates of first-ever stroke from the prospective L’Aquila registry and from the other registries were compared after age and sex standardization to the 1996 European population. The rates were then correlated with the proportion of individuals aged 65 and over in the corresponding resident populations by means of the Poisson regression analysis. Results: In the L’Aquila registry, the crude annual incidence of first-ever stroke was 281/100,000 (95% confidence interval 271–293) based on 2,515 patients included during a 3-year period. The rate standardized to the European population was 249/100,000. Standardized incidence ratios indicated a significant excess of first-ever strokes in the L’Aquila registry up to 51% with respect to most of the compared studies. A significant correlation was also found between crude (p < 0.0001) and standardized (p = 0.0012) stroke incidence rates and proportions of individuals aged 65 and over in the different populations. Conclusions: The L’Aquila experience suggests that any further aging of a population will increase the stroke occurrence for both the reasons of a direct and predictable effect of the growing proportion of elderly individuals within that population and a disproportionately increased stroke risk in the older age groups.

The Italian version of the lower extremity functional scale was reliable, valid, and responsive.

OBJECTIVE To determine the measurement properties of an Italian Version of the Lower Extremity Functional Scale (LEFS) in patients with lower extremity musculoskeletal dysfunction. STUDY DESIGN AND SETTING This is a prospective methodological study of repeated measures with a sample of 250 consecutive patients. Reliability, validity, and responsiveness were evaluated. RESULTS The Italian version of the LEFS showed a high degree of internal consistency with a Cronbach alpha of 0.94 (95% confidence interval [CI]: 0.91, 0.96). The test-retest reliability was high for both intra-interviewer and inter-interviewer measures with an ICC((2,1 and 2,k)) of 0.91 (95% CI: 0.86, 0.93) and 0.89 (95% CI: 0.83, 0.91), respectively. The LEFS showed a better correlation with the 36-Item Short-Form Health Survey (SF-36) physical component summary score rather than with the SF-36 mental component summary score both at the initial assessment (r=0.61 and 0.26, respectively) and at the discharge (r=0.72 and 0.22, respectively). Receiver operating characteristic curve analysis revealed a large responsiveness for the LEFS (area under the curve [AUC]=0.97) and a moderate responsiveness for the SF-36 (AUC=0.68). CONCLUSION The Italian version of the LEFS is a valid, reliable, and responsive tool that can be used to measure function in Italian patients with lower extremity musculoskeletal dysfunction.

Mortality study on a cohort of Italian licensed pesticide users

This study describes the mortality experience in a cohort of 23,401 farmers, residing in southern Piedmont, Italy, and licensed to use pesticides. From 1970 to 1986 the cohort included 340,794 person-years and 2683 deaths were observed. A strong attenuation of the death risk was found due to the healthy worker effect (seen as an active role in the application for the license by the members of the cohort) and due to the limited comparability of the cohort with respect to the reference population. The standardized mortality ratios (SMRs) were remarkably < 100 for all causes (SMR = 59; 95% confidence interval = 57-61) and for all tumors (SMR = 60; 95% CI 55-64), but they increased with the increasing duration of the follow-up. A risk increase was observed with respect to melanomas and eye tumors in the entire cohort and lymphoma and tumors of the connective tissue in the subcohort of subjects living in villages with mainly arable land.

Enhanced soluble CD40 ligand and Alzheimer's disease: Evidence of a possible pathogenetic role

It has been suggested that cerebrovascular factors contribute to Alzheimers disease. Soluble CD40 ligand (sCD40L) is directly involved in the development of vascular damage. We tested the hypothesis that sCD40L may be enhanced in Alzheimers disease and predictive of its clinical course. Plasma sCD40L levels were evaluated in three groups of 40 consecutive patients each referring for mild or moderate or severe Alzheimers disease, as assessed by the Clinical Dementia Rating (CDR), and in 40 healthy subjects. Seventy-seven patients with mild or moderate disease were re-evaluated after 2 years. Cross-sectional comparisons revealed higher plasma sCD40L levels in Alzheimers disease patients than in controls (9.3+/-4.7 ng/mL versus 3.4+/-1.3 ng/mL, p<0.0001). Circulating sCD40L levels significantly increased through the three CDR stages (p=0.0011 or less) and were correlated with MMSE (r=-0.574, p<0.0001) and ADAS-cog subscale (r=0.538, p<0.0001) scores. Longitudinal evaluation identified sCD40L as an independent predictor of MMSE (beta=-0.157, t=-3.650, p=0.0005) and ADAS-cog subscale (beta=0.484, t=3.890, p=0.0002) score changes after 2 years. Patients with plasma sCD40L level>or=6.0 ng/mL, identified by ROC curve analysis as the best discriminating value for disease progression, had a three-fold increase in the risk of progression toward a worse CDR stage (odd ratio: 3.0, C.I. 95% 1.2-8.1). In conclusion, circulating sCD40L is enhanced in patients with Alzheimers disease and independently associated with the severity and progression of the disease. These data might suggest a pathogenetic role for sCD40L in Alzheimers disease.

AMOUNT AND DURATION OF ALCOHOL INTAKE AS RISK FACTORS OF SYMPTOMATIC LIVER CIRRHOSIS: A CASE-CONTROL STUDY

We carried out a hospital based case-control study involving 320 patients with symptomatic liver cirrhosis (LC) and 320 pair-matched control individuals, in order to estimate the dose-response relationship between both the daily amount and the duration of alcohol intake and the risk of LC. Lifetime alcohol consumption was measured by a standardized and reproducible questionnaire, and expressed as lifetime daily alcohol intake (LDAI) and duration of alcohol consumption (DAC). The odds ratio (OR) for LC was estimated by the conditional logistic regression. It increased from 1.0 for lifetime abstainers to 4.2 for LDAI of 225 g or more. Comparing durations of alcohol consumption of < or = 10 and > or = 30 years in the model, the ORs consistently decreased for all the LDAI categories: from 4.1 to 0.6 in the 25-50 g category; from 15.1 to 0.9 in the 75-100 g category; from 67.2 to 1.5 in the 125 g or more category. Our results suggest that the dose-dependent relationship between alcohol and LC may be mediated by the degree of individual susceptibility to the detrimental effect of alcohol to the liver.

Alcohol Consumption and Micronutrient Intake as Risk Factors for Liver Cirrhosis: A Case-Control Study

PURPOSE: The purpose of this study was to assess the relationship of alcohol consumption and intake of 15 selected micronutrients with risk of liver cirrhosis. METHODS: Data from a case-control study performed in 1989–1990 in central Italy involving 115 incident cases and 167 hospital controls were used. RESULTS: Cases and controls did not differ for mean daily intake of calories, carbohydrates, lipids, and proteins. Significant direct dose-response relationships between the intakes of vitamin A and iron and the risk cirrhosis were observed, while significant protective effects were obtained for the intakes of vitamins B2 (riboflavin) and B12. Different patterns of the joint effect of nutrients and alcohol were also observed. The intakes of vitamin A and iron were significantly associated with the risk of cirrhosis in lifetime teetotalers (odds ratios (OR) and 95% confidence intervals (CI) of 33.6 (1.2–979.9) and 37.9 (1.8–819.4) for higher intake of vitamin A and iron, respectively) and in consumers of <50 g/day of alcohol (vitamin A: OR 45.0; 95% CI, (2.6–774.6); iron: OR, 73.6; 95% CI, 4.3–999). The OR associated with intakes of vitamins B2 (riboflavin) and B12 were not significant for the first two categories of alcohol use, while a higher intake of these two vitamins reduced the risk of cirrhosis associated with alcohol consumption above 50 g/day; the ORs (95% CI) were 23.0 (2.7–198.9) and 104.4 (7.2–999), respectively, for higher and lower intakes of riboflavin and 12.8 (1.8–88.1) and 138.4 (14.0–999), respectively, for higher and lower intake of vitamin B12. CONCLUSION: These findings might explain at least a portion of the individual susceptibility to alcohol-induced liver damage.

Exploring the combined action of lifetime alcohol intake and chronic hepatotropic virus infections on the risk of symptomatic liver cirrhosis

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables, a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.

Is alcohol a risk factor for liver cirrhosis in HBsAg and anti-HCV negative subjects?

BACKGROUND/AIMS In order to evaluate the association between alcohol intake and the risk of liver cirrhosis in the absence of B and C hepatitis viruses, we analyzed data from three hospital-based case-control studies performed in various Italian areas. METHODS From the case and control series we excluded HBsAg and/or anti-HCV positive patients. Cases were 221 cirrhotic patients admitted for the first time to hospital for liver decompensation. Controls were 614 patients admitted to the same hospitals during the same period as the cases for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). RESULTS We found a dose-effect relationship between LDAI and the risk of liver cirrhosis (LC). Considering the extreme LDAI categories (LDAI = 0 g: lifetime teetotallers and LDAI > or = 100 g), the LC odds ratio (OR) increased from 1.0 (reference category) to 44.7 (95% confidence interval: 95% CI: 20.0-99.9). An increased risk of LC associated with the female gender independent of alcohol consumption was also observed (OR = 2.9; 95% CI: 1.8-4.6). CONCLUSIONS Alcohol intake acts as a risk factor for symptomatic liver cirrhosis also in the absence of HBV and/or HCV infection. Besides alcohol and viruses, some unknown gender-related factors might be involved in the occurrence of the disease.

Maintenance immunotherapy in recurrent ovarian cancer: Long term follow-up of a phase II study

OBJECTIVES Vascular endothelial growth factor (VEGF), a mediator of tumor-associated immunodeficiency, plays a key role in angiogenesis and is a prognostic factor in advanced ovarian cancer (AOC). Previously, we showed that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) improved the tumor-associated immunodeficiency and decreased VEGF in patients with AOC. Here, we report long term follow-up of a group of patients with platinum-sensitive AOC who were treated with IL-2 and RA. METHODS Sixty-five patients with AOC who had a clinical benefit from second line chemotherapy and elevated serum levels of VEGF were entered into the study from 04/98 to 04/05. Therapy consisted of low-dose subcutaneous IL-2 and oral RA, administered on intermittent schedules for up to 5 years. RESULTS A statistically significant improvement in lymphocyte and NK counts and a decrease in VEGF levels were observed with respect to baseline values among the 65 evaluable patients. Five-year progression-free survival and overall survival rate were 29% and 38%, respectively. CONCLUSIONS These data show that patients treated with low-dose IL-2 and RA have a statistically significant improvement in their lymphocyte and NK counts, a decrease in VEGF, and seem to have an improved clinical outcome.