Search

Purpose Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. Methods PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59–88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. Conclusion The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

Background Vulnerability and inequality are exacerbated in undocumented migrants, the most invisible to health systems. Objectives To estimate maternal and perinatal health needs in undocumented migrants and test a methodology for systematic monitoring & evaluation. Methods Population-based retrospective cohort study based on routine data through maternity records and temporary registration code in a sub-national Health Management Information System. Results 420924 deliveries including 1524 undocumented migrants having accessed maternity care through the NHS in Lombardy Region (Italy) from 2016 to 2021 were included. Demographics and social determinants: undocumented migrants were born in Europe (non-EU) (36%), Americas (30%), Africa (6%), Western Pacific (3%), South-East Asia (2%), Italy (2%), were stateless (7%); 52% had no/low schooling, 92% were unemployed and 52% non-married, compared to 15%, 20%, and 44% Italians. Obstetric history and antenatal care: 22% undocumented migrants had a previous abortion and 15% a previous cesarean delivery; 58% had ≥5 antenatal visits, 67% first ANC visit in trimester 1, 64% ≥ 2 ultrasounds incl. first in trimester 1, 6% full laboratory tests, compared to 90%, 97%, 97%, and 66% Italians. Intra-partum and perinatal care: 45% undocumented migrants delivered in a public hospital with neonatal intensive care unit; 69% had a normal delivery, 5% instrumental delivery, 10% and 27% emergency and total cesarean section; 2.6% neonates had emergency resuscitation and 49% were breastfed Conclusions Maternal and perinatal health was poor in undocumented migrants, varying by birthplace. Social determinants, health coverage and outcomes showed vulnerability and inequality compared to the general population. Key messages • Tailored interventions are needed: outreach health promotion on safe motherhood and neonatal care, healthcare provider training, cultural mediation, translation, and functional language learning. • A systematic monitoring and evaluation system needs to routinely collect, integrate, and analyze data on key indicators.

Study question Does the association between Assisted Reproductive Technologies (ART) and birth defects change over time? Summary answer The increased incidence of birth defects in ART pregnancies is not steady over time. A decline of this risk emerged in most recent years. What is known already The incidence of birth defects is increased in pregnancies after ART. The latest meta-analysis showed that infants born following IVF-ICSI have a 40% increased risk (Zhao et al., 2020). Even if infertile women are exposed to higher risk per se, some ART related factors may also contribute. To note, ART procedures are continuously evolving, and it cannot be excluded that the magnitude of the association of ART and birth defects may have changed in recent years. We failed to identify in the literature studies reporting on the trends of birth defects in IVF-ICSI pregnancies over time. Study design, size, duration This is a population-based study using the automated system of healthcare utilization databases from Lombardy, a region located in Northern Italy accounting for about 10 million inhabitants. We identified deliveries occurring between January 2014 and December 2020 from women beneficiaries of the public health system using the standard discharge form and the certificate of delivery assistance. We excluded cases with incomplete information and pregnancies obtained by intrauterine insemination or ovarian hyperstimulation alone. Participants/materials, setting, methods The rate of newborns affected by major defects was calculated among natural and IVF-ICSI pregnancies. A logistic regression model was used to adjust for maternal sociodemographic features (i.e., age, nationality, marital status, education, and employment). Data are presented as adjusted odd ratio (aOR) and corresponding 95% Confidence Interval (CI) of major defects among IVF-ICSI pregnancies compared to natural conceptions. Analyses were repeated for every calendar year. Main results and the role of chance A total of 508,421 live births were included, of whom 14,067 (2.8%) were achieved with IVF-ICSI. The proportion of non-spontaneous conceptions per year progressively increased over the years, being 2.1%, 2.3%, 2.6%, 2.8%, 3.2%, 3.4% and 3.2% in 2014, 2015, 2016, 2017, 2018, 2019, and 2020, respectively (p Limitations, reasons for caution The diagnosis of malformation is based on information detected at the time of delivery, and not during the subsequent infant’s hospitalization, or later in lifetime. Further, we have no information on pregnancies terminated early. Finally, data was collected from registries and this modality may expose the findings to some inaccuracies. Wider implications of the findings The increased risk of birth defects in IVF-ICSI pregnancies is not steady over time. A decline of this risk emerged in our region. Policy changes in ART may explain this beneficial effect. Evidence obtained more than one decade ago may not be valid in the modern era of IVF. Trial registration number not applicable

Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity.A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy.From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No G1 acute and late toxicities were reported.The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Background and aims Meta-analyses of randomized control trials investigating the association between incident diabetes and statin use showed an increased risk of new-onset diabetes (NOD) from 9% to 13% associated with statins. However, short follow-up period, unpowered sample size, and lack of pre-specified diagnostic criteria for diabetes detection could be responsible of an underestimation of this risk. We conducted a meta-analysis of published observational studies to evaluate the association between statins use and risk of NOD. Methods and results PubMed, EMBASE and MEDLINE databases were searched from inception to June 30, 2016 for cohort and case–control studies with risk of NOD in users vs nonusers, on ≥1000 subjects followed-up for ≥1 year. Two review authors assessed study eligibility and risk of bias and undertook data extraction independently. Pooled estimates were calculated by a random-effects model and between-study heterogeneity was tested and measured by I 2 index. Furthermore, stratified analyses and the evaluation of publication bias were performed. Finally, the meta-analysis included 20 studies, 18 cohort and 2 case–control studies. Overall, NOD risk was higher in statin users than nonusers (RR 1.44; 95% CI 1.31–1.58). High between-study heterogeneity (I 2 = 97%) was found. Estimates for all single statins showed a class effect, from rosuvastatin (RR 1.61; 1.30–1.98) to simvastatin (RR 1.38; 1.19–1.61). Conclusions The present meta-analysis confirms and reinforces the evidence of a diabetogenic effect by statins utilization. These observations confirm the need of a rigorous monitoring of patients taking statins, in particular pre-diabetic patients or patients presenting with established risk factors for diabetes.

Purpose: To assess the effectiveness of an informative intervention on general practitioners aimed at improving patients' adherence to statin therapy. Methods: In the local health unit (LHU) of Bergamo, Lombardy (Italy), each general practitioner received a synthetic scientific document on dyslipidaemia and statins and aggregated data on adherence in 2006 for his/her patients compared to the means in the LHU and in his/her working district. Furthermore, a sample of seven districts received also a table of adherence levels for single patients. Patient's level data were retrieved from the health care utilisation databases of the LHU. Adherence parameters (proportion of patients with only one prescription, medication possession ratio [MPR] and proportion of non-persistent patients) were assessed after 1 year of follow-up. Results: Overall, 5833 and 4788 new statin users were enrolled before and after the intervention, respectively. The percentage of patients with only one prescription decreased from 28.0 to 23.9 % (p < 0.001). MPR increased from 70.3 to 76.0 % (p < 0.001), and proportion of patients with MPR =80 % increased from 45.4 to 56.4 % (p < 0.001). The persistence also showed an improvement, both in terms of decreasing proportion of non-persistent (from 51.9 to 41.4 %, p < 0.001) and of increasing duration of continued therapy (from 235 to 264 mean days of persistent therapy, p < 0.001). There were not significant differences between the two types of intervention. Conclusions: This intervention resulted in an overall improvement of the short-term adherence to therapy. This tool can be replicated in other local contexts and with other chronic therapies.

Table S1. ICD-9 CM, ATC and exemption codes used in the reference algorithm and comparison algorithms applied to capture COPD and asthma cases among the beneficiaries of the Regional Health Service. Lombardy, Italy. (DOCX 15 kb)

Background. Concerns have been raised about the cardiac safety profile of trastuzumab for the adjuvant treatment of early stage breast cancer in clinical practice. We assessed tras- tuzumab-related cardiotoxicity and its predictors in a large co-hort of Italian women. Methods. Through a record linkage between four regional health care databases, we identified the rate of severe car-diac adverse events among women treated with trastu-zumab for early breast cancer in Lombardy. The cumulative risk of cardiotoxicity was estimated using the Kaplan-Meier method, and independent predictors were assessed using the Cox model. Results. Of 2,046 trastuzumab users, 53 (2.6%) experienced at least one hospitalization for a cardiac event, and there were two cardiac deaths. The cumulative risk of cardiotoxicity in- creased up to 2 years after starting treatment, reaching a pla-teau at 2.8%. The risk was low (0.2%) among young women, whereas the incidence was approximately 10% in women aged >70 years, irrespective of cardiovascular risk factors. Age and history of cardiac disease were strong predictors of cardiotoxicity, with a hazard ratio of 11.3 (95% confidence in-terval [CI]: 3.5-36.6) for women aged >70 years as compared with those

Statins are among the most commonly prescribed drugs used to manage dyslipidemia. Hepatocellular carcinoma is the third leading cause of cancer mortality and its rates have recently been increasing in central and northern Europe and USA. To quantify the association between statin use and risk for HCC, we performed a meta-analysis of published studies. We conducted a MEDLINE search for observational studies reporting the association between exposure to statins and risk for incident liver cancer until March 2012. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Moreover, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Five observational studies (two case-control and three cohort studies) based on 2574 cases of HCC were included. Statin treatment, compared with no treatment, was inversely related to HCC (summary RR=0.58; 95% CI 0.46-0.74). Between-study heterogeneity was significant (P

Background/objective: Almost two-thirds of the coronary death rate decrease in the northern Italian Brianza MONICA male population, between 1993–4 and 1997–8, are attributable to a reduction in 28-day myocardial infarction (MI) case-fatality. The present paper investigates the factors associated with MI case-fatality decrease and in particular the role of socio-occupational classes (SOCs). Methods: Standardised information on acute coronary care and intervention before and during the hospitalisation was collected for all coronary events (n = 1817) registered in 1993–4 and in 1997–8 among 35–64-year-old male residents in Brianza. Deaths within 28 days after MI were carefully investigated. Five SOCs were defined adopting the Erikson-Goldthorpe-Portocarero method. Differences in 28-day MI case-fatality and in acute phase intervention and treatment over time and among SOCs in each period were assessed. Results: 28-day MI case-fatality reduction (27.2%) can be mainly attributed to a decreased proportion of MI events that were fatal before reaching the hospital. In the lower SOCs significant changes in MI case-fatality were detected between 1993–4 and 1997–8. Differences in acute phase intervention and treatment between the periods were observed. SOC differences both in prevalence of out-of-hospital cardiac arrest and in the pre-hospital qualified intervention score were detected in the first period only. Conclusions: In the study population MI case-fatality reduction can be mainly attributed to a more effective and prompt management before hospitalisation and to an improvement in acute treatment during hospitalisation. This enhancement is made available to the whole population overtaking social differences.

Aim: As the treatment of hyperglycaemia during pregnancy with diet or insulin reduces the risk of adverse maternal outcomes and perinatal complications, screening for gestational diabetes mellitus (GDM) is included, albeit to variable extents, in all guidelines of care for pregnant women. The aim of the present investigation was to estimate the proportion of pregnancies screened for GDM in Lombardy between 2007 and 2010, and to identify predictors of screening. Methods: A retrospective cross-sectional study using regional healthcare utilization databases of Lombardy was conducted. The study included all residents of Lombardy without pregestational diabetes who delivered between 1 January 2007 and 31 December 2010. The proportion of pregnancies with at least one screening test for GDM was calculated, along with the odds ratios and 95% confidence intervals associated with selected covariates for GDM screening. Results: Of the 362,818 pregnancies included in the sample, 30% were screened for GDM. The proportion of pregnancies screened increased slightly from 2007 (27%) to 2010 (33%) and with maternal age (from 28% among women.

Purpose To evaluate the effect of the consumption of caffeine-containing beverages on the risk of symptomatic liver cirrhosis (LC). Methods From 1994 to 1998, all the consecutive cirrhotic inpatients admitted in 19 collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (274 cases) and one or two gender, age, and place of residence pair matched individuals (458 controls) were recruited. Data on years of education, lifetime cigarette use, lifetime intake of alcohol- and caffeine-containing beverages, usual consumption of 180 food items, and on markers of hepatitis B and C viral infection were collected. Results A statistically significant trend toward lowered cirrhosis risk with increasing exposure to coffee was observed. The LC odds ratios decreased from 1.0 (reference category: lifetime abstainers from coffee) to 0.47 (95% confidence interval: 0.20, 1.10), 0.23 (0.10, 0.53), 0.21 (0.06, 0.74), and 0.16 (0.05, 0.50) in 1, 2, 3, and 4 or more cups of coffee drinkers, respectively. There was no convincing evidence that coffee consumption modifies the effects of the known risk factors of liver cirrhosis (alcohol intake and viruses infection). Conclusions These findings support the hypothesis that coffee, but not other beverages containing caffeine, may inhibit the onset of alcoholic and nonalcoholic liver cirrhosis.

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% CIL 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 cirrhrosis should become a rare disease.

BACKGROUND: The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response. AIM: To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease. METHODS: The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without involvement of the caecum/ascending colon, were enrolled. Of these, 101 were randomly allocated to receive 4.0 g/day of mesalazine (Asacol, Giuliani SpA, Milan, Italy) and 105 to receive 2.4 g/day, starting 2 weeks after surgery. The primary outcome was endoscopic recurrence, at 12 months after surgery. Three different degrees of endoscopic recurrence were evaluated (endoscopic scores: > 0, > 1 and > 2). The secondary outcome was clinical recurrence, defined as a Crohn's disease activity index of more than 150 points or an increase in the Crohn's disease activity index of 100 points or more. For statistical analysis, chi-square, Wilcoxon and Cox regression model tests were used, when appropriate. RESULTS: Eighty-four patients in the 4.0 g/day group and 81 patients in the 2.4 g/day group were evaluable by endoscopy. Endoscopic recurrence of > 0 was significantly higher in the 2.4 g/day group than in the 4.0 g/day group (62% vs. 46%; P < 0.04). No difference was observed between the two groups with regard to the other two endoscopic outcomes (> 1 and > 2) or clinical recurrence. CONCLUSIONS: A 4.0 g/day regimen of mesalazine does not offer a clinically significant advantage over a 2.4 g/day regimen in the prevention of post-operative endoscopic and clinical recurrence of Crohn's disease at 1 year of follow-up

Background Dementia is a major public health problem because of its high prevalence in elderly individuals, particularly in the growing category of subjects aged 80 years or more. There is accumulating evidence that cholesterol may be implicated in the pathogenesis of dementia, and this has led us to assess the relationship between time spent with statins available and the risk of hospitalization for dementia. Methods A population-based, nested case-control study was carried out by including the cohort of 152,729 patients from Lombardy (Italy) aged 40 years or older who were newly treated with statins between 2003 and 2004. Cases were the 1380 patients who experienced hospitalization for dementia disease from initial prescription until 2010. Up to twenty controls were randomly selected for each case. Logistic regression was used to model the risk of dementia associated with the cumulative time during which statins were available. Monte-Carlo and rule-out sensitivity analyses were performed to account for unmeasured confounders. Results Compared with patients who had very short statins coverage (less than 6 months), those on 7–24, 25–48, and >48 months of coverage respectively had risk reductions of 15% (OR: 0.85; 95% CI: 0.74 to 0.98), 28% (OR: 0.72; 95% CI: 0.61 to 0.85), and 25% (OR: 0.75; 95% CI: 0.61 to 0.94). Simvastatin and atorvastatin were both associated with a reduced risk of dementia, while no similar evidence was observed for fluvastatin and pravastatin. Conclusions Long-term use of statins seems effective for the prevention of dementia.

Summary In the elderly patients, cognitive impairment is often associated with diabetes, especially with memory loss. The underlying mechanism of this phenomenon have not been cleared up. Metabolic changes can play an important role, because either low or high blood sugar levels can affect the cognitive performance. Here we report our preliminary data from an ongoing study on cerebrovascular deficits in diabetic elderly patients.

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

To investigate the association between the mean daily alcohol intake and positivity for serum anti-hepatitis C virus antibodies in patients with chronic liver disease of varying severity. To test the hypothesis that alcohol intake and hepatitis C virus infection have an independent role in determining chronic liver disease. Retrospective study using a multivariate analysis model. In 212 consecutive patients with chronic liver disease, serum anti-hepatitis C virus antibodies were detected using a second-generation test and recombinant immunoblotting assay. The lifetime mean daily alcohol intake was measured by a standardized questionnaire. Patients were subsequently divided according to the histological presence or absence of liver cirrhosis and stratified into progressive categories of alcohol intake. The dose-effect relationship between anti-hepatitis C virus status and mean daily alcohol intake was assessed by a model of unconditional logistic regression, where age, gender, degree of severity of liver disease and chronic hepatitis B virus infection were considered as covariates. There was a strong negative association between the mean daily alcohol intake and the presence of anti-hepatitis C virus antibodies, with odds ratio decreasing down to 0.01 for the category of highest alcohol intake; no association was found for the other variables considered. Our data support the hypothesis that alcohol intake and infection with hepatitis viruses are independent determinants of chronic liver disease.

To assess the risk of developing liver cirrhosis associated with alcohol consumption, HBV and HCV infection markers, we carried out a case-control study involving 115 patients admitted to the medical departments of the general hospitals in the province of L'Aquila (Abruzzo, Italy) who received for the first time the diagnosis of liver cirrhosis, and 167 controls randomly selected among patients admitted to the same hospitals as the cases. Alcohol intake was measured in all 282 subjects using an already validated standardized questionnaire, and expressed as mean lifetime daily alcohol intake in grams. The mean lifetime daily alcohol intake showed a dose-dependent effect on the risk of cirrhosis: the relative risk significantly rose to 3.8 (95% CI: 2.0 − 7.3) for a mean daily intake of ≥101 g alcohol; for HBsAg positivity the relative risk of cirrhosis was 23.0 (95% CI: 4.9 − 107.8) and for anti-HCV positivity it was 8.7 (95% CI: 4.3 − 17.6). After applying a multiple logistic regression analysis in a multivariate model including mean lifetime alcohol intake and anti-HCV status, both variables were significantly associated with the risk of cirrhosis (relative risks = 5.3 − 95% CI: 2.3 −12.2 and 9.9 − 95% CI: 4.4 − 22.0, respectively). The combination of these two variables was found to fit an additive - but not multiplicative - model relative to the risk of cirrhosis: furthermore, the interaction of the anti-HCV status with the presence or absence of cirrhosis did not result in a significant source of variability for the mean lifetime daily alcohol intake. We conclude that alcohol intake, HBsAg positivity and anti-HCV positivity are significantly associated with the risk of cirrhosis, but the risk associated with alcohol intake is independent of anti-HCV status.

The alcohol-attributable mortality is a positive function of two quantities: the relative risk, which has a biological specificity, and the proportion of exposed, which has a temporal and geographic specificity. Unfortunately, only little knowledge is available on these quantities.To estimate alcohol-attributable mortality we approached the problem by estimating: i) the prevalence of drinkers to various amounts of alcohol in the Italian population from 1970 to 1993; ii) the dose-response relation between alcohol consumption and risk of each alcohol-related condition through a meta-analytic approach; iii) the alcohol-attributable risks from 1970 to 1993 by using the drinkers prevalence estimates and relative risks evaluated previously; iv) the proportion of deaths related to alcohol consumption in Italy for the same period.Decreasing averages of per capita alcohol consumption (-44%) were observed from 1970 to 1993. In the same period was observed a reduction of -80%, -51% e -15%, respectively for heavy drinkers'prevalence (100 g/die), moderate drinkers'prevalence (more than 50 g/die) and for drinkers'prevalence (any consumption). The greatest alcohol-attributable risks were observed for hepatic cirrhosis and for upper digestive and respiratory tract cancers. Applying the alcohol-attributable fractions to all deaths of 1993 about 44000 (corresponding to the 8% of overall mortality) were attributable to alcohol and about 32000 deaths were attributable to moderate intake (or =100 g/die).The main suggestion from this study is that the best strategy in preventing alcohol-related problems should consider as target the whole population.

AIMS/HYPOTHESIS: Post-prandial glucose may be a risk factor for cardiovascular disease and chronic diabetic complications. We tested the hypothesis that post-prandial hyperglycaemia is common in type 2 diabetes, even among patients in apparently good glycaemic control, and that simple clinical characteristics identify subsets of diabetic patients with frequent post-prandial hyperglycaemia. SUBJECTS AND METHODS: Three self-assessed daily blood glucose profiles over a 1-week period, including 18 glucose readings before and 2 h after meals, were obtained from 3,284 unselected outpatients (men 51%; age 63+/-10 years) with non-insulin-treated type 2 diabetes mellitus attending 500 different diabetes clinics operating throughout Italy. RESULTS: A post-prandial blood glucose value >8.89 mmol/l (160 mg/dl) was recorded at least once in 84% of patients, and 81% of patients had at least one Delta glucose > or =2.22 mmol/l (40 mg/dl). Among patients with apparently good metabolic control, 38% had >40% of post-prandial blood glucose readings >8.89 mmol/l (> or =4 of 9 meals in total), and 36% had >40% Delta glucose > or =2.22 mmol/l. In multivariate analysis adjusted for pre-prandial glucose levels, older age, longer duration of diabetes, absence of obesity, hyperlipidaemia and hypertension, as well as treatment with sulfonylureas, were significantly associated with greater glucose excursions after meals. CONCLUSIONS/INTERPRETATION: These results indicate that post-prandial hyperglycaemia is a very frequent phenomenon in patients with type 2 diabetes mellitus on active treatment; can occur even when metabolic control is apparently good; and can be predicted by simple clinical features.

OBJECTIVE: Recurrence of Crohn's disease quite inevitably occurs after resection of distal small bowel and proximal colon, involving the neoterminal ileum close to the anastomosis. Oral 5-aminosalicylic acid (5-ASA) administered soon after surgery delays recurrence and reduces its severity. We recently observed that in operated patients submitted to prophylactic treatment with oral 5-ASA the rate of recurrence was significantly higher in those with end-to-end anastomosis than in those with other types of anastomosis (end-to-side, side-to-side). The hypothesis investigated in the present study was that patients with end-to-side or side-to-side anastomosis would benefit from a higher mucosal concentration of 5-ASA with respect to patients with end-to-end anastomosis. Therefore, the mucosal 5-ASA concentration was measured in the perianastomotic area of both groups. METHODS: The study was carried out in 19 patients submitted to radical surgery for Crohn's ileitis or ileocolitis, under oral prophylactic treatment with 5-ASA (Asacol). All patients were on regular endoscopic follow-up and were free of recurrence. Two biopsies were collected 3 cm from the anastomosis, in the neoterminal ileum, and two biopsies were collected at the colonic site 3 cm below the anastomosis. 5-ASA concentrations (ng/mg) were measured in tissue homogenates by high-performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: The mucosal concentration of 5-ASA in the neoterminal ileum was significantly lower in patients with end-to-end anastomosis than in those with other types of anastomosis (median values: 29.4 ng/mg vs 92.9 ng/mg respectively; p < 0.001). Six of 10 patients (60%) with end-to-end anastomosis, but none of the nine patients with other types of anastomosis, showed 5-ASA mucosal concentrations 90 ng/mg, compared with the 57% of patients in the group with other types of anastomosis. No differences were observed for colonic biopsies. CONCLUSIONS: The different mucosal concentrations in these two groups may be explained by the difference in segmental transit time induced by the different anastomotic configurations. A slower preanastomotic transit time, demonstrated in patients with end-to-side or side-to-side anastomosis, could offer a prolonged contact time between the intestinal content and the mucosa, resulting in an increase in drug absorption

Even though endoscopy is considered to be the gold standard for the detection of post-operative recurrence in Crohn's disease, the Crohn's disease activity index continues to be used for this purpose.The aim of this study was, therefore, to assess the accuracy of Crohn's disease activity index to detect post-operative recurrence in Crohn's disease in comparison to endoscopy.The study was performed in 110 patients submitted to intestinal resection for Crohn's disease of the terminal ileum. Crohn's disease activity index score was assessed at 6, 12, 24 and 36 months after surgery. At the same intervals colon-ileoscopy was performed in all patients. The Receiver Operating Characteristic analysis was used to assess the accuracy of the Crohn's disease activity index score. Some routine laboratory variables were also analyzed.Crohn's disease activity index was able to discriminate patients with and without recurrence in 65% of the cases. Considering 150 the standard cut-off value of Crohn's disease activity index, this figure corresponds to a specificity of 89% and a sensitivity of 30%. Out of the laboratory variables erythrocyte sedimentation rate, chloraemia and serum albumin, globally considered in a discriminant function, showed a predictive ability significantly better than Crohn's disease activity index (z = 1.97; two tailed p-value = 0.04). These variables were able to discriminate patients with and without recurrence in 88% of the cases, and at the same value of specificity for the Crohn's disease activity index reached double value of sensitivity (65%). Positive and negative predictive values of laboratory variables (80% and 78%, respectively) were better than the corresponding values of the Crohn's disease activity index score (71% and 56%, respectively).These results indicate that the Crohn's disease activity index alone is inadequate for detection of post-operative recurrence in Crohn's disease.

A population-based epidemiological study that concerns the estimate of incidence rates of Hodgkin's Disease (HD) and Non Hodgkin's Lymphoma (NHL) in a Central Italy area was performed. All the new cases of HD and NHL diagnosed from 1982 till 1994 in the target population were collected by multiple information sources. The temporal trend of incidence rates and their relation with age, gender and histological variant were analyzed. In the considered period 95 cases of HD and 297 cases of NHL were collected. Constant age-adjusted incidence rates of HD were observed, while an increasing trend of NHL incidence rates was observed especially for cases at presentation in stage III and IV and for histotypes G, H and I. The investigations carried out on patients with HD have shown that this condition prevails in women in the younger age groups, while in men presentation occurs more frequently at an advanced age. Moreover the authors have confirmed previous reports of a distinctly increased incidence of nodular sclerosis in contrast to the other three histological variants which do not show a juvenile peak but a gradual increase in incidence with advancing age. The epidemiological features of NHL's observed correspond to the standard incidence rates obtained in Europe and throughout the world. NHL's appear to be a pathological entity typical of elderly patients: however high-grade NHL's, in contrast to low-grade NHL's, was present with increased frequency also in childhood and in patients under the age of 30.

The authors evaluated the efficacy and toxicity of the combination of carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer. From March 1994 through March 1996, 56 previously untreated patients with stage IIIB or stage IV non-small-cell lung cancer with measurable lesions and good performance status were entered in the study. The chemotherapy schedule was as follows: carboplatin 100 mg/m2 and ifosfamide 1,500 mg/m2 with mesna on days 1, 2, and 3; vinorelbine 25 mg/m2 on days 1 and 8, every 21 days; for a total of six courses. Among 55 evaluable patients there were three complete responses (5%) and 22 partial responses (40%), for a response rate of 45% (95% confidence interval, 32-59%). The median response duration was 10.3 months (range, 2.5-27.7 months), and median survival time was 11.3 months (range, 1.1-28.1 months). The survival rate at 1 year was 48%. Toxicity included hematologic toxicity in 60% of the 247 treatment cycles administered, nausea, alopecia, and neuropathy. One pathologic complete response was observed in a patient with stage IIIB disease who became operable after four courses of chemotherapy. The outpatient treatment with carboplatin, ifosfamide, and vinorelbine shows activity in advanced non-small-cell lung cancer. The toxicity was well tolerated by patients with a good performance status.