Alice Mannocci

Smoking status and gastric cancer risk: an updated meta-analysis of case-control studies published in the past ten years

BACKGROUND A meta-analysis of published studies was performed in order to clarify the risk of gastric cancer associated with cigarette smoking status. METHODS Eligible studies were all the case-control studies investigating an association between smoking status and gastric cancer published from January 1, 1997, until June 30, 2006. In order to evaluate the quality of the published data, a qualitative scoring of papers was applied. The principal outcome measure was the odds ratio for the risk of gastric cancer associated with the smoking status using a random effects model. Cigarette smoking status was assessed in two ways: ever (current and ex) versus never smokers; current versus never smokers. RESULTS We found a statistically significant result for the association between ever smoking status and gastric cancer risk (OR = 1.48; 95% CI, 1.28-1.71), considering 14,442 cases and 73,918 controls. Moreover, we found an odds ratio of 1.69 for current smoker status in comparison to never smokers (95% CI, 1.35-2.11). Considering only high quality studies, the odds ratio increased by 43% for gastric cancer risk in ever smokers (OR = 1.43; 95% CI, 1.24-1.66; Q = 378.60, P < 0.00001; 12 = 90%) and by 57% in current smokers (OR = 1.57; 95% CI, 1.24-2.01). We also considered separately Caucasians and Asian studies, finding for ever smokers an odds ratio of 1.46 (95% CI, 1.25-1.70; Q = 125.68, P < 0.00001; 12 = 82.5%) and of 1.47 (95% CI, 1.13-1.91; Q = 366.77, P < 0.00001; I2 = 94%), respectively. CONCLUSIONS From the results of this quantitative meta-analysis, it appears that cigarette smoking has to be considered an important risk factor. The use of qualitative scoring decreases the magnitude of the relationship both for ever and current smoker exposure by 5-12%. Future studies on this topic need to clarify the biological interaction between environmental factors (such as cigarette smoking) and different polymorphisms on gastric cancer.

Skin ulcers in systemic sclerosis: Determinants of presence and predictive factors of healing

BACKGROUND Skin ulcers are common vascular complications of systemic sclerosis (SSc). OBJECTIVE The aim of the study was to identify clinical, biologic, and imaging parameters that constitute risk factors for the occurrence and persistence of skin ulcers. METHODS One hundred thirty Italian SSc patients were examined at entry and after 20 months of follow-up. RESULTS The diffuse SSc phenotype with avascular areas on capillaroscopy, thrombophilia, and systemic inflammation as defined by interleukin 6 plasma levels, represented the major risk factors for ulcer development. Infection was associated with a risk of poor or no healing, and cardiopulmonary involvement was a major comorbid factor in patients with ulcers. The presence of infection and avascular areas represented the main determinants for ulcer healing. LIMITATIONS Our data should be confirmed with a longer follow-up period since skin ulcers represent a frequent vascular complication in scleroderma patients. CONCLUSION Aggressive therapies aiming at improving angiogenesis and controlling infection and the course of the disease appear to be crucial to obtain ulcer healing.

PTPN22 1858C>T Polymorphism Distribution in Europe and Association with Rheumatoid Arthritis: Case-Control Study and Meta-Analysis

Objective The PTPN22 rs2476601 polymorphism is associated with rheumatoid arthritis (RA); nonetheless, the association is weaker or absent in some southern European populations. The aim of the study was to evaluate the association between the PTPN22 rs2476601 polymorphism and RA in Italian subjects and to compare our results with those of other European countries, carrying out a meta-analysis of European data. Methods A total of 396 RA cases and 477 controls, all of Italic ancestry, were genotyped for PTPN22 rs2476601 polymorphism. Patients were tested for autoantibodies positivity. The meta-analysis was performed on 23 selected studies. Results The PTPN22 T1858 allele was significantly more frequent in RA patients compared to controls (5.7% vs. 3.7%, p = 0.045). No clear relationship arose with the autoantibodies tested. The 1858T allele frequency in Italian RA patients was lower than the one described in northern European populations and similar to the frequency found in Spain, Turkey, Greece, Tunisia. A clear-cut North-South gradient arose from the analysis. Conclusions The PTPN22 T1858 allele is associated with RA in the Italian population. A North-South gradient of the allele frequency seems to exist in Europe, with a lower prevalence of the mutation in the Mediterranean area.

Biomarkers of good EULAR response to the B cell depletion therapy in all seropositive rheumatoid arthritis patients: Clues for the pathogenesis

Objective To find out whether a high number of auto-antibodies can increase the probability of a “good-EULAR response” and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT). Patients and Methods One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNFα blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined. Results At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count <1875/uL (OR = 10.74), a RF-IgG level >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final predictors were no-steroid therapy and low lymphocyte count. Discussion The number of AABs increased the chances of being a “good-EULAR” responder. The only predictors, however, at the baseline of a good response in this seropositive cohort of RA patients were 2 simple variables – no steroids and lymphocyte count – and two laboratory assays – IgG-RF and BAFF.

Use of trastuzumab in HER2-positive metastatic breast cancer beyond disease progression: a systematic review of published studies

Aims and background Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of ErbB, has determined clinical benefit for women affected by metastatic or early stage HER2-positive breast cancer and never previously treated with trastuzumab. Trastuzumab is generally used as first-line treatment of HER2+ metastatic breast cancer and is currently administered beyond progression even without clear evidence supporting such clinical practice. In fact, HER2-positive metastatic breast cancer has a high risk of progressing after first-line therapy, and second-line treatments vary. The aim of the study was to investigate by a systematic review the efficacy of trastuzumab-based treatments beyond progression in HER2-positive metastatic breast cancer. Materials and methods We performed a systematic review using Medline, Embase and Cochrane Library data bases and publications in principal meetings or congresses of oncology in Europe and America until September 2008. The main selection criterium was the reporting of time to progression, calculated from the start of each trastuzumab-based therapy to the date of progressive disease or death. Results Twelve studies were selected that included a total of 516 patients. The weighted mean time to progression was 23.66 weeks (standard deviation, 4.37) and the median was 26 weeks (range, 13–39). Interestingly, combined trastuzumab plus vinorelbine treatment showed a lower mean and median time to progression (20.59 and 19.57 weeks, respectively), whereas trastuzumab plus capecitabine yielded a mean time to progression of 30.33 weeks. Conclusions The added value of the present study has been to provide a quantitative summary measure of time to progression which can be used for comparisons between current and future available regimens.

Determinants of within-country variation in traffic accident mortality in Italy: a geographical analysis

ObjectiveTo identify determinants of regional differences in traffic accident mortality in Italy.Data and methodsMultiple linear regression models were conducted assessing the associations between regional differences in traffic mortality, case fatality and accident rates (dependent variables) with socio-demographic factors, and variables describing road behaviour, vehicles, infrastructure and medical care (independent variables). Data were derived from the National Institute of Statistics, the National Institute of Health and the Italian Automobile Club. In addition to analyses for the whole country of Italy, separate models were conducted for Northern and southern regions.ResultsIn Italy large regional differences in traffic mortality rates can be observed, ranging from 5.5 to 20 per 100.000 person-years. There is a North-South gradient with higher mortality rates in the Northern part of Italy. Strong predictors of regional differences in both traffic mortality and accident rates are the employment rate (directly associated) and alcohol use (directly associated). This is observed in the whole of Italy, and separately in Northern and southern regions.ConclusionOur study has shown the need for regional policies to improve road behaviour to reduce traffic accident and mortality rates in identified high-risk areas.

An assessment of the effect of hepatitis B vaccine in decreasing the amount of hepatitis B disease in Italy

BackgroundHepatitis B (HBV) infection is an important cause of morbidity and mortality and it is associated to a higher risk of chronic evolution in infected children. In Italy the anti-HBV vaccination was introduced in 1991 for newborn and twelve years old children. Our study aims to evaluate time trends of HBV incidence rates in order to provide an assessment of compulsory vaccination health impact.MethodData concerning HBV incidence rates coming from Acute Viral Hepatitis Integrated Epidemiological System (SEIEVA) were collected from 1985 to 2006. SEIEVA is the Italian surveillance national system that registers acute hepatitis cases. Time trends were analysed by joinpoint regression using Joinpoint Regression Program 3.3.1 according to Kims method. A joinpoint represents the time point when a significant trend change is detected. Time changes are expressed in terms of the Expected Annual Percent Change (EAPC) with 95% confidence interval (95% CI).ResultsThe joinpoint analysis showed statistically significant decreasing trends in all age groups. For the age group 0–14 EAPC was -39.0 (95% CI: -59.3; -8.4), in the period up to 1987, and -12.6 (95% CI: -16.0; -9.2) thereafter. EAPCs were -17.9 (95% CI: -18.7; -17.1) and -6.7 (95% CI: -8.0; -5.4) for 15–24 and ≥25 age groups, respectively. Nevertheless no joinpoints were found for age groups 15–24 and ≥25, whereas a joinpoint at year 1987, before compulsory vaccination, was highlighted in 0–14 age group. No joinpoint was observed after 1991.DiscussionOur results suggest that the introduction of compulsory vaccination could have contribute partly in decreasing HBV incidence rates. Compulsory vaccination health impact should be better investigated in future studies to evaluate the need for changes in current vaccination strategy.

A survey of visually induced symptoms and associated factors in spectators of three dimensional stereoscopic movies

BackgroundThe increasing popularity of commercial movies showing three dimensional (3D) computer generated images has raised concern about image safety and possible side effects on population health.This study aims to (1) quantify the occurrence of visually induced symptoms suffered by the spectators during and after viewing a commercial 3D movie and (2) to assess individual and environmental factors associated to those symptoms.MethodsA cross-sectional survey was carried out using a paper based, self administered questionnaire. The questionnaire includes individual and movie characteristics and selected visually induced symptoms (tired eyes, double vision, headache, dizziness, nausea and palpitations). Symptoms were queried at 3 different times: during, right after and after 2 hours from the movie.ResultsWe collected 953 questionnaires. In our sample, 539 (60.4%) individuals reported 1 or more symptoms during the movie, 392 (43.2%) right after and 139 (15.3%) at 2 hours from the movie. The most frequently reported symptoms were tired eyes (during the movie by 34.8%, right after by 24.0%, after 2 hours by 5.7% of individuals) and headache (during the movie by 13.7%, right after by 16.8%, after 2 hours by 8.3% of individuals). Individual history for frequent headache was associated with tired eyes (OR = 1.34, 95%CI = 1.01-1.79), double vision (OR = 1.96; 95%CI = 1.13-3.41), headache (OR = 2.09; 95%CI = 1.41-3.10) during the movie and of headache after the movie (OR = 1.64; 95%CI = 1.16-2.32). Individual susceptibility to car sickness, dizziness, anxiety level, movie show time, animation 3D movie were also associated to several other symptoms.ConclusionsThe high occurrence of visually induced symptoms resulting from this survey suggests the need of raising public awareness on possible discomfort that susceptible individuals may suffer during and after the vision of 3D movies.

The Health Technology Assessment of bivalent HPV vaccine Cervarix in Italy

INTRODUCTION Health Technology Assessment (HTA) approach was applied to Human Papilloma Virus (HPV) vaccine in the Italian context. METHODS Epidemiology and costs of HPV infection and related diseases, vaccine efficacy, clinical and economic impact of the HPV vaccination and womens knowledge and attitudes towards vaccination were assessed. RESULTS HPV infections pooled prevalence in Italy was 19% (95%CI: 10-30%) and cervical cancer incidence was 9.8/100,000 per year. The mean costs for in situ and invasive carcinoma hospitalisation were estimated respectively in euro1745.87 and euro2616.16. HPV vaccines have demonstrated high efficacy and good safety profile. The meta-analysis on efficacy results in preventing persistent cervical infections by HPV16 and 18 for both HPV vaccines resulted in 87% (95%CI: 80-91%) and 78% (95%CI: 62-87%). Modelling the impact of vaccination with bivalent vaccine, it would reduce cancer cases by 67% and be cost-effective, with a cost per Quality Adjusted Life Years (QALYs) gained of euro22,055. CONCLUSION The thoroughness of the evaluation allowed us accounting for all the aspects of HPV infection/diseases. The HTA report on the HPV vaccine demonstrated to be a comprehensive tool for an informed decision making process.

Bronchoalveolar lavage fluid and progression of scleroderma interstitial lung disease

Introduction:  So far no clinical or experimental evidences clearly explain how and which systemic sclerosis (SSc) patients will experience a functional and radiological progression of interstitial lung disease (ILD).