Impact of the environment on the health: From theory to practice.

The Erice 56 Charter titled "Impact of the environment on the health: from theory to practice" was unanimously approved at the end of the 56th course of the "International School of Epidemiology and Preventive Medicine G. D'Alessandro" held from 3rd to November 7, 2019 in Erice - Sicily (Italy) and promoted by the Study Group of "Environment and Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of "One Health" and "Global Health", also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

The Use of Integra Dermal Regeneration Template Versus Flaps for Reconstruction of Full-Thickness Scalp Defects Involving the Calvaria: A Cost-Benefit Analysis.

BACKGROUND: INTEGRA® Dermal Regeneration Template is a well-known and widely used acellular dermal matrix. Although it helps to solve many challenging problems in reconstructive surgery, the product cost may make it an expensive alternative compared to other reconstruction procedures. This retrospective study aims at comparing INTEGRA-based treatment to flap surgery in terms of cost and benefit. PATIENTS AND METHODS: We considered only patients treated for scalp defects with bone exposure in order to obtain two groups as homogeneous as possible. We identified two groups of patients: 17 patients treated with INTEGRA and 18 patients treated with flaps. All patients were admitted in our institution between 2004 and 2010, and presented a defect of the scalp following trauma or surgery for cancer, causing a loss of the soft tissues of the scalp with bone exposure without pericranium. To calculate the cost in constant euros of each treatment, three parameters were evaluated for each patient: cost of the surgical procedure (number of doctors and nurses involved, surgery duration, anesthesia, material used for surgery), hospitalization cost (hospitalization duration, dressings, drugs, topical agents), and outpatient cost (number of dressing changes, personnel cost, dressings type, anti-infective agents). The statistical test used in this study was the Wilcoxon Mann-Whitney (α = 0.05). RESULTS: No significant difference was characterized between the two groups for gender, age, presence of diabetes, mean defect size, and number of surgical procedures. All patients healed with good quality and durable closure. The median total cost per patient was €11,121 (interquartile range (IQR) 8327-15,571) for the INTEGRA group and €7259 (IQR 1852-24,443) for the flap group (p = 0.34). A subgroup of patients (six patients in the INTEGRA group and five patients in the flap group) showing defects larger than 100 cm2 were considered in a second analysis. Median total cost was €11,825 (IQR 10,695-15,751) for the INTEGRA group and €23,244 (IQR 17,348-26,942) for the flap group. CONCLUSION: Both treatments led to a good healing of the lesions with formation of soft and resistant tissue. No significant difference was characterized between the two groups for days of hospitalization and costs. In cases of patients with defects larger than 100 cm2 for whom major surgery is needed, the treatment with INTEGRA seemed to be less expensive than the treatment with free flaps or pedicle flaps. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors. www.springer.com/00266 .

Prognostic factors and outcome of Epstein-Barr virus DNAemia in high-risk recipients of allogeneic stem cell transplantation treated with preemptive rituximab.

AIMS AND METHODS: This study assessed incidence, predictive factors, and outcome of Epstein-Barr virus (EBV) DNAemia in 100 recipients of allogeneic hematopoietic stem cell transplant. A total of 68 patients received anti-thymocyte globulin before unrelated grafts. RESULTS: Cumulative incidence of high-load EBV DNAemia defined by levels >10,000 copies/mL was 14% at 12 months. In multivariate analysis, a CD4+ T-lymphocyte count >50 µL at day +30 was the only factor significantly associated with a reduced risk of high-load EBV DNAemia. Thirteen of 16 patients with high viral loads were preemptively treated with rituximab and achieved EBV DNA negativity. Three patients had already developed post-transplant lymphoproliferative disorder (PTLD) at the time of detection of high EBV DNA loads, and they obtained complete response after rituximab infusions and chemotherapy. Patients with high EBV DNA load had a significantly higher transplant-related mortality (TRM) compared with patients with negative or low viral load (54% vs. 16%, P = 0.009) and a trend to lower overall survival (55% vs. 29%, P = 0.060). CONCLUSION: We conclude that CD4+ cell count at day +30 is a predictive factor for EBV DNAemia and may help identify patients requiring closer monitoring. Although only 3% of patients progressed to PTLD and were all successfully managed, EBV reactivation was associated with higher TRM, mainly because of infections.

[Road traffic crashes, alcohol, meals, sleep and work hours: a case-crossover study at the Emergency Room of Udine, Italy]. / Incidenti stradali, alcol, pasti, sonno e ore di lavoro: uno stu- dio di case-crossover presso il Pronto Soccorso di Udine.

In case-crossover studies, useful for assessing the effect of acute transient exposures, each case acts as his/her own control, therefore, interpersonal confounding is controlled for by study. We used such design for studying the effect of the acute consumption of alcohol and meals, and of sleep and work hours on the risk of road traffic crashes. Subjects, enrolled at the Emergency Room (ER) of Udine from 12/3/2007 to 11/3/2008, were a sample of the drivers who arrived alive at the ER after a crash. They were interviewed by trained interviewers, who systematically covered predefined shifts, using a semi-structured questionnaire. The questionnaire collected information on the subjects, vehicles, and crashes, and contained a hourly diary of the exposure to driving, sleeping, working in the 48 hours before the crash and to alcohol and meals 24 hours before the crash. The statistical analysis was based on the matched pair interval approach. The exposures in the hours immediately before the crash (case window) were compared with those in previous hours (control window). Different window durations were chosen for different exposures. The relative risk (RR) of having a crash and 95% confidence intervals (95% CI) were estimated with conditional logistic regression, adjusting for potential confounders such as day of the week and time. We observed a statistically significant two-fold increase in the RR for drivers who had consumed alcohol (even small amounts) and a four-fold increase for those who had worked > 12 ore. The RR was increased by 10 times for drivers who had been awake for at least 16 hours. Meals were not associated with the risk of crash; the findings regarding sleep amount were controversial. In conclusion, the study confirms an increased risk of road crashes after consuming alcohol, even for amounts below the legal limit, and suggests that extended work hours and prolonged wakefulness may increase the risk of crashes.

Author Correction: A Systematic Evaluation of Hospital Performance of Childbirth Delivery Modes and Associated Factors in the Friuli Venezia Giulia Region (North-Eastern Italy), 2005-2015.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Determinants of length of stay after cesarean sections in the Friuli Venezia Giulia Region (North-Eastern Italy), 2005-2015.

Since Italy has the highest cesarean section (CS) rate (38.1%) among all European countries, the containment of health care costs associated with CS is needed, along with control of length of hospital stay (LOS) following CS. This population based cross-sectional study aims to investigate LoS post CS (overall CS, OCS; planned CS, PCS; urgent/emergency CS, UCS), in Friuli Venezia Giulia (a region of North-Eastern Italy) during 2005-2015, adjusting for a considerable number factors, including various obstetric conditions/complications. Maternal and newborn characteristics (health care setting and timeframe; maternal health factors; child's size factors; child's fragility factors; socio-demographic background; obstetric history; obstetric conditions) were used as independent variables. LoS (post OCS, PCS, UCS) was the outcome measure. The statistical analysis was conducted with multivariable linear (LoS expressed as adjusted mean, in days) as well as logistic (adjusted proportion of LoS > 4 days vs. LoS ≤ 4 days, using a 4 day cutoff for early discharge, ED) regression. An important decreasing trend over time in mean LoS and LoS > ED was observed for both PCS and UCS. LoS post CS was shorter with parity and history of CS, whereas it was longer among non-EU mothers. Several obstetric conditions/complications were associated with extended LoS. Whilst eclampsia/pre-eclampsia and preterm gestations (33-36 weeks) were predominantly associated with longer LoS post UCS, for PCS LoS was significantly longer with birthweight 2.0-2.5 kg, multiple birth and increasing maternal age. Strong significant inter-hospital variation remained after adjustment for the major clinical conditions. This study shows that routinely collected administrative data provide useful information for health planning and monitoring, identifying inter-hospital differences that could be targeted by policy interventions aimed at improving the efficiency of obstetric care. The important decreasing trend over time of LoS post CS, coupled with the impact of some socio-demographic and obstetric history factors on LoS, seemingly suggests a positive approach of health care providers of FVG in decision making on hospitalization length post CS. However, the significant role of several obstetric conditions did not influence hospital variation. Inter-hospital variations of LoS could depend on a number of factors, including the capacity to discharge patients into the surrounding non-acute facilities. Further studies are warranted to ascertain whether LoS can be attributed to hospital efficiency rather than the characteristics of the hospital catchment area.

Understanding Factors Leading to Primary Cesarean Section and Vaginal Birth After Cesarean Delivery in the Friuli-Venezia Giulia Region (North-Eastern Italy), 2005-2015.

Although there is no evidence that elevated rates of cesarean sections (CS) translate into reduced maternal/child perinatal morbidity or mortality, CS have been increasingly overused almost everywhere, both in high and low-income countries. The primary cesarean section (PCS) has become a major driver of the overall CS (OCS) rate, since it carries intrinsic risk of repeat CS (RCS) in future pregnancies. In our study we examined patterns of PCS, pl compared with planned TOLAC anned PCS (PPCS), vaginal birth after 1 previous CS (VBAC-1) and associated factors in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from its 11 maternity centres (coded from A to K) during 2005-2015. By fitting three multiple logistic regression models (one for each delivery mode), we calculated the adjusted rates of PCS and PPCS among women without history of CS, whilst the calculation of the VBAC rate was restricted to women with just one previous CS (VBAC-1). Results, expressed as odds ratio (OR) with 95% confidence interval (95%CI), were controlled for the effect of hospital, calendar year as well as several factors related to the clinical and obstetric conditions of the mothers and the newborn, the obstetric history and socio-demographic background. In FVG during 2005-2015 there were 24,467 OCS (rate of 24.2%), 19,565 PCS (19.6%), 7,736 PPCS (7.7%) and 2,303 VBAC-1 (28.4%). We found high variability of delivery mode (DM) at hospital level, especially for PCS and PPCS. Breech presentation was the strongest determinant for PCS as well as PPCS. Leaving aside placenta previa/abuptio placenta/ante-partum hemorrhage, further significant factors, more importantly associated with PCS than PPCS were non-reassuring fetal status and obstructed labour, followed by (in order of statistical significance): multiple birth; eclampsia/pre-eclampsia; maternal age 40-44 years; placental weight 600-99 g; oligohydramios; pre-delivery LoS 3-5 days; maternal age 35-39 years; placenta weight 1,000-1,500 g; birthweight < 2,000 g; maternal age ≥ 45 years; pre-delivery LoS ≥ 6 days; mother's age 30-34 years; low birthweight (2,000-2,500 g); polyhydramnions; cord prolaspe; ≥6 US scas performed during pregnancy and pre-term gestations (33-36 weeks). Significant factors for PPCS were (in order of statistical significance): breech presentation; placenta previa/abruptio placenta/ante-partum haemorrhage; multiple birth; pre-delivery LoS ≥ 3 days; placental weight ≥ 600 g; maternal age  40-44 years; ≥6 US scans performed in pregnancy; maternal age ≥ 45 and 35-39 years; oligohydramnios; eclampsia/pre-eclampsia; mother's age 30-34 years; birthweight <2,000 g; polyhydramnios and pre-term gestation (33-36 weeks). VBAC-1 were more likely with gestation ≥ 41 weeks, placental weight <500 g and especially labour analgesia. During 2005-2015 the overall rate of PCS in FVG (19.6%) was substantially lower than the corresponding figure reported in 2010 for the entire Italy (29%) and still slightly under the most recent national PCS rate for 2017 (22.2%). The VBAC-1 rate on women with history of one previous CS in FVG was 28.4% (25.3% considering VBAC on all women with at least 1 previous CS), roughly three times the Italian national rate of 9% reported for 2017. The discrepancy between the OCS rate at country level (38.1%) and FVG's (24.2%) is therefore mainly attributable to RCS. Although there was a marginal decrease of PCS and PPCS crudes rates over time in the whole region, accompained by a progressive enhancement of the crude VBAC rate, we found remarkable variability of DM across hospitals. To further contain the number of unnecessary PCS and promote VBAC where appropriate, standardized obstetric protocols should be introduced and enforced at hospital level. Decision-making on PCS should be carefully scrutinized, introducing a diagnostic second opinion for all PCS, particularly for term singleton pregancies with cephalic presentation and in case of obstructed labour as well as non-reassuring fetal status, grey areas potentially affected by subjective clinical assessment. This process of change could be facilitated with education of staff/patients by opinion leaders and prenatal counseling for women and partners, although clinical audits, financial penalties and rewards to efficient maternity centres could also be considered.

Small peptides as potent mimetics of the protein hormone erythropoietin.

Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the receptor for the cytokine erythropoietin (EPO). In a panel of in vitro biological assays, the peptides act as full agonists and they can also stimulate erythropoiesis in mice. These agonists are represented by a 14- amino acid disulfide-bonded, cyclic peptide with the minimum consensus sequence YXCXXGPXTWXCXP, where X represents positions allowing occupation by several amino acids. The amino acid sequences of these peptides are not found in the primary sequence of EPO. The signaling pathways activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the design of small molecule mimetics of EPO.

A Systematic Evaluation of Hospital Performance of Childbirth Delivery Modes and Associated Factors in the Friuli Venezia Giulia Region (North-Eastern Italy), 2005-2015.

Cesarean sections (CS) have become increasingly common in both developed and developing countries, raising legitimate concerns regarding their appropriateness. Since improvement of obstetric care at the hospital level needs quantitative evidence, using routinely collected health data we contrasted the performance of the 11 maternity centres (coded with an alphabetic letter A to L) of an Italian region, Friuli Venezia Giulia (FVG), during 2005-15, after removing the effect of several factors associated with different delivery modes (DM): spontaneous vaginal delivery (SVD), instrumental vaginal delivery (IVD), overall CS (OCS) and urgent/emergency CS (UCS). A multivariable logistic regression model was fitted for each individual DM, using a dichotomous outcome (1 = each DM; 0 = rest of hospital births) and comparing the stratum specific estimates of every term with their respective reference categories. Results were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The Benjamini-Hochberg (BH) false discovery rates (FDR) approach was applied to control alpha error due to the large number of statistical tests performed. In the entire FVG region during 2005-2015, SVD were 75,497 (69.1% out of all births), IVD were 7,281 (6.7%), OCS were 26,467 (24.2%) and UCS were 14,106 (12.9% of all births and 53.3% out of all CS). SVD were more likely (in descending order of statistical significance) with: higher number of previous livebirths; clerk/employed occupational status of the mother; gestational age <29 weeks; placentas weighing <500 g; stillbirth; premature rupture of membranes (PROM). IVD were predominantly more likely (in descending order of statistical significance) with: obstructed labour, non-reassuring fetal status, history of CS, labour analgesia, maternal age ≥35 and gestation >40 weeks. The principal factors associated with OCS were (in descending order of statistical significance): CS history, breech presentation, non-reassuring fetal status, obstructed labour, multiple birth, placental weight ≥ 600 g, eclampsia/pre-eclampsia, maternal age ≥ 35 and oligohydramnios. The most important risk factors for UCS were (in descending order of statistical significance): placenta previa/abruptio placenta/ antepartum hemorrage; non-reassuring fetal status, obstructed labour; breech presentation; PROM, eclampsia/pre-eclampsia; gestation 33-36 weeks; gestation 41+ weeks; oligohydramnios; birthweight <2,500 g, maternal age ≥ 35 and cord prolapse. After removing the effects of all other factors, we found great variability of DM rates across hospitals. Adjusting for all risk factors, all hospitals had a OCS risk higher than the referent (hospital G). Out of these 10 hospitals with increased adjusted risk of OCS, 9 (A, B, C, D, E, F, I, J, K) performed less SVD and 5 (A, C, D, I, J) less IVD. In the above 5 centres CS was therefore probably overused. The present study shows that routinely collected administrative data provide useful information for health planning and monitoring. Although the overall CS rate in FVG during 2005-15 was 24.2%, well below the corresponding average Italian national figure (38.1%), the variability of DM rates across FVG maternity centres could be targeted by policy interventions aimed at reducing the recourse to unnecessary CS. In some clinical conditions such as obstructed labor, non-reassuring fetal status, breech presentation, history of CS, higher maternal age and multiple birth, consideration may be given to more conservative DM. The overuse of CS in nulliparas and repeat CS (RCS) should be carefully monitored and subject to audit.

Macronutrients, fatty acids and cholesterol intake and endometrial cancer.

BACKGROUND: There is some evidence that dietary habits may influence the risk of endometrial cancer independently of body mass, although the role of diet on endometrial carcinogenesis is unclear. PATIENTS AND METHODS: We carried out a multicenter case-control study from 1992 to 2006 in Italy on 454 women with incident, histologically confirmed endometrial cancer (age range 18-79 years) and 908 controls (age range 19-79 years) admitted to hospitals for acute, non-neoplastic diseases. A validated food-frequency questionnaire was used to estimate macronutrients, fatty acids and cholesterol intake. Logistic regression models, conditioned on age and study centre, and adjusted for major known risk factor of endometrial cancer and residual of energy intake were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Significant direct associations were observed with intake of energy (OR = 1.7 for the highest versus the lowest quintile, 95% CI = 1.1-2.5), and cholesterol (OR = 2.1, 95% CI = 1.4-3.2), while a direct borderline association emerged with saturated fatty acids (OR = 1.3, 95% CI = 0.9-2.0). There was no association with proteins, sugars, starch, total fat and other selected fatty acids. CONCLUSION: Energy and cholesterol intake were associated with endometrial cancer.

Increased potency of an erythropoietin peptide mimetic through covalent dimerization.

We have synthesized a chemically defined, dimeric form of an erythropoietin mimetic peptide (EMP) that displays 100-fold increased affinity for the erythropoietin receptor (EPOR) and correspondingly elevated potency in cell-based assays and in mice. The dimeric EMP1 was synthesized using a C-terminal lysine residue as a branch point. A beta-alanine residue was coupled to the main-chain (alpha) amino group of the lysine residue in order to provide a pseudosymmetrical scaffold where both the side-chain and main-chain were of approximately equal length. Using an orthogonal protection system, independently disulphide-cylized EMP1 moieties were synthesized upon this scaffold. The proposed mechanism of increased potency of the dimer over the parental compound EMP1 is consistent with the structure of a cocrystal of EMP1 and the extracellular domain of the EPOR in which a noncovalent peptide dimer is seen spanning the cleft between two molecules of the EPOR extracellular domain.

Prulifloxacin versus levofloxacin in the treatment of chronic bacterial prostatitis: a prospective, randomized, double-blind trial.

Ninety-six patients with chronic bacterial prostatitis (CBP) and evidence of infection were randomized to receive a 4-week oral course of either prulifloxacin (a new fluoroquinolone) 600 mg or levofloxacin 500 mg once daily. They were evaluated with the Meares-Stamey test and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at baseline and one week after therapy completion. Patients with microbiological eradication were evaluated again with the Meares-Stamey test 6 months after therapy completion. The microbiological eradication rate was 72.73% for prulifloxacin and 71.11% for levofloxacin (p=0.86) and the reduction in the NIH-CPSI was 10.75 and 10.73, respectively (p=0.98). Safety was comparable, with 18.18% adverse events for prulifloxacin and 22.22% for levofloxacin (p=0.79). Thus, a 4-week course of prulifloxacin 600 mg once daily is at least as effective and safe as levofloxacin 500 mg once daily in the treatment of CBP.

[Physicians working at the NHS Prevention Department: a national survey in Italy]. / Profilo ed aspettative del medico operante presso il Dipartimento di Prevenzione in Italia.

In Italy NHS Prevention Departments (PDs) are central in Public Health (PH) management. Objective was to describe profile of Medical Doctors (MDs) working at Italian PDs. The study, part of another survey, was conducted in 2003, using a phone questionnaire to administer to a sample of Italian MDs in PH. Response rate was 72.3% (603/833). Physicians of PDs were 255, 42.3% of whole sample. Job satisfaction mean (scale: 0-100) was 66.6 (SD = 19.3). 81.6% (208/225) of MDs said that Regions must monitor health status to identify collective risks and problems, while 77.3% (197/255) of them answered that function of State is to develop politics and planes to pursue individual and collective health. The study gives a positive frame of MDs at PDs. They were satisfied and persuaded of importance of State and Regions in PH management.

[Exposure to organic halogen compounds in drinking water of 9 Italian regions: exposure to chlorites, chlorates, thrihalomethanes, trichloroethylene and tetrachloroethylene]. / Valutazione dell'esposizione a composti organoalogenati nelle acque potabili di 9 Province Italiane: indagine sulla presenza di cloriti, clorati, trialometani, trielina e tetracloroetilene.

This study investigated the exposure to organohalogens compounds in drinking water from 9 Italian towns (Udine, Genova, Parma, Modena, Siena, Roma, L'Aquila, Napoli and Catania). Overall, 1199 samples collected from 72 waterworks were analyzed. THMs, trichloroethylene and tetrachloroethylene were evaluated using the head-space gas chromatographic technique (detection limit of 0.01 microg/l; chlorite and chlorate analysis was performed by ion chromatography (detection limit of 20 microg/l). THMs were evidenced in 925 samples (77%) (median value: 1.12 micro/l; range: 0.01-54 mciro/l) and 7 were higher than the THMs Italian limit of 30 microg/l. Chlorite and chlorate levels were higher than the detection limit in 45% for chlorite and in 34% for chlorate samples; median values were 221 microg/l and 76 microg/l, respectively. Chlorite values were higher than the chlorite Italian limit (700 microg/l) in 35 samples (8.7%). Trichloroethylene and tetrachloroethylene were measured in 29% and 44% of the investigated samples and showed values lower than the Italian limit (highest levels of 6 microg/l and 9 microg/l, respectively). The low levels detected of THMs, trichloroethylene and tetrachloroethylene have no potentials effects on human health, whereas, the levels of chlorite and chlorates should be further evaluated and their potential effects for the populations using these drinking waters, better understood.

Amino-terminal dimerization of an erythropoietin mimetic peptide results in increased erythropoietic activity.

BACKGROUND: Erythropoietin (EPO), the hormone involved in red blood cell production, activates its receptor by binding to the receptor's extracellular domain and presumably dimerizing two receptor monomers to initiate signal transduction. EPO-mimetic peptides, such as EMP1, also bind and activate the receptor by dimerization. These mimetic peptides are not as potent as EPO, however. The crystal structure of the EPO receptor (EBP) bound to EMP1 reveals the formation of a complex consisting of two peptides bound to two receptors, so we sought to improve the biological activity of EPO-mimetic peptides by constructing covalent dimers of EMP1 and other peptide mimetics linked by polyethylene glycol (PEG). RESULTS: The potency of the PEG-dimerized EPO peptide mimetics both in vitro and in vivo was improved up to 1,000-fold compared to the corresponding peptide monomers. The dimers were constructed using peptide monomers which have only one reactive amine per molecule, allowing us to conclude that the increase in potency can be attributed to a structure in which two peptides are linked through their respective amino termini to the difunctional PEG molecule. In addition, an inactive peptide was converted into a weak agonist by PEG-induced dimerization. CONCLUSIONS: The potency of previously isolated peptides that are modest agonists of the EPO receptor was dramatically increased by PEG-induced dimerization. The EPO receptor is thought to be dimerized during activation, so our results are consistent with the proposed 2:2 receptor : peptide stoichiometry. The conversion of an inactive peptide into an agonist further supports the idea that dimerization can mediate receptor activation.

Alcohol and cancers of the upper aerodigestive tract in men and women.

In order to explore the potential differences in the effect of alcohol in men and women we took advantage of a case-control study of upper aerodigestive tract tumors conducted between 1986 and 1991 in Northern Italy Five hundred forty-six incidence cases of cancer of the oral cavity and pharynx (of whom 81 were women), 410 of cancer of the esophagus (of whom 67 were women), and 388 with cancer of the larynx, (of whom 19 were women) were interviewed. The control group included 2263 inpatients (of whom 557 were women) with acute conditions unrelated to alcohol and tobacco consumption. Among alcohol drinkers, similar odds ratios were detected in men and women. In the highest, well comparable intake category (i.e., > or = 42 drinks/week in women and 42-55 drinks/week in men), odds ratios were 4.5 and 3.8 for cancer of the oral cavity and pharynx, 3.0 and 4.7 for cancer of the esophagus, and 2.6 and 2.0 for cancer of the larynx in women and men, respectively, as compared to light drinkers. However, for all cancer sites a reduced risk was found among abstaining women but not in abstaining men, when compared with light-to-moderate drinkers. The present study, therefore, does not support the hypothesis that women may be substantially more vulnerable than men to alcohol carcinogenesis, at least at the level of the upper aerodigestive tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Attributable risk for laryngeal cancer in northern Italy.

Using data from a case-control study conducted between 1986 and 1992 in Northern Italy on 367 cases of laryngeal cancers (350 men and 17 women) and 1931 hospital controls (1373 men and 558 women), we estimated the relative risks (RR) and the population attributable risks (AR) for laryngeal cancer in relation to tobacco and alcohol consumption and a diet containing little fresh fruit and vegetables (low beta-carotene intake). In men, the RR and their 95% confidence interval (CI), derived from multiple logistic regression, including terms for center, age, and education, plus, simultaneously, tobacco, alcohol, and beta-carotene) were 3.3 (95% CI, 1.9 to 5.5) for ex- or moderate smokers (< 15 cigarettes/day) and 8.8 (95% CI, 5.2 to 14.8) for heavy current smokers compared to never smokers; the RR were 1.5 (95% CI, 1.0 to 2.2) for drinkers of 6 to < 8 alcoholic drinks/day and 2.2 (95% CI, 1.6 to 3.0) for drinkers of 8 or more drinks/day compared to teetotallers or moderate drinkers; with respect to carotene intake the RR were 1.4 (95% CI, 1.0 to 2.0) for the intermediate tertile and 1.8 (95% CI, 1.3 to 2.5) for the lowest tertile, as compared to the highest tertile of intake. AR were estimated assuming a multiplicative model: the single factor with the largest AR was smoking, which accounted for about 77% of laryngeal cancers in men; alcohol intake explained about 25% of cases, low beta-carotene intake accounted for about 18% of cases, and together the three factors were responsible for about 86% of laryngeal cancers in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined analysis of MIB-1 and thyroid transcription factor-1 predicts survival in non-small cell lung carcinomas.

The prognostic value of combined immunohistochemical analysis for the thyroid transcription factor-1 (TTF-1) and the proliferation marker MIB-1 was assessed in a consecutive series of non-small cell lung carcinomas (NSCLC). Tumor immunoreactivity for TTF-1 and MIB-1 was classified in three groups (-,+,++) and in two groups (-,+), respectively. Comparison across groups for TTF-1 reactivity showed significantly different survival curves (P=0.04). In particular, the best prognosis was associated with a TTF-1 negative pattern, whereas the TTF-1 '++' cases showed the worst prognosis. A trend towards better prognosis was observed for MIB-1 negative cases (P=0.09). Multivariate analysis confirmed independent prognostic significance of TTF-1 (P=0.002), MIB-1 (P=0.01) and pStage (P=0.04). Accordingly, analysing TTF-1 and MIB-1 together, a better prediction of survival was obtained (P=0.02), with the poorest prognosis for the 'TTF-1++/MIB-1+' cases.