Confirmatory validation of the Mesothelioma Psychological Distress Tool-Patients: A brief patient-reported outcome measure assessing psychological distress in malignant mesothelioma patients.

OBJECTIVE: Psychological suffering in patients with Malignant Mesothelioma (MM) is different from the one experienced by patients with other cancers due to its occupational or environmental etiology and its peculiar symptomatology and prognosis (i.e., poor prognosis, reduced effectiveness of the therapies, poor quality of residual life, and advanced age at the time of diagnosis). Therefore, the Mesothelioma Psychological Distress Tool-Patients (MPDT-P) has been developed to evaluate the specific profile of psychological suffering in this population. This paper describes the item selection, factor analysis, and psychometric evaluation of the revised MPDT-P. METHODS: The analyses of the current work aimed to confirm the factorial structure found in the first version of the MPDT-P. In the case of nonfit, it aimed to find an alternative structure and causes of nonfit in the model. The search for the fit of the factorial model was conducted using a Bayesian approach. RESULTS: The two-factor model reported in the first version of the instrument did not fit the data. Confirmatory Bayesian analyses showed adequate fit for the three-factor solution. Based on the content of the items, we labeled the factors as dysfunctional emotions, claims for justice, and anxieties about the future. CONCLUSIONS: Integrating the MPDT-P into clinical practice could help clinicians gain insight into the specific suffering related to MM and investigate potential differences related to different occupational and environmental exposure contexts.

Cerebral and systemic near infrared spectroscopy patterns in preterm infants treated by caffeine.

AIM: To investigate the effects of caffeine loading/maintenance administration on near-infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. METHODS: We conducted a multicentre case-control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. RESULTS: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. CONCLUSION: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long-term effect of caffeine in preterm infants.

A Review on The Role of Environmental Exposures in IgG4-Related Diseases.

PURPOSE OF REVIEW: Immunoglobulin G4-related diseases (IgG4-RDs) are immune-mediated fibroinflammatory multisystemic conditions identified by the presence of tumefactive lesions with a rich infiltrate of IgG4-positive plasma cells, and often by a high IgG4 serum concentration. IgG-RDs have a prevalence of at least 1 case every 100,000 persons, and they are mostly diagnosed after age 50, with a male to female ratio of about 3:1. IgG4-RD pathophysiology is still uncertain: it has been proposed that both genetic predisposition and chronic environmental exposures may play a role by triggering abnormal immune activation that perpetuates the disease. The purpose of this review is to summarize the evidences supporting the hypothesis that certain environmental/occupational exposures can trigger IgG4-RDs, focusing on the possible role of asbestos in an emerging IgG4-RD called idiopathic retroperitoneal fibrosis (IRF). RECENT FINDINGS: Although some studies suggested a relationship between tobacco smoking and IgG4-RD risk, occupational exposures seem to have the most interesting effects. Positive history of blue-collar work increases the risk of developing an IgG4-RD, and mineral dusts and asbestos were the most strongly associated industrial compounds. Asbestos has been found to be a risk factor for IRF years before its classification as IgG4-RD, and later in two large case-control studies. In the most recent one, conducted on 90 patients and 270 controls, asbestos exposure conferred an increased IRF risk, quantified by odds ratios from 2.46 to 7.07. Further structured studies including serum IgG4 evaluation should be conducted to clarify the effect of asbestos on patients with confirmed diagnosis of IgG4-related IRF. Environmental exposures, especially of occupational origin, appear to play a role in the development of different types of IgG-RDs. In particular, although first suggested very recently, the relationship between asbestos and IRF deserves to be explored in more structured studies, especially because of the biological plausibility of the role of asbestos in IRF pathogenesis.

Unprecedented long-term survival in a patient with malignant pleural mesothelioma treated with subsequent systemic chemo- and immunotherapeutic regimens.

Pleural mesothelioma is a rare disease with a dismal prognosis and few therapeutic options. Until recently the median overall survival for a pleural mesothelioma patient was up to 2 years, with few exceptional cases of patients achieving a longer survival. Here, we report the clinical case of a patient whose survival spanned over 10 years. The patient underwent several systemic treatments, including three different chemotherapy lines (cisplatin-pemetrexed, vinorelbine and platinum rechallenge) and two immunotherapy regimens using immune checkpoint inhibitors (anti CTLA-4 tremelimumab and anti PD-1 nivolumab). At the time this report was written, the patient was off-treatment, asymptomatic and with a stable radiological disease. Our case demonstrates that a prolonged survival with a preserved quality of life may be reached in selected patients through the exploitation of the available treatments in an expertise setting.

A machine learning approach for predicting high risk hospitalized patients with COVID-19 SARS-Cov-2.

BACKGROUND: This study aimed to explore whether explainable Artificial Intelligence methods can be fruitfully used to improve the medical management of patients suffering from complex diseases, and in particular to predict the death risk in hospitalized patients with SARS-Cov-2 based on admission data. METHODS: This work is based on an observational ambispective study that comprised patients older than 18 years with a positive SARS-Cov-2 diagnosis that were admitted to the hospital Azienda Ospedaliera "SS Antonio e Biagio e Cesare Arrigo", Alessandria, Italy from February, 24 2020 to May, 31 2021, and that completed the disease treatment inside this structure. The patients'medical history, demographic, epidemiologic and clinical data were collected from the electronic medical records system and paper based medical records, entered and managed by the Clinical Study Coordinators using the REDCap electronic data capture tool patient chart. The dataset was used to train and to evaluate predictive ML models. RESULTS: We overall trained, analysed and evaluated 19 predictive models (both supervised and unsupervised) on data from 824 patients described by 43 features. We focused our attention on models that provide an explanation that is understandable and directly usable by domain experts, and compared the results against other classical machine learning approaches. Among the former, JRIP showed the best performance in 10-fold cross validation, and the best average performance in a further validation test using a different patient dataset from the beginning of the third COVID-19 wave. Moreover, JRIP showed comparable performances with other approaches that do not provide a clear and/or understandable explanation. CONCLUSIONS: The ML supervised models showed to correctly discern between low-risk and high-risk patients, even when the medical disease context is complex and the list of features is limited to information available at admission time. Furthermore, the models demonstrated to reasonably perform on a dataset from the third COVID-19 wave that was not used in the training phase. Overall, these results are remarkable: (i) from a medical point of view, these models evaluate good predictions despite the possible differences entitled with different care protocols and the possible influence of other viral variants (i.e. delta variant); (ii) from the organizational point of view, they could be used to optimize the management of health-care path at the admission time.

Escherichia coli resistance to amoxiclavulanate therapy in pediatric urinary tract infections: a rising problem.

BACKGROUND: Urinary tract infections (UTIs) are a frequent disorder of childhood, mainly caused by Escherichia coli. The aim of this study was to evaluate the antimicrobial susceptibility trend in bacterial isolates in urine cultures in pediatric environment, analyzing data from our laboratory in a 6-year period. METHODS: A retrospective study was performed in AO SS. Antonio e Biagio e Cesare Arrigo (Pediatric Hospital) of Alessandria in Piedmont, North Ital. From 2015 to 2020, in a 6-year period, 1299 urinocultures were collected. Data collection was focused on demographic characteristics (age and sex) and laboratory findings (positive urocultures, antibiogram). RESULTS: Positive urocultures were 577, in which Escherichia coli represented most isolates (428, 74.2%). We found a statistically significant trend toward amoxiclavulanate resistance in the E. coli positive urinoculture comparing the period 2015-2018 vs. 2019-2020. CONCLUSIONS: Actual guidelines mostly recommend for amoxicillin-clavulanate prescription as first-line option for pediatric UTI management, this indication might be partially reconsidered. Our data underline the importance to conduct surveillance studies to determine local prevalence of antibiotic resistance to optimize therapeutic management.

Long-Term Survival among Patients Hospitalized for COVID-19 during the First Three Epidemic Waves: An Observational Study in a Northern Italy Hospital.

The mortality rate of hospitalized COVID-19 patients differed strongly between the first three pandemic waves. Nevertheless, their long-term survival has been poorly assessed. The aim of this study was to compare the clinical characteristics and mortality rates of 825 patients with coronavirus disease 2019 (COVID-19) infection who were hospitalized at the Alessandria hub hospital, in Northern Italy, during the first fifty days of the first three pandemic waves. Each subject was followed in terms of vital status for six months from the date of hospital admission or until deceased. Patients admitted during the three waves differed in age (p = 0.03), disease severity (p < 0.0001), Charlson comorbidity index (p = 0.0002), oxygen therapy (p = 0.002), and invasive mechanical ventilation (p < 0.0001). By the end of follow-up, 309 deaths (38.7%) were observed, of which 186 occurred during hub hospitalization (22.5%). Deaths were distributed differently among the waves (p < 0.0001), resulting in being higher amongst those subjects admitted during the first wave. The COVID-19 infection was reported as the main cause of death and patients with a higher mortality risk were those aged ≥65 years [adjusted HR = 3.40 (95% CI 2.20-5.24)], with a higher disease severity [adjusted HR = 1.87 (95%CI 1.43-2.45)], and those requiring oxygen therapy [adjusted HR = 2.30 (95%CI 1.61-3.30)]. In conclusion, COVID-19 patients admitted to our hub hospital during the second and the third waves had a lower risk of long-term mortality than those admitted during the first. Older age, more severe disease, and the need for oxygen therapy were among the strongest risk factors for poor prognosis.

Intragastric prepyloric enteral nutrition, bolus vs continuous in the adult patient: A systematic review and meta-analysis.

Bolus and continuous nutrition are commonly used enteral nutrition (EN) administration methodologies. Currently, there is insufficient evidence to establish which is the most effective method for reducing gastrointestinal complications in adult patients. The aim of this review is to evaluate the impact of bolus/intermittent EN compared with continuous EN for the following outcomes: diarrhea, constipation, emesis/vomiting, gastric residual volume, aspiration, and glycemic control in adult patients receiving intragastric prepyloric EN in the hospital setting. Bibliographical research was performed on the following databases: PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. The review included all randomized and nonrandomized controlled trials of patients aged ≥18 years with preserved gastrointestinal function. Meta-analysis was performed by Review Manager V.5.3. Seven studies including 551 patients were included in the meta-analysis. Five of these studies reported that the diarrhea rate was higher in the bolus feeding group (risk ratio [RR] = 2.50; 95% CI, 1.17-5.34; P = 0.02), and another five of these studies indicated that the aspiration rate was higher in the continuous feeding group (RR = 0.55; 95% CI, 0.35-0.87; P = 0.01). There were no significant differences for the other outcomes. In conclusion, intermittent EN appears to reduce the incidence of aspiration in the hospital setting; however, it may increase the risk of diarrhea. For future research, we hypothesize the joint use of continuous nutrition until the patient reaches tolerance and then passing to bolus nutrition, thus reducing the incidence of aspiration and enabling a physiological nutrition intake.

Pilot Study to Evaluate Serum Soluble Mesothelin-Related Peptide (SMRP) as Marker for Clinical Monitoring of Pleural Mesothelioma (PM): Correlation with Modified RECIST Score.

A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker for diagnosis of pleural mesothelioma (PM) and the most used for monitoring treatment. Radiological assessment of PM, based on modified RECIST (mRECIST) criteria, is challenging. This pilot study was designed to evaluate whether SMRP levels correlated over time with mRECIST score. Serial serum samples from PM patients were collected and SMRP levels were measured and compared with the mRECIST score obtained through centralized CT scans by blinded review. The within-patient SMRP-mRECIST relationship over time was estimated through a normal random-effects regression approach applied to the log-transformed mRECIST score. Overall, 58 PM patients were included (46 males and 12 females) with a median age at diagnosis of 67 years (min-max = 48-79), 44 (76%) with epithelioid and 14 (24%) with non-epithelioid histology. The total number of SMRP measurements and CT scans considered for analysis was 183. There was a statistically significant correlation between SMRP and mRECIST score in the 2 cohorts considered both separately and jointly. These results, although exploratory, suggest that SMRP measurement might be considered as an adjunct to monitor PM patients in order to delay CT scans time interval, thus warranting further investigation.

Simple Parameters from Complete Blood Count Predict In-Hospital Mortality in COVID-19.

INTRODUCTION: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. MATERIALS AND METHODS: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients (F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. RESULTS: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) (χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio (χ 2 7.6; p = 0.006), and platelet count (χ 2 5.39; p = 0.02), along with age (χ 2 87.6; p < 0.001) and gender (χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/µL was, conversely, protective (OR: 0.45 (0.32-0.63)). CONCLUSION: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Baseline clinical characteristics and prognostic factors in hospitalized COVID-19 patients aged ≤ 65 years: A retrospective observational study.

BACKGROUND: Individual differences in susceptibility to SARS-CoV-2 infection, symptomatology and clinical manifestation of COVID-19 have thus far been observed but little is known about the prognostic factors of young patients. METHODS: A retrospective observational study was conducted on 171 patients aged ≤ 65 years hospitalized in Alessandria's Hospital from 1st March to 30th April 2020 with laboratory confirmed COVID-19. Epidemiological data, symptoms at onset, clinical manifestations, Charlson Comorbidity Index, laboratory parameters, radiological findings and complications were considered. Patients were divided into two groups on the basis of COVID-19 severity. Multivariable logistic regression analysis was used to establish factors associated with the development of a moderate or severe disease. FINDINGS: A total of 171 patients (89 with mild/moderate disease, 82 with severe/critical disease), of which 61% males and a mean age (± SD) of 53.6 (± 9.7) were included. The multivariable logistic model identified age (50-65 vs 18-49; OR = 3.23 CI95% 1.42-7.37), platelet count (per 100 units of increase OR = 0.61 CI95% 0.42-0.89), c-reactive protein (CPR) (per unit of increase OR = 1.12 CI95% 1.06-1.20) as risk factors for severe or critical disease. The multivariable logistic model showed a good discriminating capacity with a C-index value of 0.76. INTERPRETATION: Patients aged ≥ 50 years with low platelet count and high CRP are more likely to develop severe or critical illness. These findings might contribute to improved clinical management.

Innovation in organizational model of the Health Professions Research Unit in an hospital.

BACKGROUND: The organizational model of the Health Professions Research Unit is unique in Italy. It is a centralized sector within of the Intercompany Department of Integrated Activities Research Innovation, afferent to the Complex Infrastructure Research Training Innovation of the SS Antonio e Biagio e Cesare Arrigo Hospital of Alessandria. It emerges from a need to promote, structure and broaden research in the clinical-healthcare field with the primary aim of improving patient care. Its internal organization is represented by a Coordinator Director (PhD) with a function assignment and three research nurses. AIM: Increase scientific production, promote partnerships with scientific communities, encourage the development of professional healthcare networks. METHODS: The definition of specific result indicators on which to estimate the trend of annual activities. The institution of a company network of Department and Structure and the establishment of collaborations with Institutions and Universities. RESULTS: From 2019 to 2021, 11 departmental and 67 Structure referents have been identified; 13 collaborations with National and 3 International Institutions have been activated (42% Increase), 23 clinical trials have been activated (92% increase), 7 articles on impacted journals have been published (100% increase) and 7 are under publication, 27 grey literature papers have been produced (47% increase)and have participated to 5 sponsored calls (100% increase) CONCLUSIONS: The new organizational model established has achieved the objectives set, proving reproducibility in other national and international realities. NURSING IMPLICATIONS: The model could increase at national and international level the scientific production related to the Healthcare professions with important benefits on the clinical outcomes of patients.

Physiopathology of the diabetic bladder.

OBJECTIVE: To investigate the incidence of diabetic cystopathy in relation to age, gender, type of diabetes, duration of diabetic disease and clinical evidence of peripheral neuropathy and to analyze the physiopathology of the various forms of diabetic cystopathy due to sensory impairment, motor-sensory impairment, motor impairment and hyperreflexia. MATERIALS AND METHODS: In a retrospective multicenter cohort study the medical records of a cohort of 126 diabetic patients with (128 patients) or without (48 patients) urological symptoms were analyzed. Patients were observed at the Città di Alessandria Clinic of Policlinico di Monza and/or at the outpatient clinic of Alessandria Hospital from June 2018 to June 2020. The study excluded patients with central and/or peripheral neuropathy, spina bifida (mylomeningocele or meningocele) or spina bifida occulta; with persistent urinary infections; in anticholinergic treatment for enteric dysfunctions; in medical treatment for cervical-prostatic-urethral obstruction; with vaginal and/or rectal prolapse of II, III, IV degree; with previous spinal or pelvic surgery including radical prostatectomy, Wertheim hysterectomy or colorectal surgery. All the patients were studied with computed tomography (CT) scan of the urinary tract, voiding cystourethrography (VCUG), uroflowmetry, cystomanometry with intrinsic pressure assessment and compliance evaluation, electromyography (EMG) of the anal sphincter, pressure flow analysis, urethral pressure profile and, when advised, pharmacological tests. RESULTS: Out of 126 diabetic patients, 48 did not show any signs or symptoms of urine voiding dysfunction; 30 were men and 18 women with an average age of 62.6 years; 20 had type I diabetes and were in treatment with insulin and 28 type II diabetes treated with oral hypoglycemic medication. The remaining 78 patients (48 men and 30 women), with an average age of 64.8 years, presented urological symptoms; 31 had type I diabetes and 47 had II type diabetes. CONCLUSIONS: Diagnosis of the various forms of diabetic cystopathy and early treatment decreases complications and consequently accesses to outpatient facilities and hospital admissions, resulting in an improved quality of life.

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

A feasibility exploratory study of a novel modality of using patient-reported outcomes (PROsEXPLOR) in the real world.

INTRODUCTION: Patient-reported outcomes (PROs) can help clinicians better evaluate chemotherapy and immunotherapy toxicity based on patient perspectives. In this exploratory study, we tested a simplified PRO questionnaire (sPQ) in routine clinical practice and patient satisfaction with this tool. METHODS: We included 16 items related to the main toxicities of chemotherapy and immunotherapy to be filled in by patients. A baseline sPQ was completed by patients before starting treatment and then in the interval between courses for a total of 4 sPQs. Patients communicated the results to a data manager, who alerted the referral oncologist in case of replies differing from the basal or previous sPQ. According to the severity of symptoms, the patient was then referred to the team nurse, the general practitioner, or another specialist. A satisfaction survey was also completed. RESULTS: In a 3-month interval, 27 patients were enrolled. Fatigue and nausea were the most frequent symptoms reported as worsening during treatment. The oncologist was involved in the management of adverse events in 4 cases, home therapy variations were recommended by the dedicated nurse in 14 cases, additional visits were performed in 6 patients, and 1 patient was admitted to the oncology ward. None of the patients had unplanned visits to the emergency department or to the hospital. The sPQ was judged to be simple, useful, and satisfactory. CONCLUSIONS: Using sPQs in routine clinical practice was feasible and well-accepted by patients. PROs allowed us to recognize and promptly manage adverse events, reducing unplanned emergency department or hospital visits to zero.

Asbestos fibers in the gallbladder of patients affected by benign biliary tract diseases.

PURPOSE: This exploratory study aimed to evaluate the presence of asbestos fibers in the biliary tract of patients living in an asbestos-polluted area using scanning electron microscopy. METHODS: Thin gallbladder sections were obtained from five patients who were operated on for gallbladder stones and the bile fluid of one of the patients was analyzed using variable-pressure scanning electron microscopy coupled with energy-dispersive spectroscopy. All patients were from Casale Monferrato, Italy, a well-known asbestos-polluted city, where the Eternit factory had operated since the beginning of the century until 1985. RESULTS: All the inorganic phases found in the gallbladder were analyzed for morphology and chemistry. Fibers and particles consistent with minerals defined by law as 'asbestos' were detected in three out of five patients. CONCLUSION: These findings suggest that asbestos fibers can be found in the gallbladder of patients exposed to asbestos, although how they reach the biliary tract remains unknown. Further studies to confirm these results are under way.

Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma.

Malignant mesothelioma (MM) is a rare and aggressive tumor of the pleura. The most important causal factor for the development of MM is occupational exposure to asbestos. Different lines of evidence suggest a role of genetic background in MM development, as for other cancers. Two published studies observed an association between MM and N-acetyl-transferase 2 (NAT2) polymorphisms. First, a Finnish study observed that the NAT2 slow acetylator phenotype was associated with an increased risk of MM. Conversely, MM risk was higher in Italian subjects carrying the NAT2 fast acetylator genotypes. The conflicting results obtained in Finland and Italy could be ascribed to random chance, considering the small panel of patients and controls in the two studies, but also ethnic or other differences may have been important. To ascertain the role of NAT2 genotype, we performed a study on 252 MM patients and 262 controls recruited in two Northern Italy areas that were characterized by high asbestos exposure, due to intense industrial activities (an asbestos cement factory in Casale Monferrato, mainly shipyards and refineries in Liguria). Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). NAT2 fast acetylator genotypes showed an increased OR, although not statistically significant, both in asbestos-exposed subjects (OR=1.47; 95% CI=0.96-2.26) and in the entire population (OR=1.38; 95% CI=0.93-2.04). These results suggest that NAT2 polymorphisms do not exert a strong effect on individual susceptibility to MM.

Long-term mortality from pleural and peritoneal cancer after exposure to asbestos: Possible role of asbestos clearance.

Models based on the multistage theory of carcinogenesis predict that the rate of mesothelioma increases monotonically as a function of time since first exposure (TSFE) to asbestos. Predictions of long-term mortality (TSFE >or= 40 years) are, however, still untested, because of the limited follow-up of most epidemiological studies. Some authors have suggested that the increase in mesothelioma rate with TSFE might be attenuated by clearance of asbestos from the lungs. We estimated mortality time trends from pleural and peritoneal cancer in a cohort of 3,443 asbestos-cement workers, followed for more than 50 years. The functional relation between mesothelioma rate and TSFE was evaluated with various regression models. The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalized to include a term representing elimination over time. We observed 139 deaths from pleural and 56 from peritoneal cancer during the period 1950-2003. The rate of pleural cancer increased during the first 40 years of TSFE and reached a plateau thereafter. In contrast, the rate of peritoneal cancer increased monotonically with TSFE. The model allowing for asbestos elimination fitted the data better than the traditional model for pleural (p = 0.02) but not for peritoneal cancer (p = 0.22). The risk for pleural cancer, rather than showing an indefinite increase, might reach a plateau when a sufficiently long time has elapsed since exposure. The different trends for pleural and peritoneal cancer might be related to clearance of the asbestos from the workers' lungs.

[Mortality in the cohort of the asbestos cement workers in the Eternit plant in Casale Monferrato (Italy)]. / Mortalità nella coorte dei lavoratori del cemento amianto della Eternit di Casale Monferrato.

OBJECTIVE: The present report updates the mortality cohort study of "Eternit" workers in Casale Monferrato, one of the major plant for the production of corrugated and plain sheets, tubes and high-pressure pipes in asbestos-cement in Italy active between 1907-1986. DESIGN: Retrospective cohort study. SETTING: The cohort included 3,443 blue-collar workers (2,663 men and 780 women) active between 1950 and 1986. Nine subjects had been excluded because of incomplete data. The follow-up ended in 2003. Mortality in the cohort was compared to the cause-specific rates for age and period of the Piedmont population and the SMR values were calculated for the period 1965-2003. MAIN OUTCOME: Analysis of cause-specific mortality. RESULTS: Follow-up was completed for 99.0% of the subjects. At the end of follow-up, 42% of the subjects were alive, 57% deceased and 1% lost to follow-up or moved abroad. In both sexes, a statistically significant increase of morality for all causes (men: SMR 135.1; 1,438 obs vs 1,064.1 exp; p < 0.01; women: RSM 149.5; 371 obs vs 248.2 exp; p < 0.01) was observed. The SMRs for lung, pleural and peritoneal cancer and for asbestosis increased according to duration of exposure and latency. For pleural cancer, increasing risks at shorter latencies were observed as exposure length increased. In men, the increase in the SMRs for lung and pleural cancer was reduced in the category of longest latency; still increased but declining SMRs were also observed at longer time since first exposure. Mortality from peritoneal cancer and asbestosis on the contrary increased with latency and with time since last exposure. Among women, a significant increase of mortality for uterine cancer (SMR 2569; 15 obs vs 5.8 exp; p < 0.01), ovarian cancer (SMR 227.3; 9 obs vs 4.0 exp; p < 0.05) and rectum cancer (SMR 318.6; 9 obs vs 2.8 exp; p < 0.01) was observed. CONCLUSION: a significant increase in mortality from the main asbestos-related diseases was confirmed by duration of exposure. In relation to latency The SMRs for lung and pleural cancer present a curvilinear trend with a decrease for longest latency periods (after 30 years from the cessation of exposure). The SMRs for peritoneal cancer and asbestosis showed a monotonic increase.